Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

OBJECTIVES: Acute lung injury (ALI) is an acute respiratory failure syndrome characterized by impaired gas exchange. Due to the lack of effective targeted drugs, it is associated with high mortality and poor prognosis. Tripterygium wilfordii (TW) has demonstrated anti-inflammatory activity in the treatment of various diseases. This study aims to investigate the effects and underlying mechanisms of TW on myeloid-derived suppressor cells (MDSCs) in ALI, providing experimental evidence for TW as a potential adjuvant therapy for ALI. METHODS: Eighteen specific pathogen-free (SPF) C57BL/6 mice were randomly divided into normal control (NC; intranasal saline), lipopolysaccharide (LPS; 5 mg/kg intranasally to induce ALI), and LPS+TW (50 mg/kg TW by gavage on the first day of modeling, followed by 5 mg/kg LPS intranasally to induce ALI) groups (n=6 each). Lung injury and edema were assessed by histopathological scoring and wet-to-dry weight ratio. Cytokine levels [interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α (TNF-α)] in lung tissue lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to assess the proportions of MDSCs, polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs) in bone marrow, spleen, peripheral blood, and lung tissue, as well as reactive oxygen species (ROS) levels in lung tissues. Messenger RNA (mRNA) expression levels of inducible nitric oxide synthase (iNOS) and arginase-1 (ARG-1) in lung tissues were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). PMN-MDSCs sorted from the lungs of LPS-treated mice were co-cultured with splenic CD3⁺ T cells and divided into NC, triptolide (TPL)-L, and TPL-H groups, with bovine serum albumin, 25 nmol/L TPL, and 50 nmol/L TPL, respectively. Flow cytometry was used to detect the effect of PMN-MDSCs on T-cell proliferation, and RT-qPCR was used to measure iNOS and ARG-1 mRNA expression. RESULTS: Compared with the NC group, the LPS group showed marked lung pathology with significantly increased histopathological scores and wet-to-dry ratios (both P<0.001). TW treatment significantly alleviated lung injury and reduced both indices compared with the LPS group (both P<0.05). Cytokine levels were significantly decreased in the LPS+TW group compared with the LPS group (all P<0.001). The proportions of MDSCs in CD45⁺ cells from spleen, bone marrow, peripheral blood, and lung, as well as PMN-MDSCs from spleen, peripheral blood, and lung, were significantly reduced in the LPS+TW group compared with the LPS group (all P<0.05), accompanied by reduced ROS levels in lung tissues (P<0.001). iNOS and ARG-1 mRNA expression in lung tissues was significantly lower in the LPS+TW group than in the LPS group (both P<0.001). In vitro, compared with the TPL-L group, the TPL-H group showed significantly increased CD3⁺ T-cell proliferation (P<0.001), and decreased iNOS and ARG-1 mRNA expression (all P<0.05). CONCLUSIONS TW alleviates the progression of LPS-induced ALI in mice, potentially by reducing the proportion of MDSCs in lung tissues and attenuating the immunosuppressive function of PMN-MDSCs.
Animals ; Acute Lung Injury/chemically induced* ; Myeloid-Derived Suppressor Cells/cytology* ; Tripterygium/chemistry* ; Mice, Inbred C57BL ; Mice ; Cell Differentiation/drug effects* ; Male ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/genetics* ; Cytokines/metabolism* ; Reactive Oxygen Species/metabolism* ; Diterpenes/pharmacology* ; Epoxy Compounds ; Phenanthrenes

OBJECTIVES: To investigate the effect of Haematococcus pluvialis (HP) on bleomycin (BLM)-induced pulmonary fibrosis in mice and on TGF-β1-induced human fetal lung fibroblasts (HFL1). METHODS: Thirty male C57BL/6 mice were randomly divided into control group, BLM-induced pulmonary fibrosis model group, low- and high-dose HP treatment groups (3 and 21 mg/kg, respectively), and 300 mg/kg pirfenidone (positive control) group. The effects of drug treatment for 21 days were assessed by examining respiratory function, lung histopathology, and expression of fibrosis markers in the lung tissues of the mouse models. In TGF-β1-induced HFL1 cell cultures, the effects of treatment with 120, 180 and 240 μg/mL HP or 1.85 μg/mL pirfenidone for 48 h on expression levels of fibrosis markers were evaluated. Transcriptome analysis was carried out using the control cells and cells treated with TGF-β1 and 240 μg/mL HP. RESULTS: HP obviously alleviated BLM-induced lung function damage and fibrotic changes in mice, evidenced by improved respiratory function, lung tissue morphology and structure, inflammatory infiltration, and collagen deposition and reduced expressions of fibrotic proteins. HP at the high dose produced similar effect to PFD. In TGF-β1-induced HFL1 cells, treatment with 240 μg/mL HP significantly reduced the mRNA and protein expression levels of α-SMA and FN. Transcriptome analysis revealed that multiple key genes and pathways mediated the protective effect of HP against pulmonary fibrosis. CONCLUSIONS HP alleviates pulmonary fibrosis in both the mouse model and cell model, possibly as the result of the synergistic effects of its multiple active components.
Animals ; Pulmonary Fibrosis/chemically induced* ; Bleomycin/adverse effects* ; Mice, Inbred C57BL ; Male ; Mice ; Fibroblasts/drug effects* ; Lung/pathology* ; Transforming Growth Factor beta1/pharmacology* ; Myofibroblasts/drug effects* ; Humans ; Pyridones

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization(MR)approach.Methods We obtained data pertaining to colorectal cancer from Genome-Wide Association Study(GWAS)datasets and used 91 inflammatory protein markers as the exposure variables.A two-sample MR analysis model was used to assess the causal link between the inflammatory markers and colorectal cancer risk.The robustness of the results was evaluated through heterogeneity,pleiotropy,and sensitivity analyses using 5 MR models:Inverse Variance Weighted(IVW),Weighted Median,MR Egger,Simple Mode,and Weighted Mode.We examined the mRNA expressions of PD-L1,AXIN1,and β-NGF using RT-qPCR in 86 untreated patients with colorectal adenocarcinoma admitted in Nanfang Hospital between December,2021 and December 2023,and analyzed their correlation with the clinical characteristics of the patients.Results Using the IVW model,MR analysis revealed significant causal associations between a reduced risk of colorectal cancer and lowered expressions of AXIN1(OR=0.866,95%CI:0.754-0.994,P=0.040),β-NGF(OR=0.914,95%CI:0.843-0.990,P=0.028;OR=0.884,95%CI:0.784-0.998,P=0.047 using Weighted Median model),and PD-L1(OR=0.903,95%CI:0.824-0.989,P=0.028).No significant heterogeneity or pleiotropy was observed,indicating good stability of the results.Sensitivity analysis confirmed the reliability of the findings.The clinical study demonstrated a significant correlation between PD-L1 expression and TNM staging,particularly in stage IV patients(P=0.007).AXIN1 and β-NGF expression levels were significantly correlated with the degree of tumor differentiation,and their expressions were higher in poorly differentiated samples(P<0.001).Conclusion Lowered expressions of inflammatory protein markers AXIN1,β-NGF,and PD-L1 are causally correlated with a reduced risk of colorectal cancer and their expression levels are associated with TNM staging and tumor differentiation.These markers may thus serve as potential targets for colorectal cancer treatment and prevention.

Objective To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization(MR)approach.Methods We obtained data pertaining to colorectal cancer from Genome-Wide Association Study(GWAS)datasets and used 91 inflammatory protein markers as the exposure variables.A two-sample MR analysis model was used to assess the causal link between the inflammatory markers and colorectal cancer risk.The robustness of the results was evaluated through heterogeneity,pleiotropy,and sensitivity analyses using 5 MR models:Inverse Variance Weighted(IVW),Weighted Median,MR Egger,Simple Mode,and Weighted Mode.We examined the mRNA expressions of PD-L1,AXIN1,and β-NGF using RT-qPCR in 86 untreated patients with colorectal adenocarcinoma admitted in Nanfang Hospital between December,2021 and December 2023,and analyzed their correlation with the clinical characteristics of the patients.Results Using the IVW model,MR analysis revealed significant causal associations between a reduced risk of colorectal cancer and lowered expressions of AXIN1(OR=0.866,95%CI:0.754-0.994,P=0.040),β-NGF(OR=0.914,95%CI:0.843-0.990,P=0.028;OR=0.884,95%CI:0.784-0.998,P=0.047 using Weighted Median model),and PD-L1(OR=0.903,95%CI:0.824-0.989,P=0.028).No significant heterogeneity or pleiotropy was observed,indicating good stability of the results.Sensitivity analysis confirmed the reliability of the findings.The clinical study demonstrated a significant correlation between PD-L1 expression and TNM staging,particularly in stage IV patients(P=0.007).AXIN1 and β-NGF expression levels were significantly correlated with the degree of tumor differentiation,and their expressions were higher in poorly differentiated samples(P<0.001).Conclusion Lowered expressions of inflammatory protein markers AXIN1,β-NGF,and PD-L1 are causally correlated with a reduced risk of colorectal cancer and their expression levels are associated with TNM staging and tumor differentiation.These markers may thus serve as potential targets for colorectal cancer treatment and prevention.

Objective To investigate the epidemiological characteristics and trends in the prevalence of tuberculosis among in the six urban districts of Tianjin from 2014 to 2023, so as to provide scientific basis for the prevention and control of tuberculosis. Methods Data on the occurrence of new tuberculosis cases among in the six urban districts of Tianjin from 2014 to 2023 were collected through the Tianjin Infectious Disease Report Information Management System, and the epidemiological characteristics of new tuberculosis cases were descriptively analyzed. Then the Average Annual Percentage Change (AAPC) statistics were used to characterize the magnitude and direction of trends. Results A total of 17 818 tuberculosis cases were reported in the six urban districts of Tianjin from 2014 to 2023 , with an average annual reported prevalence rate of 25.61/100 000. The prevalence rate of tuberculosis in the six urban districts of Tianjin from 2014 to 2023 showed a decreasing trend, reporting a prevalence rate of 35.47/100 000 in 2014 and 22.72/100 000 in 2023, and AAPC is -4.86% (-7.13% to -1.56%) , with statistical difference (P<0.05). In terms of gender, the overall prevalence rate of tuberculosis was 31.17/100,000 in males and 19.47/100,000 in females, with statistical difference (χ²=276.12 , P<0.05). The incidence in people younger than 25 years and older than 55 years is on the rise from 2014 to 2023. In terms of occupation, household duties, unemployed people, retired people and office clerks showed a high prevalence rate of tuberculosis. Conclusion The overall prevalence of adult tuberculosis in the six urban districts of Tianjin from 2014 to 2023 shows a decreasing trend, whereas the prevalence rate of males is higher than that of females, and the elderly, families, unemployed people, retirees and office clerks are high-risk groups, so targeted preventive and control measures, health education and screening should be strengthened.

The disease spectrum of ABCB4 gene mutation involves various diseases such as progressive familial intrahepatic cholestasis type 3 （PFIC3）， gallstone disease， intrahepatic cholestasis of pregnancy， portal hypertension， liver cirrhosis， and even primary hepatic and biliary malignancies. A young male patient was admitted to Department of Hepatobiliary Medicine， Eastern Hepatobiliary Surgery Hospital， and was initially diagnosed with liver cirrhosis and gallstones， and he was planned to receive laparoscopic cholecystectomy. Preoperative examination showed abnormal liver function， liver cirrhosis， splenomegaly， and mild esophageal varices， and next-generation sequencing was performed to make a confirmed diagnosis of ABCB4 gene mutation-associated liver cirrhosis with gallstones. The liver function of the patient gradually returned to normal after cholagogic treatment with ursodeoxycholic acid capsules.