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.

Objective To compare the efficacy and safety of computed tomography (CT)-guided percutaneous versus electromagnetic navigation bronchoscopy (ENB)-guided microwave ablation (MWA) for the treatment of pulmonary nodules. Methods A retrospective analysis was conducted on the data of high-risk pulmonary nodule patients who underwent MWA at the Nanjing Drum Tower Hospital between 2022 and 2023. The pathological diagnosis rate, complications, and progression-free survival (PFS) rate were compared between the CT group and the ENB group. Results There were 61 patients in the CT group, including 30 males and 31 females, with an average age of (67.22±9.13) years. There were 53 patients in the ENB group, including 29 males and 24 females, with an average age of (65.29±13.76) years. The pathological diagnosis rate in the CT group was slightly higher than that in the ENB group (88.52% vs. 71.69%, P=0.03). However, the ENB group exhibited a lower incidence of perioperative complications, including pneumothorax (16.39% vs. 3.77%, P=0.03), hemoptysis (19.67% vs. 5.66%, P=0.05), and pain (22.95% vs. 7.55%, P=0.03). There was no statistically significant difference in PFS rate between the two groups [HR=1.17, 95%CI (0.23, 5.81), P=0.85]. Conclusion Both CT-guided and ENB-guided MWA are effective treatment modalities for high-risk pulmonary nodules.

Epidemiological investigations and clinical studies have shown that inappropriate ambient temperatures (high and low temperatures) are the independent risk factors for ischemic stroke, but their underlying physiological mechanisms are not fully understood. This article systematically reviews the potential mechanisms by which inappropriate ambient temperatures promote the occurrence of ischemic stroke through multiple pathways, such as activating the sympathetic-renin-angiotensin system, inducing systemic inflammation and oxidative stress, damaging the integrity of the intestinal barrier and blood-brain barrier, and disrupting coagulation-fibrinolysis balance.

Autoimmune disease is a kind of disease characterized by immune imbalance,abnormal activation of immune cells,massive production of inflammatory factors and immune complexes,which leads to the damage of multiple organs and systems.Autoimmune disease is easy to recur in clinical practice.The previous studies showed that there is a correlation between dampness syndrome in traditional Chinese medicine(TCM)and immune dysfunction.This paper explains the theoretical basis for the correlation between dampness syndrome of TCM and the recurrence of autoimmune diseases,and the similarities between the two in macro appearance,pathogenesis characteristics,etc.,analyzes the possible correlation about biological mechanism between dampness syndrome and autoimmune diseases,and discussed the correlation between pathogenic dampness of TCM and the recurrence of autoimmune diseases such as psoriasis,rheumatoid arthritis,ulcerative colitis,and nephrotic syndrome.It is pointed out that pathogenic dampness of TCM is an important pathogenic factor for the recurrence of autoimmune diseases,and is closely related to the recurrence of autoimmune diseases.Autoimmune diseases can be treated from the perspective of pathogenic dampness in TCM,and therapy of invigorating spleen,replenishing qi and removing dampness is frequently adopted,which is beneficial to alleviating the clinical symptoms of patients and reducing the recurrence of autoimmune disease.

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 prenatal features and genetic etiology of a fetus with Short-rib cage dysplasia (SRTD) due to variants of DYNC2H1 gene. METHODS: A pregnant women presented at Xinxiang Central Hospital in June 2020 for abnormal prenatal ultrasound findings was selected as the study subject. With informed consent obtained, amniotic fluid sample was extracted from the woman, and clinical data of the fetus were collected. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Xinxiang Central Hospital [Ethics No.: 2025-214-01(K)]. RESULTS: At 25⁺⁶ weeks gestation, genetic testing revealed that the fetus has harbored compound heterozygous variants of the DYNC2H1 gene, namely c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly), which were derived from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) variants were classified as pathogenic (PVS1+PM2_supporting+PM3+PP5) and likely pathogenic (PM1+PM2_supporting+PM3+PP3), respectively. Bioinformatics analysis suggested that both variants may affect the 3D structure of the DYNC2H1 protein. CONCLUSION The compound heterozygous variants of c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) of the DYNC2H1 gene probably underlay the pathogenesis of SRTD in the fetus. Above findings had facilitated prenatal diagnosis and genetic counseling for the couple.
Humans ; Female ; Pregnancy ; Cytoplasmic Dyneins/chemistry* ; Prenatal Diagnosis ; Adult ; Short Rib-Polydactyly Syndrome/diagnostic imaging* ; Mutation ; Exome Sequencing ; Fetus/abnormalities* ; Ultrasonography, Prenatal

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.