The interleukin-10 （IL-10） family is expressed in various types of cells and has a wide range of biological functions， and it plays an important role in the development and progression of hepatic fibrosis. Hepatic fibrosis is a chronic liver disease characterized by abnormal repair of hepatic tissues after injury， activation of hepatic stellate cells， and excessive accumulation of extracellular matrix. The IL-10 family members include IL-10， IL-19， IL-20， IL-22， IL-24， IL-26， IL-28， IL-29， and IL-35， with similarities in structure and function， and changes in their expression levels are closely associated with the progression of hepatic fibrosis. Moderate upregulation of the expression of IL-10 family members can help maintain the quiescent state of hepatic stellate cells， promote the transformation of macrophages to anti-inflammatory phenotype， and regulate the activity of natural killer cells， thereby inhibiting inflammatory response， regulating cell apoptosis and autophagy， and finally reversing the progression of hepatic fibrosis. This article discusses the mechanism of action of IL-10 family members and their application in traditional Chinese medicine and Western medicine therapies， in order to provide new thoughts for the treatment of hepatic fibrosis.

Liver failure （LF） is a severe clinical syndrome characterized by severe impairment or decompensation of liver function. At present， the key role of immune molecules in the pathogenesis of LF has been well established. These molecules not only directly participate in the pathological process of LF， but also influence the course of LF by modulating the behavior of immune cells. In addition， immune molecules can be used as potential biomarkers for evaluating the prognosis of LF. This article summarizes the role of immune molecules in LF and explores the therapeutic strategies based on these immune molecules， in order to provide new directions for the diagnosis and treatment of LF.

Aim To study the effects of different peri-ods of hypoxia on gastrointestinal stress in mice by sim-ulating hypoxia environment at high altitude in a low-pressure oxygen chamber.Methods The normal con-trol group and the model group for 1,3 and 5 days were set up according to different periods of hypobaric hypoxia.The intestinal propulsion rate,visceral sensi-tivity and pathological damage of gastrointestinal tract were detected after hypobaric hypoxia treatment.The contents of IL-1 β,IL-6 and TNF-α in gastrointestinal tract and the contents of gastrointestinal hormone,di-amine oxidase and D-lactic acid were detected by en-zyme-linked immunosorbent assay(ELISA).The ex-pressions of tight-junction protein and tight junction in-jury pathway protein in intestinal tissues were detected by Western blot.Results Compared with the control group,the intestinal propulsion rate of the model group was accelerated,and the intestinal sensitivity in-creased.The expression of intestinal mucosal injury markers increased.Gastrointestinal motility inhibiting hormone decreased and gastrointestinal motility promo-ting hormone increased.The expression of tight junc-tion proteins ZO-1,claudin-1,occludin and VASP of tight junction injury-related pathway decreased,while the expression of NF-κB,HIF-1α and VEGF in tight junction injury-related pathway increased.The expres-sions of IL-1 β,IL-6 and TNF-α in gastrointestinal tis-sue increased.The content of pepsin in gastric tissue increased.The injury of gastrointestinal tissue was less in the 1-day group,and more serious in the 3-day and 5-day groups.Conclusions Stress injury occurs in the gastrointestinal tract of mice at different time points in hypoxia and hypoxia environment,and the gastroin-testinal function injury is more serious after three days of exposure,which may be related to the activation of NF-κB/HIF-1α/VEGF/VASP pathway.

AIM: To explore the correlation between the integrity of the macular microstructures and the visual outcomes before and after idiopathic macular epiretinal membrane(IMEM)surgery.METHODS: A total of 43 patients(43 eyes)with IMEM who were treated in our hospital between January 2017 and December 2019 were selected. The best corrected visual acuity(BCVA)of each patient was examined preoperatively and at 3, 6, 9mo after surgery. Moreover, metamorphopsia(M-chart)examination was given, and spectral domain-optical coherence tomography(SD-OCT)was used to measure central foveal thickness(CFT), subfoveal choroidal thickness(SFCT), the thickness of ganglion cells-inner plexiform layer(GC-IPL)and the length of interdigitation zone(IZ)defect.RESULTS: The BCVA and the metamorphopsia were gradually improved at postoperative 3, 6 and 9 mo(all P<0.05). Moreover, the BCVA was positively correlated with CFT and the length of the IZ defect(P<0.05), while it was not correlated with SFCT and the thickness of GC-IPL(P>0.05). The metamorphopsia assessment was positively correlated with the CFT at postoperative 3, 6, and 9mo(P<0.05), while it was not correlated with SFCT, the thickness of GC-IPL and the length of IZ defect(P>0.05).CONCLUSIONS: The CFT and the length of IZ defect were significantly correlated with the BCVA after IMEM surgery, which can be used as indicators to predict the recovery of visual function after IMEM surgery.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To explore the correlation between the attachment type of lateral pterygoid muscle (LPM) and the position of temporomandibular joint (TMJ) disc in patients with temporomandibular disorders (TMD) by using wireless amplified magnetic resonance imaging detector (WAND) coupled with conventional head and neck joint coil for high resolution imaging of TMJ. Methods: Eighty-five patients with TMD diagnosed by oral and maxillofacial surgeons of Guizhou Provincial People's Hospital from October 2019 to January 2022 were collected. A total of 160 TMJ were included. There were 16 males and 69 females, aged (32.7±14.2) years. All patients were scanned with open, closed oblique sagittal and coronal WAND coupled head and neck coils with bilateral TMJ. Based on TMJ and LPM high resolution imaging, to explore the correlation between LPM attachment types and the position of TMJ disc in TMD patients, and to evaluate the potential clinical value of LPM attachment types in TMD patients. χ² test and Pearson correlation analysis were used to evaluate the correlation between LPM attachment type and TMJ disc location. Results: There were three types of LPM attachment: type Ⅰ in 51 cases [31.9% (51/160)], type Ⅱ in 77 cases [48.1% (77/160)] and type Ⅲ in 32 cases [20.0% (32/160)]. There was a significant correlation between the type of LPM attachment and the position of articular disc (χ²=28.20, P=0.002, r=0.776). There was no statistical significance between the type of LPM attachment and the reversible displacement of articular disc (χ²=0.24, P=0.887, r=0.825). Conclusions: There is a correlation between the attachment type of LPM and the position of the disc in TMD patients. WNAD coupled with conventional head and neck joint coil TMJ high resolution scan can provide reliable imaging evidence for TMD patients in evaluating the type of LPM attachment and the location of disc.
Male ; Female ; Humans ; Temporomandibular Joint Disc/pathology* ; Pterygoid Muscles/pathology* ; Joint Dislocations ; Temporomandibular Joint Disorders/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Temporomandibular Joint/pathology*

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.
Male ; Mice ; Animals ; Testis/metabolism* ; Ferroptosis ; Semen ; Oxidative Stress

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

OBJECTIVE: To investigate the therapeutic mechanism of emodin in the treatment of rheumatoid arthritis (RA) using a network pharmacology-based method and validate this mechanism in a fibroblast-like synovial cell line. METHODS: The PubChem, Targetnet, SwissTargetPrediction, Genecards, OMIM, and DisGeNET databases were searched to obtain emodin targets and RA-related genes. A protein-protein interaction (PPI) network was constructed, and GO and KEGG pathway enrichment analyses were carried out to analyze the intersection genes. AutoDock4.2.6 software was used to simulate molecular docking between emodin and its candidate targets. In a cultured fibroblast-like synovial cell line (MH7A), the effects of different concentrations of emodin on proliferation of tumor necrosis factor-α (TNF-α)-induced cells were investigated using CCK-8 assay, cell scratch experiment and flow cytometry; the changes in the expressions of nuclear factor-κB (NF-κB) pathway proteins were detected using Western blotting, and the mRNA expressions of the hub genes were examined with RT-qPCR. RESULTS: We identified 32 intersection genes of emodin and RA, and the key targets including CAPS3, ESR1, and MAPK14 involved mainly the NF-κB signaling pathway. Cell scratch experiment and flow cytometry demonstrated a strong inhibitory effect of emodin on MH7A cell proliferation. Treatment with TNF-α significantly increased the cellular expressions of the NF-κB pathway proteins, which were obviously lowered by treatment with 80 μmol/L emodin. The results of RT-qPCR showed that TNF-α treatment obviously up-regulated the expressions of the hub genes COX2 and P38MAPK, and emodin treatment significantly down-regulated the expressions of MAPK and PTGS2 and up-regulated the expression of CASP3. CONCLUSION The therapeutic effect of emodin on RA is mediated mainly through regulation of cell proliferation, apoptosis, and the NF-κB pathway.
Arthritis, Rheumatoid/pathology* ; Emodin/pharmacology* ; Humans ; Molecular Docking Simulation ; NF-kappa B/metabolism* ; Network Pharmacology ; Tumor Necrosis Factor-alpha/pharmacology*

Yi Yin, a famous medical scientist and culinary master in the late Xia Dynasty and early Shang Dynasty, developed the Chinese medicinal liquids and Chinese medicinal prescriptions emerged after that. Chinese medicinal prescriptions have attracted much attention because of their unique advantages in the treatment of chronic multifactorial diseases, representing an important direction of drug discovery in the future. Yiyin decoction theory is the superior form of personalized combined medication with advanced consciousness. It is different from not only the magic bullet theory of single component action but also the connotation of modern multi-target drugs. The core of Yiyin decoction theory can be summarized as compound compatibility, multiple effects, and moderate regulation. Compound compatibility refers to that the formulation of Chinese medicinal prescriptions involves the complex synergy and interactions between sovereign, minister, assistant, and guide medicinal materials. Multiple effects mean that the prescriptions employ a variety of mechanisms to exert comprehensive pharmacological effects of nonlinear feedback. Moderate regulation reflects that the prescriptions can accurately regulate the multiple points of the disease biological network as a whole. To solve the mystery of Yiyin decoction theory, we should not only simply study the known active substances(components) and their independent target effects in the mixture, but also mine the "dark matter" and "dark effect" of Chinese medicinal prescriptions. That is, we should learn the neglected atypical pharmacological effects of Chinese medicinal prescriptions and the multi-point nesting mechanism that plays a precise regulatory function in the body. Yiyin decoction theory focuses on the overall pharmacological effect to reflect the comprehensive clinical value of Chinese medicinal prescriptions, which is of great significance for the development of a new model for the evaluation and application of new Chinese medicinal prescriptions in line with the theory of traditional Chinese medicine.
China ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Prescriptions