Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

ObjectiveThis study aims to explore the potential mechanism of the Xiezhuo Jiedu formula in regulating pyroptosis for the treatment of ulcerative colitis （UC） using bioinformatics and in vivo animal experiments. MethodsDifferentially expressed genes （DEGs） in colon tissues of UC patients were retrieved from the Gene Expression Omnibus （GEO） database. Pyroptosis-related genes were obtained from the GEO and GeneCards databases. The intersection of these datasets yielded pyroptosis-related DEGs （Pyro-DEGs）. Pyro-DEGs were subjected to Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using the Metascape database. A protein-protein interaction （PPI） network was constructed using the STRING database. Least absolute shrinkage and selection operator （LASSO） prediction model and receiver operating characteristic （ROC） analysis were conducted to identify core Pyro-DEGs with diagnostic and therapeutic potential. Immune infiltration analysis of the UC datasets was performed using the deconvolution method （CIBERSORT）， along with correlation analysis with core Pyro-DEGs. Sixty male Sprague-Dawley （SD） rats were randomly divided into a control group， a model group， high-， medium-， and low-dose groups of Xiezhuo Jiedu formula （26.64， 13.32， 6.66 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. UC was established by intrarectal administration of 3，5-trinitrobenzenesulfonic acid （TNBS） dissolved in ethanol. The control and model groups were given distilled water by gavage， while the treatment groups were administered the corresponding drugs for 7 consecutive days. Hematoxylin-eosin （HE） staining was used to observe the colon histopathology. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors such as interleukin-1β （IL-1β）， IL-10， IL-18， and transforming growth factor-β （TGF-β）. Immunohistochemistry （IHC） and Western blot were applied to detect the expression of Caspase-1， gap junction alpha-1 protein （GJA1）， peroxisome proliferator-activated receptor gamma （PPARG）， and S100 calcium-binding protein A8 （S100A8）. Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to measure mRNA expression of Caspase-1， GJA1， PPARG， and S100A8. Western blot was performed to assess protein expression levels of Caspase-1， GJA1， PPARG， and S100A8. ResultsGEO datasets GSE87466 and GSE87473 yielded 64 Pyro-DEGs. KEGG analysis indicated that these genes were enriched in the NOD-like receptor signaling pathway， tumor necrosis factor （TNF） signaling pathway， and hypoxia-inducible factor 1 （HIF-1） signaling pathway. Four core Pyro-DEGs （Caspase-1， GJA1， PPARG， and S100A8） were identified. Immune infiltration analysis showed that expression of these genes was positively correlated with mast cells， neutrophils， M0 macrophages， M1 macrophages， and dendritic cells. Animal experimental results indicated that compared with the control group， the model group had significantly increased levels of IL-1β and IL-18， significantly decreased levels of IL-10 and TGF-β. The model group showed enhanced Caspase-1， GJA1， and S100A8 staining， and significantly increased mRNA and protein expression of Caspase-1， GJA1， and S100A8 （P<0.01）. In contrast， the expression of PPARG was reduced in the model group （P<0.01）. After treatment， all dosage groups showed varying degrees of improvement （P<0.05， P<0.01）， with the high-dose group showing the most significant improvement （P<0.01）. ConclusionCaspase-1， GJA1， PPARG， and S100A8 are core Pyro-DEGs closely associated with the pathogenesis of UC. These genes may collaborate with immune cells such as mast cells， neutrophils， and M0 macrophages to mediate disease development. The Xiezhuo Jiedu formula may regulate the expression of core Pyro-DEGs through the NOD-like receptor， TNF， and HIF-1 core signaling pathways， thereby modulating immune homeostasis in UC rats and effectively alleviating UC.

[摘 要] 目的：分析胃癌骨转移患者的临床病理特征及影响预后的因素，探讨不同治疗方案对同时与异时骨转移患者生存的影响。方法：纳入2015年至2023年间南京大学医学院附属鼓楼医院胃癌骨转移患者120例，其中同时骨转移36例，异时骨转移84例。采用χ2检验比较胃癌同时与异时骨转移患者临床病理特征，采用Cox比例风险回归模型分析影响胃癌骨转移患者骨转移后总生存期（OS-BM）的风险因素，使用Kaplan-Meier法分析不同治疗方式对同时与异时骨转移OS-BM的影响。结果：120例胃癌骨转移患者中，有104例（86.6%）合并全身其他器官转移灶。在同时与异时骨转移患者的病理特征比较中，同时骨转移患者血C-反应蛋白（CRP）升高、血浆白蛋白减少；而异时骨转移患者外周血白细胞以及中性粒细胞低于正常值（均P < 0.05）。异时骨转移[HR = 2.35, 95% CI（1.47, 3.74），P < 0.01]、血清CA125 ≥ 30.2U/mL [HR = 1.6，95% CI（1.03, 2.48），P = 0.036]、血白细胞 ≥ 9.5 × 109/L [HR = 2.15，95% CI（1.17, 3.92），P = 0.013]，以及未接受免疫治疗[HR = 2.26，95% CI（1.5, 3.39），P < 0.01]是影响患者预后的独立危险因素。免疫治疗的联合使用相较于未使用免疫治疗，可明显延长胃癌骨转移患者的OS-BM（9.63 vs 4.53个月，P = 0.002）。异时骨转移患者比同时骨转移患者对免疫治疗响应更佳（中位OS-BM：10.8 vs 7.3个月，P = 0.004）。结论：免疫治疗是胃癌骨转移患者生存的独立保护因素，建议此类患者在化疗基础上尽早采用以免疫治疗为主的联合治疗，以延长患者的生存期。

Objective To evaluate the short-term clinical efficacy of unilateral biportal endoscopic(UBE)technique in the treatment of adjacent segment disease after lumbar interbody fusion.Methods The clinical data of 21 patients with adjacent segment disease after lumbar interbody fusion who treated with UBE technique and followed up for more than 3 months in our hospital from March 2020 to January 2023 were retrospectively analyzed.The operation time,decrease value of hemoglobin 1 day before and after operation,drainage volume of the operation area,time of bed rest and complications were recorded.The Japanese Orthopaedic Association(JOA)score was used to evaluate lumbar function 1 day before operation,3 days and 3 months after operation to determine the improvement.The visual analogue scale(VAS)score was used to evaluate the pain 1 day before operation,3 days and 3 months after operation.Results The operation time was 60～175 minutes,with an average of(95.38±18.64)minutes;the decrease value of hemoglobin was 2～6 g/L,with an average of(1.42±0.18)g/L;the time of bed rest was 27～88 hours,with an average of(36.42±15.33)hours;the drainage volume of the operation area was 50～315 mL,with an average of(85.56±15.65)mL;and one case of dural tear occurred during the operation,who was converted to open surgery for repairing dural sac.There was statistically significant difference in VAS score before operation compared with that 3 days and 3 months after operation(P<0.05).There was statistically significant difference in the JOA score before operation compared with that 3 days and 3 months after surgery(P<0.05).Conclusion UBE technique is effective in the treatment of adjacent segment disease after lumbar interbody fusion,with the advantages of small trauma,little bleeding and short time of bed rest.However,patients with the serious adjacent segment degeneration and severe spinal stenosis may have dural tear during operation.Once it occurs,active repair should be performed to avoid cauda equina herniation and necrosis,or switch to open surgery,if necessary.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To assess respondents' understanding of the items in the Neck Dissection Impairment Index (NDII) through cognitive interviews and to revise the items accordingly.Methods:Totally 30 postoperative neck dissection patients returning for follow-up at Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University from November 2023 to February 2024, were selected by purposive sampling for two rounds of cognitive interviews. Based on the interview results, the Chinese version of the NDII was revised.Results:The Chinese version of the NDII included ten items. The first round of interviews identified issues such as "incomplete expression, abstract language, and written form, " leading to revisions of five items. The second round of interviews showed that all respondents understood the revised items, and no new suggestions for modification were made.Conclusions:Cognitive interviews can improve respondents' comprehension of the Chinese version of the NDII, identify cognitive biases caused by cultural differences and improper linguistic expressions during the translation process, and enhance the understanding and acceptance of the scale's content among the target population.

Background and Aims:Parastomal hernia is a common complication after colostomy,with a high incidence rate.Laparoscopic Sugarbaker repair is currently the mainstream surgical approach for treating parastomal hernia.However,compared to other abdominal wall hernia repair techniques,the recurrence rate of parastomal hernia after laparoscopic Sugarbaker repair remains relatively high.Furthermore,the recurrence rate after surgery for recurrent parastomal hernias is significantly higher than that after the initial surgery,with inadequate lateral mesh coverage being one of the major contributing factors.This study was performed to analyze the efficacy of two-point mark-guided laparoscopic Sugarbaker repair in patients with terminal colostomy parastomal hernia,so as to provide evidence-based references for clinical practice. Methods:The clinical data of 120 patients with terminal colostomy parastomal hernia,who underwent laparoscopic Sugarbaker repair guided by the two-point mark of mesh at the Department of Hernia and Obesity Surgery,the First Affiliated Hospital of the University of Science and Technology of China,from January 2015 to December 2023,were retrospectively collected.The parastomal hernias were classified according to the European Hernia Society classification.Postoperative symptomatic and radiological recurrence rates were analyzed,as well as the incidence of complications such as bowel obstruction,stoma infection,and intestinal fistula in recurrent and non-recurrent patients. Results:Of the 120 patients,2(1.7％)were lost to follow-up.The mean follow-up duration was 48(6-96)months.The postoperative symptomatic recurrence rate was 5.1％(6/118),and the radiological recurrence rate was 6.8％(8/118).There were no statistically significant differences between recurrent(n=8)and non-recurrent patients(n=110)in terms of sex,age,body mass index(BMI),or hernia defect size(all P＞0.05),but the operative time in recurrent patients was longer than that in non-recurrent patients(P＜0.05).The overall postoperative complication rate was 8.5％(10/118),including stoma skin-mucosa separation(3 cases),stoma infection(2 cases),delayed bowel obstruction(2 cases),early bowel obstruction(1 case),hernia sac effusion(1 case),and delayed fistula formation in the hernia sac cavity(1 case).According to the Clavien-Dindo classification,there were 6 cases of grade Ⅱ,3 cases of gradeⅢa,and 1 case of grade Ⅳ complications.There were no statistically significant differences between patients with and without complications regarding sex,BMI,hernia defect size,operative time,and comorbidities(all P＞0.05);however,patients with complications were older than those without(P＜0.05). Conclusion:The application of laparoscopic Sugarbaker repair under the guidance of two-point mesh identification can effectively reduce the recurrence rate of parastomal hernia and It has high clinical applicability.