OBJECTIVE To investigate the clinical characteristics of drug-induced liver injury （DILI） induced by glucagon- like peptide-1 receptor agonists （GLP-1RAs）， and to provide a reference for safe clinical medication. METHODS Using search terms such as “GLP-1”“GLP-1RAs”“semaglutide” “drug-induced liver injury”， relevant studies from PubMed， Embase， the Cochrane Library， CNKI， Wanfang Data and VIP were retrieved. Descriptive analysis was performed on cases of DILI induced by GLP-1RAs. RESULTS A total of 11 studies， comprising 11 patients， were included. Among them， 4 were male （36.4%） and 7 were female （63.6%）. Patient ages ranged from 17 to 64 years； 5 patients （45.5%） were between 50 and 65 years old. Six patients were treated for diabetes， and five for weight loss. Ten patients had underlying diseases. The shortest time to the onset of DILI was 5 days after medication， while the longest was approximately 180 days. The DILIs induced by GLP-1RAs were mainly hepatocellular injury type （6 cases）； severity levels included severe （3 cases）， moderate （6 cases）， and mild （2 cases）. Gastrointestinal symptoms and jaundice were the most common clinical manifestations. The association between DILI and GLP- 1RAs was assessed as “probable” in 10 cases and “possible” in 1 case. All 11 patients improved after drug discontinuation and （or） corresponding treatment. CONCLUSIONS DILI induced by GLP-1RAs is relatively concentrated in patients aged 50-65， with a higher incidence in females. The risk may be further increased in patients with underlying diseases. Clinical use of these agents should enhance pharmaceutical care， including identification of high-risk populations and patient education （especially symptom recognition）. When relevant symptoms appear， the drug should be discontinued immediately， with liver-protective therapy initiated when necessary， to ensure patient safety of drug use.

Objective:To clarify the changes in incidence and mortality of various cancers based on analysis on registration data of malignant tumor incidence and mortality from Dehui City and Yanji City in Jilin Province.Methods:The incidence and mortality data of malignant tumors from 2009 to 2016 in Dehui City and Yanji City in Jilin Province,were collected from the Chinese Cancer Registry Annual Report published by the National Cancer Center.The number of cases,deaths,crude incidence rate,crude mortality rate,age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and annual percentage change(APC)of the malignant tumors were analyzed by cancer sites and genders.Results:From 2009 to 2016,the CIR of malignant tumors in Dehui City(APC=1.2%,P=0.019)and Yanji City(APC=3.6%,P=0.058)showed an increasing trend.After standard population age adjustment,the ASIR in males in Dehui City showed a significant decline(APC=-5.7%,P=0.021),while the ASIR in females exhibited an overall downward trend,but the difference was not significant(APC=-2.2%,P=0.111).In Yanji City,the ASIR in males(APC=-1.4%,P=0.535)and females(APC=0.0%,P=0.988)showed no significant changes.The CMR of malignant tumors in Dehui City(APC=1.9%,P=0.001)and Yanji City(APC=5.9%,P=0.001)showed a continuous upward trend.After age-standardization,the ASMR in males(APC=-3.1%,P=0.100)and females(APC=-4.2%,P=0.053)in Dehui City,as well as in males(APC=-1.3%,P=0.438)in Yanji City,showed a slight downward trend.Although the ASMR in females in Yanji City showed a slight increase,the difference was not statistically significant(APC=0.5%,P=0.838).In 2016,the most common malignant tumor in terms of both incidence and mortality in Dehui City was lung cancer,with a CIR of 60.76/100 000 and a CMR of 46.96/100 000.In Yanji City,the most common malignant tumor was liver cancer,with a CIR of 49.04/100 000 and a CMR of 51.09/100 000.Conclusion:Lung cancer,liver cancer,and gastric cancer are the major malignant tumors threatening residents in Dehui City,Yanji City,and even the entire Jilin Province,and should be prioritized in cancer prevention and control efforts.Early diagnosis and treatment should be strengthened.

Objective To develop an instrument for predicting postoperative constipation risks in patients with osteoporotic thoracolumbar fracture(OTLF)who have undergone percutaneous kyphoplasty(PKP).Methods A total of 858 OTLF patients who underwent PKP surgery between January 2020 and December 2024 were enrolled.The patients were randomly assigned to a training set(n=600)and a validation set(n=258)in a 7∶3 ratio.According to whether the patients had postoperative constipation,the training set was divided into a constipation group(n=205)and a non-constipation group(n=395),and the validation set was divided into a constipation group(n=90)and a non-constipation group(n=168).Logistic regression analysis was conducted to analyze the factors influencing postoperative constipation in OTLF patients after PKP,and a nomogram model was constructed accordingly.The receiver operating characteristic(ROC)curve and the calibration curve of the model were plotted,and the Hosmer-Lemeshow test for goodness of fit was performed.Results A total of 205 OTLF patients(34.17%)in the training set and 90 OTLF patients(34.88%)in the validation set experienced constipation after PKP.Univariate analysis revealed significant differences between the constipation and non-constipation groups in terms of operative time,postoperative water intake,time to first postoperative meal,postoperative bed rest time,the levels of Bifidobacterium,Lactobacillus,Enterococcus,and Enterobacter,the Nutrition Risk Screening 2002(NRS-2002)score,and the levels of sodium,potassium,and HbA1c(P<0.05).Least absolute shrinkage and selection operator(LASSO)regression was performed and operative time,time to first postoperative meal,the levels of Bifidobacterium,Lactobacillus,Enterococcus,and Enterobacter,the NRS-2002 score,and the levels of sodium,potassium,and HbA1c were identified as candidate predictors.Multivariate logistic analysis showed that the time to first postoperative meal,the levels of Bifidobacterium and Lactobacillus,the NRS-2002 score,and the levels of sodium and HbA1c were influencing factors of postoperative constipation in OTLF patients(P<0.05).The ROC curves showed that the area under the curve(AUC)of the training set was 0.842(95%CI:0.793-0.892),while that of the validation set was 0.860(95%CI:0.830-0.889).The calibration curves demonstrated good agreement between the prediction curve and the standard curve in both the training set and the validation set.Conclusion The time to the first postoperative meal,the NRS2002 score,and the levels of Bifidobacterium,Lactobacillus,sodium,and HbA1c are influencing factors of post-PKP constipation in OTLF patients.The nomogram model built based on these factors exhibited good predictive performance.

Objective To explore the effects and underlying molecular mechanisms of high fat diet(HFD)on in-testinal barrier damage and inflammatory reaction in mice with irritable bowel syndrome(IBS)induced by sodium dextran sulfate(DSS).Methods C57BL/6 mice were randomly divided into four groups(n=6):Normal group,DSS group(1.5％DSS solution for one week),HFD+DSS group,and HFD+DSS+WY14643 group(intraperitone-ally injected daily with PPARα agonist WY14643 6 mg/kg).The body weight and liver weight of mice were measured.Colon pathology was observed by HE staining.The protein expression of zonula occludens-1(ZO-1)and occludin was detected by immunohistochemistry.The mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-β(IL-1β),and interleukin-17(IL-17)were determined by qRT-PCR.PPARα protein expression was determined by Western blot.Results The body weight and liver weight of mice in the HFD+DSS group were significantly higher than those in the DSS group(P＜0.001).HE staining showed normal colonic tissue structure in Normal group,while other three groups exhibited varying degrees of mucosal damage with a small amount of in-flammatory cell infiltration and epithelial cell shedding.Among these,the HFD+DSS group displayed the most se-vere intestinal mucosal damage and inflammatory infiltration.Compared with the DSS group,the HFD+DSS group showed decreased ZO-1 and Occludin protein expression(P＜0.001),elevated TNF-α,IL-1 β,and IL-17 mRNA levels(all P＜0.001),and downregulated PPARα protein expression(P＜0.01).Compared with the HFD+DSS group,mice in HFD+DSS+WY14643 group showed improvement in intestinal mucosal damage and reduced infiltration of inflammatory cells.The protein expression of ZO-1 and occludin in colon of mice in the HFD+DSS+WY14643 was increased(all P＜0.05),while the expression of TNF-α,IL-1 β,and IL-17 mRNA was downregulated(P＜0.01 or P＜0.05),and the protein expression of PPAR α was upregulated(P＜0.05).Conclusions HFD-induced obesity aggravates intestinal mucosal damage,intestinal barrier destruction and in-flammatory response in IBS mice,and its molecular mechanism is potentially related to downregulation of PPARαexpression in intestinal tissues.

Objective To evaluate the clinical application of CT-guided coaxial needle biopsy in pancreatic puncture-cutting biopsy via adipose tissue space.Methods The clinical data of 30 patients,who received CT-guided pancreatic coaxial needle biopsy via adipose tissue space at the Pingdu Hospital Area of Affiliated Hospital of Qingdao University of China from June 2021 to April 2024,were retrospectively analyzed.The patients included 20 males and 10 females with a mean age of(65.1±8.7)years.The lesions were located in the pancreatic head(n=7),pancreatic neck(n=4),pancreatic body(n=7),pancreatic tail(n=10)and uncinate process(n=2).Under CT guidance,a 17 G co-axial guiding needle was inserted to establish a puncture pass through adipose tissue space,then an 18 G biopsy needle was used to make tissue sampling.A total of 32 procedures of pancreatic puncture-cutting biopsy were performed,two of these patients received two times of biopsy.After sampling,a self-made blocking agent(a mixed liquid of gelatin sponge particles and snake venom hemagglutinin),was used to occlude the puncture channel so as to prevent complications such as bleeding,pancreatic leakage,needle tract implantation metastasis,etc.Results A total of 32 procedures of pancreatic puncture-cutting biopsy with coaxial guiding needle via adipose tissue space were performed,including two patients who received two times of biopsy.The success rate of puncturing was 100％(32/32),the success rate of sampling was 93.8％(30/32),and the accuracy of sampling was 93.8％(30/32).No serious puncture-related complications occurred in all patients.Conclusion CT-guided pancreatic coaxial needle biopsy via adipose tissue space is clinically safe,accurate in sampling and minimally-invasive.This interventional diagnostic technique is worth applying in clinical practice.

Objective:The purpose of this study was to examine the clinical features and initial treatment outcomes of elderly individuals with idiopathic membranous nephropathy.Methods:This study retrospectively analyzed the clinical characteristics and therapeutic effect of hospitalized patients aged 60 years or older with renal-biopsy-proven idiopathic membranous nephropathy for at least one year.Results:This study enrolled a total of 91 elderly patients with IMN, consisting of 51 males(56.0%)and 40 females(44.0%). The median age of the patients was 67 years.The urinary protein creatinine ratio(uPCR)and urinary albumin creatinine ratio(uACR)of the patients were 4 454.3 mg/g and 2 258.5 mg/g, respectively.The median 24-hour urinary protein and urinary albumin levels were 5 098.2 mg/24 h and 2 800.6 mg/24 h, respectively.The average estimated glomerular filtration rate(eGFR)was(60.5±20.4)ml·min -1·1.73 m -2.Out of the total of 61 patients, 67.0% achieved remission, including complete and partial remission, within a year of renal biopsy.The levels of uPCR and uACR were significantly higher in the non-remission group compared to the remission group(5 462.5 vs.2 271.1 mg/g, P<0.001; 2 774.4 vs.1 320.0 mg/g, P=0.001). Additionally, the levels of 24h urinary protein and urinary albumin were significantly higher in the non-remission group compared to the remission group(6 526.4 vs.3 210.4 mg/g, P=0.002; 3 067.7 vs.2 102.4 mg/g, P=0.007). The remission group had a higher proportion of patients receiving immunosuppressive therapy(85.2% vs.33.3%, P<0.001). The remission rates were higher in patients treated with glucocorticoid combined with cyclophosphamide, glucocorticoid combined with calcineurin inhibitors, or glucocorticoid combined with mycophenolate mofetil compared to those receiving conservative treatment(88.2% vs.31.0%, P=0.001; 80.0% vs.31.0%, P<0.001; 100.0% vs.31.0%, P=0.007). There was no significant difference in remission rate between the three immunosuppressive therapy groups( P>0.05). However, upon further analysis, it was found that the levels of uPCR, uACR, and serum cystatin C(CysC)were higher in the immunosuppressive therapy groups compared to conservative treatment.Additionally, serum total protein and albumin were lower in the immunosuppressive therapy groups, and these differences were statistically significant( P<0.05). Conclusions:The majority of elderly patients diagnosed with IMN have multiple comorbidities.For those at high risk with elevated urinary protein levels, early initiation of immunosuppressive therapy may lead to a higher initial urinary protein remission rate.Therefore, it is advisable to develop individualized treatment plans for elderly patients with IMN based on their clinical characteristics, as well as the risks and benefits associated with immunosuppressive therapy.

ObjectiveTo evaluate the therapeutic effect of stewed Polygoni Multiflori Radix on androgenic alopecia （AGA） and study the treatment mechanism. MethodNinety-nine SPF-grade male C57BL/6J mice were randomized into control， model， positive drug （finasteride， 0.65 mg·kg^-1）， low （0.78 g·kg^-1）， medium （1.56 g·kg^-1）， and high （3.12 g·kg^-1）-dose stewed Polygoni Multiflori Radix， and Polygoni Multiflori Radix Praeparata groups by the random number table method. The mouse model of AGA was constructed by subcutaneous multi-point injection of testosterone propionate diluent for 60 days， and the mice were administrated with corresponding drugs by gavage from day 11. The therapeutic effects of stewed Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata on AGA were evaluated by newly hair area， hair length， hair weight in the hair removal area， and hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to determine the levels of testosterone （T）， dihydrotestosterone （DHT）， and 5α-reductase （5-AR） in the skin tissue of mice. Western blot was employed to determine the expression levels of key proteins in the Wnt/β-catenin signaling pathway. ResultCompared with the control group， the model group （after 60 days of modeling） showed reductions in the newly hair area， hair length and weight in the back hair removal area， and ratio of hair follicles containing melanin to total hair follicles （P<0.05， P<0.01）， elevated levels of T， DHT， and 5-AR， up-regulated expression level of glycogen synthase kinase-3β （GSK-3β） （P<0.05， P<0.01）， and down-regulated expression levels of β-catenin， phospho-glycogen synthase kinase-3β （p-GSK-3β）， and p-GSK-3β/GSK-3β （P<0.05， P<0.01） in the skin tissue. Compared with the model group， the positive drug， low-， medium-， and high-dose stewed Polygoni Multiflori Radix， and low-， medium-， and high-dose Polygoni Multiflori Radix Praeparata improved the newly hair area and hair length of mice （P<0.01）， and stewed Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata at low and medium doses improved the weight of newly formed hair in mice （P<0.05， P<0.01）. The positive drug， low-， medium-， and high-dose stewed Polygoni Multiflori Radix， and low- and high-dose Polygoni Multiflori Radix Praeparata increased the ratio of hair follicles containing melanin to total hair follicles in the skin tissue （P<0.05， P<0.01）. Compared with Polygoni Multiflori Radix Praeparata at the same doses， the medium and high doses of stewed Polygoni Multiflori Radix increased the ratio of melanin-containing hair follicles to total hair follicles （P<0.05）. Compared with the model group， stewed Polygoni Multiflori Radix lowered the levels of T and DHT， down-regulated the expression level of GSK-3β （P<0.01）， and up-regulated the expression levels of β-catenin， p-GSK-3β， and p-GSK-3β/GSK-3β （P<0.05， P<0.01） in the skin tissue of the mice. ConclusionStewed Polygoni Multiflori Radix can ameliorate androgenic alopecia in mice by reducing the androgen level and promoting Wnt/β-catenin signaling.

Objective To explore the correlation of serum glutamate(Glu)and gamma-aminobutyric acid(GABA)levels with clinical symptoms in chronic schizophrenia patients,and to assess their diagnostic value for cognitive impairment.Methods A total of 92 patients with chronic schizophrenia and another 80 healthy individuals in Wuhan Mental Health Center/Wuhan Hospital for Psychotherapy from January 2021 to July 2022 were enrolled as study group and control group,respectively.The patients in the study group were divid-ed into the cognitive impairment group(44 cases)and the cognitive normal group(48 cases)according to Montreal Cognitive Assessment Scale(MoCA).Clinical symptoms were assessed by using Positive and Nega-tive Syndrome Scale(PANSS).MoCA was used to evaluate the cognitive function.The levels of Glu and GA-BA in plasma were determined by high-performance liquid chromatography/electrospray tandem mass spec-trometry.The scores of PANSS and MoCA as well as serum levels of Glu and GABA were compared between two groups.Then the correlation of serum Glu and GABA levels with clinical symptoms and the diagnostic value for cognitive impairment in the patients in the study group were investigated.Results The Glu level in the study group was higher than that in the control group,and the GABA level was lower than that in the con-trol group(P＜0.05).The serum Glu levels in both the cognitive impairment group and the cognitive normal group were higher than the normal range,and the Glu level in the cognitive impairment group was higher than that in the cognitive normal group(P＜0.05).The serum GABA levels in both the cognitive impairment group and the cognitively normal group were lower than the normal range,and the GABA level in the cogni-tive impairment group was lower than that in the cognitive normal group(P＜0.05).In the study group,ser-um Glu level was positively correlated with negative,positive,general psychopathological symptom scores,and overall score in PANSS(P＜0.05),while GABA level was negatively correlated with negative,positive,gener-al psychopathological symptom scores,and overall score in PANSS(P＜0.05).The sensitivity of the single and combined detection of serum Glu and GABA for the diagnosis of cognitive impairment in patients with chronic schizo-phrenia was 77.3％,72.7％and 93.2％,respectively,and the specificity was 72.9％,72.9％,and 75.0％,respec-tively,and the area under the curve was 0.778,0.769,and 0.868,respectively.Conclusion Serum Glu level in patients with chronic schizophrenia is higher than that in healthy individuals,while GABA level is lower than that in healthy individuals,and the above two indicators are correlated with PANSS score,which have high value in diagnosing cognitive impairment and could be used as effective biological indicators to help clinical doctors judge patients'cognitive function.