Objective To analyze the correlation between serum soluble Klotho protein(sKL)and tendino-C(TN-C)and the severity of disease and oxidative stress in children with immunoglobulin A(IgA)nephropa-thy.Methods A total of 85 children with IgA nephropathy admitted to the hospital from July 2019 to August 2022 were selected as IgA nephropathy group,and 85 healthy patients who underwent physical examination in the hospital during the same period were selected as healthy group.Serum sKL and TN-C levels were com-pared between the two groups.Receiver operating characteristic(ROC)curve was drawn to analyze the value of serum sKL,TN-C and their combination in predicting the occurrence of IgA nephropathy.IgA nephropathy group was divided into mild group(28 cases),moderate group(39 cases)and severe group(18 cases)accord-ing to 24 h urinary protein quantity.Serum sKL,TN-C levels and oxidative stress indexes[malondialdehyde(MDA),superoxide dismutase(SOD)and advanced oxidation protein product(AOPP)]of the three groups were compared.The correlation between serum sKL and TN-C levels and oxidative stress indexes was ana-lyzed by Spearman correlation,and the correlation between serum sKL and TN-C levels and the severity of IgA nephropathy in children was examined by Kendall's Tau-b.Results The serum sKL level in IgA ne-phropathy group was lower than that in healthy group,and the serum TN-C level was higher than that in healthy group,the difference was statistically significant(P＜0.05).ROC curve showed that the area under the curve and 95％CI of serum sKL,TNC and their combination predicted the occurrence of IgA nephropathy were 0.726(95％CI:0.648-0.803),0.853(95％CI:0.796-0.909)and 0.891(95％CI:0.845-0.937).The level of serum sKL in severe group was lower than that in moderate and mild groups,while the level of serum TN-C was higher than that in moderate and mild groups,and the difference was statistically significant(P＜0.05).The serum SOD level of severe group was lower than that of moderate group and mild group,and the serum AOPP and MDA levels were higher than those of moderate group and mild group,the difference was statistically significant(P＜0.05).Spearman correlation showed that sKL level was positively correlated with SOD(r＞0,P＜0.05),and negatively correlated with AOPP and MDA(r＜0,P＜0.05).TN-C level was negatively correlated with SOD(r＜0,P＜0.05),and positively correlated with AOPP and MDA(r＞0,P＜0.05).Conclusion The levels of serum sKL and TN-C in children with IgA nephropathy are related to the severity of disease and oxidative stress,and the combination of SKL and TN-C can effectively predict the occurrence of IgA nephropathy.

Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Objective:To investigate the clinical outcome of endovascular treatment vs. drug treatment in patients with symptomatic non-acute long-segment occlusion of the internal carotid artery. Methods:Based on prospective cohort registration research data, patients with symptomatic non-acute long-segment occlusion of internal carotid artery were retrospectively included. They were divided into a drug treatment group and an endovascular treatment group according to the actual treatment received. The latter was further divided into a successful recanalization group and an unsuccessful recanalization group. The endpoint events included ipsilateral ischemic stroke, any stroke, and all-cause death. Multivariate logistic regression analysis was used to compare the endpoint events between groups during the perioprocedural period (within 30 days), and multivariate Cox proportional hazards model was use to compare the endpoint events between the groups during the long-term follow-up. Results:A total of 684 patients were included, of which 570 (83.33%) were male, median aged 63 years (interquartile range, 56-70 years). Three hundred and fifty-three patients (51.6%) received drug treatment; 331 (48.4%) received endovascular treatment, of which 161 (48.6%) had successful recanalization. The median follow-up time was 1 223 days (interquartile range, 646.5-2 082 days), with 109 patients (15.9%) experiencing stroke recurrence events (including 87 ipsilateral ischemic stroke) and 78 (11.4%) experiencing all-cause mortality. The risk of any stroke during the perioprocedural period in the successful recanalization group was significantly higher than that in the drug treatment group (odds ratio 3.679, 95% confidence interval 1.038-13.036; P=0.044), but the risk of ipsilateral ischemic stroke recurrence (risk ratio 0.347, 95% confidence interval 0.152-0.791; P=0.012) and all-cause mortality (risk ratio 0.239, 95% confidence interval 0.093-0.618; P=0.003) during the long-term follow-up were significantly lower than those in the drug treatment group. Conclusions:In patients with symptomatic non-acute long-segment occlusion of the internal carotid artery, endovascular treatment can increase the risk of stroke recurrence within 30 days, but successful recanalization can reduce the risks of long-term ipsilateral ischemic stroke recurrence and all-cause mortality.

Objective By population survey,to explore the epidemiological characteristics of gastric precancerous lesions in Lishui District of Nanjing and provide objective basis for the prevention and treatment of early gastric cancer.Methods From July 2021 to December 2022,21 977 patients who received endoscopy and/or 13C-UBT in Lishui District People's Hospital and 6 medical community units in Nanjing City were retrospectively analyzed for demography characteristics,detection rate of gastric precancerous lesions,and H.Pylori infection rate.Results(1)590 cases of gastric precancerous lesions were detected(detection rate 2.68%);(2)The total detection rate of precancerous lesions and three pathological types in males were all higher than those in females(all P<0.001);(3)The minimum age for the total detection rate of precancerous lesions in males and the mini-mum age for each pathological type were lower than in females(P<0.001,0.009,0.005,0.002);(4)The popu-lation total H.pylori infection rate was 23.10%,the H.pylori infection rate in patients with precancerous lesions was higher than that in non-precancerous lesions(P<0.001),both H.pylori infection rate of male and female in precancerous lesions were all higher than those of non-precancerous lesions of the same sex(all P<0.001),in addition,the H.pylori infection rate of male whether in precancerous or non-precancerous lesions was higher than that of female(all P<0.001);(5)The precancerous lesions detection rate in male,female,and the overall age range of 20～29 to 70～79 years is positively correlated with age growth(P<0.001),and rapidly decreases after the age of 79,the of H.pylori infection rate was also positively correlated with age growth(P<0.001),and the trend of age change(P<0.001)was parallel to the precancerous lesions detection rate.Conclusions The detec-tion rate of gastric precancerous lesions in this region is above the average level in China;the total H.pylori infec-tion rate is at a relatively low level in China;the H.pylori infection rate is parallel to the age trend of the detection rate of gastric precancerous lesions,and increases with age.

Objective To investigate whether there are sex differences in inflammatory bowel disease(IBD)among the offspring of mice with IBD.Methods BALB/c female mice were randomly divided into Na?ve and DSS groups.The mice in the Na?ve group drank autoclaved water freely,and the DSS group freely drank 2％dextran sodium sulfate(DSS)for 7 days before it was replaced with autoclaved water for 10 days.A total of 3～4 cycles were applied,and the IBD female mice were paired with healthy male mice in cages.When the pups were 8 weeks old,they were divided into the Con group and IBD group.The Con group drank autoclaved water freely for 7 days,and the IBD group drank 3％DSS for 7 days.During the modeling period,disease activity index was scored by monitoring body weight,fecal consistency,and the presence of blood in stool every day.Pathological sections were taken to observe changes in goblet cells and the mucus layer of colon tissues.The concentrations of interleukin(IL)-6,IL-1β,IL-33,and IL-10 in the colon were detected by enzyme-linked immunosorbent assay.Real-time quantitative PCR was used to determine the mRNA expression levels of tight-junction proteins and MUC-2 in the colon.Results Compared with female IBD mice,male IBD mice had higher DAI scores,significantly shorter colons,larger amounts of inflammatory infiltrate,more crypt abnormalities,and a higher absence of goblet cells in the colon;their relative mRNA expression of occludin mRNA was significantly reduced,levels of IL-6 and IL-33 were significantly increased,and level of IL-10 was significantly decreased.Conclusions The symptoms of colitis in the offspring of IBD mice were more severe in male than in female mice,a result that was mainly attributed to the more severely impaired intestinal epithelial barrier function in males.

Capsular warning syndrome (CWS) is a rare clinical syndrome characterized by recurrent and transient episodes of focal neurological deficits. Patients with CWS are at high risk of developing infarction. However, the exact physiological mechanism of CWS remains unclear. This paper presents an imaging assessment of penetrating arteries in the context of CWS using advanced time-of-flight magnetic resonance angiography and high resolution magnetic resonance imaging. This case reveals atherosclerosis of the lenticulostriate artery as a potential etiological factor contributing to CWS.

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.

Objective:To investigate predictive factors for successful endovascular recanalization in patients with non-acute symptomatic internal carotid artery occlusion (SICAO), to develop a decision tree model using the Classification and Regression Tree (CART) algorithm, and to evaluate the predictive performance of the model.Methods:Patients with non-acute SICAO received endovascular therapy at 8 comprehensive stroke centers in China were included retrospectively. They were randomly assigned to a training set and a validation set. In the training set, the least absolute shrinkage and selection operator (LASSO) algorithm was used to screen important variables, and a decision tree prediction model was constructed based on CART algorithm. The model was evaluated using the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test and confusion matrix in the validation set.Results:A total of 511 patients with non-acute SICAO were included. They were randomly divided into a training set ( n=357) and a validation set ( n=154) in a 7:3 ratio. The successful recanalization rates after endovascular therapy were 58.8% and 58.4%, respectively. There was no statistically significant difference ( χ2=0.007, P=0.936). A CART decision tree model consisting of 5 variables, 5 layers and 9 classification rules was constructed using the six non-zero-coefficient variables selected by LASSO regression. The predictive factors for successful recanalization included fewer occluded segments, proximal tapered stump, ASITN/SIR collateral grading of 1-2, ischemic stroke, and a recent event to endovascular therapy time of 1-30 d. ROC analysis showed that the area under curve of the decision tree model in the training set was 0.810 (95% confidence interval 0.764-0.857), and the optimal cut-off value for predicting successful recanalization was 0.71. The area under curve in the validation set was 0.763 (95% confidence interval 0.687-0.839). The accuracy was 70.1%, precision was 81.4%, sensitivity was 63.3%, and specificity was 79.7%. The Hosmer-Lemeshow test in both groups showed P>0.05. Conclusion:Based on the type of ischemic event, the time from the latest event to endovascular therapy, proximal stump morphology, the number of occluded segments, and the ASITN/SIR collateral grading constructed the decision tree model can effectively predict successful recanalization after non-acute SICAO endovascular therapy.

Objective:In order to understand the difference of clinical efficacy between original TNF-α inhibitors (TNFi) and their biosimilars, Bayesian mesh Meta-analysis was compare Etanercept, Infliximab, Adalimumab with their biosimilars in the treatment of ankylosing spondylitis (AS).Methods:A systematic literature search was performed, using Ovid Biomedical, Embase, Cochrane Library, CNKI, Wanfang Database and Weipu Database (up to March 8, 2023 for all resources above), to search publications of randomized controlled trial (RCT) about all original and biosimilar TNFi for the treatment of AS in all language. Two reviewers independently identified the eligible trails, evaluated bias risk and extracted relevant data. Based on Bayesian network, data analysis of included studies was conducted using statistical software R3.6.1 and R Studio.Results:The results of the network meta-analysis showed that, no significant differences was observed among. Etanercept, Infliximab,Adalimumab, and their biosimilars for ASAS20 when Infliximab was compared with Etanercept [ OR (95% CI)=1.4 (0.54, 3.5)], placebo was compared with Etanercept [ OR (95% CI)=0.35 (0.17,0.67)], No significant differences were observed among Etanercept, Infliximab, Adalimumab, and their biosimilars for BASDAI, when Infliximab was compared with Ctanercept [ OR (95% CI)=-0.89 (-1.8, 0.081)], placebo was compared with Etanercept [ OR(95% CI)=1.7(0.86, 2.5)], No significant differences were observed among Etanercept, Infliximab, Adalimumab, and their biosimilars for BASFI, when Infliximab was compared with Etanercept [ OR(95% CI)=-0.46(-1.3, 0.47)], placebo was compared with Etanercept [ OR(95% CI)=1.6(0.8, 2.3)]. Conclusion:Etanercept, Infliximab, Adalimumab with their biosimilars are significantly superior to placebo and sulfasalazine in terms of ASAS20, BASDAI, BASFI, CRP, ESR. Limited evidence have shown that the efficacy of biological biosimilars are similar to that of their corresponding original drugs.

Objective:To compare the efficacy and safety of percutaneous nephrolithotomy (PCNL) with negative pressure suction sheath and PCNL with traditional expanded sheath in the treatment of infectious renal calculus.Methods:From May 2019 to June 2022 in our department, 35 patients with infectious renal calculus who received PCNL with negative pressure suction sheath (negative pressure sheath group, NPS group) and another 35 patients with infectious renal calculus who received PCNL with traditional expanded sheath (control group) were determined in our research. Propensity score matching (PSM) was conducted. Preoperative clinical data of the 2 groups was similar and there were no statistical differences between the 2 groups in the age [(45.5±6.8)vs. (44.9±7.3) years old, P=0.723], gender (man/woman 19/16 cases vs. 21/14 cases, P=0.629), body mass index(BMI) [(24.2±4.2)kg/m 2vs. (24.5±3.9)kg/m 2, P=0.758], American Society of Anesthesiologists risk score(ASA) (grade 1/grade 2: 30/5 cases vs. 29/6 cases, P=0.743), sides of calculus (left/right: 18/17 cases vs. left 17/18 cases, P=0.811), Guy’s stone score (grade Ⅰ/Ⅱ/Ⅲ: 3/25/7 cases vs. 1/29/5 cases, P=0.443), CT value of calculus [(629.2±98.8)HU vs. (608.5±105.1)HU, P=0.399], urinary leucocyte (-/+ /+ + : 29/5/1 cases vs. 28/5/2 cases, P=0.839), hypertension(3 cases vs. 5 cases, P=0.707), diabetes(2 cases vs. 2 cases, P=1.000). The ureteral catheter on the affected side was indwelled in the lithotomy position, and ultrasound guided positioning puncture was performed on the affected renal side of the posterior axillary line in the prone position. The puncture channel was established and then expanded to F20 successively, and the lithotriptic sheath was placed to establish the lithotriptic channel. Compared with the traditional expanded sheath, the negative pressure suction sheath was different in that the collateral suction channel was added on the main gravel channel and connected with continuous negative pressure suction. The negative pressure was 40 kPa. All patients were treated with pneumatic ballistic lithotripsy combined with holmium laser. KUB was performed within 1 week after surgery. We defined stone removal as either no residual stones or clinically insignificant residual stones (≤4 mm) which did not cause urinary obstruction. The intraoperative duration of operation and postoperative clinical parameters [white blood cell(WBC), procalcitonin(PCT), C-reactive protein(CRP), hemoglobin(Hb), stone clearance rate] and incidence of perioperative complications were compared between the 2 groups. Results:The operation time of NPS group was lower than that in control group [(35.6±19.5)min vs. (45.4±20.2)min, P<0.05]. The proportion of patients with increased WBC, PCT and CRP in blood after operation in NPS group was lower than that in control group, and there were (WBC: 25.7% vs. 54.3%, P<0.05), (PCT: 42.9% vs.68.6%, P<0.05) and (CRP: 62.9% vs.85.7%, P<0.05) respectively. There was no significant difference in the proportion of patients with decreased Hb postoperatively between the 2 groups (2.9% vs. 8.6%, P=0.607). There was no significant difference in calculus clearance rate postoperatively between the 2 groups (97.1% vs. 94.3%, P=1.000). Postoperative calculus component analysis of the 2 groups suggested that all patients had infected calculus dominated by ammonium magnesium phosphate and phosphate apatite. The incidence of perioperative complications in NPS group was lower than that in control group (22.9% vs. 51.4%, P<0.05). The proportion of patients with fever (body temperature>37.5℃) postoperatively in NPS group was lower than that in control group (14.3% vs. 37.1%, P<0.05). There were 2 and 3 patients respectively required upgraded antibiotic therapy after operation in the 2 groups ( P=1.000). There was one patient respectively with urinary tract obstruction and renal colic due to blood clots postoperatively in each group ( P=1.000). There was one patient with urinary sepsis in control group after operation ( P=0.476). Conclusions:Compared with PCNL with traditional expanded sheath, PCNL with negative pressure suction sheath can save operation time for infectious renal calculus, and reduce the incidence of postoperative infection and perioperative complications. Therefore, the safety of negative pressure suction sheath is higher. However, there is no difference in stone clearance rate between them.