Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective:To analyze the epidemiological characteristics of wasting, spinal curvature abnormalities and multimorbidity among children and adolescents aged 6-18 in Inner Mongolia and explore the related factors of these two health problems.Methods:In September 2022, a stratified random cluster sampling method was employed to select 188 635 children and adolescents aged 6-18 in Inner Mongolia for physical examinations and questionnaire surveys. Data on height, weight, as well as dietary behavior, physical activity, classroom environment, academic tasks, writing posture, and screen behavior were collected. The epidemiological characteristics of wasting, spinal curvature abnormalities and multimorbidity were analyzed. Additionally, a multivariate logistic regression model was used to analyze the factors associated with wasting, spinal curvature abnormalities and multimorbidity.Results:A total of 188 635 children and adolescents aged 6-18 years participated in this study, including 95 393 boys (50.6%) with an average age of (11.53±3.32) years. The detection rate of wasting was 3.79%, with a higher detection rate in boys (4.18%) than in girls (3.38%) ( P<0.001). The detection rate of spinal curvature abnormalities was 3.64%, with a higher detection rate in girls (4.04%) than in boys (3.25%) ( P<0.001). The detection rate of multimorbidity between wasting and spinal curvature abnormalities was 0.17%, and there was no statistically significant difference between genders ( P>0.05). The detection rates of wasting, spinal curvature abnormalities, and multimorbidity all increased with age ( P t<0.001). The multivariate logistic regression analysis showed that, after adjusting for gender, age, urban/rural status, and school grade, compared to children and adolescents who exercised ≥1 hour of moderate-to-vigorous physical activity (MVPA) for at least 5 days per week and had daily screen time <2 hours, those who exercised <5 days per week ( OR=1.28, 95% CI: 1.19-1.37) and had daily screen time ≥2 hours ( OR=1.11, 95% CI: 1.03-1.19) had a higher risk of wasting. Compared to children and adolescents who had ≥5 physical education (PE) classes per week, adjusted desk and chair height,<1 hour of after-school study/writing time, and whose parents or teachers rarely or never reminded them about posture, those with <5 PE classes per week ( OR=1.11, 95% CI: 1.02-1.21), unadjusted desk and chair height ( OR=1.08, 95% CI: 1.01-1.15),≥1 hour of after-school study/writing time ( OR=1.15, 95% CI: 1.07-1.24), frequent reminders from parents ( OR=1.16, 95% CI: 1.09-1.23), and frequent reminders from teachers ( OR=1.10, 95% CI: 1.04-1.16) had a higher risk of spinal curvature abnormalities. Compared to children and adolescents who did not consume sugary drinks daily, exercised ≥1 hour of MVPA for at least 5 days per week, and whose teachers rarely or never reminded them about posture, those who consumed sugary drinks daily ( OR=1.61, 95% CI: 1.00-2.46), exercised <5 days per week ( OR=1.33, 95% CI: 1.01-1.79), and had teachers who frequently reminded them about posture ( OR=1.35, 95% CI: 1.05-1.75) had a higher risk of multimorbidity between wasting and spinal curvature abnormalities. Conclusion:The detection rates of wasting, spinal curvature abnormalities and multimorbidity among children and adolescents aged 6-18 in Inner Mongolia are generally low, with an increasing trend observed with age. Both lifestyle and school environmental factors are associated with wasting, spinal curvature abnormalities and multimorbidity.

Objective:To understand the occurrence of different patterns of multimorbidity among children and adolescents aged 9-18 in Tianjin City and analyze the cumulative effects of lifestyle on these patterns of multimorbidity.Methods:From September to November 2022, a stratified cluster random sampling method was used to select students from primary schools, junior high schools, general high schools, and vocational schools in 16 districts of Tianjin to screen for height, weight, blood pressure, distant vision, and diopter. One year later, a follow-up measurement and questionnaire survey were conducted. The log-binomial model was used to analyze the strength of the association between lifestyle factors and different patterns of multimorbidity.Results:The age of 9 488 students was (12.37±2.49) years old, including 4 999 boys and 4 489 girls. The detection rates of three patterns of multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia were 6.63%, 9.32%, and 4.21%, respectively. The detection rates of the three types of multimorbidity in boys were higher than those in girls (all P<0.001). The detection rate of overweight obesity and high blood pressure in suburban areas was higher than that in urban areas ( P=0.002). The detection rate of overweight obesity and myopia in suburban areas was lower than that in urban areas ( P=0.034). The detection rate of overweight obesity and myopia among those aged 9-12 years old was higher than other age groups (all P<0.001). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity and high blood pressure was 0.79 (0.68-0.92). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity with high blood pressure and myopia was 0.82 (0.67-0.99). Compared with children and adolescents with 0-2 favorable lifestyle factors, those with 4-5 favorable lifestyle factors had a lower risk of overweight obesity and high blood pressure ( ARR=0.84, 95% CI: 0.59-0.92). Conclusion:Boys aged 9-18 in Tianjin City are more prone to multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia. Children and adolescents with 4-5 favorable lifestyle factors have a reduced risk of occurrence of overweight obesity and high blood pressure. Lifestyle has cumulative effects on multimorbidity of overweight obesity and high blood pressure.

[Objective]To evaluate the utility of left atrial(LA)volume and strain measured by 4D auto left atrial quantification(4D auto LAQ)in differentiating pre-capillary from post-capillary pulmonary hypertension(PH),and to compare its discriminative performance with echocardiographic pulmonary to left atrial global strain ratio(ePLAGS).[Methods]A total of ninety-eight subjects with intermediate to high probability of PH were prospectively enrolled.Clinical history and laboratory data were collected.All patients underwent comprehensive transthoracic echocardiography,and LA volume and strain parameters were measured by dedicated commercial software for LA 4D analysis.[Results]Based on pulmonary arterial wedge pressure,patients were divided into pre-capillary PH group[n=39;mean age(53±24)years]and post-capillary PH group[n=59;mean age(57±18)years].Compared to the pre-capillary PH group,the post-capillary PH group showed significantly higher LAVImax,LAVImin and LAVIpreA but markedly lower LASr and LAScd.Multivariate logistic regression identified LAVImax[OR:1.40;95%CI:(1.052,1.872);P=0.021]and LAScd[OR:1.76;95%CI:(1.183,2.489);P=0.004]as independent predictors of post-capillary PH.ROC analysis demonstrated that LAVImax(AUC=0.82,P＜0.001)and LAScd(AUC=0.78,P＜0.001)had strong discriminating power for predicting post-capillary PH group,with optimal cutoff values of 35.69 mL/m2(sensitivity 86%,specificity 74%)and-9%(sensitivity 80%,specificity70%).[Conclusion]LAVImax and LAScd measured with 4D auto LAQ are robust parameters for distinguishing pre-capillary PH from post-capillary PH.

Acute liver failure (ALF) is lack of broadly approved therapeutic strategy except liver transplantation. As a glycogen metabolic intermediate, UDP-glucose (UDP-G) has been considered to accelerate liver repairment. Nevertheless, the role of UDP-G and its receptor P2Y purinoceptor 14 (P2Y₁₄R) in ALF remains unknown. The present study aims to investigate the role and underlying mechanisms of UDP-G/P2Y₁₄R axis in ALF. In this study, hepatic P2Y₁₄R is significantly increased in TAA-induced and partial hepatectomy-induced ALF, while knockout of whole-body P2Y₁₄R aggravates liver failure, manifested by inhibiting β-Catenin-mediated liver regeneration. Consistently, P2Y₁₄R deficiency exhibits impaired liver regeneration in mice suffer partial hepatectomy. Importantly, only hepatocellular specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Alb ^cre/+ ) mice shows a similar phenomenon, rather than stellate cell specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Lrat ^cre/+ ) mice. Mechanistically, P2Y₁₄R induction regulates methylation of Dact-2 through CREB/DNMT3b signals in hepatocytes, subsequently inhibiting the expression of Dact-2 which is a stabilizer of β-Catenin degradation complex, leading to the activation of β-Catenin -mediated liver regeneration. Interestingly, the administration of exogenous UDP-G can accelerate liver regeneration and liver function recovery after partial hepatectomy in hepatocellular carcinoma mice. Together, the findings propose an unrecognized role of P2Y₁₄R in ALF and provide an effective adjuvant strategy for treatment of ALF.

Diabetic nephropathy (DN), as one of the most common complications of diabetes, is a primary cause of end-stage renal disease. The pathogenesis of DN encompasses processes such as chronic inflammation, recruitment and activation of immune cells, tubular and glomerular injury, and renal fibrosis. These processes are highly correlated with the activation of the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome and the resulting pyroptosis it mediates. Previous studies have shown that the release of pro-inflammatory cytokines, leakage of damage-associated molecular patterns (DAMPs), recruitment and activation of immune cells can be reduced by regulating the NLRP3 inflammasome and its mediated pyroptosis, thereby slowing the diffusion of inflammatory responses in adjacentcells, fibrosis, and tissue remodeling processes. Ultimately, these process can improve renal injury and dysfunction caused by diabetic nephropathy. This article summarizes the molecular regulatory mechanisms of the NLRP3 inflammasome and its mediated pyroptosis at different pathological stages of DN, proposes potential targets for regulating their activation, aiming to provide a new direction for personalized treatment of DN.

Objective To systematically review the efficacy and safety of the tislelizumab combined with anlotinib regimen for advanced non-small-cell lung cancer(NSCLC)patients.Methods PubMed,Embase,Cochrane Library,Web of Science,CNKI,WanFang Data databases were electronically searched to collect clinical studies on the combination of trastuzumab and anlotinib in the treatment of advanced NSCLC patients from inception to August 10,2024.Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was then performed by using RevMan 5.4.1 software.Results A total of 6 articles of 468 patients were included,involving 4 randomized controlled trials and 2 prospective cohort studies.Meta-analysis showed that the tislelizumab combined with anlotinib group had higher ORR[OR=2.53,95％CI(1.62,3.93),P＜0.001]and DCR[OR=4.45.95％CI(2.43,8.15),P＜0.001]than the anlotinib group.The CYFRA21-1 level in the combination group was significantly lower than that in the anlotinib group[SMD=-1.07,95％CI(-1.63,-0.51),P＜0.001].For safety,there were no significant differences in the incidence of adverse reaction of leukopenia[OR=0.91,95％CI(0.39,2.14),P=0.83],liver/kidney dysfunction[OR=1.16,95％CI(0.39,3.44)P=0.78].The descriptive analysis results indicated that there was no statistically significant difference in CEA levels between the two groups before treatment in each study(P＞0.05),and the CEA levels in the combination therapy group were lower than those in the anlotinib group after treatment(P＜0.05).Conclusion Compared to anlotinib alone,tislelizumab combined with anlotinib improves ORR,DCR,and reduces tumor markers in NSCLC patients,with comparable incidence of adverse reactions.Due to the limited quality and quantity of the included studies,more high quality studies are needed to verify the above conclusion.

Diabetic nephropathy(DN),a primary cause of end-stage renal disease(ESRD)in diabetic patients,is pathologically characterized by chronic inflammation and renal fibrosis.Chronic inflammation promotes renal cellular damage,epithelial-mesenchymal transition,and extracellular matrix(ECM)accumulation through mechanisms including immune cell activation,pro-inflammatory cytokine secretion,and initiation of multiple sig-naling pathways.Excessive ECM deposition disrupts renal architecture and drives tubulointerstitial expansion,thereby accelerating renal functional decline.Recent studies demonstrate that chronic inflammation and fibrosis synergistically propagate DN progression via bidirectional crosstalk.Inflammation serves as an early driver of fibro-genesis and further amplifies fibrotic processes through positive feedback mechanisms,establishing a self-perpetu-ating inflammation-fibrosis vicious cycle.However,the precise molecular interplay between chronic inflammation and fibrosis remains incompletely elucidated.Thus,in-depth exploration of their interaction mechanisms is crucial for developing novel DN interventions.This review delineates the pathogenic roles of chronic inflamma-tion and fibrosis in DN to advance mechanistic understanding and provide foundational insights for designing in-novative therapeutic strategies.