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Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children

  • Li-Pu Jie EMAIL logo
Published/Copyright: June 29, 2023

Abstract

The objective was to explore the efficacy of Tongdu Tuina manipulation in the treatment of primary single-symptom enuresis in children. A total of 102 children aged 5–16 with primary single-symptom enuresis were included in this study and randomly assigned to the Tuina group, the medication group and the control group, with 34 children in each group. The Tongdu Tuina group included manipulation of the Guanyuan, Qihai, Zhongji, Mingmen, kidney, Baihui, Sishencong and bladder acupoints, five times a week, the medication group was treated with 0.1 mg desmopressin acetate every night, and in the control group, the patients were given foods with high water content and underwent water deprivation 2 h before bedtime every night. The intervention time of each group was 1 month. The participants were followed up on Day 1 following treatment, as well as half a month, 1 month and 3 months after the implementation of the intervention measures, and the effective rate, the incidence of enuresis per week and the recurrence rate were calculated. As a result baseline demographic characteristics were comparable among 102 patients. Overall, 32 patients in the Tongdu Tuina group, 30 patients in the medication group and 34 patients in the control group completed the intervention. After half a month of treatment, there was no significant difference in the therapeutic efficacy among the three groups (P = 0.158), but each treatment could effectively reduce the frequency of weekly enuresis. The frequency of weekly enuresis in the Tongdu Tuina group was 3.8 ± 1.1 times, while that in the medication group was 4.0 ± 2.0 times. The frequency of weekly enuresis in the control group was 4.7 ± 1.8 times, and the difference was statistically significant (P = 0.016). After 1 month of treatment, the effective rates of the Tongdu Tuina group and the medication group were significantly increased (87.5% vs 83.33%, P < 0.0001), which was not the case with the control group. The frequency of enuresis was 1.9 ± 2.1 times per week in the Tongdu Tuina group, 2.4 ± 1.8 times per week in the medication group and 4.0 ± 0.9 times per week in the control group after 1 month of treatment. The difference between the three groups was statistically significant (P = 0.021), and there was a difference between the Tongdu Tuina group and the medication group (P < 0.0001). There was no significant difference between recurrence rate and the incidence of adverse events (P = 0.837, P = 0.856). In conclusion, both Tuina manipulation and desmopressin treatment can effectively improve children’s primary single-symptom enuresis with safety. However, Tongdu Tuina therapy may be superior to desmopressin treatment.

1 Introduction

Night enuresis, commonly known as urinary incontinence, is one of the most common developmental problems in childhood [1,2]. Enuresis refers to the occurrence of at least two instances of bed-wetting per week in children aged 5 years and above, with the issue lasting for at least 3 months [35]. Clinically, nocturnal enuresis is divided into primary and secondary nocturnal enuresis. Primary nocturnal enuresis is the most common [6,7], with the duration of this type at least 6 months [3,4]. In addition, nocturnal enuresis is also divided into single-symptom nocturnal enuresis and non-single-symptom nocturnal enuresis, with the former, also known as monosymptomatic nocturnal enuresis, having no daytime urinary tract manifestations, the only symptom being unconscious urination. However, the latter, non-monosymptomatic nocturnal enuresis, indicates that the patient has at least one additional lower urinary tract symptom, such as dysuria or diabetes insipidus [8,9].

According to statistics, around 16% of children aged five, 10% of children aged seven and 5% of children aged 11–12 have nocturnal enuresis, incidence rate is higher in males, while the gender ratio is around 1.5–2.1 [10]. While the natural recovery rate of nocturnal enuresis is around 15% per year with age, around 0.5–2% of children may continue to experience enuresis into adulthood without effective intervention [11,12]. Since enuresis has a significant impact on children’s self-esteem, sleep quality, quality of life, school performance and family life [13,14], adequate early intervention is crucial.

Desmopressin acetate is one of the first-line treatment methods [15]. This is a selective anti-diuretic hormone receptor type 2 agonist, which retains the anti-diuretic characteristics of anti-diuretic pressor activity. Previous studies have demonstrated that 60–70% of patients have improved nocturnal enuresis symptoms with this treatment, but recurrence following withdrawal is common [3,16]. Traditional Chinese medicine holds that the pathogenesis of enuresis in children is mostly deficiency-cold in the lower yuan and a weakness of the spleen and kidney, and is thus closely related to the kidney, bladder and spleen. The waist and abdomen points in the Du and Ren meridians have the functions of warming the kidney, consolidating the yuan and conditioning the bladder. Tuina massage can regulate the movement of the qi, blood and body fluid by dredging the Du and consolidating the Ren meridians, which has an impact on the visceral function and achieves a therapeutic effect, demonstrating a good curative effect in previous studies and considered to be suitable for promotion in primary medical institutions [17]. However, there exists no high-quality prospective study comparing Tuina and desmopressin acetate in the treatment of nocturnal enuresis. Therefore, this study provides a theoretical basis for the clinical application of Tongdu Tuina therapy by comparing the clinical efficacy, especially the long-term curative effect, of the two treatments.

2 Materials and methods

2.1 Research participants

Following a review of the relevant literature and an examination of the sample size of previous studies with good results [18], convenient sampling was used to select 134 patients with continuous primary single-symptom enuresis who stayed in The First People’s Hospital of Lanzhou City hospital from December 2017 to May 2018. The diagnostic criteria were determined with reference to the International Children’s Continence Society [19]. The inclusion criteria were as follows: (1) 5–16 years of age, (2) the incidence of enuresis was >3 times a week for more than 6 months, (3) independent daytime control of urination but no independent control during sleep, (4) patients who were conscious, with no mental illness, who (or their parents) agreed with the treatment and signed the informed consent form, (5) patients with no serious diseases of the heart, liver, kidney, hematopoietic system and endocrine system that may affect functional recovery and (6) patients with no organic diseases of the urinary system, urinary tract infection, diabetes insipidus, neurogenic bladder or urinary tract malformation. The exclusion criteria were as follows: (1) patients taking drugs for enuresis 14 days before the start of the study, (2) patients who met the contraindications of desmopressin acetate, (3) patients with serious heart diseases, haemorrhagic diseases or other diseases that are not suitable for Tuina treatment.

In the review stage of the study population, a detailed clinical examination was performed on the patients, and the parents were interviewed to obtain a detailed disease history of the patients. According to the clinical examination results and the disease history, 32 patients did not meet the inclusion criteria, including three who were aged >16 years, nine aged <5 years, six with fewer than three incidences of enuresis per week, seven whose parents did not agree to participate in the treatment, three with epilepsy, three with a urinary tract infection and one with a urinary system organic disease. A final total of 102 patients met the inclusion criteria and were numbered according to the admission time. The participants were then divided into the Tuina group, the oral desmopressin acetate group (medication group) and the control group using a random number table. This study received ethical approval from the hospital.

2.2 Intervention methods

In the Tongdu Tuina group, the patients were given foods with high water content and underwent water deprivation 2 h before bedtime every night. The main acupoints of Tuina are Guanyuan, Qihai, Zhongji, Mingmen, Shenshu, Baliao and chiropractic, while the accompanying acupoints are Baihui, Sishencong, bladder acupoints, large intestine acupoints, Jiaji, kidney top, Guiwei, Laogong, Waiguan, Zusanli, Sanyinjiao and Yanglingquan. In general, 3–4 acupoints are selected according to the specific situation. First, the manipulation was relaxed for a moment before the acupoints were pushed using four fingers with light, soft and deep penetration. Finally, the acupoints passed by Rendu were wiped by the palm for heating. This treatment was administered once a day, five times a week for 4 weeks.

The medication group, the patients were given foods with high water content and underwent water deprivation 2 h before bedtime every night. Half an hour before bedtime, 0.1 mg of desmopressin (DDAVP; Heyue, Hainan Zhonghe Pharmaceutical Co., Ltd) was swallowed with a small amount of water. After the medication, water intake was forbidden until the next morning, once every night, for 1 month. If adverse reactions occur during treatment, a timely examination is required and if abnormal results are returned, the drug treatment must be stopped immediately.

Control group: The patients were given foods with high water content and underwent water deprivation 2 h before bedtime every night.

2.3 Follow-up and observation indexes

Follow-ups were performed at baseline (Day 1 after treatment, t1), as well as half a month (15 days, t2), 1 month (30 days, t3) and 3 months (90 days, t4) after the end of one course of treatment. The follow-up indicators included effective number, weekly enuresis frequency and recurrence rate. The clinical efficacy was evaluated as follows: (1) cure: the enuresis symptoms had disappeared, (2) effectual: the incidence of enuresis decreased by >50%, (3) effective: the incidence of enuresis decreased by <50%, and (4) invalid: no decrease in the incidence of enuresis. The incidence of enuresis was obtained according to the daily enuresis logs recorded by the patient’s parents.

2.4 Statistical analysis

The data were analysed using SPSS26.0 software. The quantitative data were expressed in terms of mean and standard deviation ( X ̅ ± S ), and the qualitative data were expressed in terms of the adoption rate or composition ratio (%). A t-test was used to compare the two groups of quantitative data, variance analysis was used to compare the two groups of quantitative data and a Student–Newman–Keuls test was used to compare them. A chi-square test was used to compare the qualitative data, with the rank-sum test used if it was a rank variable; the test level was α = 0.05.

  1. Ethics approval and consent to participate: This study was conducted in accordance with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of The First People’s Hospital of Lanzhou City. Written informed consent was obtained from all participants.

3 Results

3.1 Basic characteristics of study population

After screening, 102 patients met the inclusion and exclusion criteria of this study. After half a month of treatment (t2), two patients in the Tuina group withdrew from the study, while one patient in the medication group withdrew and three could not complete the follow-up. The other study participants completed both the intervention and the follow-up. Figure 1 shows the screening, distribution and follow-up processes used, while Table 1 presents the basic demographic characteristics of the study population. The study population was concentrated in the 8–9 age group, and the main caregiver was the mother. The incidence of enuresis per week was 5.2 ± 0.9 in the Tuina group, 6.1 ± 2.1 in the medication group and 5.8 ± 1.2 in the control group. The basic characteristics of the three groups were comparable, with the differences not statistically significant (P = 0.652, P = 0.599, P = 0.212, P = 0.195).

Figure 1 
                  Screening, allocation and follow-up of study population.
Figure 1

Screening, allocation and follow-up of study population.

Table 1

Basic characteristics table of research object [ X ̅ ± S ; n (%)]

Group N Age (years) Male (%) Weekly enuresis times Caregiver (father/mother)
Tuina group 34 8.7 ± 2.1 15 5.2 ± 0.9 8/26
Drug group 34 8.5 ± 1.1 14 6.1 ± 2.1 5/29
Control group 34 8.1 ± 1.9 18 5.8 ± 1.2 4/30
F/χ 2 1.213 1.026 2.131 0.399
P 0.652 0.599 0.212 0.195

3.2 Treatment efficiency

Half a month after the treatment (t2), the therapeutic effect across the three groups was not significant, with the differences also not statistically significant (P = 0.158). However, 1 month after the treatment (t3), the therapeutic effect of the three groups was significantly improved. The cure rate of the Tuina group was 46.88%, and the total effective rate was 87.50%, while the cure rate of the medication group was 40.00%, with the total effective rate 83.33%, and the cure rate of the control group was 0%, with the total effective rate 14.71%. Given that the number of cases of cure, effectual or effective was relatively small, a trend chi-square test was not performed, with a chi-square test only used to evaluate the total efficiency of the three groups. While the difference in the effective rate across the three groups was statistically significant (P < 0.0001), the pairwise comparative analysis indicated that there was no significant difference in effective rate between the Tuina group and the medication group. However, compared to the control group, the enuresis was improved in the Tuina group and the medication group (P < 0.0001) (Table 2).

Table 2

Comparison of curative effect of three groups after half month and 1 month of treatment [n (%)]

Group N Cure Effectual Effective Invalid Total effective rates
Treatment for half a month
Tuina group 32 3(9.37) 1(3.13) 3(9.37) 25(78.13) 7(21.88)
Drug group 30 1(3.33) 2(6.67) 1(3.33) 26(86.67) 4(13.33)
Control group 34 0(0.00) 1(2.94) 1(2.94) 32(94.12) 2(5.88)
χ 2 3.696
P 0.158
Treatment for 1 month
Tuina group 32 15(46.88) 6(18.75) 7(21.87) 4(12.50) 28(87.50)a
Drug group 30 12(40.00) 7(23.33) 6(20.00) 5(16.67) 25(83.33)a
Control group 34 0(0.00) 2(5.88) 3(8.83) 29(85.29) 5(14.71)
χ 2 43.677
P <0.0001

Note: aThe difference was statistically significant compared with the control group, P < 0.0001.

3.3 Frequency of enuresis

The weekly enuresis frequency was significantly increased both after 1 month and after half a month of treatment. Half a month after the treatment (t2), the frequency of enuresis was 3.8 ± 1.1 times per week in the Tuina group, 4.0 ± 2.0 times per week in the medication group and 4.7 ± 1.8 times per week in the control group. The difference across the three groups was statistically significant (P = 0.016). One month after the treatment, the frequency of enuresis was 1.9 ± 2.1 times per week in the Tuina group, 2.4 ± 1.8 times per week in the medication group and 4.0 ± 0.9 times per week in the control group, with the difference across the three groups statistically significant (P = 0.021). Compared to in the control group, the frequency of enuresis in the medication and Tuina groups was significantly improved after half a month and after 1 month of treatment, and the difference was statistically significant (P < 0.0001). The frequency of enuresis in the Tuina group was significantly lower than that in the medication group, and the difference was statistically significant (P < 0.0001) (Table 3).

Table 3

Comparison of weekly enuresis frequency among three groups after half and 1 month of treatment

Group Baseline Treatment for half a month Treatment for 1 month
Tuina group 5.2 ± 0.9 3.8 ± 1.1a 1.9 ± 2.1ab
Drug group 6.1 ± 2.1 4.0 ± 2.0a 2.4 ± 1.8a
Control group 5.8 ± 1.2 4.7 ± 1.8 4.0 ± 0.9
F 2.131 3.638 3.002
P 0.212 0.016 0.021

Note: aThe difference was statistically significant compared with the control group, P < 0.0001. bThe difference was statistically significant compared with the drug group, P < 0.0001.

3.4 Recurrence rate

Three months after treatment (t4), the cured patients were followed up. One patient (6.67%) in the Tuina group and two (16.67%) in the medication group had relapsed. However, the difference between the two groups was not statistically significant (P = 0.837).

3.5 Adverse events

One case of hyponatremia occurred in the drug group during treatment, but the patient returned to normal after a limited intake of drinking water. There were two cases of eczema caused by enuresis in the Tuina group and the medication group, and three such cases in the control group. There was no significant difference in the incidence of adverse events among the three groups (P = 0.856).

4 Discussion

This study evaluated the clinical efficacy and safety of Tongdu Tuina manipulation and desmopressin acetate in the treatment of primary single-symptom enuresis. The results indicated that 21.88% of the patients in the Tuina group were improved after half a month of treatment, with the frequency of enuresis down to 3.8 ± 1.1 times per week. The effective rate after 1 month of treatment was 87.50%, with the frequency of enuresis decreasing to 1.9 ± 2.1 times per week. The effective rate was 13.33% and the frequency of enuresis was 4.0 ± 2.0 times a week after taking desmopressin acetate for half a month. One month after the medication treatment, the effective rate was 83.33% and the frequency of enuresis decreased to 2.4 ± 1.8 times a week. Three months after the treatment, the recurrence rate of the Tuina group was not statistically significant compared to that of the medication group, being 10% lower in the former, indicating a certain clinical significance.

At present, it is widely recognized that nocturnal enuresis is related to specific psychological and genetic factors, as well as neurogenesis and bladder dysfunction in children [20]. According to the theory of traditional Chinese medicine, enuresis is related to congenital defects, but the aetiology of children’s enuresis has not yet been fully elucidated. However, it can be clarified that children’s enuresis is related to deficiency-cold of the lower Yuan, deficiency of the kidney qi and damp-heat of the liver meridian [21]. Western medicine therapy mainly includes drug intervention and awakening therapy. However, previous studies have demonstrated that while wake therapy has a positive effect on the treatment of enuresis, it may repeatedly interrupt a child’s sleep, thereby reducing both sleep quality and compliance [2224]. Meanwhile, although desmopressin acetate is a first-line treatment, adverse events, such as hyponatremia, may still occur during long-term treatment [25].

Tuina manipulation has unique advantages in the treatment of nocturnal enuresis in children. A systematic evaluation of 12 randomized controlled trials indicates that the therapeutic effect of Tuina manipulation is more obvious than that of traditional Chinese medicine (risk ratio = 1.45; 95% confidence interval: 1.31, 1.61) [18]. Tuina therapy using specific acupoints (Baihui, Qihai, Zhongji, Mingmen, kidney acupoints, etc.) balances the Yin and Yang and plays a role in tonifying any deficiency, the operation of the body’s qi and blood and the visceral function activities, achieve the effect of treating infantile enuresis.

5 Limitations

This study has certain limitations. First, the study was based on a single centre and involved a comparatively small sample, meaning some bias could have been introduced and the research population may lack certain representativeness. Multi-centre data are needed to improve the credibility of the results. In addition, the study population consisted of children with good intellectual development, and the effect of Tongdu Tuina therapy and desmopressin acetate on children with poor intellectual development could not be evaluated. Finally, due to the limitation of funding in this study, only the clinical effect of 1 month of intervention was explored, meaning the effect and safety of long-term intervention could not be investigated.

6 Conclusion

In summary, Tongdu Tuina and desmopressin acetate are effective and successful treatment options for primary single-symptom enuresis in children, with both treatments effectively improving the cure rate and reducing the weekly frequency. Compared to desmopressin acetate treatment, the recurrence rate and the incidence of enuresis were clearly improved following Tongdu Tuina therapy, which provides an effective treatment option for the treatment of enuresis in children and is worthy of universal promotion in clinical practice.


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Acknowledgments

Not applicable.

  1. Funding information: Clinical efficacy of alarm bell combined with bladder training in the treatment of enuresis in children, fund number 2022-5-124.

  2. Author contributions: Jie L.P. has made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; Jie L.P. has been involved in drafting the manuscript and revising it critically for important intellectual content; Jie L.P. has given final approval of the version to be published.

  3. Conflict of interest: The author had no any personal, financial, commercial or academic conflicts of interest separately.

  4. Data availability statement: All data generated or analysed during this study are included in this article.

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Received: 2022-11-22
Revised: 2023-03-15
Accepted: 2023-04-13
Published Online: 2023-06-29

© 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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  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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