Objective To explore the effects of oleanolic acid on NF-κB/caspase-9 signaling pathway in kidneys of rat with diabetic nephropathy.Methods The diabetic nephropathy model rats were established,and the model rats were randomly divided intooleanolic acid low,medium and high dose groups,metformin group,and model group,with another 12 healthy SD rats as control group.The levels of blood glucose were measured at weeks 1,2 and 3 post-drug administration,and blood lipid and 24h urine urinary microalbumin(UMA)were measured after entire drug administration.Furthermore,we also detected the renal histopathology of rats,apoptosis of renal tubular,glomerular cells,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and protein expression of NF-κB/caspase-9 signaling pathway.Results Compared with the control group,the model group demonstrated higher levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,higher proportion of apoptotic renal tubular and glomerular,and higher expressions of caspase-9 protein and p-NF-κB p65/NF-κB p65(P＜0.05).Compared with the model group,the pathological damage of renal tissue in the metformin group and oleanolic acid low,middle and high dose groups were alleviated,the levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,the proportion of apoptotic renal tubular and glomerular,and the expressions of caspase-9 proteins and p-NF-κB p65/NF-κB p65 were decreased,and these indexes in oleanolic acid groups showed a dose-dependent manner(P＜0.05).Conclusion Oleanolic acid can improve the metabolism of glucose and lipid,reduce the pathological damage of renal tissue,inhibit the apoptosis of renal tubular and glomerular,and inhibit the NF-κB/caspase-9 pathway in diabetic nephropathy rats.

Objective·To investigate the clinical,pathological,and molecular genetic features and prognosis of epithelioid hemangioendothelioma(EHE)patients.Methods·Clinical and follow-up data of 12 EHE patients diagnosed at Renji Hospital,Shanghai Jiao Tong University School of Medicine from September 2016 to December 2023 were collected.Tissue samples were analyzed using hematoxylin-eosin(H-E)staining,immunohistochemistry(IHC),and fluorescence in situ hybridization(FISH).Results·Among the 12 patients,there were 3 males and 9 females,with a mean age of(47.17±11.15)years.Tumors were located in the liver(6 cases),lung(4 cases),mediastinum(1 case),and supraclavicular region(1 case).Nine patients were asymptomatic,while 3 presented with mild symptoms such as chest tightness and fatigue.CT imaging revealed that EHE patients with involvement of livers and lungs exhibited multiple nodules,and 2 cases had tumors in both organs.Patients with tumors in the supraclavicular region and mediastinum presented with solitary nodules.H-E staining demonstrated that tumor tissues were composed of epithelioid,dendritic,and intermediate cells,arranged in acinar,cord-like,or clustered patterns.Epithelioid cells had round vesicular nuclei and eosinophilic cytoplasm,with some showing a signet-ring appearance and cytoplasmic vacuoles.The stroma contained a mucoid matrix.IHC staining revealed that mesenchymal endothelial markers,including vimentin,CD31,ETS transcription factor ERG,and factor Ⅷ-related antigen,were positive in the tumor tissues,while epithelial markers showed low positivity with weak staining.The Ki-67 indexes were also low.FISH analysis showed that 10 patients had a calmodulin-binding transcription activator 1(CAMTA1)gene break,while 2 patients had a transcription factor E3(TFE3)gene break.Of the 12 patients,11 were followed up for 2 to 38 months,with a mean follow-up time of 21.7 months.Three patients achieved tumor-free survival,6 were alive with tumors,1 died 4 months after surgery,and 1 died of heart disease 24 months after surgery.Conclusion·EHE has atypical clinical features,a tendency to recur,a and variable prognosis.Accurate diagnosis requires a combination of histopathology,IHC,and a molecular testing.

Objective·To investigate the clinical,pathological,and molecular genetic features and prognosis of epithelioid hemangioendothelioma(EHE)patients.Methods·Clinical and follow-up data of 12 EHE patients diagnosed at Renji Hospital,Shanghai Jiao Tong University School of Medicine from September 2016 to December 2023 were collected.Tissue samples were analyzed using hematoxylin-eosin(H-E)staining,immunohistochemistry(IHC),and fluorescence in situ hybridization(FISH).Results·Among the 12 patients,there were 3 males and 9 females,with a mean age of(47.17±11.15)years.Tumors were located in the liver(6 cases),lung(4 cases),mediastinum(1 case),and supraclavicular region(1 case).Nine patients were asymptomatic,while 3 presented with mild symptoms such as chest tightness and fatigue.CT imaging revealed that EHE patients with involvement of livers and lungs exhibited multiple nodules,and 2 cases had tumors in both organs.Patients with tumors in the supraclavicular region and mediastinum presented with solitary nodules.H-E staining demonstrated that tumor tissues were composed of epithelioid,dendritic,and intermediate cells,arranged in acinar,cord-like,or clustered patterns.Epithelioid cells had round vesicular nuclei and eosinophilic cytoplasm,with some showing a signet-ring appearance and cytoplasmic vacuoles.The stroma contained a mucoid matrix.IHC staining revealed that mesenchymal endothelial markers,including vimentin,CD31,ETS transcription factor ERG,and factor Ⅷ-related antigen,were positive in the tumor tissues,while epithelial markers showed low positivity with weak staining.The Ki-67 indexes were also low.FISH analysis showed that 10 patients had a calmodulin-binding transcription activator 1(CAMTA1)gene break,while 2 patients had a transcription factor E3(TFE3)gene break.Of the 12 patients,11 were followed up for 2 to 38 months,with a mean follow-up time of 21.7 months.Three patients achieved tumor-free survival,6 were alive with tumors,1 died 4 months after surgery,and 1 died of heart disease 24 months after surgery.Conclusion·EHE has atypical clinical features,a tendency to recur,a and variable prognosis.Accurate diagnosis requires a combination of histopathology,IHC,and a molecular testing.

Objective To explore the effects of oleanolic acid on NF-κB/caspase-9 signaling pathway in kidneys of rat with diabetic nephropathy.Methods The diabetic nephropathy model rats were established,and the model rats were randomly divided intooleanolic acid low,medium and high dose groups,metformin group,and model group,with another 12 healthy SD rats as control group.The levels of blood glucose were measured at weeks 1,2 and 3 post-drug administration,and blood lipid and 24h urine urinary microalbumin(UMA)were measured after entire drug administration.Furthermore,we also detected the renal histopathology of rats,apoptosis of renal tubular,glomerular cells,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and protein expression of NF-κB/caspase-9 signaling pathway.Results Compared with the control group,the model group demonstrated higher levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,higher proportion of apoptotic renal tubular and glomerular,and higher expressions of caspase-9 protein and p-NF-κB p65/NF-κB p65(P＜0.05).Compared with the model group,the pathological damage of renal tissue in the metformin group and oleanolic acid low,middle and high dose groups were alleviated,the levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,the proportion of apoptotic renal tubular and glomerular,and the expressions of caspase-9 proteins and p-NF-κB p65/NF-κB p65 were decreased,and these indexes in oleanolic acid groups showed a dose-dependent manner(P＜0.05).Conclusion Oleanolic acid can improve the metabolism of glucose and lipid,reduce the pathological damage of renal tissue,inhibit the apoptosis of renal tubular and glomerular,and inhibit the NF-κB/caspase-9 pathway in diabetic nephropathy rats.

Objective:To explore the effect and safety of endoscopic tubular musculoskeletal tumor surgery (ETMS) technology in spinal tumors.Methods:Clinical data were retrospectively collected from 18 spinal tumor patients who were treated with ETMS technology at Tianjin Medical University Cancer Institute and Hospital ( n=16) or the Affiliated Hospital of Qingdao University ( n=2) from November 2022 to December 2023. The total cohort included 11 males and 7 females, with the age at 60.3±8.6 years (range of 41-76). Two cases were diagnosed with benign tumors, four patients were diagnosed with spinal hematologic malignancies while other 12 cases were patients with spinal metastases. After localization under the C-arm X-ray machine, the spinal endoscopic channel is established using dilators. Soft tissue is dissected under endoscopic guidance to create an artificial cavity. Subsequently, the saline medium relied upon by the spinal endoscopic technique is removed, and posterior decompression and tumor curettage are performed using tubular techniques. Frankel grade classification and paraplegia index were used to evaluate the improvement of postoperative function and the VAS score was performed in pain scoring. The surgical complications and tumor evaluation were observed by postoperative outpatient and telephone follow-up. Results:The ETMS technology was successfully completed in all 18 patients with the mean operation time of 240.3±80.2 min. The median of intraoperative bleeding was 200.0(172.5, 350.0) ml and the mean postoperative drainage was 131.4±69.5 ml. The median value of postoperative hospitalization days was 6.0(4.0, 10.25) d. The paraplegia index decreased from 1.5(0, 3.0) preoperatively to 0(0, 1.25) postoperatively ( Z=-2.599, P=0.009). All the patients presented an improvement in Frankel grading after surgery except for one patient (downgrading from grade E to grade D). There was significantly difference in Frankel grading between preoperative and postoperative groups ( Z=2.812, P=0.005). The median value of preoperative VAS score was up to 5.5(4.0, 7.0) while the median value at postoperative, one month after surgery and three months after surgery were 1.5(1.0, 2.25), 1.0(0, 1.0) and 0(0, 1.0), respectively (χ 2=44.641, P<0.001). The 3-month postoperative VAS improvement rate was 91.2% (range 75%-100%). During a mean follow-up period of 7.6±6.2 months, none of the 18 patients presented surgical complications or tumor recurrence at surgical region. Only one patient died at 3.2 months after surgery until the last follow-up due to respiratory failure after lung tumor progression. The mean survival of the total cohort was up to 13.3 [95% CI (11.5, 15.0)] months. The 16 cases with spinal metastases or spinal hematological malignancies had a mean survival of 13.2 [95% CI (11.3, 15.0)] months. Conclusion:The ETMS technology presented good efficacy and safety in treatment of spinal tumors with low blood supply and with diameter less than 5cm.

Tuberculosis （TB） and human immunodeficiency virus infection / acquired immune deficiency syndrome （HIV/AIDS） are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years， with the promotion and application of new TB and HIV detection technologies worldwide， TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening， summarizes important progress of research and applications， and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.

Objective:To explore the risk factors of hypotension in patients with hemodialysis-related superior vena cava diseases.Methods:This was a retrospective cohort study. The maintenance hemodialysis patients diagnosed as superior vena cava stenosis ≥50% or occlusion in West China Hospital of Sichuan University from January 1, 2019 to March 31, 2022 were selected. The patients were divided into hypotensive group and non-hypotensive group according to the occurrence of hypotension during non-dialysis period. The differences of general clinical data, cardiac ultrasound parameters and blood biochemical indexes between the two groups were compared. Multivariate logistic regression model was used to analyze the risk factors of hypotension in patients with hemodialysis-related superior vena cava lesions.Results:A total of 202 patients with hemodialysis-related superior vena cava lesions were included, of whom 84 patients (41.6%) developed hypotension during non-dialysis. Compared with the non-hypotensive group, patients in the hypotensive group had longer dialysis age ( Z=2.093, P=0.036), shorter left atrial diameter ( t=2.316, P=0.022), lower aortic valve orifice flow rate ( t=3.702, P=0.001) and serum calcium ( t=2.320, P=0.021), thicker left ventricular posterior wall ( t=3.042, P=0.003), lower proportions of hypertension history ( χ2=9.125, P=0.003), and higher proportion of residual superior vena cava ≤30% or occlusion ( χ2=8.940, P=0.003) and azygous vein opening ( χ2=11.067, P=0.001). Multivariate logistic regression analysis results showed that no history of hypertension ( OR=0.383, 95% CI 0.156-0.943, P=0.037), slow aortic valve orifice flow ( OR=0.207, 95% CI 0.062-0.695, P=0.011) and low blood calcium ( OR=0.236, 95% CI 0.066-0.841, P=0.026) were the independent influencing factors of hypotension in patients with hemodialysis-related superior vena cava diseases. Conclusions:Hemodialysis patients with severe stenosis or occlusion of the superior vena cava during non-dialysis have a higher risk of hypotension. No history of hypertension, slow aortic valve orifice flow, and low blood calcium are the independent risk factors of hypotension in patients with hemodialysis-related superior vena cava diseases.

Objective To explore the relationship between obesity and serum testosterone level among community adult males.Methods The stratified cluster sampling method was adopted to extract 1 166 male residents aged 20 years old and over in Zunyi City and conduct the questionnaire survey and physical examination.Fasting venous blood samples were collected for detecting the serum total testosterone(TT),sex hormone binding globulin(SHBG) and luteinizing hormone(LH).Then free testosterone index(cFT),free testosterone index(FTI) and testosterone secreting index(TSI) were calculated.Results The average levels of serum TT,SHBG,cFT,FTI,TSI and LH in 1 166 adult males were(16.83±4.90)nmol/L,(42.15 ± 20.21)nmol/L,(0.31 ±0.10)nmol/L,(0.46 ± 0.19) IU/L,(3.40 ± 2.04) IU/L and(6.77 ± 5.14) IU/L respectively;the Pearson correlation analysis showed that WHtR,BMI and WC were negatively correlated with TT,SHBG,TSI and LH,and were positively correlated with FTI,WHtR was negatively correlated with cFT,BMI and WC were negatively correlated with LH,the differences were statistically significant(P＜0.05).The multivariate linear regression analysis shown that WHtR was negatively correlated with TT,SHBG,TSI and LH;and was positively correlated with FTI,the differences were statistically significant(P＜0.01).Conclusion Adult male central obesity may be associated with the decrease of serum TT,SHBG,TSI and LH levels,and increase of FTI level.

Objective To evaluate the effect of endoplasmic reticulum stress in trophocytes,in patients with intrahepatic cholestasis of pregnancy (ICP).Methods Sixty-one pregnant women who were hospitalized in Women's Hospital,School of Medicine,Zhejiang University from January to December 2015 were recruited.Thirty-one women who were diagnosed as ICP were defined as the ICP group and 30 healthy pregnant women were defined as the control group.The localization and expression intensity of glucose regulated protein 78 (GRP-78) in placental tissues were detected by immunohistochemistry technique.Electronic microscope was used to observe ultra-microstructure change of the endoplasmic reticulum in trophocytes and cell line Swan71.Reverse transcription (RT)-PCR and western blot were used to investigate the expression of GRP-78 mRNA and protein in Swan 71 cell.Results (1) GRP-78 protein was mainly expressed in the cytoplasm of cytotrophoblasts and syncytiotrophoblasts.The protein expression of GRP-78 in placentas of the ICP group (13.2±2.4) was significantly higher than that in the control group (7.8±1.3,P＜0.01).(2) The volume of endoplasmie reticulum did not increase and the microvilli developed well,with no swelling and no expansion of endoplasmic reticulum in the control group.In the ICP group,microvilli injury,endoplasmic reticulum edema were found;the volume of endoplasmic reticulum increased,with dilation,vacuolation and significant degranulation.After treated with 100 μmol/L cholyglycine for 24 hours,universal dilatation of the endoplasmic reticulum were seen in the Swan71 cells.(3) In Swan71 cells,cholylglycine displayed a concentration-dependent up-regulation on the expression of GRP-78.The expressions of GRP-78 mRNA in 0,25,50,100 μmol/L cholylglycine experimental group were 1.01±0.17,2.17±0.16,5.47±0.36,5.65 ± 0.82,respectively.The expression of GRP-78 protein in 0,25,50,100 μmol/L cholylglycine experimental group were 1.01±0.04,1.17±0.15,1.33±0.13,1.73±0.13,respectively.The expression of GRP-78 mRNA and protein in 100 and 50 μ mol/L cholylglycine experimental group were significantly higher than 0 μmol/L (all P＜0.01).Conclusion The obvious expansion of endoplasmic reticulum and the increased expression of GRP-78 in trophocytes indicated that endoplasmic reticulum stress of trophocytes may be involved in the pathogenesis of ICP.

The effect of loss-of-function of Attractin (Atrn) on the male mouse reproduction system was examined in the study. The weights and pathological changes of testes and epididymes were compared between Atrn mutant (Atrn ( mg-3J )) mice and wild-type mice (C3HeB/FeJ) at different months of age. The number and motility of sperms were measured in the mutant and control mice. Furthermore, the testicular lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in these animals were detected. The fertility potential of the sperms was observed in vivo and in vitro. The results showed that the testes of 3-month-old Atrn ( mg-3J ) mice experienced no significantly different pathological changes from the control mice at the same month of age but the SDH activity was substantially reduced. In the 5-month-old mutant mice, as compared with the control mice, mild vacuolation was found in the testes, the density and motility of sperms were decreased in the epididymes, the sperm fertility was impaired and the testicular enzyme activity was reduced. It is concluded that the age-related Atrn gene progressively loses its function and can cause testis vacuolation and impaired sperm function, which may be responsible for the impairment of male reproductive ability.