Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Under the background of the Healthy China strategy， the integration of traditional Chinese medicine （TCM） into the public health emergency response system has become an important measure to enhance the capacity for coping with public health emergencies. In recent years， the role of TCM in responding to such emergencies has become increasingly prominent. Taking major emerging epidemics as an example， TCM has developed a rich theoretical system and practical experience in epidemic prevention and treatment over thousands of years， and has played a significant role in successive outbreaks with its unique advantages. Based on the concept of ''preventing disease before its onset'' and the theoretical framework of treatment based on syndrome differentiation， TCM has achieved remarkable results through early intervention and full participation in the integrated model of TCM and Western medicine， from severe acute respiratory syndrome （SARS） to corona virus disease-2019 （COVID-19）， in improving clinical symptoms and outcomes， reducing adverse reactions， and promoting recovery. From the perspective of the Healthy China strategy， this paper systematically reviews the historical development of TCM in epidemic prevention and treatment， with particular attention to recent epidemics such as SARS， influenza A （H1N1）， and COVID-19. It further examines the similarities and differences between TCM and Western medicine in responding to major emerging epidemics， as well as relevant policies related to TCM in epidemic prevention and control. In addition， it summarizes the existing problems in TCM's role in the prevention and treatment of major emerging epidemics， and explores measures to improve its rapid response capacity under the Healthy China strategy. This study not only provides a ''Chinese solution'' for the prevention and control of newly emerging infectious diseases worldwide， but also offers theoretical and practical references for strengthening the public health emergency response system， carrying strategic significance for promoting the modernization and internationalization of TCM.

Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

OBJECTIVES: To investigate the expression levels of marginal zone B and B1-cell-specific protein (MZB1) in pan-cancer and its association with patient prognosis and tumor microenvironment (TME). METHODS: MZB1 expression data, clinicopathological parameters, and survival data from 33 cancer types were extracted from the UCSC database for analyzing the correlations of MZB1 with clinical stage, patient prognosis, immunomodulatory genes, immune checkpoint genes, tumor stemness, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). MZB1 gene mutations in pan-cancer were assessed using cBioPortal online database, and the value of MZB1 for cancer diagnosis was evaluated using ROC curve analysis. MZB1 expression levels in myeloid leukemia and renal carcinoma cells were detected using RT-qPCR and Western blotting, and the effect of MZB1 knockdown on cell proliferation was examined using EdU assay. RESULTS: MZB1 was significantly overexpressed in 20 cancer types, including kidney renal clear cell carcinoma (KIRC), breast invasive carcinoma, and acute myeloid leukemia. Its expression was associated with TNM stage, clinical stage, overall survival, and progression-free survival in multiple cancers. In most tumors, MZB1 expression was correlated significantly with immunomodulatory genes, immune checkpoint genes, tumor stemness, immune cell infiltration, TMB, and microsatellite instability. Gene amplification was the predominant mutation type of MZB1 in pan-cancer, and MZB1 showed high diagnostic value for skin cutaneous melanoma, KIRC, and head and neck squamous cell carcinoma. MZB1 was highly expressed in different myeloid leukemia cell lines and renal carcinoma cell lines, and MZB1 knockdown significantly suppressed the proliferation of HL60 and 769-P cells. CONCLUSIONS MZB1 is highly expressed in a variety of tumors, and its aberrant expression affects the occurrence and prognosis of many tumors, suggesting its potential as a novel tumor biomarker and immunomodulatory target.
Humans ; Prognosis ; Tumor Microenvironment ; Neoplasms/pathology* ; Cell Line, Tumor ; Mutation ; Kidney Neoplasms ; Microsatellite Instability ; Cell Proliferation ; Carcinoma, Renal Cell

Purpose To compare the CT imaging features of the novel coronavirus Omicron variant and influenza A-H1N1-associated viral pneumonia,and to investigate the factors associated with the uptake process of the two pneumonias.Materials and Methods A total of 43 patients with Omicron virus pneumonia(Omicron group)and 30 patients with influenza A(H1N1)virus pneumonia[influenza A(H1N1)group]in Civil Aviation General Hospital from December 2022 to March 2023 were retrospectively collected.The clinical data of the two groups were compared,including age,gender,symptoms(fever or not),duration of symptoms and incidence of complications.White blood cells,monocytes,lymphocytes,neutrophils,C-reactive protein,etc.]and initial and follow-up CT imaging features[lesion density,distribution,signs and qualitative CT severity score(CTSS)].Results The mean age of patients in Omicron group was higher versus that in H1N1 group[(68.61±15.94)years vs.(51.20±16.39)years,P<0.000 1],and the fever rate in Omicron group(58.1%vs.86.7%,P=0.009)and monocyte count[(0.40±0.16)vs.(0.58±0.19),P<0.000 1]were lower than those in the influenza A(H1N1)group.Chest CT showed that the lesions of patients in the Omicron group were mainly distributed under the pleura,and the lesions of patients in the influenza A(H1N1)group were mainly distributed under the pleura and along the bronchovascular bundle(χ2=8.592,P=0.035).Patients in the Omicron group were more likely to have interlobular septal thickening(χ2=11.753,P=0.001),paving pattern(χ2=16.216,P<0.000 1),air bronchogram(χ2=16.216,P<0.000 1),pleural effusion(P=0.039)and pleural thickening(χ2=4.067,P=0.044)than patients in the influenza A(H1N1)group,while patients in the influenza A(H1N1)group were more likely to have nodules than those in the omicron group(χ2=6.971,P=0.008).The CTSS scores of patients in the omicron group were higher than those in the influenza A(H1N1)group at the initial diagnosis(Z=413,P=0.009)and follow-up(Z=107,P=0.027).The correlation between the change of follow-up CTSS and the initial CTSS in the Omicron group was the strongest(r=0.689,P<0.000 1).There was the strongest correlation between the change of follow-up CTSS and the duration of symptoms in influenza A(H1N1)group(r=0.954,P<0.000 1).Conclusion Patients in the Omicron group have a higher range of initial and follow-up lesions than those in influenza A(H1N1)group,and the degree of pneumonia absorption in the omicron group may be related to the initial CTSS,whereas in the influenza A(H1N1)group it may be related to the duration of symptoms.

Objective:To investigate the effect of rare ginsenosides (RGS) on reproductive injury induced by cyclophosphamide (CP) in female rats.Methods:Twenty-four female rats were divided into four groups [normal control (NC), RGS, CP, and CP+RGS group] with 6 rats in each group. CP group (the model group) and CP+RGS group (the treatment group) were intraperitoneally injected with CP 30 mg/kg for 5 days for modeling, and CP+RGS group was given RGS intragastric intervention. General growth status of rats in each group was observed, the organ index was calculated, and the pathological changes of ovary, uterus, liver and kidney were observed by hematoxylin-eosin staining. Serum levels of estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), pro-inflammatory factors interleukin (IL) 6, IL-1β, tumor necrosis factor-α were detected. The urine samples were collected after RGS treatment for metabonomics analysis. Metabolomic profiling based on ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS) was used to analyze and determine the urine metabolites of rats in each group.Results:Compared with NC group, the ovary index of CP group [(0.054±0.015) %] was significantly decreased ( P<0.05), the uterus index [(0.293±0.036) %] and estradiol level [(62.9±6.4) pmol/L] were significantly decreased (all P<0.01), serum levels of FSH, LH, IL-6 and IL-1β [(20.4±1.0) U/L, (29.0±3.0) U/L, (185.4±28.6) ng/L, (72.9±2.0) ng/L, respectively] were significantly increased (all P<0.01). Compared with CP group, the ovary index in CP+RGS group [(0.075±0.010) %] was significantly increased ( P<0.05), serum estradiol level [(122.1±16.2) pmol/L] was significantly increased ( P<0.01), serum FSH, IL-1β and IL-6 levels [(16.7±1.0) U/L, (111.8±17.4) ng/L, (60.1±2.2) ng/L, respectively] were significantly decreased (all P<0.01). Metabonomics analysis results showed that, a total of 352 metabolites were detected in urine, of which 12 were found to be potential markers associated with reproductive injury according to the screening standard. After treatment with RGS, differential metabolites were improved in the direction of NC group. Pathway enrichment suggests that the therapeutic effect of RGS was related to multiple metabolic pathways, including purine metabolism and taurine and hypotaurine metabolism. Conclusion:RGS might reduce inflammation and thus ameliorate the damage caused by CP to the reproductive system of female rats by affecting purine metabolism and other pathways.

Objective:To explore the compatibility and medication law of Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair in ancient and modern prescriptions.Methods:Ancient prescriptions and Chinese patent medicines containing Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair were retrieved from the database of ancient classic famous prescriptions 1.0 and the database of listed Chinese patent medicines 1.0 developed by the Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences. Excel 2019 was used to establish a database. The ancient and modern medical record cloud platform V2.3.5 and SPSS Modeler 18.0 software were used to perform frequency statistics, association rule analysis, clustering analysis, etc. on the data.Results:Totally 79 ancient articles with Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair were obtained, including 76 ancient prescriptions, involving 250 kinds of Chinese materia medica; 25 kinds of Chinese patent medicine were obtained, involving 186 kinds of Chinese materia medica. The drug properties of ancient prescriptions and modern TCM patent medicines were both mainly warm, cold and neutral. The main tastes of ancient prescriptions and modern Chinese patent medicines were pungent, sweet and bitter. And the drugs mainly belong to spleen, lung, liver and kidney meridians. Correlation analysis suggested the same high-frequency association compatibility of ancient and modern prescriptions, Poria-Cinnamomi Ramulus-Alismatis Rhizoma, Atractylodis Rhizoma-Cinnamomi Ramulus-Alismatis Rhizoma, Atractylodis Macrocephalae Rhizoma-Cinnamomi Ramulus-Alismatis Rhizoma. Both clinical symptoms and diseases associated with medicinal compatibility of ancient prescriptions were intestinal flora, edema and vomiting. The syndrome types included bladder impoundment, dampness trapped in the guardian surface, internal retention of phlegm and morbid fluid. The clinical symptoms associated with medicinal compatibility of modern TCM patent medicine were limb joints pain and edema. The diseases included rheumatic arthritis (RA) and kidney disease. The syndrome types included wind-cold-dampness RA, stagnation of collaterals and kidney yang deficiency. High frequency drug clustering yielded 4 clustered squares.Conclusion:The core indications treated by Cinnamomi Ramulus-Alismatis Rhizoma are exogenous diseases with dampness caused by syndrome types including internal storage of water-dampness, cold-dampness obstruction and so on, which can provide reference for further in-depth research and guidance on clinical medication.