This paper primarily investigated the protective effects and potential mechanisms of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma in alleviating isoprenaline(ISO)-induced hypertrophy and damage in H9c2 cardiomyocytes. Initially, H9c2 cardiomyocytes were used as the research subject to analyze the effects of ISO at different concentrations on cell hypertrophy and damage. On this basis, the H9c2 cardiomyocytes were divided into blank, model, and high-dose(200 μg·mL~(-1)), medium-dose(100 μg·mL~(-1)), and low-dose(50 μg·mL~(-1)) groups of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma. Cell hypertrophy and damage models were induced by treating cells with 400 μmol·L~(-1) ISO for 24 hours. The Incucyte live-cell analysis system was utilized to observe the status, size changes, and confluence of the cells in each group. Cell viability was detected by using the CCK-8 assay. Western blot analysis was employed to detect the expression of Ras-associated protein 7A(RAB7A), sequestosome 1(SQSTM1/p62), autophagy-related protein Beclin1, and microtubule-associated protein 1 light chain 3(LC3). Immunofluorescence was used to detect the expression level of the autophagy marker Beclin1 in H9c2 cells. The results demonstrated that compared with the blank group, the model group showed a significant reduction in cell viability(P<0.01) and a marked increase in cell hypertrophy, with an average cell length growth of 13.53%. Compared with the model group, the high-dose, medium-dose, and low-dose groups of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma exhibited reduced hypertrophy, with respective growths of 6.89%, 8.30%, and 8.49% and a significant decrease in growth rates(P<0.01). Cell viability in the high-dose of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma was also significantly increased(P<0.01). Western blot and immunofluorescence results indicated that compared with the blank group, the model group showed changes in Beclin1, RAB7A, and p62 expression, as well as the LC3Ⅱ/LC3Ⅰ ratio, although most changes were not statistically significant. In the groups treated with total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma, the expression of autophagy-related proteins Beclin1 and RAB7A and the LC3Ⅱ/LC3Ⅰ ratio were significantly increased(P<0.05), while p62 expression significantly decreased(P<0.05). These findings collectively suggested that pretreatment of cells with total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma significantly enhanced autophagy activity in cells. In summary, total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma inhibit ISO-induced hypertrophy and damage in H9c2 cells by promoting autophagy, demonstrating potential cardioprotective effects and providing new insights and scientific evidence for their preventive and therapeutic use in cardiovascular diseases.
Autophagy/drug effects* ; Saponins/pharmacology* ; Panax notoginseng/chemistry* ; Panax/chemistry* ; Animals ; Rats ; Cell Line ; Drugs, Chinese Herbal/pharmacology* ; Rhizome/chemistry* ; Isoproterenol/adverse effects* ; Myocytes, Cardiac/cytology* ; Hypertrophy/drug therapy*

ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action， so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group， model group， carbamazepine group （0.06 g·kg^-1·d^-1）， high-dose Lutongning group （2.70 g·kg^-1·d^-1）， and low-dose Lutongning group （1.35 g·kg^-1·d^-1） according to the stratified basic mechanical pain thresholds， with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg^-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin （HE） staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors interleukin （IL）-1， IL-6， IL-8， tumor necrosis factor （TNF）-α， neuropeptide substance P， and β-endorphins （β-EP） in the serum of rats， and Western blot was used to detect the protein expression levels of IL-1β， purinergic receptor P2X7 （P2X7R）， and phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）. ResultCompared with that in the normal group， the pain threshold of rats in the model group was significantly lower （P<0.01）. The absolute value of neutrophils （NEUT#） and the percentage of neutrophils （NEUT） were significantly improved， and the percentage of lymphocytes （LYMPH） was significantly reduced （P<0.01）. The serum levels of IL-1， IL-6， IL-8， and TNF-α were significantly increased （P<0.01）. SP content in brain tissue was significantly increased， and β-EP content was significantly decreased （P<0.01）. The relative protein expression of IL-1β， P2X7R， and p-p38 MAPK was significantly increased （P<0.05）. HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration， mild proliferation of microglial cells， reduction in the number of myelinated nerves， and obvious demyelination. The trigeminal nerve fibers of rats were disarranged， and some nerve fibers showed vacuolization. Axons were swollen， and Schwann cells proliferated. Demyelination was observed. Compared with the model group， each administration group significantly increased the pain threshold of rats （P<0.05， P<0.01）， reduced NEUT# and NEUT， and elevated LYMPH （P<0.05， P<0.01）. The administration group significantly decreased the levels of IL-1， IL-6， IL-8， and TNF-α in serum and SP in brain tissue （P<0.01） and increased the level of β-EP （P<0.01）. They significantly down-regulated the protein expression of IL-1β， P2X7R， and p-p38 MAPK（P<0.05， P<0.01） and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats， and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.

BACKGROUND: The prevalence of hypertension is high among Chinese adults, thus, identifying non-hypertensive individuals at high risk for intervention will help to improve the efficiency of primary prevention strategies. METHODS: The cross-sectional data on 9699 participants aged 20 to 80 years were collected from the China National Health Survey in Gansu and Hebei provinces in 2016 to 2017, and they were nonrandomly split into the training set and validation set based on location. Multivariable logistic regression analysis was performed to develop the diagnostic prediction model, which was presented as a nomogram and a website with risk classification. Predictive performances of the model were evaluated using discrimination and calibration, and were further compared with a previously published model. Decision curve analysis was used to calculate the standardized net benefit for assessing the clinical usefulness of the model. RESULTS: The Lasso regression analysis identified the significant predictors of hypertension in the training set, and a diagnostic model was developed using logistic regression. A nomogram with risk classification was constructed to visualize the model, and a website ( https://chris-yu.shinyapps.io/hypertension_risk_prediction/ ) was developed to calculate the exact probabilities of hypertension. The model showed good discrimination and calibration, with the C-index of 0.789 (95% confidence interval [CI]: 0.768, 0.810) through internal validation and 0.829 (95% CI: 0.816, 0.842) through external validation. Decision curve analysis demonstrated that the model was clinically useful. The model had a higher area under receiver operating characteristic curves in training and validation sets compared with a previously published diagnostic model based on Northern China population. CONCLUSION This study developed and validated a diagnostic model for hypertension prediction in Gansu Province. A nomogram and a website were developed to make the model conveniently used to facilitate the individualized prediction of hypertension in the general population of Han and Yugur.
Adult ; Humans ; Asian People ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Hypertension/epidemiology* ; Nomograms ; Ethnicity

OBJECTIVE: To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma. METHODS: We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups. RESULTS: There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729). CONCLUSION Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Humans ; Immunotherapy/methods* ; Liver Neoplasms/drug therapy* ; Prospective Studies ; Retrospective Studies

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective:To establish the reference for serum metabolomics profiles among healthy Han adults in China, and explore the variation on metabolomics profiles by geographic regions, sex, and age.Methods:Cross-sectional data and serum samples were obtained from the China National Health Survey. A total of 1 039 male and 1 032 female healthy adults(≥30 years) were included in this study. Serum metabolomics analyses were conducted with ultra-performance liquid chromatography-mass spectrometry(UPLC-MS). Orthogonal partial least squares discriminant analysis(OPLS-DA) was performed to compare the differences of metabolomics among different region, sex, and age.Results:Significant differences on metabolomics profiles were identified among region, sex, and age. A total of 114 region-related metabolites were spotted, including 53 metabolites that involved in human metabolic pathways, mainly peptides(20 metabolites) and glycerophospholipid metabolism-related(14 metabolites). Fifty-nine metabolites were pinned down to be sex-related, among which cotinine was significant in all 7 provinces. Age-related metabolites were only found in Shaanxi and Hainan, with 22 metabolites were recognized.Conclusion:Serum metabolomics varies by geographic regions, sex, and age. When metabolomics is applied for diagnosis or biomarker screening in various studies, it shall take into consideration of setting tailored references.

Objective: To investigate the risk factors of central nervous system (CNS) complications in children undergoing extracorporeal membrane oxygenation (ECMO) support. Methods: The clinical data, ECMO parameters, laboratory examination and outcome (follow-up to 90 d after discharge) of 82 children treated with ECMO in the pediatric intensive care unit (PICU) of Shanghai Children's Hospital from December 2015 to December 2021 were analyzed retrospectively in this study. The patients were divided into CNS complication group and non-CNS complication group. The ECMO mode, ECMO catheterization mode, clinical and laboratory indicators pre-ECMO and 24 h after ECMO initiation, in-hospital mortality and 90-day mortality were compared with Chi-square test, t test and nonparametric rank sum test. Kaplan-Meier method was used to draw survival curve, and Log-rank test was used to compare the difference in survival rate. The receiver operating characteristic (ROC) curve was used to evaluate the power of variables to predict CNS complications. Results: A total of 82 children were treated with ECMO, including 49 males and 33 females, aged 34 (8, 80) months. There were 18 cases suffering CNS complications, including cerebral hemorrhage in 8 cases, epilepsy in 6 cases, simple cerebral infarction in 3 cases, and cerebral hemorrhage combined with cerebral infarction in 1 case. Veno-arterial ECMO accounted for a greater proportion in CNS complication group (17/18 vs. 67% (43/64), χ²=4.02, P=0.045). A higher percentage of children with CNS complications underwent surgical cannulation compared to those in non-CNS complication group (16/18 vs. 53% (34/64), χ²=7.55, P=0.006). The laboratory results indicated that lower pre-ECMO pH value (7.24 (7.15, 7.28) vs. 7.35 (7.26, 7.45), Z=-3.65, P<0.001) and platelet count 24 h after ECMO initiation (66 (27, 135) ×10⁹/L vs. 107 (61, 157) ×10⁹/L, Z=-2.04, P=0.041) were associated with CNS complications. In the CNS complication group, 7 children died during hospitalization and 7 died during 90-day after admission, and there was no significant difference compared with those in the non-CNS complication group (7/18 vs. 31% (20/64), 7/18 vs. 34% (22/64), both P>0.05). The ROC curve analysis indicated that the area under the ROC curve for pre-ECMO pH value was 0.738 (95%CI 0.598-0.877), and the optimal cut-off value was 7.325. Conclusions: CNS complications in children undergoing ECMO support are common. Pre-ECMO pH value <7.325 is a risk factor for CNS complications. Reducing the veno-arterial ECMO and surgical cannulation can help reduce the occurrence of CNS complications.
Central Nervous System ; Cerebral Hemorrhage ; Cerebral Infarction ; Child ; China/epidemiology* ; Extracorporeal Membrane Oxygenation/adverse effects* ; Female ; Humans ; Male ; Prognosis ; Retrospective Studies ; Risk Factors

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC

To evaluate the efficacy and safety of Chinese patent medicines in the treatment of insomnia by frequency network Meta-analysis. Randomized controlled trials of Chinese patent medicines for insomnia were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase and Cochrane Library databases from the time of database establishment to October 2020. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 11 kinds of Chinese patent medicines in 27 RCTs were included. According to Meta-analysis, in term of the effective rate, Tianmeng Liquid, Zaoren Anshen Capsules, Shumian Capsules, Shensong Yangxin Capsules, Shenqi Wuweizi Tablets, Shugan Jieyu Capsules, Anshen Bunao Liquid and Qiye Anshen Tablets combined with nonbenzodiazepine drugs(NBZDs) were superior to NBZDs alone. In term of the improvement of Pittsburg sleeping quality index(PSQI) score, Tianmeng Liquid, Shumian Capsules, Shensong Yangxin Capsules, Bailemian Capsules, Shenqi Wuweizi Tablets, Shugan Jieyu Capsules, Yangxue Qingnao Granules and Yindan Xinnaotong Capsules combined with NBZDs were superior to NBZDs alone. In terms of the safety, Shumian Capsules, Shensong Yangxin Capsules, Shenqi Wuweizi Tablets and Qiye Anshen Tablets combined with NBZDs were superior to NBZDs alone. In terms of the avoidance of dizziness and headache, Qiye Anshen Tablets combined with NBZDs were superior to NBZDs alone. The results of Network Meta-analysis indicated that in term of the effective rate, top three optimal medication regimens were NBZDs combined with Shugan Jieyu Capsules, combined with Zaoren Anshen Capsules and combined with Shensong Yangxin Capsules in the order from high to low. With the respect of improvement of PSQI score, top three optimal medication regimens were NBZDs combined with Yangxue Qingnao Granules, combined with Tianmeng Liquid and combined with Yindan Xinnaotong Capsules in the order from high to low. In terms of the safety, top three optimal medication regimens were NBZDs combined with Qiye Anshen Tablets, combined with Shensong Yangxin Capsules and combined with Shenqi Wuweizi Tablets in the order from high to low. In terms of the avoidance of dizziness and headache, top three optimal medication regimens were NBZDs combined with Qiye Anshen Tablets, combined with Zaoren Anshen Capsules and combined with Shumian Capsules in the order from high to low. In terms of the avoidance of fatigue, top three optimal medication regimens were NBZDs combined with Shensong Yangxin Capsules, combined with Shumian Capsules and combined with Qiye Anshen Tablets in the order from high to low. In conclusion, Chinese patent medicines combined with NBZDs can effectively alleviate the symptoms of insomnia with a high safety. However, the conclusion of this study needs to be verified by more high-quality studies because of the low methodological quality of the included studies.
China ; Drugs, Chinese Herbal ; Humans ; Medicine, East Asian Traditional ; Network Meta-Analysis ; Nonprescription Drugs ; Sleep Initiation and Maintenance Disorders/drug therapy*