Startseite Predictors of gastrointestinal complaints in patients on metformin therapy
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Predictors of gastrointestinal complaints in patients on metformin therapy

  • Branislava Raičević EMAIL logo und Slobodan Janković
Veröffentlicht/Copyright: 29. November 2023
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Open Medicine
Aus der Zeitschrift Open Medicine Band 18 Heft 1

Abstract

Although being very effective in the treatment of diabetes and a few other conditions, metformin (MTF) cannot be tolerated by many patients due to gastrointestinal (GI) complaints. A number of risk factors for intolerance were identified, but many are still controversial or uninvestigated. The aim of this study was to further investigate possible risk factors for the occurrence of GI complaints in patients on MTF therapy. A cross-sectional design was used for this multicentric study on adult patients visiting 50 community pharmacies in Montenegro. The patients were surveyed by semi-structured questionnaire after a service of a pharmacist was delivered, and their drugs dispensed. Uni- and multi-variate regression methods were used for processing the data.

In total 330 patients participated in the study. A higher body mass index (OR = 1.113, p = 0.003), living at a higher altitude (OR = 1.725, p = 0.000), anaemia (OR = 4.221, p = 0.008), and intestinal infection in the last 3 months (OR = 2.801, p = 0.006) increased the risk of GI complaints in patients on MTF therapy, while the use of statins was protective (OR = 0.204, p = 0.016). Each case of MTF intolerance should be carefully investigated for risk and protective factors, which could be potentially eliminated or augmented, respectively, and MTF withdrawal avoided.

Keywords: metformin intolerance; risk factors; statins; anaemia

1 Introduction

1.1 Definitions and epidemiology

Metformin (MTF) is an oral antidiabetic drug that, due to its effectiveness and safety, as well as its relatively low price, represents the first pharmacological therapeutic line in the treatment of type 2 diabetes according to the guidelines of the European and American diabetes associations [1,2]. In recent years, MTF has been the subject of numerous studies that indicate the beneficial effect of MTF in many other diseases, such as numerous types of cancer, obesity, and cardiovascular and neurodegenerative diseases, as well as liver and kidney diseases [2]. However, MTF treatment is often (20–30%) associated with gastrointestinal (GI) adverse effects (AEs) [3,4]. This GI intolerance negatively affects quality of life and compliance, and 5% of patients discontinue therapy [4,5]. GI problems mostly occur at the beginning of therapy, but there are studies that indicate the occurrence of GI complaints and after a long time of drug use [5].

1.2 Known risk factors

The mechanism underlying MTF-induced GI intolerance is still unclear. There are several hypotheses trying to give an explanation: stimulation of intestinal serotonin secretion, changes in incretins and glucose metabolism, and malabsorption of bile salts [4,5]. Not much is known about risk factors for the occurence of GI intolerance, too. There are just a few studies that show the possible association of certain factors and the occurrence of GI AEs of MTF [6]. An observational study comparing 83 patients who discontinued MTF therapy due to GI AEs with 332 age- and sex-matched controls indicated a possible association between GI intolerance to MTF and rate of ischemic heart disease, left-handedness, ABO blood groups, and iron load [7]. Another study found an association between GI AEs of MTF and characteristics of large bowel microbiota [8]. There are also claims that females are more often intolerant to MTF, but more evidence is needed for this to be confirmed [9]. It is of vital importance to reveal and then control the factors associated with GI AEs of MTF, or otherwise a number of patients will stop taking MTF due to intolerance, depriving themselves of very effective and convenient drug.

The aim of this study was to further investigate possible risk factors for the occurrence of GI complaints in patients on MTF therapy.

2 Methods

2.1 The study design and population

The research was conducted as a cross-sectional study on adult patients in 50 community pharmacies out of a total of 250 pharmacies in the territory of the whole of Montenegro (Figure 1). The study was conducted from June 2022 until October 2022 on a convenient sample of patients who visited pharmacies where the researchers worked on the dispensing of medicines. Inclusion criteria were: age over 18 years, possession of MTF prescription, permanent residence in Montenegro, and signed patient consent form. Excluded from the study were pregnancy and lactation, patients prescribed with medication for psychiatric illnesses or dementia, patients with chronic disease in the terminal phase, as well as patients who came to the pharmacy for medication due to acute conditions.

Figure 1 The study flowchart.
Figure 1

The study flowchart.

  1. Ethical approval: Before its start, the study was approved by the Ethics Committee of the Faculty of Medicine, University of Montenegro, and the Ethics Committee of the Pharmaceutical Chamber of Montenegro. The patients in the study were treated according to the principles of Helsinki Declaration on the protection of human subjects of clinical investigations and to those of Good Clinical Practice.

2.2 The study procedures

The study data were collected from patients in the pharmacies they visited using questionnaires filled out by researchers based on patients’ verbal responses. Before completing the questionnaire, patients were offered brief information about the key elements of their participation, and then patients would be included if they signed a consent to participate. The survey collected patient demographic data, data on GI complaints related to taking MTF, comorbidities, and data on concomitant therapy and habits.

2.3 The sample size

The minimum sample size of 194 patients required to achieve a study power of at least 80%, with a statistical error of the first type (alpha) of 0.05, was calculated based on the z-test (difference between two independent proportions) and the expected difference in predictor frequency between the group with and the group without GI complaints of 20%.

2.4 Statistics

After testing the normality of the distribution of values of continuous variables by Kolmogorov–Smirnov test, those with normal distribution were described by mean and standard deviation, and those without were described by median and interquartile range. The study groups were compared in terms of continuous variables by Student’s T-test for independent samples if normally distributed and by Mann–Whitney U test if not following a normal distribution. Categorical variables were described by rates and percentages, and differences between the study groups were tested by the Chi-square test, or by the Fisher exact test if the frequency of one of the the categories was below 5.

To explore the influence of independent or confounding variables adjusted for other predictors on the binary categorical outcome, multivariate binary logistic regression was used, after ensuring previously that its assumptions were met: linearity, absence of outliers, independence of variables, and absence of collinearity. The final model was obtained by backward deletion procedure. Quality of the final model was examined with the Hosmer–Lemeshow test. The extent to which the final binary logistic regression model explained the outcome was estimated by Nagelkerke’s pseudo R 2 and Cox and Snellen’s pseudo R 2. The statistical tests were considered significant if the probability of the null hypothesis was below 0.05.

3 Results

3.1 Descriptive statistics

The questionnaire response rate was 89%. In total, 330 patients completed the study, of whom 73 (22.1%) had GI complaints that accompanied the use of MTF, and 257 (77.9%) of them did not have GI complaints after the introduction of MTF into therapy. The types of GI complaints that accompanied the use of MTF were distributed as follows: nausea occurred in 11 (15.1%) patients, diarrhea in 17 (23.3%) patients, nausea with abdominal pain in 6 (8.2%), flatulence in 9 (12.3%) patients, nausea, abdominal pain and diarrhea in 25 (34.3%) patients, and abdominal pain combined with flatulence in 5 (6.8%) individuals. In the largest number of patients, 42 of them (57.5%), the complaints passed spontaneously, and the patients continued taking MTF; 26 (35.6%) patients required the use of drugs to suppress GI complaints but still continued to take the drug. Only 5 patients (6.9%) were forced to discontinue MTF due to intolerance to GI complaints; after discontinuation of the drug, GI complaints disappeared in all patients. GI complaints appeared on average after 6.3 weeks from the start of taking MTF and lasted on average 33.4 weeks. On a scale from 1 to 10, the average intensity of GI complaints associated with the use of MTF in our sample was 4.3 ± 2.2 points. Detailed characteristics of the groups of patients with and without GI complaints are shown in Table 1.

Table 1

Characteristics of patients by study groups

Study variable Patients with GI complaints (n = 73) Patients without GI complaints (n = 257) Null hypothesis probability*
Age (years) 62 (19.5) 65 (13.0) 0.033§
Gender (male/female) 24/49 (32.9%/67.1%) 117/138 (45.9%/54.1%) 0.054
BMI (kg/m2) 27.5 (6.4) 26.4 (5.2) 0.047
MTF daily dose (mg) 1000.0 (1000.0) 1000.0 (1000.0) 0.594
Number of individual doses per day 2.0 (1.0) 2.0 (1.0) 0.384
MTF therapy (months) 60.0 (99.0) 60.0 (96.0) 0.263
Altitude of the patient’s residence (m) 173.0 (629.0) 44.0 (36.0) 0.003§
Charlson Comorbidity Index 3.0 (2.0) 3.0 (2.0) 0.193
Systolic blood pressure 130.0 (20.0) 130.0 (15.0) 0.707
Diastolic blood pressure 85.0 (10.0) 80.0 (10.0) 0.715
Physical activity in hours per week 7.0 (10.0) 10.0 (16.0) 0.013§
Marital status: married/not married 59 (80.8%)/14 (19.2%) 216 (84.0%)/41 (16.0%) 0.514
Zanimanje: not actively working/office jobs/manual labor jobs 40 (54.8%)/12 (16.4%)/21 (28.8%) 150 (58.4%)/24 (9.3%)/83 (32.3%) 0.226
Education: elementary/high school/higher education 4 (5.4%)/40 (54.8%)/29 (39.8%) 17 (6.6%)/150 (58.7%)/89 (34.7%) 0.313
Residency: town/village 70 (95.9%)/3 (4.1%) 246 (94.1%)/10 (3.9%) 1.000
Residency: continental/seaside 54 (74.0%)/19 (26.0%) 148 (57.8%)/108 (42.2%) 0.012§
Immediate/delayed release MTF 54 (74.0%)/19 (26.0%) 193 (75.1%)/64 (24.9%) 0.845
MTF monotherapy/fixed combination 50 (68.5%)/23 (31.5%) 207 (80.5%)/50 (19.5%) 0.052
Indication for MTF: diabetes type 2/other 62 (84.9%)/11 (15.1%) 215 (83.7%)/42 (16.3%) 0.794
Missed doses per week: none/1–2/≥3 51 (69.9%)/16 (21.9%)/6 (8.2%) 202 (78.6%)/46 (17.9%)/9 (3.5%) 0.147
Using food supplements in the last 3 months: yes/no 24 (32.9%)/49 (67.1%) 77 (30.0%)/180 (70.0%) 0.633
Using statins: yes/no 3 (4.1%)/70 (95.9%) 42 (16.3%)/215 (83.7%) 0.006§
Using ACE inhibitors: yes/no 33 (45.2%)/40 (54.8%) 101 (39.3%)/156 (60.7%) 0.365
Prior surgery: yes/no 25 (34.2%)/48 (65.8%) 80 (31.1%)/177 (68.9%) 0.614
Prior injuries: yes/no 8 (11.0%)/65 (89.0%) 38 (14.8%)/219 (85.2%) 0.405
Any drug allergy: yes/no 9 (12.3%)/64 (87.7%) 38 (14.8%)/219 (85.2%) 0.596
Any allergy: yes/no 12 (16.4%)/61 (83.6%) 25 (9.7%)/232 (90.3%) 0.109
Intestinal infections in last 3 months: yes/no 20 (27.4%)/53 (72.6%) 28 (10.9%)/229 (89.1%) 0.000§
Inflammatory bowel disease: yes/no 2 (2.7%)/71 (97.3%) 0 (0.0%)/257 (100.0%) 0.048§
Migraine or cluster headache in the last 3 months: yes/no 8 (11.0%)/65 (89.0%) 20 (7.8%)/237 (92.2%) 0.390
Tension headache in the last 3 months: yes/no 18 (24.7%)/55 (75.3%) 33 (12.9%)/224 (87.1%) 0.014§
GERD: yes/no 26 (35.6%)/47 (64.4%) 46 (17.9%)/211 (82.1%) 0.001§
Peptic ulcer: yes/no 2 (2.7%)/71 (97.3%) 4 (1.6%)/253 (98.4%) 0.617
Helicobacter pylori: yes/no 4 (5.5%)/69 (94.5%) 5 (1.9%)/252 (98.1%) 0.113
Anemia: yes/no 10 (13.7%)/63 (86.3%) 10 (3.9%)/247 (96.1%) 0.002§
Kidney disease: yes/no 7 (9.6%)/66 (90.4%) 13 (5.1%)/244 (94.0%) 0.152
Liver disease: yes/no 4 (5.5%)/69 (94.5%) 14 (5.4%)/243 (94.6%) 1.000
Smoking: no/yes/ex smoker 44 (60.3%)/18 (24.7%)/11 (15.1%) 159 (61.9%)/64 (24.9%)/34 (13.2%) 0.920
Drinking alcohol: no/yes/ex drinker 63 (86.3%)/8 (11.0%)/2 (2.7%) 212 (82.5%)/39 (15.2%)/6 (2.3%) 0.659
Drinking coffee: yes/no 60 (82.2%)/13 (17.8%) 199 (77.4%)/58 (22.6%) 0.382
Vegetarian or vegan: yes/no 1 (1.4%)/72 (98.6%) 4 (1.6%)/253 (98.4%) 1.000
Having special diet in the last 3 months: yes/no 11 (15.1%)/62 (84.9%) 20 (7.8%)/237 (92.2%) 0.060
Religious fasting in the last 3 months: yes/no 9 (12.3%)/64 (87.7%) 24 (9.3%)/233 (90.7%) 0.452
Dominant source of proteins: fish/red meat/both fish and red meat/neither fish nor red meat 9 (12.3%)/35 (47.9%)/23 (31.5%)/6 (8.2%) 39 (15.2%)/97 (37.7%)/102 (39.7%)/19 (7.4%) 0.415
Eating spicy, salty and hot food: yes/no 31 (42.5%)/42 (57.5%) 92 (35.8%)/165 (64.2%) 0.298
Adding salt or spices to already cooked food: yes/no 24 (32.9%)/49 (67.1%) 72 (28.0%)/185 (72.0%) 0.420
Sufficiently chewing food: yes/no 51 (69.9%)/22 (30.1%) 179 (69.6%)/78 (30.4%) 0.972
Eating fruits together with their seeds: yes/no 36 (49.3%)/37 (50.7%) 137 (53.3%)/120 (46.7%) 0.547

*Values of continuous variables were compared with non-parametric ones Mann–Whitney U test, because the variables were not normally distributed, while categorical variables were compared with the Chi-square test or Fisher’s test (in case the frequency of a category was less than 5). For continuous variables, variable values are presented using median and interquartile range.

§Statistically significant difference.

GERD – Gastroesophageal reflux disease.

3.2 Multivariate analysis

Multivariate binary logistic regression was used to investigate the association of independent and confounding variables with GI AEs of MTF. The model was built by backward conditional deletion method, beginning with the following potential predictors: age, sex, body mass index (BMI), daily dose of MTF, number of daily doses, length of MTF therapy, Box-Cox transformed altitude of the patient’s residence ([altitude ^ lambda − 1]/lambda, lambda = −0.15), Charlson Comorbidity Index, blood pressure, physical activity per week, marital status, occupation, education, residency, immediate/delayed release MTF, MTF formulation, diagnosis, number of missed doses per week, using food supplements in the last 3 months, using statins, using angiotensin-converting enzyme (ACE) inhibitors, prior surgery, prior injury, allergy, intestinal infections in last 3 months, inflammatory bowel disease, migraine or cluster headache in last 3 months, tension headache in the last 3 months, GERD, peptic ulcer, Helicobacter pylori, anemia, kidney disease, liver disease, smoking, drinking alcohol, drinking coffee, vegetarian or vegan, having special diet in the last 3 months, religious fasting in the last 3 months, dominant source of proteins in food, eating spicy, salty and hot food, adding salt or spices to already cooked food, sufficiently chewing food, and eating fruits together with their seeds. The assumptions of logistic regression were met: binary outcome (GI AEs or not), observations were independent, no multicollinearity (variance inflation factor – VIF was below 1.5 for all predictors), sufficient size of the sample, and no extreme outliers. The linear relationship between explanatory variables and the logit of the outcome was tested and confirmed for all continuous variables by the Box-Tidwell test (p > 0.05). The variables included in the final model of binary logistic regression are shown in Table 2; the model was a satisfactory fit of the data: Hosmer and Lemeshow test was 11.632 (df = 8, p = 0.168), Cox and Snell R square 0.166, and Nagelkerke R square 0.254.

Table 2

Predictors of GI complaints in patients on MTF therapy

Risk factors Raw OR (95% CI) p Adjusted OR (95% CI) p
BMI 1.052 (0.992–1.116) 0.091 1.113 (1.037–1.194) 0.003
Transformed altitude 1.605 (1.224–2.105) 0.001 1.725 (1.276–2.333) 0.001
Using statins 0.219 (0.066–0,730) 0.013 0.204 (0.056–0.747) 0.016
Intestinal infection in the last 3 months 3.086 (1.616–5.894) 0.001 2.801 (1.346–5.829) 0.006
Anemia 3.921 (1.564–9.830) 0.004 4.221 (1.456–12.236) 0.008

CI – confidence interval; OR – odds ratio.

4 Discussion

This study showed that a higher BMI, living at a higher altitude, anaemia, and intestinal infection in the last 3 months, increases the risk of GI complaints in patients on MTF therapy, while the use of statins is protective. While anaemia and previous intestinal infection increase the risk by 4.2 and 2.8 times, respectively, each additional unit of BMI increases the frequency of GI complaints by 11%, and an increase in altitude from 10 to 2,000 m doubles the frequency of these complaints. Concomitant therapy with statins reduces the frequency of GI complaints by about 80%.

The association of anaemia with GI complaints in patients on MTF therapy is not surprising, given that first MTF causes vitamin B12 deficiency and consequent macrocytic anaemia [10] and then that hypochromic anaemia is often caused by diseases of the gastroduodenal mucosa (peptic ulcer, gastritis), which make the mucosa more sensitive to the action of exogenous substances reaching a high concentration in the GI secretion after oral intake [11]. In our study, we did not have the insight in the laboratory results of the patients, so we could not determine whether the anaemia that the patients had was macrocytic (caused by vitamin B12) or hypochromic, microcytic (caused by bleeding from the lining of the GI tract), and confirm previous assumptions. Also, other authors have so far not found a connection between anaemia and GI complaints due to MTF use, which indicates that additional studies are necessary to confirm and explain this connection.

After GI infections, a number of patients experience chronic inflammation of the GI tract, with various complaints, which sometimes turns into post-infection irritable bowel syndrome [12]. In such a situation, the application of any drug that can further worsen the functioning of the GI tract will be accompanied by a higher frequency of complaints in that region, which is most likely to happen with the use of MTF. It is known that MTF leads to the accumulation of lactate in the mucosa of the GI tract because it gives priority to the anaerobic metabolism of glucose in the mucosa due to the very high concentration it achieves in the tissue [6]. A high level of lactate creates acidosis locally in the mucous membrane, which stimulates the contraction of smooth muscles and creates a sensation of pain. All these changes will be more pronounced and have more unfavourable consequences when the mucous membrane is already damaged by previous GI infections.

A study on patients from China [13] found no influence of BMI equal to or greater than 25 kg/m2 on the frequency of GI complaints in patients on MTF therapy. In our study as well, univariate analysis did not associate BMI with the occurrence of GI complaints, but after adjusting for the effects of other factors in multivariate analysis, an increase in BMI significantly increased the likelihood of GI complaints. The difference in the obtained effects is most likely due to the higher statistical power of the study when BMI is taken as a continuous rather than a categorical variable (greater or less than 25 kg/m2). People who are overweight or obese have more frequent GI symptoms, primarily due to unhealthy habits when eating, like aerophagia, swallowing unchewed food, fast eating, and eating or drinking large volumes of food. They frequently complain of bloating, abdominal pain, retching, vomiting, diarrhoea, or incomplete evacuation, which are symptoms often encountered in patients taking MTF, too [14].

Since both drugs, MTF and statins, affect glucose metabolism as well as lipid metabolism, it is not surprising that MTF–statin combination therapy is prescribed to many patients with type 2 diabetes mellitus. In recent years, several studies have been conducted that indicate the positive effects of combined therapy with MTF and statins on various diseases, such as cardiovascular diseases, some cancers, as well as in the treatment of polycystic ovaries [15,16]. There is a study that confirms the finding that the simultaneous use of statins and MTF shows a positive effect on GI side effects. A higher percentage of MTF-tolerant patients used statins (66%) compared to MTF-intolerant patients (48%) [7]. The answer is probably related to the ability of statins to affect the gut microbiota by directly affecting the number of gut bacteria and bile acid metabolism in the gut [17]. Research conducted on mice also shows a positive effect of one statin (rosuvastatin) on the composition and diversity of intestinal microbiota, bile acid metabolism, and immunity of the GI tract [18].

GI problems at high altitude are commonplace [19]. The impact can be explained through the influence of hypoxia at higher altitude on the physiological changes in the digestive system, which can further result in altered absorption, distribution, metabolism, and excretion of drugs. The increase in GI complaints with the use of MTF in people living at higher altitudes can be explained by the effect of hypoxia on slowing down the metabolism of MTF, by increasing both the mean retention time and the half-life time (t1/2) of MTF. A study conducted in rats after exposure to simulated hypoxia at high altitude revealed significant changes in the pharmacokinetics of MTF. The key effect of hypoxia is reflected in the reduction of the expression of organic cation transporter 2, which leads to a significant increase in the t1/2 of MTF [20].

A possible mechanism by which MTF causes GI AE probably includes stimulation of adenosin-monophosphate-activated protein kinase and consequent inhibition of the mammalian target of rapamycin (mTOR). The mTOR-regulated pathway is responsible for protein synthesis and cell proliferation in normal circumstances; therefore, MTF induces apoptosis of cells in GI epithelium [21–24]. The effect of MTF in our study could have been augmented by pharmacokinetic interactions with drugs that inhibit its membrane transporters OCT1, MATE1, and MATE2K [25]. Although an increase in oxidative stress may have a certain role in GI AEs of MTF, too [26], roles of prohibitin 1 and β-catenin cannot be excluded [27,28]. Since antioxidants phenylethanoid glycoside verbascoside and beta-carotene effectively protect renal podocytes and subcellular structures involved in glucose metabolism from free radicals, we may speculate that the use of antioxidants in general could ameliorate GI AEs of MTF, at least in some patients [29,30].

If one considers the possible relationship between the independent predictors of GI AEs of MTF, hypoxia could be the common denominator. While increased altitude and anaemia both directly contribute to tissue hypoxia, obesity (i.e., increased BMI) is associated with obstructive sleep apnea and consequent chronic intermittent hypoxia [31]. Hypoxia causes chronic activation of hypoxia-inducible factors in the GI tract, which lead to tissue injury and inflammation, making intestines more sensitive to additional stimuli like MTF [32]; a similar causal relationship exists between intestinal infection and MTF.

Our study has several limitations. First of all, due to the attachment of the researchers to certain community pharmacies, the sample could not be random, which opens up the possibility of bias in the selection of respondents. Second, the data collected by the survey could not have been verified in the patients’ medical records. Also, the relatively limited number of subjects made it impossible to detect more subtle influences of potential predictors, which, taken together, can change the overall picture of the conditioning of GI complaints during MTF therapy.

In conclusion, each case of MTF intolerance should be carefully investigated for risk factors, since some of them could be neutralized and the patient prevented from being derived from this very useful drug. Anaemia could be corrected, reinstitution of MTF could be attempted later after a GI infection, the drug could be introduced more gradually in patients living at high altitudes, and sometimes introduction of a statin for some other reason may be helpful.

  1. Funding information: This work was supported by the Ministry of Education, Science and Technological Development under Grant No. 175007 and contract No. 451-03-47/2023-01/200111.

  2. Conflict of interest: The authors have no financial or non-financial interests that are directly or indirectly related to the work submitted for publication.

  3. Data availability statement: The original data from this study are available on reasonable request to the corresponding author.

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Received: 2023-08-22
Revised: 2023-10-27
Accepted: 2023-11-13
Published Online: 2023-11-29

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

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  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
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  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
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  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
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  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
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  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0871
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metformin intolerance; risk factors; statins; anaemia
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Artikel in diesem Heft

  1. Research Articles
  2. Exosomes derived from mesenchymal stem cells overexpressing miR-210 inhibits neuronal inflammation and contribute to neurite outgrowth through modulating microglia polarization
  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
  17. SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
  19. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
  20. Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide β glypeptide: A cross-sectional study in elder Chinese population
  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
  24. Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
  25. Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
  27. LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
  28. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
  29. Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
  31. Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
  32. Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model
  33. A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma
  34. WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
  35. Radiomics model using preoperative computed tomography angiography images to differentiate new from old emboli of acute lower limb arterial embolism
  36. Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks
  37. Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy
  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
  39. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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