Xiaohuang Qudan decoction (XHQDD) is a classical traditional Chinese medicine (TCM) formula widely used in the treatment of cholestatic liver injury. Despite its widespread use, the protective mechanism of XHQDD against cholestatic liver injury remains incompletely understood. The aim of this study was to investigate whether XHQDD mediates its beneficial effects by inhibiting the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway and regulating TH17/Treg balance. To this end, the researchers used Sprague-Dawley (SD) rats and established a cholestatic liver injury model by oral administration of alpha-naphthylisothiocyanate (ANIT). The experimental group was divided into six groups: Control (CON), ANIT, ursodeoxycholic acid (UDCA), XHQDD-low dose (XHQDD-L) group, XHQDD-medium dose (XHQDD-M) group, and XHQDD-high dose (XHQDD-H) groups. Then, after 7 d of treatment, various tests were performed to verify the results. Firstly, XHQDD and its drug-containing serum were analyzed by ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), and 14 blood-entry components were identified. Then, bile flow was monitored and found to be significantly reduced in the model group, which was significantly reversed in the UDCA and XHQDD groups. To further assess ANIT-induced liver injury, hematoxylin and eosin (H&E) and Sirius red staining, alongside transmission electron microscopy (TEM), were employed to observe liver tissues, revealing hepatocellular injury, cholestasis, and hepatic fibrotic changes. Serum inflammatory factors and liver injury indicators were assessed using enzyme-linked immunosorbent assay (ELISA), indicating an inflammatory state in ANIT-induced liver injury rats. The expression levels of JAK2/STAT3-related genes and proteins in liver and intestinal tissues were measured via quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, immunofluorescence (IF) staining, and Western blottting (WB) assays. These studies revealed that the inflammatory state of liver-injured rats was inextricably linked to the inflammatory cascade associated with the JAK2/STAT3 pathway and that XHQDD may exert anti-inflammatory efficacy by inhibiting the JAK2/STAT3 pathway. Flow cytometry was used to determine the percentage of T helper 17 (Th17)/regulatory T (Treg) cells in serum and hepatocytes, and it was further found that XHQDD was able to regulate Th17/Treg immune homeostasis in liver-injured rats. The findings suggest that XHQDD markedly alleviates inflammation in ANIT rats, potentially treating cholestasis and liver injury through JAK2/STAT3 inhibition and Th17/Treg balance regulation.
Animals ; STAT3 Transcription Factor/immunology* ; Janus Kinase 2/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Rats, Sprague-Dawley ; 1-Naphthylisothiocyanate/adverse effects* ; Male ; Rats ; Th17 Cells/immunology* ; Cholestasis/immunology* ; Signal Transduction/drug effects* ; T-Lymphocytes, Regulatory/immunology* ; Chemical and Drug Induced Liver Injury/immunology* ; Liver/drug effects*

Objective:To screen serum biomarkers of polycystic ovary syndrome (PCOS) patients by high throughput data independent acquisition (DIA) proteomics technology.Methods:This was a case-control study. A total of 39 peripheral blood samples were collected at Reproductive Medical Center of Jiangxi Maternal and Child Health Hospital from March to November 2021. Among which, 20 cases were from PCOS patients, and 19 cases were from women who underwent assisted reproduction due to male factors causing infertility. DIA proteomics technology combined with bioinformatics analysis were performed to screen for differential protein expression profiles in the serum of PCOS patients. Typical differentially expressed proteins were selected for expression analysis and receiver operating characteristic (ROC) curve analysis, followed by enzyme-linked immunosorbent assay (ELISA) validation.Results:The results of DIA proteomics combined with bioinformatics analysis showed that compared with control group, 194 significantly differentially expressed proteins were screened in the peripheral blood of PCOS patients, including 64 upregulated proteins and 130 downregulated proteins. The ROC curve analysis results showed that the area under curve values of PSMD8, RPS15A, NDUFB1, GM2A, and TOP2A were all above 0.9, indicating that these proteins have good diagnostic value. The ELISA validation results showed that the content of TOP2A in peripheral blood of PCOS patients was significantly upregulated ( P=0.046), while the content of GM2A was significantly downregulated ( P=0.021), when compared with control group, which consistent with the DIA results. Conclusion:DIA proteomics can be used to screen the differential expression of peripheral blood proteins in PCOS patients, among which, PSMD8, RPS15A, NDUFB1, GM2A and TOP2A can be used as serum biomarkers for PCOS diagnosis and treatment.

Sinomenine hydrochloride is an alkaloid preparation commonly used in clinical practice in traditional Chinese medicine, and allergic reactions induced by occupational exposure to it are relatively rare in clinical settings. This article analyzes a case of allergic contact dermatitis in a medical worker after occupational exposure to sinomenine hydrochloride. The patient developed generalized skin rashes with the fingertips as the initial site three months after exposure to sinomenine hydrochloride. The treatment effect was poor without cessation of exposure, while symptoms significantly improved after cessation. The condition persisted, exhibiting a contact-reaction pattern of recurrence upon re-exposure. The serum total IgE level met the criteria for extremely severe allergy. No similar symptoms were observed among colleagues in the same position. After differential diagnosis, the possibility of dermatomyositis was ruled out, and the patient was diagnosed with occupational allergic contact dermatitis.

Sinomenine hydrochloride is an alkaloid preparation commonly used in clinical practice in traditional Chinese medicine, and allergic reactions induced by occupational exposure to it are relatively rare in clinical settings. This article analyzes a case of allergic contact dermatitis in a medical worker after occupational exposure to sinomenine hydrochloride. The patient developed generalized skin rashes with the fingertips as the initial site three months after exposure to sinomenine hydrochloride. The treatment effect was poor without cessation of exposure, while symptoms significantly improved after cessation. The condition persisted, exhibiting a contact-reaction pattern of recurrence upon re-exposure. The serum total IgE level met the criteria for extremely severe allergy. No similar symptoms were observed among colleagues in the same position. After differential diagnosis, the possibility of dermatomyositis was ruled out, and the patient was diagnosed with occupational allergic contact dermatitis.

Objective:To screen serum biomarkers of polycystic ovary syndrome (PCOS) patients by high throughput data independent acquisition (DIA) proteomics technology.Methods:This was a case-control study. A total of 39 peripheral blood samples were collected at Reproductive Medical Center of Jiangxi Maternal and Child Health Hospital from March to November 2021. Among which, 20 cases were from PCOS patients, and 19 cases were from women who underwent assisted reproduction due to male factors causing infertility. DIA proteomics technology combined with bioinformatics analysis were performed to screen for differential protein expression profiles in the serum of PCOS patients. Typical differentially expressed proteins were selected for expression analysis and receiver operating characteristic (ROC) curve analysis, followed by enzyme-linked immunosorbent assay (ELISA) validation.Results:The results of DIA proteomics combined with bioinformatics analysis showed that compared with control group, 194 significantly differentially expressed proteins were screened in the peripheral blood of PCOS patients, including 64 upregulated proteins and 130 downregulated proteins. The ROC curve analysis results showed that the area under curve values of PSMD8, RPS15A, NDUFB1, GM2A, and TOP2A were all above 0.9, indicating that these proteins have good diagnostic value. The ELISA validation results showed that the content of TOP2A in peripheral blood of PCOS patients was significantly upregulated ( P=0.046), while the content of GM2A was significantly downregulated ( P=0.021), when compared with control group, which consistent with the DIA results. Conclusion:DIA proteomics can be used to screen the differential expression of peripheral blood proteins in PCOS patients, among which, PSMD8, RPS15A, NDUFB1, GM2A and TOP2A can be used as serum biomarkers for PCOS diagnosis and treatment.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective:To explore application effect of early respiratory training schemes based on 4E mode (Engage, Educate, Execute, Evaluate) in children with bronchiolitis obliterans (BO) and provide evidence for the clinical implementation of early respiratory rehabilitation in children with BO.Methods:This was a quasi-experimental study. The children with BO who were admitted to 2 wards of the Department of Respiratory Medicine of Hunan Children's Hospital from January 1 to December 31, 2021 were selected as the research objects. They were randomly divided into the control group and the experimental group, with 23 cases in each group. The control group received routine treatment, nursing and rehabilitation guidance. The experimental group established a multidisciplinary team based on the control group, and used the early respiratory training program based on the 4E model to implement intervention. The clinical symptom severity scale was used to evaluate the improvement of the clinical symptoms of the children within 24 hours of being diagnosed as BO, the day of discharge, and 1 and 3 months after discharge for re-examination, and the hospitalization time of the children and the incidence of adverse events related to respiratory training were counted by using medical records and questionnaires.Results:The clinical symptom severity scores of the experimental group within 24 hours of admission diagnosis and the day of discharge were (20.00 ± 2.51) and (11.30 ± 2.46)points respectively, while those of the control group were (20.57 ± 2.21) and (11.70 ± 2.42) points respectively, with no statistically significant difference ( t=0.81, 0.54, both P>0.05). The clinical symptom severity scores of the experimental group were(10.52 ± 2.31) and (8.55 ± 1.06) points, lower than (12.32 ± 1.39) and (12.45 ± 2.19) points of the control group when they returned to the hospital for re-examination 1 and 3 months after discharge, with a statistically significant difference ( t=3.14, 7.25, both P<0.05). The experimental group was hospitalized for (11.78 ± 1.17) days, which was showter than (13.74 ± 1.63) days in the control group, with a statistically significant difference ( t=4.68, P<0.05). No respiratory training-related adverse events occurred in both groups of children during hospitalization. During home respiratory training after discharge, 1 and 2 respiratory training-related adverse events occurred in the experimental group 1 and 3 months after discharge, respectively, compared with 6 and 9 in the control group. The difference was statistically significant ( χ2=4.64, 5.94, both P<0.05). Conclusions:Early respiratory training solutions based on the 4E mode can improve the clinical symptoms of BO children, shorten the hospitalization time, reduce the number of adverse events related to respiratory training, and promote the recovery of children.

Atherosclerosis (AS) is a chronic and progressive arterial disease. It is an important cause of the occurrence and development of cardiovascular and cerebrovascular diseases. With the development of Traditional Chinese Medicine (TCM), TCM has many advantages in the therapy of AS, with less adverse reactions. Studies have shown that TCM can resist AS, and the mechanism mainly belongs to regulating lipid metabolism, anti-lipid peroxidation, anti-inflammation, anticoagulation, and protecting the structure and function of vascular endothelial cells. The mechanism of TCM for AS is warranted to be studied systematically, and the chemical components need to be further clarified.

Zinc-α2-glycoprotein (ZAG), encoded by the AZGP1 gene, is a major histocompatibility complex I molecule and a lipid-mobilizing factor. ZAG has been demonstrated to promote lipid metabolism and glucose utilization, and to regulate insulin sensitivity. Apart from adipose tissue, skeletal muscle, liver, and kidney, ZAG also occurs in brain tissue, but its distribution in brain is debatable. Only a few studies have investigated ZAG in the brain. It has been found in the brains of patients with Krabbe disease and epilepsy, and in the cerebrospinal fluid of patients with Alzheimer disease, frontotemporal lobe dementia, and amyotrophic lateral sclerosis. Both ZAG protein and AZGP1 mRNA are decreased in epilepsy patients and animal models, while overexpression of ZAG suppresses seizure and epileptic discharges in animal models of epilepsy, but knowledge of the specific mechanism of ZAG in epilepsy is limited. In this review, we summarize the known roles and molecular mechanisms of ZAG in lipid metabolism and glucose metabolism, and in the regulation of insulin sensitivity, and discuss the possible mechanisms by which it suppresses epilepsy.
Adipocytes ; metabolism ; Animals ; Brain ; metabolism ; Carrier Proteins ; metabolism ; Epilepsy ; metabolism ; Glucose ; metabolism ; Glycoproteins ; metabolism ; Humans ; Insulin Resistance ; Lipid Metabolism ; Neurons ; metabolism ; Signal Transduction

Objective To investigate the effects of artesunate combined with arsenic trioxide (ATO) on the proliferation and apoptosis of NB4 cells.Methods The NB4 cells were treated with different concentrations of artesunate and arsenic trioxide respectively for 48 h.The cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) method.The cells were divided into 4 groups:control group,artesunate group,arsenic trioxide group,and the combination of artesunate and arsenic trioxide group.The cell cycle and apoptosis were detected by flow cytometry (FCM).The protein expression levels of Bcl-2 and Bax were detected by Western blot.Results The MTT results showed that compared with the control group,the proliferation inhibition rates of 0.25,0.50,1.00,2.00,4.00 μmol/L artesunate group (19.26％ ± 3.59％,36.53％ ± 2.67％,61.32％ ± 2.50％,70.30％ ± 3.15％,86.92 ± 0.02％) significantly increased (P＜0.05);the proliferation inhibition rates of 1,2,4,8,16 μmol/L arsenic trioxide group (12.69％ ± 2.43％,64.26％ ± 2.02％,85.10％ ± 2.67％,92.06％ ± 2.21％,93.67％ ± 3.36％) significantly increased (P＜0.05);and the proliferation inhibition rate (40.17％ ± 5.49％ vs.32.23％ ± 3.52％) of combination of artesunate and arsenic trioxide group significantly higher than the arsenic trioxide group (P＜0.05).Compared with the arsenic trioxide group,the percentage of G0/G1 phase cells (74.20％ ± 1.43％ vs.66.14％ ± 1.78％),the apoptosis rate (58.00％ ± 2.41％ vs.34.57％ ± 1.22％),and the expression level of Bax protein (1.35 ± 0.09 vs.1.13 ± 0.09) in the combination of artesunate and arsenic trioxide group significantly increased (P＜0.05),the expression level of Bcl-2 protein (0.45 ± 0.09 vs.1.03 ± 0.10) in the combination of artesunate and arsenic trioxide group significantly decreased (P＜0.05).Conclusions Artesunate can significantly enhance the proliferation inhibition and apoptosis induced by arsenic trioxide on NB4 cells.The possible mechanism of proliferation inhibition and apoptosis of NB4 cells by artesunate combined with arsenic trioxide may be related to reduce the expression of anti-apoptotic protein Bcl-2 and increase the expression of apoptotic protein Bax.