Objective To investigate the cross-sectional associations between different fatty liver classifications and cardiac structure and function in people undergo health examination. Methods A total of 6 545 adults who underwent health examinations at the Health Management Center of Zhongshan Hospital, Fudan University between January 1 and December 31, 2017, were retrospectively included. Demographic characteristics and laboratory data were collected. The hepatic steatosis was graded by ultrasonography. And patients with fatty liver were further stratified according to alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, as well as the degree of liver fibrosis. Cardiac morphology and function were assessed by transthoracic echocardiography, and left ventricular geometric patterns were classified accordingly. Multivariate logistic regression analysis was performed to evaluate the associations between fatty liver classifications and cardiac abnormalities. Results There were 2 795 patients (42.7%) with fatty liver, of whom 832 (29.8%) had significant cardiac structural alterations and 1 500 (53.7%) had diastolic dysfunction. Severe fatty liver was risk factor for concentric remodeling and increased relative wall thickness (RWT), with odds ratios (ORs) of 1.27 (P＝0.012) and 1.27 (P＝0.009), respectively. Fatty liver accompanied by elevated ALT or AST was risk factor for concentric remodeling (OR＝1.45,1.56; P＝0.001, 0.001), increased RWT (OR＝1.48,1.57; P＜0.001, ＜0.001), and diastolic dysfunction (OR＝1.27, 1.32; P＝0.035, 0.040), respectively. Fatty liver with liver fibrosis was risk factor for concentric remodeling (OR＝1.83, P＝0.046) and diastolic dysfunction (OR＝2.64, P＝0.034). Conclusions Advanced fatty liver, including severe hepatic steatosis, accompanied by elevated liver enzymes or liver fibrosis, could increase risks of cardiac remodeling and diastolic dysfunction, while systolic function is preserved. For patients with fatty liver, it is recommended to undergo regular ultrasonography examination.

As one of the common systemic vasculitides in children， IgA vasculitis is closely associated with the interaction of "Wind pathogen" and "turbid stasis" in its pathogenesis. Based on the blood turbidity theory， this paper proposes "wind agitating blood turbidity and collateral damage" as the core pathogenesis. Regarding treatment， the sequential therapeutic principle of "stanch bleeding， activating blood circulation， and nourishing blood" is adopted， and combined with the dynamic application of wind-dispelling medicinals to "expel， search， and guard against wind"， turbidity-removing method is applied throughout all stages. In the acute stage，it is recommended to clear heat and purify turbidity， stanch bleeding and secure the collaterals. In the prolonged stage， the method of dissipating stasis and clearing up turbidity should be used， as well as activating blood circulation and unblocking the collaterals. In the recovery stage， it is advised to nourish blood to flourish the collaterals， reinforce healthy qi and resolve turbidity. This therapeutic system integrates the elimination of pathogens and the reinforcement of healthy qi to clear and resolve blood turbidity， ultimately achieving holistic collateral repair through securing， unblocking， and nourishing the collaterals， which provides new insights into the treatment of this disease in traditional Chinese medicine.

Based on the viewpoint of "sweat pore-qi and liquid-kidney collaterals"， it is believed that children's nephrotic syndrome is caused by the core mechanism of sweat pore constraint and closure， qi and liquid imbalance， and kidney collaterals impairment， and it is proposed that the treatment principle is to nourish the sweat pore， regulate qi and fluid， and supplement the kidney and unblock the collaterals. In clinic， guided by sequential therapy and according to the different disease mechanism characteristics of the four stages， including early stage of the disease， hormone induction stage， hormone reduction stage， hormone maintenance stage， the staged dynamic identification and treatment was applied. For early stage of the disease with edema due to yang deficiency， modified Zhenwu Decoction （真武汤） was applied to warm yang and drain water； for hormone induction stage with yin deficiency resulting in effulgent fire， modified Zhibai Dihuang Pill （知柏地黄丸） plus Erzhi Pill （二至丸） was used to enrich yin and reduce fire； for hormone reduction stage with qi and yin deficiency， modified Shenqi Dihuang Decoction （参芪地黄汤） was used to boost qi and nourish yin； for hormone maintenance stage， modified Shenqi Pill （肾气丸） was used to supplement yin and yang. Meanwhile， the treatment also attaches importance to the combination of vine-based or worm medicinals to dredge collaterals， so as to providing ideas for clinical treatment.

Objective:To explore the predictive value of human cartilage glycoprotein 39 (YKL-40) and growth differentiation factor 15 (GDF-15) for clinical outcomes of patients with Parkinson disease (PD).Methods:A total of 109 patients with PD admitted to Xinxiang Central Hospital from February 2021 to February 2023 were selected and treated with regular anti-PD medications for 4 weeks, with dosage appropriately adjusted according to clinical status and individual response.Clinical outcomes were evaluated after 2 months of treatment, and the predictive value of serum YKL-40 and GDF-15 at admission for clinical outcomes was analyzed.Data were analyzed by independent sample t-test, χ2 test and Logistic regression using SPSS 26.0. Results:PD patients with poor outcomes exhibited higher serum levels of YKL-40((3.18±0.67)mg/L, (2.34±0.41)mg/L) and GDF-15((457.82±142.83)pg/mL, (282.95±105.96)pg/mL) than those with good outcomes, and the differences were statistically significant ( t=8.082, 7.349, both P<0.05).Logistic regression analysis showed that elevated serum levels of YKL-40( B=0.664, OR=1.943, 95% CI=1.237-3.052) and GDF-15( B=0.185, OR=1.787, 95% CI=1.145-2.789) both influenced the clinical outcomes of PD patients(both P<0.05).Serum YKL-40 combined with GDF-15 demonstrated a predictive sensitivity of 87.23%, specificity of 90.32%, and AUC of 0.927(95% CI=0.861-0.968) for clinical outcomes in PD patients.The AUC was significantly higher than that achieved by either indicator alone (YKL-40: AUC (95% CI)=0.722 (0.628-0.804); GDF-15: AUC (95% CI)=0.797 (0.709-0.868)). Conclusion:The elevated levels of YKL-40 and GDF-15 in PD patients are associated with clinical outcomes, which may be the potential markers for predicting clinical outcomes of patients with PD.

Objective To explore the effects of long non-coding RNA(LncRNA)metastasis associated in lung denocarcinoma transcript 1(MALAT1)on high glucose-induced cardiomyocyte injury by regulating miR-320-3p-protein kinase B3(Akt3)axis.Methods H9c2 cells were divided into normal control(NC)group and high glucose(HG)group.After transfection,the cells were cultured in HG group were further divdided into subgroups as follows:HG+MALAT1 knock-down(HG+sh-MALAT1)group,HG+sh-NC group,HG+miR-320-3p mimic group,HG+mimic-NC group,HG+sh-MALAT1+miR-320-3p inhibitor group and HG+sh-MALAT1+pcDNA3.1-Akt3 group.Cell activity,apoptosis rate,B-cell lymphoma 2-related protein X(Bax),B-cell lymphoma factor 2(Bcl-2),cleaved caspase-3,Akt3 protein,MALAT1,miR-320-3p,Akt3 mRNA expression,interleukin(IL-1β),IL-6,tumor necrosis factor-α(TNF-α)were compared among the groups.Results The apoptosis rate of cardiomyocytes,the expressions of IL-1β,IL-6,TNF-α,Bax,cleaved caspase-3/caspase-3 protein,MALAT1 and Akt3 mRNA increased(P<0.05),while the expression of Bcl-2 protein and miR-320-3p decreased in HG group(P<0.05).After knocking down LncRNA MALAT1,apoptosis rate of HG-induced cardiomyocytes and levels of inflammatory factors were decreased(P<0.05).MALAT1 could negatively regulate expression of miR-320-3p,and miR-320-3p could negatively regulate expression of Akt3 protein.The overexpression of miR-320-3p could decrease apoptosis rate and inflammation level,while overexpression of Akt3 or inhibition of miR-320-3p expression could increase apoptosis rate of cardiomyocytes and inflammation level(P<0.05).Conclusions LncRNA MALAT1 can promote the expression of Akt3 protein by inhibiting miR-320-3p expression,thereby reduce activity of HG-induced cardiomyocytes and aggravate cardiomyocytes injury.

Objective:To explore the predictive value of human cartilage glycoprotein 39 (YKL-40) and growth differentiation factor 15 (GDF-15) for clinical outcomes of patients with Parkinson disease (PD).Methods:A total of 109 patients with PD admitted to Xinxiang Central Hospital from February 2021 to February 2023 were selected and treated with regular anti-PD medications for 4 weeks, with dosage appropriately adjusted according to clinical status and individual response.Clinical outcomes were evaluated after 2 months of treatment, and the predictive value of serum YKL-40 and GDF-15 at admission for clinical outcomes was analyzed.Data were analyzed by independent sample t-test, χ2 test and Logistic regression using SPSS 26.0. Results:PD patients with poor outcomes exhibited higher serum levels of YKL-40((3.18±0.67)mg/L, (2.34±0.41)mg/L) and GDF-15((457.82±142.83)pg/mL, (282.95±105.96)pg/mL) than those with good outcomes, and the differences were statistically significant ( t=8.082, 7.349, both P<0.05).Logistic regression analysis showed that elevated serum levels of YKL-40( B=0.664, OR=1.943, 95% CI=1.237-3.052) and GDF-15( B=0.185, OR=1.787, 95% CI=1.145-2.789) both influenced the clinical outcomes of PD patients(both P<0.05).Serum YKL-40 combined with GDF-15 demonstrated a predictive sensitivity of 87.23%, specificity of 90.32%, and AUC of 0.927(95% CI=0.861-0.968) for clinical outcomes in PD patients.The AUC was significantly higher than that achieved by either indicator alone (YKL-40: AUC (95% CI)=0.722 (0.628-0.804); GDF-15: AUC (95% CI)=0.797 (0.709-0.868)). Conclusion:The elevated levels of YKL-40 and GDF-15 in PD patients are associated with clinical outcomes, which may be the potential markers for predicting clinical outcomes of patients with PD.

Objective:To explore the effects of ubiquitin-conjugating enzyme E2L3 (UBE2L3) on the proliferation and apoptosis of head and neck squamous cell carcinoma (HNSCC) cell line UMSCC-1 in vitro and its potential mechanisms, and to investigate the relationship between UBE2L3 and immune cell infiltration in the HNSCC tumor microenvironment.Methods:The plasmid carrying UBE2L3 gene sequence was transfected into UMSCC-1 cells by using liposome transfection technology (UBE2L3 overexpression group), and UMSCC-1 cells transfected with the empty plasmid was treated as the control group. The quantitative polymerase chain reaction (qPCR) was used to detect the expression level of UBE2L3 mRNA after transfection, and the transfection efficiency was evaluated. The proliferation levels of the 2 groups of cells were detected by using CCK-8 assay and the cell proliferation rate was calculated. The apoptosis rates of the 2 groups of cells after etoposide induced apoptosis for 24 h were detected by using flow cytometry. The expression levels of Cyclin D1, apoptosis-related proteins bcl-2, and Bax in the 2 groups of cells were detected by using Western blotting. The samples of 504 HNSCC tissues in the Cancer Genome Atlas (TCGA) were analyzed by using the single-sample gene set enrichment analysis (ssGSEA) database. The median expression level of UBE2L3 was used to distinguish between high and low expression of UBE2L3 transcriptional level. The differences in immune cell enrichment score between high and low expression samples were compared, and the relationship between UBE2L3 expression level and immune cell number was analyzed.Results:qPCR results showed that the relative expression level of UBE2L3 mRNA in UMSCC-1 cells carrying UBE2L3 gene sequence plasmid was higher than that in UMSCC-1 cells transfected with the empty plasmid (9.32±1.15 vs. 1.00±0.02), and the difference was statistically significant ( t = 7.23, P < 0.001), indicating successful transfection. The CCK-8 assay showed that the cell proliferation rate of UMSCC-1 cells in the UBE2L3 overexpression group for 24 h and 48 h of culture was higher than that in the control group [24 h: (184.0±7.9)% vs. (100.0±5.6)%; 48 h: (165.5±5.3)% vs. (100.0±5.3)%], and the differences were statistically significant (both P < 0.001). Flow cytometry showed that the apoptosis rate of UMSCC-1 cells in the UBE2L3 overexpression group was lower than that in the control group [(9.9±1.3)% vs. (15.6±1.3)%], and the difference was statistically significant ( t = 2.78, P = 0.005). Western blotting showed that the relative expression levels of Cyclin D1 and bcl-2 proteins in UMSCC-1 cells of the UBE2L3 overexpression group were higher than those in the control group, while the relative expression level of Bax protein was lower than that in the control group, and the differences were statistically significant (all P < 0.05). The ssGSEA analysis showed that the enrichment scores of B cells, CD8 + T cells, neutrophils, T cells, T helper 17 (Th17) cells, and regulatory T cells (Treg) in 252 HNSCC tissues samples with low UBE2L3 transcriptional expression level were higher than in 252 samples with high UBE2L3 transcriptional expression level in the TCGA database, while the enrichment scores of natural killer (NK) cells and T helper 2 (Th2) cells in patients with low UBE2L3 expression were lower than those in those with high UBE2L3 expression, and the differences were statistically significant (all P < 0.05). Correlation analysis showed that the expression level of UBE2L3 in HNSCC tissues was positively correlated with the number of Th2 cells ( R = 0.182) and NK cells ( R = 0.172), and negatively correlated with the number of Treg cells ( R = -0.095), dendritic cells ( R = -0.099), Th17 cells ( R = -0.129), CD8 + T cells ( R = -0.146), mast cells ( R = -0.161), T cells ( R = -0.171), and B cells ( R = -0.188), and the differences were statistically significant (all P > 0.05). Conclusions:UBE2L3 can promote the proliferation and inhibit the apoptosis of HNSCC cells probably by regulating the cell cycle and apoptosis signaling pathways through Cyclin D1, bcl-2, and Bax. UBE2L3 may be associated with immune cell infiltration in the HNSCC microenvironment.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, which not only affects the digestive tract, but also involves extraintestinal organs and tissues such as joints and eyes, and ultimately endangers human health and affects the quality of life of patients. With the development of information technology, there is an increasing application of digital therapeutics in the management of IBD. This article aims to comprehensively analyze the characteristics, use, and challenges of digital therapeutics in the management of IBD, and explore its potential to improve treatment adherence, disease surveillance, and improve patients' quality of life.

Objective:To investigate the association between anti-rituximab antibodies (ARA) and relapse after rituximab (RTX) therapy in children with frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS).Methods:A retrospective cohort study was conducted. Clinical and laboratory data were collected from 48 FRNS or SDNS children treated with RTX in the Department of Pediatrics, General Hospital of Eastern Theater Command, between April 2024 and October 2024. Data included RTX dosing frequency, relapse events, peripheral CD20? B-cell counts, and ARA levels. With a 6-month observation period after the last RTX therapy, the children were divided into an ARA-positive group and an ARA-negative group based on ARA test results. Chi-square test, independent sample t-test, or Mann-Whitney U test were used to compare relapse rates and laboratory indicators between the two groups. The predictive value of ARA levels for relapse was evaluated using univariate receiver operating characteristic (ROC) curve analysis. Results:Among the 48 children (36 males, 12 females), the age of disease onset was 3.5 (2.0, 6.0) years, the ages at the first and last RTX treatments were 7.0 (5.0, 12.0) years and 9.5 (7.0, 13.0) years, respectively. The overall ARA positive rate was 29% (14/48). The relapse rate in the ARA-positive group was significantly higher than that in the negative group ( P<0.05). The ARA level was 0.01 (0.01, 5.88) μg/L, and all 12 children with ARA levels >5.88 μg/L relapsed. ROC curve analysis showed that ARA levels predicted relapse after RTX treatment in FRNS or SDNS children with an area under the curve (AUC) of 0.73, sensitivity of 0.50, specificity of 1.00, and an optimal cut-off value of 5.02 μg/L. All children received single-dose RTX therapy, with no significant difference in treatment frequency between the two groups ( P>0.05). At 3 months after the last rituximab therapy, CD20? B cell counts were significantly higher in the ARA-positive group ( P<0.05). During follow-up, 15% (7/48) of the children experienced infusion-related adverse reactions, with no significant difference in incidence between the two groups ( P>0.05). Conclusion:ARA is significantly associated with relapse in FRNS or SDNS children after RTX therapy.

Objective:To provide reference for improving the ability of Investigator-Initiated Trials (IIT) research ethics review in the new era by analyzing the situation of clinical research projects and ethical review in hospitals under the increasingly standardized management requirements of clinical research.Methods:Taking the IIT projects reviewed by the Ethics Committee of our Institute from 2012 to 2023 as examples, the development trend, types, characteristics and the situation of ethical review were comprehensively compared and analyzed.Results:From 2012 to 2023, the number of IIT projects in our hospital increased rapidly, especially the multi-center and high-risk projects. IIT researches in the field of oncology and neurology are hot topics at present. After the addition of scientific review, the passing rate of ethical review increased. After the promulgation of the new regulations, the application rate of follow-up examination increased to a certain extent.Conclusions:In view of the current types and distribution characteristics of IIT, as well as key weaknesses in ethical review, the ethics Committee should strengthen the qualification management of main researchers and research teams, standardize the annual follow-up review of IIT research through multiple channels such as research ethics education and information platform, promote the establishment of the responsibility system of research liaison officers, and improve the review process of off-label drug use research. High-risk IIT projects should strengthen ethical supervision, case-by-case reporting and tracking system, and vulnerable groups projects should strengthen ethical review and supervision of informed consent process, and explore the establishment of a high-quality ethical management system from the above aspects.