This study aims to investigate the effects and mechanisms of the effective-compounds of Jinshui Huanxian formula (ECC-JHF) in improving pulmonary fibrosis. Animal experiments were approved by the Ethics Committee of the Animal Experiment Center of Henan University of Chinese Medicine (approval number: IACUC-202306012). The mouse model of pulmonary fibrosis was induced using bleomycin (BLM). Hematoxylin-eosin (H&E) staining was used to detect the histopathological changes of lung tissues. Masson staining was used to assess the degree of fibrosis in lung tissues. Immunofluorescence (IF) and real-time quantitative PCR (qPCR) were performed to measure the expression of collagen type I (COL I), α-smooth muscle actin (α-SMA), fibronectin (FN), interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) in lung tissues. Flow cytometry (FCM) was employed to detect the proportion of M1 and M2 macrophages in the bronchoalveolar lavage fluid (BALF) of mice. IF and qPCR were also used to detect the expression of lipase family member N (LIPN) in lung tissues. Free fatty acid assay kit was used to detect the level of free fatty acids in lung tissue. Bone marrow-derived macrophages (BMDMs) were treated with interleukin-4 (IL-4) to induce M2 polarization. FCM was used to measure the proportion of CD206⁺ M2 macrophages. IF was utilized to detect LIPN expression and lipid droplet decomposition. The results showed that in BLM-induced pulmonary fibrosis mice, ECC-JHF significantly attenuated BLM-induced alveolar inflammation and collagen deposition, inhibited fibroblast activation in lung tissues, and decreased the proportion of M2 macrophages in BALF. It also significantly suppressed LIPN expression and free fatty acid level in lung tissues. In the IL-4 induced BMDMs M2 polarization model, ECC-JHF significantly inhibited the proportion of CD206⁺ M2 macrophages, down-regulated the expression of LIPN, and blocked lipid droplet catabolism. These results suggest that ECC-JHF may alleviate bleomycin-induced pulmonary fibrosis by inhibiting lipid droplet decomposition and M2 macrophage polarization.

As the number of patients with compromised immune function increases and fungal resistance develops, so does the risk of contracting deadly fungi in humans. Both fungi and humans are eukaryotes, so identifying unique targets for antifungal drug development is difficult. In addition, the existing antifungal drugs are limited by toxicity, drug interaction and drug resistance in practical application, which leads to the increasing incidence and fatal rate of fungal infections. Therefore, it is urgent to develop new antifungal drugs. The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation. This paper will introduce the current status of natural antifungal drugs in clinical use, as well as the latest progress in the research and development of new semi-synthetic antifungal drugs, and summarize their mechanism of action, structural modifications, advantages and disadvantages, so as to provide reference for the subsequent development of new antifungal drugs.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Air Pollution/analysis* ; Environmental Exposure/analysis* ; China/epidemiology* ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Monitoring

The prevalence of Lyme disease in endogenous populations in Urumqi,Xinjiang was investigated.In total,795 serum samples were collected from residents of three townships in the surrounding area of Urumqi City from 2022 to 2023,which included 383 from Lucaogou Town,145 from Shuixigou Town,and,267 from Tori Township.Serum levels of IgG and IgM antibodies were screened with an enzyme linked immunosorbent assay(ELISA)and confirmed by western blot(WB)analysis.Clinical data of WB-positive indi-viduals were collected and comprehensive analysis was con-ducted for case diagnosis.The chi square test was used for statistical analysis of the results and the P＜0.05 was consid-ered statistically significant.In total,110(13.84％)of 795 samples were positive.The positivity rates was higher in females than males[16.26％(73/449)vs.10.69％(37/346),x2=5.076,P=0.024],while there was no significant difference among age groups(x2=2.569,P=0.766).The positivity rates for serum antibodies in Shuixigou Town,Lucaogou Town,and Tuoli Township were 17.98％(48/267),14.48％(21/145),and 10.70％(41/383),respectively,with a significantly higher rate in Tuoli Township than Lucaogou Town(x2=7.041,P=0.008).Of 110 individuals who were initially positive for IgG and IgM antibodies with the ELISA,82(10.31％)were con-firmed positive by WB analysis.In total,20(2.52％)patients were diagnosed with Lyme disease based on clinical manifesta-tions.Lyme disease is epidemic among the population in Urumqi,as the infection rate is higher than the national average.Hence,continued surveillance is recommended for prevention of Lyme disease.

Aim To investigate whether catechin can play against CCl

OBJECTIVE: To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients. METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro. RESULTS: The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4⁺ and CD8⁺ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4⁺ and CD8⁺ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01). CONCLUSION The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.
Humans ; Anemia, Aplastic ; CD8-Positive T-Lymphocytes ; Melatonin ; Blood Cell Count

OBJECTIVE: We aimed to assess the feasibility and superiority of machine learning (ML) methods to predict the risk of Major Adverse Cardiovascular Events (MACEs) in chest pain patients with NSTE-ACS. METHODS: Enrolled chest pain patients were from two centers, Beijing Anzhen Emergency Chest Pain Center Beijing Bo'ai Hospital, China Rehabilitation Research Center. Five classifiers were used to develop ML models. Accuracy, Precision, Recall, F-Measure and AUC were used to assess the model performance and prediction effect compared with HEART risk scoring system. Ultimately, ML model constructed by Naïve Bayes was employed to predict the occurrence of MACEs. RESULTS: According to learning metrics, ML models constructed by different classifiers were superior over HEART (History, ECG, Age, Risk factors, & Troponin) scoring system when predicting acute myocardial infarction (AMI) and all-cause death. However, according to ROC curves and AUC, ML model constructed by different classifiers performed better than HEART scoring system only in prediction for AMI. Among the five ML algorithms, Linear support vector machine (SVC), Naïve Bayes and Logistic regression classifiers stood out with all Accuracy, Precision, Recall and F-Measure from 0.8 to 1.0 for predicting any event, AMI, revascularization and all-cause death ( vs. HEART ≤ 0.78), with AUC from 0.88 to 0.98 for predicting any event, AMI and revascularization ( vs. HEART ≤ 0.85). ML model developed by Naïve Bayes predicted that suspected acute coronary syndrome (ACS), abnormal electrocardiogram (ECG), elevated hs-cTn I, sex and smoking were risk factors of MACEs. CONCLUSION Compared with HEART risk scoring system, the superiority of ML method was demonstrated when employing Linear SVC classifier, Naïve Bayes and Logistic. ML method could be a promising method to predict MACEs in chest pain patients with NSTE-ACS.
Humans ; Acute Coronary Syndrome/epidemiology* ; Bayes Theorem ; Feasibility Studies ; Risk Assessment/methods* ; Chest Pain/etiology* ; Myocardial Infarction/diagnosis*