ObjectiveTo investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. MethodsA total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study， and according to the results of abdominal color Doppler ultrasound， they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients， including demographic data， medical history， family history， physical examination， Color Doppler ultrasound， and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index （TyG）， TyG-body mass index （BMI） index， atherogenic index of plasma （AIP）， and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio （NHHR）； the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio （NLR）， neutrophil percentage-to-albumin ratio （NPAR）， and monocyte-to-lymphocyte ratio （MLR）； the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin （ALBI） score， NAFLD fibrosis score （NFS）， fibrosis-4 （FIB-4） index， and aspartate aminotransferase-to-platelet ratio index （APRI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis， restricted cubic spline analysis， and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. ResultsThe prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex， age， smoking history， diabetes， hypertension， lymphocytes， platelets， glucose， albumin， serum uric acid， alanine aminotransferase， aspartate aminotransferase， red blood cell， NLR， NPAR， MLR， NFS， FIB-4 index， and ALBI score （all P<0.05）. The multivariate Logistic regression analysis showed that NLR （odds ratio ［OR］=1.091， 95% confidence interval ［CI］： 1.028　—　1.160， P<0.05）， NPAR （OR=1.073， 95%CI： 1.042　—　1.105， P<0.05）， MLR （OR=1.142， 95%CI： 1.057　—　1.232， P<0.05）， NFS （OR=1.239， 95%CI： 1.190　—　1.291， P<0.05）， and FIB-4 index （OR=1.326， 95%CI： 1.241　—　1.417， P<0.05） were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone （non-linear P<0.05）. The mediating effect analysis further showed that the association of NLR， MLR， and NPAR with gallstones was partially mediated by NFS or FIB-4 index， with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%， respectively. ConclusionNFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients， and they also mediate the association of NLR， NPAR， and MLR with the risk of gallstone.

ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque （CP） in patients with lean metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort， with the presence or absence of CP as the outcome， and fibrosis-4 （FIB-4） index and nonalcoholic fatty liver disease fibrosis score （NFS） were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis， the restricted cubic spline analysis， the receiver operating characteristic curve， and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group（n=607）， the CP group （n=350） had a significantly higher proportion of male patients， a significantly higher proportion of patients with smoking/diabetes/hypertension， and significantly higher levels of age， creatinine， blood urea nitrogen， triglycerides， fasting blood glucose， aspartate aminotransferase， aspartate aminotransferase/alanine aminotransferase ratio， NFS， and FIB-4 index， as well as significantly lower levels of platelet count and albumin （all P<0.05）. The multivariate logistic regression analysis showed that after adjustment for confounding factors， FIB-4 index （odds ratio［OR］=2.979， 95% confidence interval［CI］：2.141 — 4.219， P<0.001） and NFS （OR=1.747， 95%CI： 1.499 — 2.046， P<0.001） were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers， and its mediating effect accounted for 39.5% — 40.8% of the total effect （P<0.001）. ConclusionIn patients with lean MAFLD， NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP， and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.

Objective:To evaluate the effect of preoperative cognitive behavioral therapy (CBT) on pain catastrophizing in the patients with orthopedic trauma.Methods:A total of 120 patients with lower extremity bone trauma, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 18-28 kg/m 2, with Pain Catastrophic Scale (PCS) score on admission >16, scheduled for surgical treatment, were enrolled.The patients were divided into 2 groups ( n=60 each) by the stratified randomization method based on the type of fracture: CBT group and routine group (group R). Group CBT received CBT for pain through the internet on the day of admission and one day before operation.The patients in both groups underwent reduction and internal fixation of lower extremity fractures under combined spinal-epidural anesthesia.The PCS scores were recorded immediately after admission and on the morning of the operation day.The effective pressing times of the patient-controlled analgesia pump, consumption of analgesics for rescue analgesia, and occurrence of nausea and vomiting within 48 h after operation were recorded.The visual analogue scale score of the surgical site during activity and occurrence of the score >3 at 3 months after operation and use of opioids within 3 months after operation were recorded. Results:Compared with group R, the PCS score was significantly decreased on the morning of the operation day, the pressing times of the patient-controlled analgesia pump, consumption of analgesics for rescue analgesia and incidence of nausea and vomiting within 48 h after operation were decreased, the requirement for opioids within 3 months after operation was decreased ( P<0.05), and no significant change was found in VAS score during activity and occurrence of the score >3 at 3 months after operation in group CBT ( P>0.05). Conclusions:Preoperative CBT can reduce the degree of pain catastrophizing and is helpful in increasing the quality of postoperative analgesia in the patients with orthopedic trauma.

Objective:To systematically evaluate the dose-response relationships of resistance exercise intensity in frail elderly.Methods:A comprehensive search of randomized controlled trials on the dose-response relationships of resistance exercise for frail elderly in PubMed, Embase, The Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Database. The documents that met the conditions were screened out, and after the data were extracted and the quality of the documents were evaluated, the RevMan 5.3 software was used for Meta analysis.Results:A total of 10 eligible randomized controlled trials were included in this study. The subjects of the study were 454 cases of frail and pre-frail elderly. After Meta analysis, there was a dose-response relationships between the training intensity of resistance exercise and the muscle strength, muscle endurance, and physical function of frail elderly. Both low-intensity and high-intensity resistance exercises can significantly increase the leg muscle strength of frail elderly people ( MD=4.58, 95% CI 3.34-5.82, P<0.05) and muscle endurance ( MD=12.27, 95% CI 6.54-17.99, P<0.05). Compared with low-intensity resistance exercise, high-intensity resistance exercise increased leg muscle strength of frail elderly people ( MD=7.97, 95% CI 0.85-15.09, P<0.05) and muscle endurance ( MD=6.94, 95% CI 5.21-8.66, P<0.05) showed more obvious advantages. The analysis of the results of the chair sitting test and the stairs climbing test shows that low-intensity resistance exercise has no obvious advantage in improving the physical function of frail elderly people, while high-intensity resistance exercise can significantly improve the physical function of frail elderly people ( MD=-5.8, 95% CI -7.3--4.29, P<0.05; MD=-1.20, 95% CI-2.17--0.23, P<0.05). Conclusions:Resistance exercise can significantly improve the muscle strength, muscle endurance and physical function of the frail elderly. High-intensity resistance exercise is more effective than low-intensity resistance exercise.

Objective: To investigate the influences of antibiotic-induced gut microbiota dysbiosis on Mycoplasma pneumoniae (Mp) airway infection. Methods: C57BL/6J mice were treated with vancomycin and gentamicin for 21 d by oral delivery and then intranasally infected with Mp. Quantitative real-time PCR (qPCR) was performed to detect five major phyla of gut microbiota in mouse fecal specimens before and after antibiotic treatment and the loads of Mp in lung tissues on 3 d and 7 d after infection. Pathological changes in lung tissues were evaluated with HE staining. IFN-γ and IL-4 secreted by spleen CD4⁺ T cells and CD8⁺ T cells were analyzed by flow cytometry. Mp-specific IgM and IgG in mouse serum samples were measured by indirect enzyme-linked immunosorbent assay (ELISA). Results: Vancomycin and gentamicin treatment significantly reduced the number of Bacteroidetes in mouse feces, but increased the amount of Firmicutes. Meanwhile, the numbers of δ, γ-Proteobacteria, Actinomycetes and Tenericutes also changed. These antibiotic-induced gut microbiota alterations in mice with Mp infection increased the loads of Mp in lung tissues and the pathological scores of lung tissue inflammation on 3 d and 7 d after infection, and reduced the number of IFN-γ-secreting spleen CD4⁺ T lymphocytes on 7 d. Conclusions Antibiotic-induced gut microbiota dysbiosis aggravated Mp airway infection.

ObjectiveTo investigate the expression and clinical significance of OX40/OX40L (CD134/CD134L) in CD4+ T cells, CD8+ T cells, monocytes, and B lymphocytes in peripheral blood of patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and their overlap syndrome before and after standardized treatment. MethodsA total of 74 patients with AIH, PBC, and their overlap syndrome who were diagnosed in Subei People’s Hospital of Jiangsu from August 2015 to August 2019 were enrolled, and according to related diagnostic criteria, they were divided into AIH group (group A) with 29 patients, PBC group (group P) with 26 patients, and overlap syndrome group (group C) with 19 patients. A healthy control group with 30 individuals was also established. Peripheral blood samples were collected before and after standardized treatment to measure the expression of OX40/OX40L on the surface of peripheral blood cells by immunofluorescence flow cytometry, and the expression of OX40/OX40L was compared before and after treatment and between the three groups and the healthy control group to investigate its clinical significance. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the paired t-test was used for comparison of paired samples between two groups. ResultsThere were no significant differences in sex composition and age composition between the three groups (P＞0.05). Before treatment, the positive rate of OX40 in peripheral blood CD4+ T cells gradually increased in groups A, P, and C, and groups A, P, and C had a significantly higher positive rate of OX40 than the control group (14.80%±4.99%/17.11%±2.71%/25.18%±5.55% vs 6.67%±2.26%, F=14.823, P＜0.001); groups A, P, and C had a significantly higher positive rate of OX40 in CD8+ T cells than the control group (4.86%±1.54%/6.40%±1.88%/7.33%±2.12% vs 4.09%±2.69%, F=5.486, P＜0.001); the positive rate of OX40L in CD14+ monocytes was 19.84%±6.11% in group A, 21.17%±4.35% in group P, 29.13%±6.32% in group C, and 4.86%±2.34% in the control group, and there was a significant difference between groups (F=17004, P＜0.001); the positive rate of OX40L in CD19+ B cells was 17.62%±3.86% in group A, 14.75%±4.32% in group P, 1013%±2.56% in group C, and 4.50%±1.38% in the control group, showing a trend of gradual reduction, and groups A, P, and C had a significantly higher positive rate than the control group (F=12.221, P＜0.001). After treatment, the positive rate of OX40 in CD8+ T cells decreased significantly to a similar level as the control group, and there was no significant difference between groups (F=0731, P=0.538). For the other three types of cells, although there were varying degrees of reduction in the positive rate of OX40/OX40L after treatment, groups A, P, and C still had a significantly higher positive rate than the control group; in CD4+ T cells, the positive rate of OX40 was 11.00%±1.98% in group A, 13.72%±1.03% in group P, 19.72%±3.47% in group C, and 6.67%±2.26% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=11.365, P＜0.001); in CD14+ monocytes, the positive rate of OX40L was 11.82%±2.23% in group A, 15.19%±4.42% in group P, 24.51%±4.09% in group C, and 4.86%±2.34% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=13748, P＜0.001); in CD19+ B cells, the positive rate of OX40L was 9.09%±3.25% in group A, 6.81%±2.20% in group P, 748%±2.85% in group C, and 4.50%±1.38% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=8.052, P＜0.001). Groups A, P, and C had significant reductions in the expression of OX40/OX40L in peripheral blood CD4+ T cells, CD8+ T cells, CD14+ monocytes, and CD19+ B lymphocytes after treatment (all P＜0.05). ConclusionThe expression of OX40/OX40L in peripheral blood increases in patients with AIH, PBC, and their overlap syndrome and decreases after treatment, indicating that the OX40/OX40L pathway is involved in the pathogenesis of the above diseases, and the role of OX40 on the surface of CD8+ T cells may better reflect the treatment outcome.

Objective: To investigate the correlation between the diversity of biliary bacterial flora and the recurrence of common bile duct stones. Methods: From September 2018 to March 2019, 48 patients underwent endoscopic retrograde cholangiopancreatography (ERCP) at the First Affiliated Hospital of Nanjing Medical University were enrolled and divided into primary choledocholithiasis (primary group, 38 patients) and recurrent choledocholithiasis group (recurrent group, 10 patients). The bile of the patients of the two groups was collected and analyzed with high-throughput sequencing of 16S rRNA. The Chao1 estimator indicated the richness of the biliary bacterial flora, and Shannon index and Simpson index demonstrated the diversity of biliary bacterial flora. The bacterial flora distribution was explored from different levels of phylum, class, order, family, genus and species. Chi-square test and t test were performed for statistical analysis. Results: The Chao1 estimator of the primary group was higher than that of the recurrent group (419.413±118.704 vs. 396.000±70.483), and the difference was statistically significant (t=3.130, P=0.003). At the level of the phylum, the highest abundance of bacteria in the primary group was Firmicute (56.48%), the highest abundance of bacteria in the recurrent group was Proteobacteria (57.79%). The dominant bacteria of the recurrent group was Proteobacteria, which was inconsistent with that of the primary group, and there were significant differences in the distribution of Proteobacteria and Firmicute between two groups (χ²=0.962 and -2.619, both P<0.05). At the genus level, the abundance of Bacillus and Lactococcus of the recurrent group were both lower than those of the primary group (9.75% vs. 20.77%, 10.86% vs. 22.01%, respectively), and the differences were statistically significant (χ²=0.354 and 0.503, both P<0.05). The abundance of Morganella of the recurrent group was higher than that of the primary group (9.00% vs. 0.44%), and the difference was statistically significant (χ²=-2.025, P=0.049). At the species level, the abundance of Bacillus unclassified, Carnobacterium maltaromaticum and Bacillus circulans of the primary group were all higher than those of the recurrent group (17.78% vs. 8.84%, 2.39% vs. 1.11%, 2.59% vs. 0.74%, respectively), and the differences were all statistically significant (χ²=2.540, 2.643 and 2.515, all P<0.05). The abundance of Aeromonas veronii of recurrent group was higher than that of the primary group (2.04% vs. 0.01%), and the difference was statistically significant (χ²=-2.397, P=0.021). The bacteria that had significant effects in the primary group included Lactococcus (P=0.012), Lactobacillus (P=0.033) and Geobacillus (P=0.021), while in the recurrent group, which included Enterobacter (P=0.007), Aeromonadaceae (P=0.001), Actinomycetes (P=0.009), and Aeromonas (P=0.001). Conclusions There are differences in abundance and composition of biliary bacterial flora between the recurrent group and the primary group. It remains to be further studied whether the changes of some bacterial flora correlated with the recurrence of common bile duct stones.

ObjectiveTo investigate the clinical value of ultrasound-guided percutaneous drainage in the treatment of liver abscess from the aspects of laboratory markers and size of abscess. MethodsA total of 79 patients with liver abscess who underwent ultrasound-guided percutaneous drainage in Department of Gastroenterology in Northern Jiangsu People’s Hospital from January 2013 to August 2018 were enrolled, among whom 36 patients who were lost or transferred, abandoned treatment, had an age pf ＜18 years, or were not followed up in the outpatient service were excluded. A total of 43 patients were finally included in the retrospective study. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsAll 43 patients achieved a one-time success of puncture and placement of drainage tube. Of all 43 patients, 36 had fear of cold and pyrexia, among whom 31 (86.1%) had a normal body temperature on day 3 after surgery, and there were significant changes in leukocyte count, percentage of neutrophils, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase after surgery (t=6.668, 6.255, 2337, 3.001, and 5.198, all P＜0.05). There was a significant reduction in the diameter of abscess after surgery (74±31 mm vs 31±28 mm, t=18.517, P＜0.05). The average length of hospital stay was 19.84±9.37 days. Of all 43 patients, 19(44.2%) were cured and 24(55.8%) had response to treatment. Of all 43 patients, 38 had positive results of liver abscess culture, among whom 25(65.8%) had Klebsiella pneumoniae infection, suggesting that Klebsiella pneumoniae was the most common pathogenic bacteria. ConclusionUltrasound-guided percutaneous drainage has a high success rate, few complications, and reliable clinical efficacy in the treatment of liver abscess. Therefore, it is recommended as the first choice for the clinical treatment of liver abscess.

Objective To investigate the distribution differences of human papillomavirus(HPV) genotypes in the patients with cervical intraepithelial neoplasia grade Ⅱ/Ⅲ and the patients with cervical cancer. Methods 260 cases of cervical cancer and 280 cases of cervical intraepithelial neoplasia grade Ⅱ /Ⅲ patients who were admitted to our hospital from January 2010 to October 2017 were selected and divided into cancer group and neoplasia group respectively. The HPV infection of patients was detected and typing identification was performed. The distribution differences of HPV genotypes in cancer group and neoplasia group were compared. The differences of genotypes of HPV infection in different types of tissues in cancer group were also compared. Results The negative constituent ratio of HPV infection in cancer group was lower than that in neoplasia group(P＜0. 05), and the constituent ratio of all the high-risk types in single infection was significantly higher than that in the neoplasia group(P＜0. 05). The constituent ratio of all the low-risk types in single infection was significantly similar to that in the neoplasia group(P＞0. 05). The constituent ratio of multiple infections in cancer group was significantly higher than that in neoplasia group(P＜0. 05); the constituent ratios of negative HPV infections and 18 types of single infections in cervical squamous cell carcinoma was much lower than that of cervical adenocarcinoma(P＜0. 05). The constituent ratios of 16 types of HPV and multiple infections in cervical squamous cell carcinoma were much higher than that of cervical adenocarcinoma(P＜0. 05). Conclusion The risk of HPV infection in cervical cancer patients is significantly higher than that of cervical intraepithelial neoplasia grade Ⅱ /Ⅲ, the infection rate of cervical cancer high-risk type HPV is higher, and the risk of multiple infections is also higher. The tissue types of cervical cancer can be determined according to HPV typing.

Aim To observe the effect of total flavonoid from Mori folium(TFMF) on renal interstitial fibrosis in type 1 diabetic mice and its possible mechanism.Methods Diabetic mice were induced by intraperitoneal injection of streptozotocin(STZ) dissolved in 0.01 mol·L-1 citrate buffer(pH 4.5) at 150 mg·kg-1 body weight after 12 h of food deprivation.Forty model mice were divided randomly into four groups: model group, and low-(0.25 g·kg-1), moderate-(0.5 g·kg-1), high-dose groups(1 g·kg-1) fed with TFMF once daily.In addition, eight normal mice were used as normal group.After 12 weeks, the fasting blood glucose(FBG), serum creatinine(Cr), blood urea nitrogen(BUN) and microalbuminuria(mAlb) were measured.Masson staining, Sirius red staining and collagen type Ⅳ immunohistochemical staining were used to detect the expression of collagen protein in the cortex, while laminin staining to assess the degree of glomerular and renal tubular basement membrane thickening.The protein expressions related to epithelial-mesenchymal transition and PI3K/Akt/mTOR in the renal cortex of mice were detected by Western blot.Results The moderate and high dose of TFMF could significantly decrease the levels of FBG, Cr, BUN and mAlb in diabetic mice, meanwhile decreasing the expression of α-SMA protein by inhibiting the activation of PI3K/Akt/mTOR signaling pathway, which led to the amelioration of the pathological alterations of renal tissue.Conclusions The moderate and high dose of TFMF can reduce the level of renal interstitial fibrosis in type 1 diabetic mice, and its mechanism may be related to the inhibition of activation of PI3K/Akt/mTOR signaling pathway.