BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

To summarize the clinical features of pancreatic tuberculosis, analyze its endoscopic ultrasonography (EUS) findings, aspiration histopathology and etiological results, the medical history, clinical manifestations, laboratory tests, imaging findings, EUS findings, pathological and etiological results of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy, of 14 patients with pancreatic tuberculosis in Wuhan Union Hospital from January 2018 to January 2022 were retrospectively analyzed. Among the patients with pancreatic tuberculosis, 7 were male and 7 were female with the age of 39.7±16.0 years. The main clinical manifestations were abdominal distention, abdominal pain, loss of appetite, weight loss, abdominal mass, obstructive jaundice, skin pruritus, asymptomatic. Seven patients with pancreatic tuberculosis were complicated with tuberculosis in other organs, including 3 patients with pulmonary tuberculosis. Laboratory examination results showed 7 patients with anemia, 3 with elevated serum amylase, 2 with elevated bilirubin and 10 with positive anti-tuberculosis antibody, 12 positive for tuberculosis T-SPOT. Levels of CA19-9 in all patients were within normal range. Imaging examination results showed that 9 cases were solid mass, 4 cystic solid mass, 1 cystic mass, 4 with enlarged peripancreatic lymph node, and 2 with dilated bile duct. EUS showed that head of pancreas was the most common location of pancreatic tuberculosis. All the lesions were hyperechoic without vascular invasion, including 8 cases with homogeneous hyperecho, 6 cases with inhomogeneous hyperecho, 2 cases with hyperechoic calcification and 1 case of echoless colliquative necrosis area. The diameter of the mass was 3.9±1.6 cm, with 5 cases <3 cm and 9 cases ≥3 cm. Pathological biopsy showed 12 cases of caseous granuloma. Etiological examination results showed that 11 cases were positive for polymerase chain reaction for mycobacterium tuberculosis, 3 positive for acid-fast stain, 1 positive for culture. All the patients were treated with regular anti-tuberculosis drugs, and 3 patients with jaundice were treated with endoscopic retrograde cholangiopancreatography and biliary stent placement. All patients showed good prognosis during the follow-up period. For patients with pancreatic space-occupying lesions, the possibility of pancreatic tuberculosis should be considered. The current diagnostic method relies on tissue biopsy and aetiological examination. EUS-FNA is the preferred method for obtaining pancreatic tissue to avoid unnecessary surgery, and to provide timely and accurate diagnosis. Regular anti-tuberculosis treatment is the main treatment for pancreatic tuberculosis.

Objective:To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis.Methods:The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included. According to the conditioning regimen, the patients were divided into two groups: the TBI plus cyclophosphamide (TBI/Cy) group ( n=53) and the busulfan plus cyclophosphamide (Bu/Cy) group ( n=42). Hematopoietic reconstitution after transplantation, GVHD, transplantation-related complications, relapse rate (RR), non-relapse mortality (NRM), OS, and LFS were compared, and the factors related to prognosis were analyzed. Results:The median time of neutrophil engraftment was 14 (10-25) days in the TBI/Cy group and 14 (10-24) days in the Bu/Cy group ( P=0.106). The median time of megakaryocyte engraftment was 17 (10-42) days in the TBI/Cy group and 19 (11-42) days in the Bu/Cy group ( P=0.488). The incidence of grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively ( P=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD in these two groups was 24.5% and 4.8%, respectively ( P=0.009). The incidence of severe chronic GVHD in the two groups was 16.7% and 13.5%, respectively ( P=0.689). The incidence of cytomegalovirus infection, Epstein-Barr virus infection, severe infection, and hemorrhagic cystitis in the two groups was 41.5% and 35.7% ( P=0.565), 34.0% and 35.7% ( P=0.859), 43.4% and 33.3% ( P=0.318), and 20.8% and 50.0% ( P=0.003), respectively. The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups, respectively. The 2-year cumulative RR was 17.0% in the TBI/Cy group and 42.9% in the Bu/Cy group ( P=0.017). The 2-year cumulative NRM was 24.5% and 7.1%, respectively ( P=0.120). The 2-year LFS was 58.5% and 50.0%, respectively ( P=0.466). The 2-year OS rate was 69.8% and 64.3%, respectively ( P=0.697). In the multivariate analysis, the conditioning regimen containing TBI was a protective factor for relapse after transplantation ( HR=0.304, 95% CI 0.135-0.688, P=0.004), whereas the effect on NRM was not significant ( HR=1.393, 95% CI 0.355-5.462, P=0.634). Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL. Conclusion:allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL, compared with chemotherapy regimen. While the incidence o grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.

Case 1: A 27-year-old female with ALK-positive anaplastic large cell lymphoma/leukemia; Case 2: A 27-year-old male with acute myeloid leukemia; Case 3: A 56-year-old male with myelodysplastic syndrome. These three patients underwent haploid hematopoietic stem cell transplantation and experienced severe oral mucosal inflammation, nausea, vomiting, diarrhea, and other symptoms over a long period, which significantly restricted eating. Neurological and psychiatric symptoms appeared at 50, 38, and 50 days following transplantation, respectively. The diagnosis of Wernicke encephalopathy was made by head magnetic resonance imaging, whereas the condition improved significantly after intravenous infusion of vitamin B 1.

Objective To analyze the influence of drainage volume on prognosis of acute hydrocephalus(AHC)after aneurysmal subarachnoid hemorrhage(aSAH)by continuous lumbar drainage.Methods A retrospective trial was conducted on 82 AHC patients after aSAH admitted to the First Affiliated Hospital of Chongqing Medical University between January 2017 and January 2022.In 6 months after discharge,modified Rankin Scale(mRS)score was used to evaluate the prognostic outcomes.Univariate and multivariate logistic regression analyses were performed on demographic factors,severity of subarachnoid hemorrhage(SAH)at admission,medical history,cerebral vasospasm,and lumbar drainage data.Then a nomogram prediction model was constructed.Results Univariate analysis found that World Federation of Neurosurgical Societies(WFNS)score,Hunt-Hess grade,modified Fisher grade,time for continuous lumbar drainage,shunt dependence,cerebral vasospasm,and drainage volume were factors affecting the prognosis of the patients.Then logistic regression analysis revealed that high WFNS score(OR:3.25,95％CI:1.11～9.48),high modified Fisher grade(OR:3.66,95％CI:1.08～12.35),shunt dependence(OR:15.56,95％CI:1.22～198.57),and cerebral vasospasm(OR:22.24,95％CI:3.08～160.68)were independent predictors for mRS score,while volume of continuous lumbar drainage(OR:0.57,95％CI:0.40～0.82)was an independent protective factor.ROC curve analysis indicated a good predictive performance of the model(AUC=0.898,95％CI:0.935～0.861).Internal validation through Bootstrap method demonstrated excellent discriminatory ability of the model(C-index=0.950,95％CI:0.904～0.996;adjusted C-index:0.934).Conclusion Increased volume of lumbar drainage is an independent protective factor for poor prognosis following aSAH and can improve the prognosis of SAH patients.

Objective To explore the effects of Jinghou Zengzhi Granules(JHZZG),on ovarian GDF9 secretion and granulosa cells(GCs)apoptosis in controlled ovarian hyperstimulation(COH)rats through p38MAPK/CK2/IκBα/NF-κB pathway.Methods A model of COH rats was prepared and 18 rats were randomly divided into 3 groups,including natural ovulation group(NO group),COH group,and COH+JHZZG group.The expression of p38MAPK,CK2,IκBα,NF-κB,GDF9 mRNA and protein were detected by qRT-PCR and Western blot,and the apoptosis rate of ovarian GCs by TUNEL.Results Compared with the NO group,the expression of p38MAPK and NF-κB in the ovarian tissue of rats in the COH group increased,while the expression of CK2,IκBα and GDF9 decreased,and the apoptosis rate of ovarian GCs increased(all P<0.01).Compared with the COH group,the expression of p38MAPK and NF-κB in the ovarian tissue of rats in the COH+JHZZG group decreased,while the expression of CK2,IκBα and GDF9 increased(all P<0.01),and the apoptosis rate of ovarian GCs decreased(P<0.05).Conclusion Jinghou Zengzhi Granules could promote the secretion of ovarian GDF9 and inhibit the apoptosis of ovarian GCs of COH rats through p38MAPK/CK2/IκBα/NF-κB signaling pathway,which thereby improve the quality of COH oocytes.

ObjectiveTo understand the death status of major chronic diseases among the registered residents in Xuhui District， Shanghai from 2007 to 2021， and to analyze the probability and trend of premature death， so as to provide an evidence for the policy-making of disease control and prevention. MethodsBased on the data from the death registration system of the registered residents in Xuhui District， Shanghai from 2007 to 2021， the mortality rate of major chronic diseases， life expectancy without cause of death， potential years of life lost （PYLL）， average years of life lost （AYLL）， and premature death rate were calculated. Joinpoint 4.8 software was used to calculate the annual percentage change （APC） of premature death rate and its trend. ResultsIn 2021， the mortality rate and standardized mortality rate of four major chronic diseases， namely cardiovascular and cerebrovascular diseases， malignant tumors， diabetes mellitus and chronic lower respiratory diseases among the registered residents in Xuhui District， Shanghai was 767.75/100 000 and 234.69/100 000， respectively， accounting for 85.63% of the total causes of death among the residents in Xuhui District， Shanghai. The PYLL， AYLL and PYLL rate were 10 710.00 person-years， 1.49 years per person， and 11.43‰， respectively. Life expectancy increased by 14.91 years after removing the four major chronic diseases. From 2007 to 2021， the premature death rate of chronic diseases among the registered residents in Xuhui District decreased from 9.38% to 7.91% （APC=-1.09%，P<0.05）. Malignant tumors had the highest rate in premature death， and the premature death rate was higher in males than that in females， with a slower rate of decline than in females. Cardiovascular and cerebrovascular diseases， malignant tumors and chronic lower respiratory diseases showed a significant decreasing trend in premature death rate （APC=-1.30%， -1.20%， -5.42%， P<0.05）， while diabetes mellitus showed a significant increasing trend in premature death rate （APC=3.20%， P<0.05）. There was a significant increasing trend in the rate of premature death from diabetes mellitus in males （APC=5.15%， P<0.05） and a decreasing trend in the rate of premature death from diabetes mellitus in females （APC=-0.76%， P<0.05）. ConclusionCardiovascular and cerebrovascular diseases， malignant tumors， diabetes mellitus and chronic lower respiratory diseases are the main causes of death among the registered residents in Xuhui District. The probability of premature death of the residents in Xuhui District from major chronic diseases is at a low level， indicating that the prevention and control of chronic diseases in Xuhui District has achieved some success， but it is still difficult to realize the goals of the Outline of the "Healthy China 2030" Plan. Therefore， it is necessary to comprehensively carry out the control of risk factors such as tobacco use， harmful alcohol consumption， salt intake， hypertension， hyperglycemia and obesity， especially to strengthen the control of risk factors for male residents， as well as early diagnosis and treatment of malignant tumors， cardiovascular and cerebral vascular diseases and diabetes mellitus， and to implement the disease management mechanism to reduce premature death.

Objective:To analyze the efficacy of unilateral arytenoid chondroplasty combined with minimally invasive mucosal flap plasty in the management bilateral vocal cord paralysis.Methods:A total of 66 patients with bilateral vocal cord paralysis hospitalized in the First Hospital of Sun Yat-sen University from January 2018 to December 2023 were retrospectively analyzed, among whom there were 8 males and 58 females, with ages ranging from 35 to 86 years old(mean age (57.8±11.6) years). All patients underwent suspension laryngoscopic CO 2 laser unilateral arytenoid chondroplasty and mucosal flap under general anesthesia. Postoperative follow-up period extended from 6 months to 6 years, with a median duration of 28 months. The study compared the degree of dyspnea and voice quality (subjective and objective evaluation) of the patients pre- and post-operatively, and analyzed the clinical differences between patients with and without preoperative or intraoperative tracheotomy, the extubation rate of tracheotomized patients, the recurrence rate, and the complication rate. Continuous variables conforming to normal distribution were tested by t-test and categorical variables by χ2 test,the Wilcoxon rank-sum test was used to analyze the improvement in dyspnea before and after surgery. Results:Compared with the preoperative period, 59 patients showed improvement in postoperative dyspnea ( U=161.5, P<0.01); there was no significant difference in voice disorder index 10, subjective auditory-perceptual assessment, and maximal vocalization time ( P>0.05), all of which remained within the relative normal range. Tracheotomy was performed in 32 out of 66 patients, with predominantly degree Ⅲ- dyspnea (46.9%, 15/32), including 26 patients with preoperative tracheotomy and 6 patients with intraoperative tracheotomy. Among the 34 patients who did not undergo tracheotomy, the majority presented with degree Ⅱ-dyspnea (82.4%, 28/34). All patients achieved successful extubation following surgery, with a mean median time to extubation of 1 month. Conclusions:The combination of unilateral arytenoid chondroplasty and minimally invasive mucosal flap plasty represents a refined and effective therapeutic approach for bilateral vocal cord paralysis. This minimally invasive technique has the potential to reduce the rate of tracheotomy.

OBJECTIVE To investigate the multi-target mechanism of action of Poecilobdella manillensis lyophilized powder(SZ) against hyperuricemia(HUA) based on network pharmacology and transcriptomics approaches, combined with animal experiments. METHODS Utilizing Symmap, SwissTargetPrediction, and Pharmmapper databases, the potential active components and corresponding targets of SZ were obtained. Through the Gene Cards and OMIM databases, HUA-related targets were obtained. By taking the intersection mapping, the common targets of SZ and HUA were identified. Cytoscape 3.9.0 software was used to construct a drug component-disease target interaction network, and in combination with the STRING database, a protein interaction network was built and core targets were screened. The DAVID database was used to perform GO biological function annotation and KEGG pathway enrichment analysis on the intersecting targets. A mouse model of HUA was constructed using potassium oxyzate combined with high purine diet, and the effects of SZ on these mice were examined using ELISA and biochemical index detection. qRT-PCR was used to validate the results of RNA-Seq and network pharmacology enrichment analysis. RESULTS Network pharmacological analysis identified 11 major bioactive substances in SZ and 72 potential targets involved in the treatment of hyperuricemia, involving multiple biological processes and different signaling pathways. It was shown that SZ significantly reduced serum uric acid, creatinine and urea nitrogen levels in hyperuricemic mice by inhibiting xanthineoxidase activity. SZ also reduced the levels of URAT1 while increasing the levels of ABCG2. RNA sequencing analysis revealed that there were 112, 536 and 107 differentially expressed genes in the model group vs treated group, control group vs model group and control group vs treated group, respectively. qRT-PCR results indicated that SZ downregulated the expression of genes related to Th17 cell differentiation as well as mRNA of genes on IL-17 and PI3K/Akt signaling pathways. CONCLUSION SZ has therapeutic effects on hyperuricemia. The mechanism of action maybe related to the inhibition of hepatic xanthineoxidase activity, down-regulation of URAT1 levels, up-regulation of ABCG2 levels, affecting the differentiation of Th17 cells and thus the IL-17 signaling pathway, thereby reducing the inflammatory response.

Percutaneous nephrolithotripsy is the first line treatment for complete staghorn calculi, but there are risks such as renal function damage, bleeding, and infection. A case of complete staghorn calculi 8.3 cm×4.5 cm and mean CT value of 1 321 HU was reported. Urine culture suggested proteus mirabilis infection. The patient was given sensitive antibiotics for 3 days, and was treated with one session of natural orifice transluminal endoscopic lithotripsy with intelligent control of renal pelvic pressure. KUB on the first postoperative day showed residual stones of 1.0 cm×0.5 cm. There were no complications.