AIM: To investigate the effects of insulin-like growth factor 1(IGF-1)on the secretion of transforming growth factor β2(TGF-β2), matrix metalloproteinase 2(MMP-2)and hypoxia-inducible factor 1α(HIF-1α)in human scleral fibroblasts(HSF)and their mechanism.METHODS: The cells were cultured with IGF-1 and PI3K/AKT pathway inhibitor LY294002, respectively. CCK-8 method was used to detect cell viability and determine the optimal concentration and time of drug action. Cell migration activity was observed by cell scratch method. To determine the effects of IGF-1 on HSF cells and the regulatory role of PI3K/AKT pathway, HSF cells were divided into control group(without drugs), IGF-1(80 μg/L)group, IGF-1+LY294002(80 μg/L+5 mmol/L)group, and LY294002(5 mmol/L)group, and were cultured for 24 h; the protein expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT were detected by Western blot; the fluorescence expression of TGF-β2, MMP-2 and HIF-1α was detected by cellular immunofluorescence.RESULTS: The results of CCK-8 showed that the cell viability of the 80 μg/L IGF-1 group cultured with different concentrations of IGF-1 was the highest(all P<0.05), and the cell viability of the 80 μg/L IGF-1 group at 24 h was the highest under different culture times. Therefore, the concentration of IGF-1 was selected as 80 μg/L for 24 h. The viability of cells cultured with different concentrations of LY294002 gradually decreased from 6 h(all P<0.05). According to the IC50 value, therefore, the concentration of LY294002 was selected as 5 mmol/L for 24 h. The cell scratch results showed that compared with the control group, the cell mobility of 40 μg/L and 80 μg/L IGF-1 groups was increased(all P<0.05). Compared with the control group, cell mobility in the 2.5 and 5 mmol/L LY294002 groups was decreased(all P<0.05). Western blot results showed that compared with the control group, the protein expressions of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1+LY294002 group were decreased(all P<0.05). The results of cell immunofluorescence showed that compared with the control group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1+LY294002 group were significantly decreased(all P<0.05).CONCLUSION: IGF-1 promoted the proliferation and migration of human HSF. IGF-1 may up-regulate the expression of TGF-β2, MMP-2 and HIF-1α in HSF through the PI3K/AKT signaling pathway, and participate in the occurrence and development of myopia.

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective: To explore the association between physical activity, anxiety symptoms and academic performance among junior high school students, so as to provide data support for optimizing school physical education and health work and formulating physical activity guidelines. Methods: From September to December 2022, a convenience cluster sampling method was used to survey 2 800 junior high school students in a middle school from Anqing City, Anhui Province. Data were collected on the students anxiety symptoms, academic performance, 24 hour physical activity [moderate to vigorous intensity physical activity(MVPA), light intensity physical activity(LPA), sedentary behavior(SB), and sleep(SLP) duration] as well as demographic characteristics. Compositional data analysis was used to explore the associations between 24 hour physical activity, anxiety symptoms and academic performance among junior high school students, and to predict the optimal time use combination pattern. Results: Among the junior high school students, 16.0% (447 students) reported anxiety symptoms, and 42.0% (1 175 students) achieved excellent or good academic performance. Compositional data analysis showed that increased SLP duration was associated with both reduced anxiety symptoms ( β =-0.18) and decreased academic performance ( β =-0.03) among junior high school students; increased MVPA duration was correlated with fewer anxiety symptoms ( β =-0.02) and lower academic performance ( β =-0.13); in contrast, increased SB duration was linked to more anxiety symptoms ( β =0.09) and higher academic performance ( β =0.09) (all P <0.01). LPA duration exhibited a non linear relationship with anxiety symptoms and academic performance in junior high school students (all P >0.05). The time use combination pattern corresponding to the lowest anxiety symptoms and highest academic performance (top 5%) in adolescents was 611 (520-640) minutes of SLP, 258 (230-320) minutes of SB, 454 (280-610) minutes of LPA, and 117 (20-200) minutes of MVPA per day. Conclusions The 24 hour physical activity of junior high school students is associated with anxiety symptoms and academic performance. Therefore, it is recommended to increase the time spent on SB, MVPA, and LPA for junior high school students, while reducing SB.

Objective To compare the positioning errors,required planning target volume(PTV)outer expansion boundary and three-dimensional displacement of two different positioning fixation devices CIVCO Uni-frame carbon fiber adjustable angle head frame and domestic integrated board in radiotherapy for the pa-tients with head tumor,and to investigate the application value of CIVCO headrest in the positioning of head tumor radiotherpay.Methods The clinical data of 82 patients with head tumors who underwent radiotherapy in this hospital from January to December 2023 were analyzed retrospectively.The patients were divided into the adjustable angle head frame group and integrated plate group,41 cases in each group.Both groups were fixed with U-shaped thermoplastic head film.Radiotherapy was performed by using ELEKTA infinity linear accelerator.The cone beam computed tomography(CBCT)image guidance was used,combined with bone reg-istration and manual calibration to obtain the patient positioning errors in three directions:X axis,Y axis and Z axis.The positioning error data of each CBCT was recorded;based on the PTV outward expansion boundary formula(2.5∑+0.7σ),the PTV outward expansion boundaries required by the two fixation devices in all di-rections for the treatment of head tumors were calculated;the 3-dimensional spatial displacement was calculat-ed based on the patient's single radiotherapy positioning error.Results The absolute positioning errors in the X,Y,and Z directions of the adjustable angle head frame group were 0.13(0.07,0.22),0.16(0.16,0.27),0.10(0.05,0.18)cm respectively,which in the integrated board group were 0.14(0.07,0.24),0.18(0.08,0.32),0.09(0.04,0.10)cm respectively.The absolute error of the Y direction in the adjustable angle head frame group was smaller than that of the integrated board group(P=0.006),and the difference in the relative error between the two groups was not statistically significant(P＞0.05).According to the PTV expansion formula,the calculated expansion boundaries of the X,Y,and Z directions in the adjustable head frame group were 0.24,0.30,0.22 cm,which in the integrated plate group were 0.21,0.36,0.21 cm,respectively.The three-dimensional space comprehensive positioning error value could be calculated by the formula calculation using the positioning error values in three directions.The mean values of the three-dimensional space positio-ning errors of the adjustable angle headstock group and domestic integrated plate group were 0.320 cm and 0.340 cm respectively,there was no statistically significant difference between the two groups.Conclusion The absolute error in Y direction and the median value of three-dimensional displacement of the CIVCO adjustable angle head rest are smaller than those of the domestic integrated plate,which is worthy of clinical promoted applica-tion if conditions permit.

Objective:To explore the predictive value of T cell subtype characteristics and peripheral blood inflammatory indicators in patients with liver cancer for myelosuppression after hepatic artery infusion chemotherapy.Methods:A total of 115 patients with primary hepatocellular carcinoma who received transcatheter arterial chemoembolization (TACE) treatment in the Department of Oncology of Taizhou Jiangyan Traditional Chinese Medicine Hospital from May 2022 to May 2024 were enrolled as the research subjects. According to whether myelosuppression occurred after TACE treatment, the patients were divided into a non-myelosuppression group ( n=93) and a myelosuppression group ( n=22). The clinical data, the proportions of T cell subsets before TACE treatment, and the differences in the levels of peripheral blood inflammatory indexes were compared between the two groups. Spearman correlation analysis and multivariate logistic regression analysis were used to screen out the influencing factors of myelosuppression after TACE treatment in patients with primary hepatocellular carcinoma. The receiver operator characteristic (ROC) curve was used to analyze the efficacy of each influencing factor in predicting the myelosuppression of patients. Results:There were no statistically significant differences in age, sex, history of hypertension, body mass index, type of hepatitis virus infection, status of hypersplenism, Barcelona staging, Child-Pugh classification of liver function, number of TACE treatments, and the proportion of CD8 + T cells between the patients in the myelosuppression group and non-myelosuppression group (all P>0.05). However, there were statistically significant differences in diabetes ( χ2=3.94, P=0.047), history of alcohol consumption ( χ2=5.47, P=0.019), the longest diameter of the tumor ( Z=2.31, P=0.021), the presence of ascites ( χ2=4.10, P=0.043), the proportion of CD4 + T cells ( t=4.66, P<0.001), the ratio of CD4 +/CD8 + ( t=4.98, P<0.001), the neutrophil/lymphocyte ratio (NLR) ( t=4.98, P<0.001), the monocyte/lymphocyte ratio (MLR) ( t=2.31, P=0.023), and the systemic immune inflammation index (SII) ( t=5.31, P<0.001). Spearman correlation analysis showed that diabetes ( r=0.19, P=0.048), history of alcohol consumption ( r=0.22, P=0.019), the presence of ascites ( r=0.19, P=0.043), the longest diameter of the tumor ( r=0.22, P=0.020), NLR ( r=0.39, P<0.001), MLR ( r=0.30, P=0.001), and SII ( r=0.36, P<0.001) were all positively correlated with myelosuppression after TACE treatment in patients with primary hepatocellular carcinoma, while the proportion of CD4 + T cells ( r=-0.37, P<0.001) and the ratio of CD4 +/CD8 + ( r=-0.40, P<0.001) were negatively correlated with myelosuppression after TACE treatment in patients with primary hepatocellular carcinoma. Multivariate logistic regression analysis showed that the ratio of CD4 +/CD8 + ( OR=0.01, 95% CI: 0.01-0.11, P=0.002) was an independent protective factor for myelosuppression after TACE treatment in patients with primary hepatocellular carcinoma, and NLR ( OR=1.82, 95% CI: 1.31-5.60, P=0.013) and SII ( OR=1.03, 95% CI: 1.01-1.05, P=0.002) were both independent risk factors for myelosuppression after TACE treatment in patients with primary hepatocellular carcinoma. ROC curve analysis showed that the areas under the curve (AUCs) of the ratio of CD4 +/CD8 +, NLR, and SII for predicting myelosuppression after TACE treatment in patients with primary hepatocellular carcinoma alone were 0.79 (95% CI: 0.70-0.89), 0.78 (95% CI: 0.65-0.92), and 0.76 (95% CI: 0.65-0.87), respectively. The AUC of the combined prediction of the three was 0.91 (95% CI: 0.83-0.99), which was higher than that of the ratio of CD4 +/CD8 + ( Z=4.21, P<0.001), NLR ( Z=4.36, P<0.001), and SII ( Z=4.48, P<0.001) for prediction alone. Conclusions:The ratio of CD4 +/CD8 +, as well as NLR and SII levels before TACE treatment are independent factors influencing the occurrence of myelosuppression after treatment in patients with primary hepatocellular carcinoma, and are expected to be important indicators for predicting myelosuppression after hepatic artery infusion chemotherapy in patients with primary hepatocellular carcinoma.

Objective To establish a prediction model for lymph node metastasis(LNM)of gastric cancer based on routine laboratory indicators using machine learning algorithms.Methods This study collected data of 741 gastric cancer patients at Affiliated Hospital of Nantong University between January 2020 and January 2022 for model training and testing.Additionally,data of 102 gastric cancer patients between January 2023 and October 2023 were collected for model validation.XGBoost algorithm was used to calculate the importance of indicators and filter out a set of important indicators from 66 indicators.Five machine learning algorithms,including K-Nearest Neighbor,Support Vector Machine,Multilayer Perceptron,Random Forest and Adaboost,were constructed and trained for comparative analysis.Furthermore,the stability and accuracy of the model were further validated on the validation set.Results This study selected a set of important indicators composed of 9 routine laboratory indicators and trained the gastric cancer LNM prediction model,named V9.Additionally,through comparative experiments,it was found that the Adaboost algorithm based on the boosting strategy had the best performance,with evaluation metrics such as area under the curve,F1 score,accuracy,sensitivity,and specificity ranging from 0.833 to 0.968.The accuracy of the predictions on the validation set was 94.12%.Conclusion V9 was a gastric cancer LNM prediction model that has auxiliary clinical diagnostic value.It can be used to assess the risk of patients accurately and provide a basis for clinical decision-making.

Objective:To analyze and summarize the clinical, genotypic and pathological characteristics of children with PAX2 gene mutation in China, and to provide information for the monitoring, treatment and prognosis of the disease. Methods:It was a case series analysis study. The clinical data of children with PAX2 gene mutation in Pediatric Nephrology Department, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2022 were collected, and peripheral blood gene DNA was extracted and sequenced for whole exome sequencing. The clinical, pathological and genotypic characteristics of PAX2 gene variation of children in China were summarized by searching PubMed, Medline, China National Knowledge Infrastructure and Wanfang database and compared with the cases in this single center. Results:Among the 13 children with PAX2 gene mutation, there were 9 males and 4 females, 12 patients with abnormal urine tests, 7 patients with small kidney volume by imaging examination, and 5 patients with renal cysts. The clinical phenotypes were congenital renal and urinary tract malformations in 8 cases, renal coloboma syndrome in 1 case, and hematuria or proteinuria in 3 cases. Five patients underwent renal biopsies, showing focal segmental glomerulosclerosis and C3 glomerulopathy in 1 case, focal segmental glomerulosclerosis in 1 case, thin basement membrane lesion in 1 case, and IgA nephropathy in 2 cases. The genetic testing in 13 children showed 9 de novo mutations and 4 new mutations of c.321G>A, c.213-8C>G, c.63C>A and c.449C>T. There were 2 cases of 76dupG (p.V26Gfs*28) mutant. A total of 51 Chinese children with PAX2 gene mutation were found in the literature search. There were 32 males and 19 females, 8 cases with small kidney volume and 12 cases with renal cysts. The clinical phenotypes were congenital anomalies of kidney and urinary tract in 28 cases, renal coloboma syndrome in 17 cases, and hematuria or proteinuria in 6 cases. Seven patients underwent renal biopsies, including 2 cases with focal segmental glomerulosclerosis, 1 case with minimal lesion, 1 case with mesangial proliferative glomerulonephritis, 1 case with IgA nephropathy, 1 case with membranous nephropathy and a case with focal proliferative sclerosing purpura nephritis combined with glomerular hypertrophy. Thirty-four cases were de novo mutations, and 12 mutations were from the father or mother. The father or mother of 5 children had no clinical manifestations, with normal renal function. There were 11 cases of 76dupG (p.V26Gfs*28) mutant. Conclusions:The clinical phenotypes and genotypes of PAX2 gene variation in Chinese children are diverse. The most common clinical phenotype of PAX2 gene variation is congenital anomalies of kidney and urinary tract. c.76dupG (p.V26Gfs*28) is the most common of PAX2 gene variant.

Objective:To better evaluate the prevalence and epidemiological characteristics of metabolic-associated fatty liver disease (MAFLD) based on liver transient elastography.Methods:It was a cross-sectional study. A total of 6 961 patients without hepatitis, who underwent liver transient elastography examination at the Department of Hepatology, Zhongnan Hospital of Wuhan University from November, 2021 to April, 2022 were included. The patients were categorized into normal and mild, moderate, severe MAFLD groups according to FibroTouch controlled attenuation parameters (CAP). The CAP values among different body mass index (BMI) groups were compared using analysis of variance. The distribution characteristics and the incidence of MAFLD in different age, gender, body mass index(BMI), blood glucose and lipids groups using the chi-square test.Results:The total detection rate of MAFLD and severe MAFLD in the population with a BMI≥28.0 kg/m 2 was 99.6% and 71.8%, respectively. The detection rate of MAFLD in people with normal BMI was 28.4%. The detection rate of MAFLD in women of childbearing age or in the perimenopausal period were both significantly lower than that in men of the same age (40.3% vs 54.9%, χ 2=20.78, P<0.001; 43.1% vs 58.4%, χ 2=27.43, P<0.001), but there was no statistically significant difference in MAFLD detection rate between postmenopausal women and men of the same age. The detection rates of MAFLD in the group with abnormal blood glucose and lipids were both significantly higher than those in the group with normal blood glucose and lipids [69.7%(196/281) vs 35.2%(2 354/6 680), χ 2=138.36, P<0.001; 54.3%(1 696/3 124) vs 37.1%(1 420/3 837), χ 2=207.99, P<0.001]. Conclusion:Non-hepatitis patients had a higher prevalence of MAFLD. The BMI, gender, age, blood glucose, and lipids levels are all strongly associated with MAFLD.

Objective:To explore the impact of intradialytic hypotension (IDH) on brain component volume, as well as its relationship with depression and cognitive function changes in maintenance hemodialysis patients.Method:It was a cross-sectional observational study. Clinical data of 119 patients under maintenance hemodialysis in Peking Union Medical College Hospital from July 2013 to July 2014 were collected, retrospectively. Patients were divided into IDH group and non-IDH group. 3.0T Magnetic resonance imaging examination of the head for all patients was completed and the results of volume analysis of each component of the brain were extracted. Cognitive function was assessed by the Chinese version of the simplified mental state examination scale (C-MMSE) and the Chinese version of the Montreal cognitive assessment scale (C-MoCA). Depressive status was assessed by the Hamilton depression scale 17 (HAMD_17) and living ability was assessed by the Alzheimer's disease collaborative study-daily living ability assessment questionnaire. In addition, the Philadelphia word learning test was used to measure memory, the Boston naming test to measure language, the connection test A and B to measure executive ability, and the Stroup test C to measure attention. The differences in brain component volume, cognitive function, emotion, and life ability between two groups of patients were compared, and the correlation between IDH and brain component volume was explored by regression analysis.Result:A total of 119 patients were included in this study, of whom 22 (18.5%) had hypotension during dialysis. The volumes of amygdala, cuneiform lobe, and posterior cingulate gyrus in IDH group were significantly smaller than those in the non-hypotension group [ (1.6±0.2) mm 3vs. (1.7±0.2) mm 3, t=2.674, P=0.009; (6.9±0.8) mm 3vs. (7.4±1.0) mm 3, t=2.187, P=0.031; (6.9±0.8) mm 3vs. (7.4±0.9) mm 3, t=2.252, P=0.024]. The differences of gray matter, white matter volume between the two groups showed a similar trend but did not reach statistical significance. And lacunar infarction and cerebral microbleeds were more common in IDH group. The daily living ability scores of the two groups were similar (65.51±11.52 vs. 65.71±11.53, Z=-0.456, P=0.648). The proportion of patients with cognitive abnormalities was higher in the IDH group, without statistical significance. The proportion of depression was similar. Univariate linear regression analysis showed that IDH was significantly negatively correlated with the volume of amygdala, cuneiform cortex, and posterior cingulate gyrus, which control emotions in the brain ( B=-0.117, 95% CI -0.203--0.030, P=0.009; B=-0.484, 95% CI -0.923--0.046, P=0.031; B=-0.485, 95% CI -0.911--0.058, P=0.026). After multivariate adjustment, decreased amygdala volume was still correlated with IDH ( B=-0.111, 95% CI -0.198--0.025, P=0.026). Conclusion:Recurrent IDH may lead to atrophy of various brain components, which may be one of the reasons for cognitive and emotional changes in maintenance hemodialysis patients.

Objective:To preliminarily investigate the applicability of a poliovirus pseudovirus-based neutralization assay in evaluating the immunogenicity of recombinant poliovirus vaccines and their in vivo potency in rats. Methods:Serum samples from rats immunized with recombinant poliovirus vaccines were tested using both the pseudovirus neutralization assay and the live-virus neutralization assay with Sabin strain. The consistency and correlation of the two methods were analyzed using the Kappa test and Spearman′s rank correlation.Results:For the neutralizing antibodies against typeⅠ, Ⅱ, and Ⅲ polioviruses, the Kappa values for consistency analysis of the two methods were 0.914, 1.000, and 0.751, respectively ( P<0.001), and the correlation coefficients ( R values) were 0.833, 0.927, and 0.859, respectively ( P<0.001). Conclusions:The test results of the two methods are consistent and show a good correlation, indicating that the pseudovirus neutralization assay can be applied to evaluating the immunogenicity of poliovirus vaccines and also can be used in rat potency tests.