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.

Small cell carcinoma of the prostate is a rare and highly malignant tumor of the urinary system. It is less common for prostate small cell carcinoma coexisting with bladder carcinoma. One such case was reported in this paper. The patient underwent ultrasound-guided transrectal prostate biopsy, and transurethral bladder endoscopy + bladder tumor electric resection. Postoperative pathology and immunohistochemistry showed prostate small cell carcinoma accompanied by high-grade invasive urothelial carcinoma of the bladder and small cell carcinoma. The patient underwent local bladder perfusion chemotherapy, relying on etoposide plus lobaplatin systemic chemotherapy and toripalimab immunotherapy. Prostate MRI, cystoscopy, and prostate-specific antigen (PSA) were performed 12 months after operation. The size of the lesions in the prostate and seminal vesicles had decreased, and there was a significant reduction in PSA levels. Additionally, no masses were detected in the bladder.

Objective To explore the related factors of lymph node metastasis in early gastric cancer and to analyze the clinical efficacy between laparoscopic D2 radical resection and endoscopic submucosal dissection(ESD).Methods A retrospective cohort study was conducted on 404 patients with early gastric cancer undergoing surgical treatment in our hospital from June 2018 to June 2022 were recruited in this study.According to their surgical treatment,they were divided into laparoscopy group(n=271)and ESD group(n=133).The lymph node metastases were compared in the patients with different clinical features,and the factors affecting lymph node metastasis were analyzed with multivariate logistic regression analysis.The lymph node metastasis rate of patients with absolute and expanded indications of ESD was calculated.Kaplan-Meier survival analysis was used to compare the long-term efficacy of ESD and laparoscopic D2 radical resection in these patients.Stratified regression analysis was applied to explore the relationship between surgical methods and long-term outcome in them.Results In the 404 patients with early gastric cancer,the rate of lymph node metastasis was 12.38％(50/404).Univariate analysis showed that 7 clinical features,such as ulcer,tumor pathological features and pathological differentiation,were related to lymph node metastasis.Multivariate logistic regression analysis revealed that low differentiation and tumor infiltration depth of submucous membrane(SM)were related factors affecting lymph node metastasis in early gastric cancer.The overall survival rate was 96.29％(389/404)in the 404 patients,96.31％in the laparoscopic group and 96.24％in the ESD group,and no statistical difference was seen between the 2 groups(P＞0.05).There was no obvious difference in 5-year survival rate between the patients who met the absolute indications for ESD and underwent laparoscopic D2 radical surgery and those receiving ESD treatment(96.00％vs 96.55％),and between those who were in accordance with the expanded indications for ESD and underwent laparoscopic D2 radical surgery and those receiving ESD treatment(94.74％vs 91.67％).After adjusting the clinical features such as lesion size,pathological differentiation and depth of tumor invasion by stratified regression analysis,the mode of operation for early gastric cancer was still correlated with the long-term efficacy(β=1.173,P=0.003).Conclusion The depth of tumor infiltration and differentiation are closely related to lymph node metastasis in early gastric cancer patients.The efficacy of laparoscopic D2 radical surgery on the patients with absolute and expanded indications for ESD is comparable to that of ESD treatment.

Objective To explore the value of probe-based confocal laser endomicroscopy(pCLE)in the differential diagnosis of fundic gland polyps.Methods A total of 63 patients who underwent conventional white light image(WLI)and suggested with gastric polyps in our gastroenterology endoscopy center during June and December 2023 were enrolled,and their clinical data,WLI,narrow band images(NBI),pCLE images and postoperative histopathological findings were collected.The characteristics of fundic gland polyps under pCLE were statistically verified,and the sensitivity,specificity,accuracy and consistency of different endoscopic diagnoses were calculated respectively.Results Under pCLE,fundic gland polyps were mainly manifested as elongated gastric pit opening,"hand-in-hand"gastric pit opening,well-arranged blood vessels around the pit opening,and no luciferin oozing.The sensitivity,specificity,accuracy of WLI were 72.73％,75.00％,73.13％and 0.343 for fundic gland polyps,and 81.82％,71.43％,71.64％and 0.354 for hyperplastic polyps,respectively.While,the above values of NBI were 87.27％,83.33％,86.57％and 0.673 for fundic gland polyps,and 81.82％,85.71％,85.07％and 0.554 for hyperplastic polyps;and those of pCLE were 92.73％,91.67％,92.53％and 0.769 for fundic gland polyps,and 90.91％,94.64％,94.03％and 0.797 for hyperplastic polyps pCLE had better sensitivity,specificity and accuracy than WLI and NBI,and had the results consistent with histopathological findings.Conclusion pCLE can be used in the differential diagnosis of fundic gland polyps.

ObjectiveTo explore the possible mechanism of Yiqi Yangyin Huoxue prescription in the prevention and treatment of kidney injury of diabetic kidney disease（DKD）rats based on NOD-like receptor protein 3（NLRP3）/cysteine protease-1（Caspase-1）/gasdermin D （GSDMD）pyroptosis pathway. MethodFifty male SD rats were randomly divided into normal group （n=8） and modeling group （n=42）. The modeling group was given a one-time intraperitoneal injection of streptozotocin （STZ） after high-sugar and high-fat diet for 6 weeks to induce the establishment of a DKD rat model. After successful modeling， the rats were randomly divided into model group， valsartan group （8.33 mg·kg^-1）， and Yiqi Yangyin Huoxue prescription low-dose and high-dose group （11，22 g·kg^-1）. After continuous gavage for 6 weeks， the fasting blood glucose （FBG）， total cholesterol （CHO）， triglyceride （TG）， blood urea nitrogen （BUN）， serum creatinine （SCr） and 24-hour urine protein quantification （24 h-UTP） were detected in each group of rats. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of kidney tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum interleukin-1β （IL-1β） and interleukin-18 （IL-18） levels. The protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue of rats in each group were determined by Western blot and real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in normal group， the levels of FBG， CHO， TG， BUN， SCr， 24 h-UTP and serum IL-1β and IL-18 as well as the protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue in model group were increased （P<0.01）， and the kidney tissue lesions were severe. Compared with the conditions in model group， the levels of FBG， CHO， TG， BUN， SCr， 24 h-UTP and serum IL-1β and IL-18 as well as the protein and mRNA expression levels of NLRP3/Caspase-1/GSDMD in kidney tissue in each intervention group were decreased （P<0.05， P<0.01）， and the degree of kidney tissue lesions was improved， with Yiqi Yangyin Huoxue prescription high-dose group showing the optimal effect. ConclusionYiqi Yangyin Huoxue prescription could inhibit pyroptosis by regulating the NLRP3/Caspase-1/GSDMD pathway， and thus relieve the inflammatory response of DKD rats and alleviate the pathological damage of the kidneys.

Chromatin modification contributes to pluripotency maintenance in embryonic stem cells(ESCs).However,the related mechanisms remain obscure.Here,we show that Npac,a"reader"of histone H3 lysine 36 trimethylation(H3K36me3),is required to maintain mouse ESC(mESC)pluripotency since knockdown of Npac causes mESC differentiation.Depletion of Npac in mouse embryonic fibroblasts(MEFs)inhibits reprogramming efficiency.Furthermore,our chromatin immunoprecipitation followed by sequencing(ChIP-seq)results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs.Interestingly,we find that Npac interacts with positive transcription elongation factor b(p-TEFb),Ser2-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser2P),and Ser5-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser5P).Furthermore,depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rifl.Taken together,we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interact-ing with RNA Pol Ⅱ Ser2P and Ser5P.

Objective Objective To explore the best dog urethra rectum fistula operation method.Methods In June 2016 to October 2016,15 healthy male dogs were selected as research objects,aged 2-3 years (mean 2.5 years),with a body mass of 12-15 kg (mean 13.5 kg).They were randomly divided into three groups,each group of five.5 male dogs were cut through the rectum.5 male dogs were cut through the perineum.5 male dogs were cut through the rectal sphincter of the anus.Postoperative retrograde urethrectomy rectum angiography,the urethral pressure injection of methylene blue white gauze aizen rectum fistula and histologic evaluation of each group were compared 1,2,3 moths after the operation.Results Anal rectum drag cold knife cut group,1,2,3 moths after the operation,postoperative indicated the exist of orificium fistulae.The urethral pressure injection of methylene blue could observe rectum white gauze aizen,and pathological histology suggested the mucosal lamina propria disorder.There were a large number of inflammatory cells,5 dogs models were successfully built.Abdominal perineal pathway group:1 dog was killed by itself.1 dog one month after operation in anus at 2 cm below diameter about 3 cm appeared in a mixture of urine fistula and urethral orifice outflow,no urine outflow.More than 3 dogs after a week in the edge of serious infection,a canine model of severe dysuria,1,2,3 moths after the operation,postoperative indicated the exist of orificium fistulae.The urethral pressure injection of methylene blue could observe rectum white gauze aizen.3 dogs models were built.Through anal sphincter incision group:five dogs of the urethral fistula were successful,and one dog was incontinent with fecal incontinence.Conclusions The rectal rectum could successfully produce the animal model of the urethral rectal fistula and provide the experimental subjects for the treatment of iatrogenic urethral fistula.

Objective To investigate the relation between fragmentation of the Golgi apparatus and expression changes of Rab30 in HT22 neurons.Methods The routinely cultured HT22 neurons were divided into control group,thapsigargin 3 h group and thapsigargin 5 h group;neurons in the thapsigargin 3 h group and thapsigargin 5 h group were given 0.1 μg/mL thapsigargin treatment for 3 or 5 h,respectively.Morphology of Golgi apparatus and location of Rab30 were observed with cytochemistry immunofluorescence.The Rab30 mRNA expression was detected by real-time fluorescent quantitative PCR.The protein expressions ofRab30,cis-Golgi matrix protein 130 (GM130),and golgi anti-apoptotic protein (GAAP) were detected by Western blotting.Results Thapsigargin induced markedly Golgi fragmentation in HT22 neurons.The longer the neurons were exposed to thapsigargin,the more the Golgi fragmentation.Hippocampal neurons also expressed Rab30,which was mostly localized on Golgi apparatus.The Rab30 mRNA and protein expressions in the control group,thapsigargin 3 h group and thapsigargin 5 h group were decreased in sequence (relative transcript level:1.00±0.00,0.73±0.05 and 0.53±0.01),with significant differences (P＜0.05).The GM130 and GAAP protein expressions in control group,thapsigargin 3 h group and thapsigargin 5 h group were decreased in sequence,with significant difference (P＜0.05).Conclusion Thapsigargin can induce Golgi fragmentation,which may be related to the decreased expression of Rab30 in HT22 neurons.

[Summary] Sixty-one patients suffering from pituitary apoplexy( PA) were mainly diagnosed according to pathologic findings, and were collected from case record, pathology, and MRI databases. They were classified into 4 types according to the clinical condition: the insidious type was characterized with only positive pathological findings;the asymptomatic type had both positive pathologic and MRI findings; the subacute type had PA associated symptoms longer than 2 weeks; and the acute type had PA associated symptoms for 2 weeks or less. The latter 2 types had positive pathological and MRI findings additionally. The basic lesions, acute or chronic symptoms, endocrinopathies and MRI findings were compared among 4 types. Results showed as followed. In all patients, there were headache(60. 7% ), blurred vision(55. 7% ), vomiting(21. 3% ), and dizziness(14. 8% ). Apoplexy associated symptoms comprised severe headache (24. 6% ), rapid vision loss (29. 5% ), and blepharopotosis or diplopia (9. 83% ). Insidious, asymptomatic, subacute, and acute types were composed of 15 (24. 6% ), 9 (14. 8% ), 19 (31. 1% ), and 18 (29. 5% ) cases, respectively. Aging and intracranial space-occupying symptoms as first complaint showed increasing trend from mild to severe types(both P<0. 05), while in chronic course it showed decreasing trend(P<0. 05). Acute massive symptoms(P<0. 01), and non-functional tumor(P<0. 01) in the 2 clinical types were much more frequent than in the two mild types. Half or more pituitary-target glands showed impaired functions in each type, and the impairment showed increasing trend through mild to severe types(P<0. 01). The present study provided a brief typing system in order to expand PA concept to a wider span covering various conditions. Some differences in tumor composition and endocrinopathies existed among the four types.

Objective:To analyze the benefit incidence and evaluate the implementation effects on catastrophic disease insurance under the New Rural Cooperative Medical System ( NRCMS) in Jilin Province and put forward sug-gestions to perfect the catastrophic disease insurance under NRCMS. Method: In-depth interviews with related staff were conducted to gain an understanding of the operating status of catastrophic disease insurance under NRCMS;cat-astrophic disease patient data of Jilin Province from 2013 were collected, with a comparative analysis of implementa-tion effects among nine districts;the benefit incidence was analyzed by means of the Sperman rank correlation analy-sis; Results: The policy of catastrophic disease insurance under the NRCMS exhibited sound implementation effects and played an important role in reducing the economic burden of catastrophic disease patients. The average individual expenditure decreased by 4336. 52 yuan, while the reimbursement rate increased by 11. 15% after NRCMS cata-strophic disease insurance reimbursements. Additionally, statistical analysis results showed that there was a weak cor-relation between benefit incidence and economic level, the benefit equality of catastrophic disease insurance under NRCMS was relatively good, but the benefit level of rich patients was slightly higher. Conclusion:The reimbursement scheme of catastrophic disease insurance under NRCMS should be refined and improved, and the benefit fairness of different districts must be ensured, thus achieving the goal of relieving the“poverty caused by illness” phenomenon.