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Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model

  • Hongbo Liu , Liyan Xie and Cong Xing EMAIL logo
Published/Copyright: December 13, 2023
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Open Life Sciences
From the journal Open Life Sciences Volume 18 Issue 1

Abstract

This study analyzes the distribution of pathogenic bacteria and their antimicrobial susceptibilities in elderly patients with cardiovascular diseases to identify risk factors for pulmonary infections. A risk prediction model is established, aiming to serve as a clinical tool for early prevention and management of pulmonary infections in this vulnerable population. A total of 600 patients were categorized into infected and uninfected groups. Independent risk factors such as older age, diabetes history, hypoproteinemia, invasive procedures, high cardiac function grade, and a hospital stay of ≥10 days were identified through logistic regression. A predictive model was constructed, with a Hosmer–Lemeshow goodness of fit (P = 0.236) and an area under the receiver operating characteristic curve of 0.795, demonstrating good discriminative ability. The model had 63.40% sensitivity and 82.80% specificity, with a cut-off value of 0.13. Our findings indicate that the risk score model is valid for identifying high-risk groups for pulmonary infection among elderly cardiovascular patients. The study contributes to the early prevention and control of pulmonary infections, potentially reducing infection rates in this vulnerable population.

Keywords: cardiovascular disease; pulmonary infection; pathogenic bacteria; drug resistance; risk prediction model

1 Introduction

The incidence of cardiovascular disorders has been escalating in recent years, a trend that is concomitant with both the aging demographic and the enhancement in living standards. In the geriatric population aged 60 years and above, approximately 10% exhibit clinical manifestations associated with cardiovascular maladies, posing a significant threat to patient morbidity and mortality [1,2]. Cardiovascular pathologies are predominantly linked to arteriosclerotic underpinnings; patients manifesting acute clinical presentations are predominantly classified as high-risk, while those with chronic conditions are more inclined toward a protracted course of the disease. This extended trajectory often culminates in attenuated immunological responses and an elevated susceptibility to pulmonary infections [3]. Pulmonary infection refers to the microbial invasion of the lower respiratory tract and pulmonary parenchyma. Particularly in the elderly, the physiological decline associated with aging manifests as diminishing immunological capabilities and a compromised capacity to fend off pathogenic onslaughts. Concurrently, age-related respiratory mucosal atrophy, aberrant ciliary motility, diminished respiratory function, and reduced lung compliance are ubiquitous phenomena. Under the influence of concomitant cardiovascular disorders, patients may exhibit various degrees of pulmonary congestion and edema, leading to alveolar reduction, diminished infection resistance, and resultant pulmonary infections. Moreover, clinical management of cardiovascular diseases frequently necessitates invasive interventions like intubation or mechanical ventilation, rendering the patient more susceptible to nosocomial pulmonary infections due to pathogenic exposure [4,5].

Overutilization of antibiotics has seen a troubling increase in recent years, precipitated by the rapid development of these therapeutic agents. This has further complicated the epidemiology and antimicrobial resistance patterns of pathogenic bacteria responsible for pulmonary infections [6]. Despite voluminous research endeavors in this domain, a reliable risk prediction model for pulmonary infections in geriatric patients with cardiovascular diseases remains elusive, thereby constraining its applicative utility in prognostic settings [7].

Against this backdrop, the present study endeavors to analyze the distribution of pathogenic bacteria and their antimicrobial susceptibilities in the context of pulmonary infections in the elderly population with cardiovascular diseases. By identifying the risk factors associated with such infections, we aim to establish a robust risk prediction model. This model intends to serve as a valuable clinical tool for the early prevention of pulmonary infections in this vulnerable population. Such predictive insights are conducive to the timely initiation of targeted preventive nursing interventions as well as the implementation of standardized diagnostic, therapeutic, and nursing protocols, as elucidated in the subsequent sections of this article.

2 Materials and methods

2.1 General data

From January 2017 to December 2019, 600 patients, 312 men and 288 females, aged 60–89, with an average age of 73.54 ± 8.76 years, were selected from our hospital’s patients with cardiovascular disease. Primary diseases included hypertension (238 cases), coronary heart disease (206 cases), pulmonary heart disease (51 cases), cardiomyopathy (48 cases), congenital heart disease (32 cases), and valvular heart disease (25 cases). Based on the pulmonary infection status, patients were divided into infected group (n = 71 cases) and uninfected group (n = 529 cases). Inclusion criteria were (1) patients with cardiovascular disease, (2) age ≥60 years, and (3) patients with complete clinical data. Exclusion criteria were (1) blood or immune system-related diseases, (2) liver and kidney insufficiency, and (3) malignant tumors. The criterion for pulmonary infection was pulmonary infection secondary to cardiovascular disease and occurred during hospitalization. The diagnosis of pulmonary infection was based on the “Diagnostic Criteria for Nosocomial Infection” [8]: (1) body temperature ≥38℃, (2) white blood cell count ≥10.0 × 109/L, (3) lung auscultation showing rales of both lungs, (4) cough, expectoration, and other symptoms, (5) X-ray films showing inflammatory changes in the lungs, and (6) sputum culture showing the growth of pathogenic bacteria. The clinical data of 600 patients were collected through the hospital database, and the data were analyzed and processed by SPSS 26.0. The Hospital Theory Committee has approved the study.

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the Hospital Theory Committee.

2.2 Methods

2.2.1 General data collection

Patient baseline data were meticulously collated and comprised the following variables: (1) general information: gender, age, previous disease history, invasive operation, cardiac function grade, and hospital stay, (2) auxiliary examination involved blood routine examination, blood gas analysis, imaging diagnosis, biochemical indicators, etc.

2.2.2 Detection of pathogenic bacteria

Prior to the diagnostic evaluation, patients were instructed to gargle multiple times with isotonic saline solution and expectorate deep respiratory tract sputum into a sterile receptacle. Pathogenic bacteria were then isolated from the expectorated sputum and cultured in accordance with the “National Clinical Laboratory Procedures” [9]. The centrifugally obtained sediment was inoculated onto sheep blood agar and MacConkey agar plates, and subsequently incubated at ambient temperature for 24 h. Pathogenic bacterial identification was performed utilizing the VITEK 2 COMPACT identification system in alignment with the protocols established by French BioMérieux. Quality control strains: Escherichia coli ATCC25922, Staphylococcus aureus ATCC25923, Pseudomonas aeruginosa ATCC27853, from the Institute of Biology, Chinese Academy of Sciences, and the drug susceptibility test was detected employing the K–B test method.

2.3 Statistical methods

Statistical analyses were performed using the SPSS version 20.0 software suite. The χ 2 test was employed to assess differences between the groups. Within the framework of this retrospective investigation, the primary outcome measure was identified as the incidence of pulmonary infections. Patients were divided into an infected group and an uninfected group according to whether pulmonary infection occurred, and the difference between the infected group and the uninfected group was analyzed. Risk variables predisposing older individuals with cardiovascular disease to subsequent pulmonary infections were scrutinized via logistic regression analysis, culminating in the development of a predictive regression model. The discriminative ability of the formulated model was subsequently assessed using receiver operating characteristic (ROC) curve analysis. A statistical significance threshold was established at P < 0.05 for all inferential analyses.

3 Results

3.1 Pathogenic bacterial distribution in elderly cardiovascular patients

A total of 93 microbial strains were isolated from the sputum samples of 71 patients. This microbial array comprised 22 Gram-positive strains, accounting for 23.66% of the total isolates, in conjunction with 67 Gram-negative strains, which constituted 72.04%, and four fungal isolates, representing 4.30%. A statistically significant predominance was observed in the proportion of Gram-negative strains relative to other microbial classifications (P < 0.05) (Table 1).

Table 1

Distribution of pathogenic bacteria in the samples from this study

Pathogenic bacteria Number of strains (n) Composition ratio (%)
Gram-positive bacteria
S. aureus 14 15.05
Streptococcus pneumoniae 6 6.45
Enterococcus faecium 1 1.08
Enterococcus faecalis 1 1.08
Gram-negative bacteria
K. pneumoniae 19 20.43
E. coli 16 17.20
P. aeruginosa 15 16.13
Acinetobacter baumannii 7 7.53
Enterobacter cloacae 6 6.45
Stenotrophomonas maltophilia 3 3.23
Proteus mirabilis 1 1.08
Fungi
Candida albicans 2 2.15
Candida tropicalis 1 1.08
Candida krusei 1 1.08

3.2 Antibiotic sensitivity and resistance profiles in key bacterial strains

Klebsiella pneumoniae, E. coli, and P. aeruginosa were sensitive to imipenem, meropenem, and teicoplanin. Conversely, the highest rate of drug resistance was observed in relation to ampicillin, with resistance frequencies exceeding 85%. Elevated resistance rates were also documented for ciprofloxacin, ceftazidime, and cefoxitin, registering above the 65% threshold. S. aureus demonstrated resistance rates surpassing 50.0% for agents such as penicillin G, streptomycin, erythromycin, and azithromycin. However, susceptibility remained relatively high with resistance rates falling below 30.0% for vancomycin, gentamicin, and tobramycin. Resistance rates for acetazolamide and teicoplanin were conspicuously elevated. For comprehensive data and a breakdown of these observations, refer Tables 2 and 3.

Table 2

Analysis of the drug resistance of major Gram-negative bacteria to commonly used antibiotics

Drugs K. pneumoniae (n = 19) E. coli (n = 16) P. aeruginosa (n = 15)
Resistant strains (n) Drug resistance rate (%) Resistant strains (n) Drug resistance rate (%) Resistant strains (n) Drug resistance rate (%)
Clindamycin 4 21.05 3 18.75 3 20.00
Ampicillin 17 89.47 14 87.50 14 93.33
Streptomycin 11 57.89 8 50.00 8 53.33
Cefoxitin 13 68.42 11 68.75 9 66.67
Ceftazidime 15 78.95 12 75.00 12 80.00
Cefepime 7 36.84 6 37.50 10 66.67
Ciprofloxacin 15 78.95 12 75.00 14 93.33
Levofloxacin 9 47.37 6 37.50 7 46.67
Norfloxacin 9 47.37 8 50.00 5 33.33
Gatifloxacin 6 31.58 6 37.50 0 0.00
Amikacin 2 10.53 1 6.25 0 0.00
Meropenem 0 0.00 0 0.00 0 0.00
Imipenem 0 0.00 0 0.00 0 0.00
Teicoplanin 0 0.00 0 0.00 0 0.00
Table 3

Analysis of the drug resistance of major Gram-negative bacteria to commonly used antibiotics

Drugs S. aureus (n = 14)
Resistant strains (n) Resistant rate (%)
Penicillin G 13 92.86
Streptomycin 10 71.43
Erythromycin 11 78.57
Azithromycin 7 50.00
Vancomycin 2 14.29
Gentamicin 4 28.57
Tobramycin 2 14.29
Amoxicillin 7 50.00
Acetazolamide 0 0.00
Teicoplanin 0 0.00

3.3 Univariate risk assessment for pulmonary infections in elderly cardiovascular patients

No significant difference was noted in the incidence of pulmonary infection in elderly patients with cardiovascular disease of different genders (P > 0.05). The incidence of pulmonary infection was greater in elderly patients with cardiovascular disease of age ≥70 years, history of diabetes, invasive operation, Ⅲ–Ⅳ grade cardiac function, hypoproteinemia, and hospital stay ≥10 days than in patients of age <70 years, having no history of diabetes, no invasive operation, I–II grade cardiac function, no hypoproteinemia, and hospital stay <10 days (P < 0.05) (Table 4).

Table 4

Univariate analysis of pulmonary infection in elderly patients with cardiovascular disease

General information n Infected group (n = 71) Uninfected group (n = 529) χ 2 value P value
Gender (cases) Male 312 38 274 0.075 0.785
Female 288 33 255
Age (years) ＜70 237 19 218 5.469 0.019
≥70 363 52 311
History of diabetes None 542 57 485 9.318 0.002
Yes 58 14 44
Invasive operation None 428 41 387 7.270 0.007
Yes 172 30 142
Cardiac function grade I–II grade 319 29 290 4.910 0.027
Ⅲ–Ⅳ grade 281 42 239
Hypoproteinemia None 434 43 391 5.575 0.018
Yes 166 28 138
Hospital stay (days) ＜10 491 49 442 8.902 0.003
≥10 109 22 87

3.4 Multivariate logistic regression analysis for predicting pulmonary infections in elderly patients with cardiovascular disease

A multivariate logistic regression model was built using simply the components that showed statistically significant differences. The assignment of values was as follows: the incidence of pulmonary infection served as the dependent variable, while variables exhibiting statistical significance functioned as independent variables. These independent variables included: age (<70 years = 0, ≥70 years = 1), invasive operation (none = 0, yes = 1), history of diabetes (none = 0, yes = 1), cardiac function grade (I–II = 0, III–IV = 1), hypoproteinemia (none = 0, yes = 1), and duration of bed rest (<10 days = 0, ≥10 days = 1). According to the logistic regression output (Table 5), factors such as advanced age, history of diabetes, hypoproteinemia, invasive operation, high cardiac function grade, and hospital stay ≥10 days were independent risk factors for pulmonary infection in elderly patients with cardiovascular disease.

Table 5

Logistic multivariate regression analysis of pulmonary infection in elderly patients with cardiovascular disease

Observation index β SE Wald P Exp (B) 95% CI
Age 1.045 0.343 9.262 0.002 2.844 1.451–5.574
History of diabetes 1.586 0.392 16.382 <0.001 4.884 2.266–10.527
Invasive operation 1.249 0.332 14.124 <0.001 3.488 1.818–6.692
Cardiac function grade 2.015 0.355 32.192 <0.001 7.499 3.739–15.040
Hypoproteinemia 1.293 0.311 17.235 <0.001 3.642 1.978–6.705
Hospitalization time 1.520 0.337 20.321 <0.001 4.573 2.361–8.857
Constant −5.166 0.500 — — — —

3.5 Establishment and validation of logistic regression model for pulmonary infection risk

The regression equation for the probability of pulmonary infection in elderly patients with cardiovascular diseases is as follows: P = 1/[1 + e−(−5.166 + 1.045* Age + 1.586* Diabetes history + 1.249* Invasive operation + 2.015* Cardiac function grade + 1.293* Hypoalbuminemia + 1.520* Hospital stay)]. The Hosmer–Lemeshow test was applied to evaluate the regression model, yielding a P-value of 0.236 (Figure 1), indicating a suitable fit. Internal validation of the model revealed an area under the ROC curve (AUC) of 0.795 [95% CI (0.743–0.847), P < 0.001], denoting high discriminative power. The model demonstrated a sensitivity of 63.40% and a specificity of 82.80%. The optimal cut-off point was identified as 0.13, as determined by the maximum Youden index (Figure 2).

Figure 1 Hosmer–Lemeshow goodness-of-fit test to evaluate the calibration ability of the prediction model.
Figure 1

Hosmer–Lemeshow goodness-of-fit test to evaluate the calibration ability of the prediction model.

Figure 2 ROC curve was used to evaluate the risk scoring system.
Figure 2

ROC curve was used to evaluate the risk scoring system.

4 Discussion

In geriatric patients afflicted with cardiovascular diseases, notably those with coronary artery disease, the myocardial tissue frequently exists in a prolonged state of hypoxia and ischemia. This condition contributes to compromised systolic heart function and pulmonary capillary congestion, thereby creating a conducive environment for the colonization of various pathogenic microorganisms, ultimately predisposing the patient to pulmonary infections. Additionally, in the context of heart failure, an elevation in pulmonary arterial pressure manifests, culminating in perturbations in the pulmonary circulation and consequently augmenting the susceptibility of the pulmonary system to infection. Moreover, cardiac enlargement during episodes of heart failure indirectly exerts compressive forces on posterior mediastinal structures, such as the trachea, thereby resulting in compromised ventilation and an elevated risk of respiratory infections [10,11].

In this study, nosocomial infections were more common among the elderly with cardiovascular disease (11.83%), according to a study by van Mens et al., than pulmonary infections among those with cardiovascular disease who had been hospitalized [12]. The older patients in this research may have a higher risk of lung infection because of their weakened immune systems, diminished resistance to disease, and impaired tissue and organ functioning as a result of the disease’s prolonged course. We isolated 93 positive strains from 71 patients in the infected group; the strains were mainly Gram-negative bacilli, accounting for 72.04%. Ranzani et al. [13] also found that the proportion of Gram-negative bacilli in hospital-acquired pneumonia has been increasing each year and are the main pathogenic bacteria responsible for hospital-acquired pneumonia; our study results are consistent with this finding. The reason for Gram-negative bacilli being the primary pathogen is attributed to this bacterium’s multiple drug resistance mechanisms, such as AmpC beta-lactamases and extended spectrum beta-lactamase enzymes; multidrug resistance occurs and is also related to the irrational use of antibacterial drugs in clinical practice [14]. Among the pathogen types isolated in this study, Gram-positive bacteria comprised mainly of S. aureus, which belongs to the group of symbiotic opportunistic pathogens that are common in parasitic sites within the population [15]. K. pneumoniae, E. coli, and P. aeruginosa were the most commonly found Gram-negative bacteria in this investigation. For example, K. pneumoniae is one of the major pathogens causing nosocomial infections and may cause a variety of illnesses affecting the gastrointestinal, respiratory, and urinary systems. The presence of E. coli is considered typical of gut flora. When the body’s immunity decreases, the likelihood of pathogenic bacteria colonizing the lungs or urinary tract increases, leading to nosocomial infections. In patients who have undergone invasive operations, P. aeruginosa is one of the significant pathogens leading to nosocomial infections [16].

The use of immunosuppressants and antibacterial drugs has become increasingly common in recent years, and the number of invasive surgeries and the reliance on antibacterial drugs have both contributed to the increase in the prevalence of drug-resistant strains of the most common infectious pathogens, such as S. aureus. The percentage of S. aureus strains resistant to gentamicin, vancomycin, and tobramycin was below 30.0%, whereas the percentage of strains sensitive to acetazolamide and teicoplanin was rather high. Among the 14 strains of S. aureus isolated in this study, there were no resistant strains to acetazolamide and teicoplanin. In this study, the most sensitive drugs for three Gram-negative bacteria, K. pneumoniae, E. coli, and P. aeruginosa, were imipenem, teicoplanin, and meropenem, with sensitivity rates of more than 90%, which could be used as the preferred antibacterial drugs when infected with this pathogen. An ampicillin resistance rate of over 90% was found, with ciprofloxacin, ceftazidime, and cefoxitin showing greater resistance rates in Gram-negative bacteria. Gram-negative bacteria in this research had a high resistance rate to antibiotics because they developed extended range β-lactamases. With the wide application of third-generation cephalosporins in lower respiratory tract infection, the emergence of third-generation cephalosporin-resistant bacteria has been observed. The main mechanism of bacterial drug resistance is the production of specific β-lactamase. The super-broad-spectrum β-lactamase bacteria are multi-drug resistant bacteria, which are easy to cause explosive epidemics and difficult to control. Under normal circumstances, the production of cephalosporin enzyme is low, but a large number of β-lactamase antibiotics induce the production of cephalosporin enzyme, making the strain resistant to cephalosporins and penicillin antibiotics, and highly sensitive to carbapenems, aminoglycosides, and enzyme-inhibiting antibiotics, Therefore, carbapenems, aminoglycosides, and enzyme inhibitor antimicrobials should be considered for clinical treatment of ultra-broad spectrum β-lactamase bacteria [17,18].

In this study, in the elderly with cardiovascular disease, the risk of lung infection was 2.844 times greater in patients aged ≥70 years compared to patients aged <70 years. With the increase in age, the body’s defense and immunity decrease; elderly patients are often affected with various underlying diseases and need to take broad-spectrum antibiotics intermittently for a long time, thus becoming a high-risk group for pulmonary infection. Mairuhu et al. [19] found that diabetes is one of the risk factors for nosocomial pneumonia; in fact, in this study, we observed diabetes as a predisposing factor for pulmonary infection in elderly patients with cardiovascular disease, consistent with the above research results. In patients with diabetes, the plasma hypertonic environment inhibits the chemotaxis and phagocytosis of neutrophils and inhibits T lymphocytes, leading to a decrease in immune function. In addition, the high-glucose environment is also more conducive to bacterial growth and reproduction, so special attention should be paid to blood glucose control in hospitalized elderly patients with cardiovascular disease [20]. Serum albumin is one of the important agents involved in the maintenance of the immune mechanism, and it also reflects the nutritional status of patients. In this study, patients with hypoalbuminemia are prone to pulmonary infection; such patients are at increased risk of pulmonary infection due to decreased immunity caused by malnutrition. During invasive operations such as nasal feeding, catheterization, and tracheal intubation, either incomplete disinfection or local mucosal damage leads to an increased risk of nosocomial infection [21]. In this study, patients who had undergone invasive surgeries had a greater chance of developing a lung infection than those who had not. Invasive procedures weaken the body’s immune system and make it easier for pathogens to invade. Under mechanical ventilation, the patient’s airway is continuously opened and exposed to the outside world; outside air cannot be filtered, and secretions accumulate between the glottis and the tracheal tube balloon. Pathogens can easily invade the lower respiratory tract and increase the risk of pulmonary infection [22]. Ericson et al. [23] indicated a higher risk of pulmonary infection in patients with coronary heart disease who had higher cardiac function grades. This study also shows that cardiac function grades are an independent risk factor for postoperative infection. Cardiac function grade often represents the degree of vascular lesions in patients. Myocardial ischemia induces chemokines to activate the adherence of leukocytes to necrotic tissues and cells and their removal. However, this process releases a large number of reactive oxygen species and free radicals, which can easily lead to inflammatory reactions, aggravate injury, and induce infection [24]. Concurrently, patients with longer hospital stays are at increased risk of infection.

To better detect and manage the risk of lung infection in patients, this research also built a risk prediction model by screening risk variables in older patients with cardiovascular disease. The ROC curve, with sensitivity on the ordinate and 1-specificity on the abscissa, was used to assess the reliability of the model. Generally, an AUC > 0.7 indicates that the model has a high accuracy; the greater the AUC, the higher the accuracy [25]. The risk model established in this study exhibited good discriminant validity and can thus be applied to clinical diagnosis and treatment. Medical staff can establish risk levels for patients according to the model and perform targeted interventions to improve the utilization efficiency of medical resources. Although the risk prediction model for pulmonary infection in elderly patients with cardiovascular disease was established, there are still many shortcomings. For example, the data source in this study is relatively limited; therefore, multi-center and large-sample data are required for subsequent validation of the model. Furthermore, the indicators included in this study are daily management indicators of nosocomial infection, and relevant iatrogenic indicators were not included; therefore, the model needs further improvement.

To conclude, this study analyzed the clinical data of elderly patients with cardiovascular disease, screened risk factors based on the regression model, and constructed a preliminary risk score prediction model for pulmonary infection based on the regression model. In older patients with cardiovascular conditions in the hospital, the model has strong discriminant validity and may be utilized to provide a foundation for the early identification of high-risk groups and effective prevention and management of pulmonary infection. The limitation of this study is that the selected cases are all cases in our hospital, which may have geographical limitations, so the selection range of cases can be expanded for further exploration, and further prospective studies are needed to verify the effectiveness and applicability of this prediction model. The clinical significance of this study is to identify elderly patients with cardiovascular disease who are susceptible to lung infection through the risk prediction model, so as to prevent and control it as early as possible.

  1. Funding information: Authors state no funding involved.

  2. Conflict of interest: Authors state no conflict of interest.

  3. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2023-07-24
Revised: 2023-09-13
Accepted: 2023-09-16
Published Online: 2023-12-13

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

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

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  19. Long noncoding RNA ACART knockdown decreases 3T3-L1 preadipocyte proliferation and differentiation
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  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
https://doi.org/10.1515/biol-2022-0756
Keywords for this article
cardiovascular disease; pulmonary infection; pathogenic bacteria; drug resistance; risk prediction model
Creative Commons
BY 4.0

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  77. Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine
  78. Inhibition of TAZ impairs the migration ability of melanoma cells
  79. Molecular complexity analysis of the diagnosis of Gitelman syndrome in China
  80. Effects of maternal calcium and protein intake on the development and bone metabolism of offspring mice
  81. Identification of winter wheat pests and diseases based on improved convolutional neural network
  82. Ultra-multiplex PCR technique to guide treatment of Aspergillus-infected aortic valve prostheses
  83. Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2
  84. Immune checkpoint inhibitors in cancer patients with COVID-19
  85. Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses
  86. Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma
  87. Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy
  88. DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway
  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
  99. Tanshinone IIA alleviates chondrocyte apoptosis and extracellular matrix degeneration by inhibiting ferroptosis
  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
  102. HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy
  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
  104. Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients
  105. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials
  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
  108. Research progress on gas signal molecular therapy for Parkinson’s disease
  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
  112. CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa
  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
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