Solanum nigrum L. berries extract ameliorated the alcoholic liver injury by regulating gut microbiota, lipid metabolism, inflammation, and oxidative stress.

Solanum nigrum L. (SN) berry is an edible berry containing abundant polyphenols and bioactive compounds, which possess antioxidant and antiinflammatory properties. However, the effects of SN on alcohol-induced biochemical changes in the enterohepatic axis remain unclear. In the current study, a chronic ethanol-fed mice ALD model was used to test the protective mechanisms of SN berries. Microbiota composition was determined via 16S rRNA sequencing, we found that SN berries extract (SNE) improved intestinal imbalance by reducing the Firmicutes to Bacteroides ratio, restoring the abundance of Akkermansia microbiota, and reducing the abundance of Allobaculum and Shigella. SNE restored the intestinal short-chain fatty acids content. In addition, liver transcriptome data analysis revealed that SNE primarily affected the genes involved in lipid metabolism and inflammatory responses. Furthermore, SNE ameliorated hepatic steatosis in alcohol-fed mice by activating AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), peroxisome proliferator-activated receptor α (PPAR-α). SNE reduced the expression of toll-like receptor 4 (TLR4), myeloid differentiation factor-88 (MyD88) nuclear factor kappa-B (NF-κB), which can indicate that SNE mainly adjusted LPS/TLR4/MyD88/NF-κB pathway to reduce liver inflammation. SNE enhanced hepatic antioxidant capacity by regulating NRF2-related protein expression. SNE alleviates alcoholic liver injury by regulating of gut microbiota, lipid metabolism, inflammation, and oxidative stress. This study may provide a reference for the development and utilization of SN resources.

New sagittal abdominal diameter and transverse abdominal diameter based equations to estimate visceral fat area in type 2 diabetes patients.

OBJECTIVE: Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) are considered gold standards for measuring visceral fat area (VFA). However, their relatively high prices and potential radiation exposure limit their widespread use in clinical practice and everyday life. Therefore, our study aims to develop a VFA estimated equation based on sagittal abdominal diameter (SAD) and transverse abdominal diameter (TAD) using anthropometric indexes. To the best of our knowledge, there have been limited studies investigating this aspect thus far. METHODS: This study was designed as a cross-sectional, retrospective cohort survey. A total of 288 patients (167 males and 121 females) aged 18-80 with type 2 diabetes (T2D) were consecutively collected from a multicenter hospital, and VFA was measured by CT. Subsequently, variables highly correlated with VFA were screened through general linear correlation analysis. A stepwise regression analysis was then conducted to develop a VFA estimated equation. Discrepancies between the estimated and actual VFA values were assessed using the Bland-Altman method to validate the accuracy of the equation. RESULTS: In the female T2D population, triglyceride (TG), SAD, TAD were found to be independently correlated with VFA; in the male T2D population, BMI, TG, SAD and TAD showed independent correlations with VFA. Among these variables, SAD exhibited the strongest correlation with VFA (r = 0.83 for females, r = 0.88 for males), followed by TAD (r = 0.69 for females, r = 0.79 for males). Based on these findings, a VFA estimated equation was developed for the T2D population: VFA (male) =-364.16 + 15.36*SAD + 0.77*TG + 9.41*TAD - 5.00*BMI (R2 = 0.75, adjusted R2 = 0.74); VFA(female)=-170.87 + 9.72*SAD-24.29*(TG^-1) + 3.93*TAD (R2 = 0.69, adjusted R2 = 0.68). Both models demonstrated a good fit. The Bland-Altman plot indicated a strong agreement between the actual VFA values and the estimated values, the mean differences were close to 0, and the majority of differences fell within the 95% confidence interval. CONCLUSIONS: In the T2D population, a VFA estimated equation is developed by incorporating SAD and TAD along with other measurement indices. This equation demonstrates a favorable estimated performance, suggesting to the development of novel and practical VFA estimation models in the future study.

Prediction of cyanidin 3-rutinoside content in Michelia crassipes based on near-infrared spectroscopic techniques.

Currently the determination of cyanidin 3-rutinoside content in plant petals usually requires chemical assays or high performance liquid chromatography (HPLC), which are time-consuming and laborious. In this study, we aimed to develop a low-cost, high-throughput method to predict cyanidin 3-rutinoside content, and developed a cyanidin 3-rutinoside prediction model using near-infrared (NIR) spectroscopy combined with partial least squares regression (PLSR). We collected spectral data from Michelia crassipes (Magnoliaceae) tepals and used five different preprocessing methods and four variable selection algorithms to calibrate the PLSR model to determine the best prediction model. The results showed that (1) the PLSR model built by combining the blockScale (BS) preprocessing method and the Significance multivariate correlation (sMC) algorithm performed the best; (2) The model has a reliable prediction ability, with a coefficient of determination (R2) of 0.72, a root mean square error (RMSE) of 1.04%, and a residual prediction deviation (RPD) of 2.06. The model can be effectively used to predict the cyanidin 3-rutinoside content of the perianth slices of M. crassipes, providing an efficient method for the rapid determination of cyanidin 3-rutinoside content.

Design of composite puncture blood collection system and research on puncture force.

Venous blood collection testing is one of the most commonly used medical diagnostic methods. Compared with conventional venous blood collection, robotic collection can reduce needle-stick injuries, medical staff workload, and infection risk; allow doctor-patient isolation; and improve collection reliability. Existing venous blood collection robots use rigid puncture needles, which can easily puncture the lower wall of blood vessels, causing vessel damage and collection failure. This paper proposes a bionic blood collection strategy based on a composite puncture needle that mimics the structure and function of mosquito mouthparts. A bionic composite puncture needle insertion system with puncture-force sensing was designed, and venipuncture forces were simulated and mathematically modelled. A prototype insertion system was built and used in an experiment, which demonstrated effective composite puncture blood collection and explored the factors influencing puncture force. Puncture force decreases with increased puncture speed and angle and with a decreased needle diameter. This provides a basis for optimising the parameters of blood collection robots.

An association between PM2.5 components and respiratory infectious diseases: A China's mainland-based study.

The particulate matter with diameter of less than 2.5 µm (PM2.5) is an important risk factor for respiratory infectious diseases, such as scarlet fever, tuberculosis, and similar diseases. However, it is not clear which component of PM2.5 is more important for respiratory infectious diseases. Based on data from 31 provinces in mainland China obtained between 2013 and 2019, this study investigated the effects of different PM2.5 components, i.e., sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and organic matter (OM), and black carbon (BC), on respiratory infectious diseases incidence [pulmonary tuberculosis (PTB), scarlet fever (SF), influenza, hand, foot, and mouth disease (HFMD), and mumps]. Geographical probes and the Bayesian kernel machine regression (BKMR) model were used to investigate correlations, single-component effects, joint effects, and interactions between components, and subgroup analysis was used to assess regional and temporal heterogeneity. The results of geographical probes showed that the chemical components of PM2.5 were associated with the incidence of respiratory infectious diseases. BKMR results showed that the five components of PM2.5 were the main factors affecting the incidence of respiratory infectious diseases (PIP>0.5). The joint effect of influenza and mumps by co-exposure to the components showed a significant positive correlation, and the exposure-response curve for a single component was approximately linear. And single-component modelling revealed that OM and BC may be the most important factors influencing the incidence of respiratory infections. Moreover, respiratory infectious diseases in southern and southwestern China may be less affected by the PM2.5 component. This study is the first to explore the relationship between different components of PM2.5 and the incidence of five common respiratory infectious diseases in 31 provinces of mainland China, which provides a certain theoretical basis for future research.

Real-world data of China: Analysis of HPV vaccine coverage and post-vaccination adverse reaction monitoring in Western Chinese provinces from 2018 to 2021.

To investigate the HPV vaccine coverage and post-vaccination adverse reactions in Gansu Province, Western China, from 2018 to 2021. Data on suspected adverse reactions to HPV vaccines were collected from the Chinese Vaccine Adverse Event Following Immunization (AEFI). Estimate the incidence rates of Common Adverse Reaction and Rare Adverse Reaction. HPV vaccine coverage among females in different age groups was calculated using data from the Gansu Provincial Immunization Information Platform. The first-dose HPV vaccine coverage rate among females aged 9 to 45 was 2.02%, with the lowest rate of less than 1% observed in females aged 9 to 14. From 2018 to 2021, the incidence rates of Common Adverse Reaction and Rare Adverse Reaction reported in females after HPV vaccination were 11.82 and 0.39 per 100,000 doses, respectively. Common Adverse Reaction included fever (5.52 per 100,000 doses), local redness and swelling (3.33 per 100,000 doses), fatigue (3.15 per 100,000 doses), headache (2.76 per 100,000 doses), as well as local induration and nausea/vomiting (1.97 per 100,000 doses). Adverse reactions mainly occurred within 1 day after vaccination, followed by 1 to 3 days after vaccination. The HPV vaccine coverage rate among females aged 9 to 14 in Gansu Province is remarkably low, and there is an urgent need to enhance vaccine coverage. From 2018 to 2021, the incidence of Adverse reaction Following Immunization HPV vaccination fell within the expected range, indicating the vaccine's safety profile.

Nuezhenoside G13 from Osmanthus fragrans fruit ameliorates Concanavalin A-induced autoimmune hepatitis by regulating the NF-κB/MAPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Osmanthus fragrans fruit (OFF) exhibits hepatoprotective function, and it is consumed as food and used in traditional medicine in China. Nuezhenoside G13 (G13) is present in the highest levels in OFF. Autoimmune hepatitis (AIH) is a manifestation of liver disease and seriously endangers health. However, it remains unclear whether G13 affects AIH. AIM OF THE STUDY: To clarify the effect of G13 on AIH and its exact underlying mechanism from a new perspective. MATERIALS AND METHODS: We used a Concanavalin A-induced AIH mouse model and lipopolysaccharide-treated Raw264.7 cells to quantify serum biochemical indicators and confirm whether G13 exhibited protective effects in the AIH mice. Furthermore, we evaluated the effect of G13 via hematoxylin and eosin and immunohistochemical staining. We used enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction to quantify the inflammatory factors. We confirmed that G13 inhibited apoptosis via terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Molecular docking, immunofluorescence, and western blotting experiments of G13 and key proteins of the NF-κB/MAPK pathway revealed that G13 alleviated inflammation. In addition, Cell Counting Kit-8, ELISA, NO detection, and western blotting assays were performed. Finally, we used an inhibitor of the p38 MAPK to verify that G13 reduced inflammation through the NF-κB/MAPK pathway in Raw264.7 cells. RESULTS: The in vivo experiments revealed that G13 improved oxidative stress and apoptosis. In addition, G13 decreased the expression levels of CD4+, CD8+, F4/80+, and Ly6G and the secretion of inflammatory factors. Interestingly, G13 reduced the phosphorylation levels of IκBα, NF-κB, JNK, ERK1/2, and p38. Additionally, the in vitro experiments revealed that G13 alleviated inflammation through the NF-κB/MAPK pathway in lipopolysaccharide-treated Raw264.7 cells. Furthermore, molecular docking demonstrated that the binding fraction of G13 with these proteins was high. CONCLUSION: G13 suppressed oxidative stress, apoptosis, and inflammation in a Concanavalin A-induced AIH mouse model. Furthermore, G13 exerted its effect through the NF-κB/MAPK pathway.

Immediate and long-term changes in infectious diseases in China at the "First-level-response", "Normalized-control" and "Dynamic-COVID-zero" stages from 2020 to 2022: a multistage interrupted-time-series-analysis.

BACKGROUND: From January 2020 to December 2022, China implemented "First-level-response", "Normalized-control" and "Dynamic-COVID-zero" to block the COVID-19 epidemic; however, the immediate and long-term impact of three strategies on other infectious diseases and the difference in their impact is currently unknown. We aim to provide a more comprehensive understanding of the impact of non-pharmacological interventions (NPIs) on infectious diseases in China. METHODS: We collected data on the monthly case count of infectious diseases in China from January 2015 to July 2022. After considering long-term trends using the Cox-Stuart test, we performed the two ratio Z tests to preliminary analyze the impact of three strategies on infectious diseases. Next, we used a multistage interrupted-time-series analysis fitted by the Poisson regression to evaluate and compare the immediate and long-term impact of three strategies on infectious diseases in China. RESULTS: Compared to before COVID-19, the incidence of almost all infectious diseases decreased immediately at stages 1, 2, and 3; meanwhile, the slope in the incidence of many infectious diseases also decreased at the three stages. However, the slope in the incidence of all sexually transmitted diseases increased at stage 1, the slope in the incidence of all gastrointestinal infectious diseases increased at stage 2, and the slope in the incidence of some diseases such as pertussis, influenza, and brucellosis increased at stage 3. The immediate and long-term limiting effects of "Normalized-control" on respiratory-transmitted diseases were weaker than "First-level-response" and the long-term limiting effects of "Dynamic-COVID-zero" on pertussis, influenza, and hydatid disease were weaker than "Normalized-control". CONCLUSIONS: Three COVID-19 control strategies in China have immediate and long-term limiting effects on many infectious diseases, but there are differences in their limiting effects. Evidence from this study shows that pertussis, influenza, brucellosis, and hydatid disease began to recover at stage 3, and relaxation of NPIs may lead to the resurgence of respiratory-transmitted diseases and vector-borne diseases.

Vaginal Delivery and Breastfeeding Benefit Infant Immune Response to Hepatitis B Vaccine: A Prospective Cohort Study.

Background and Aims: Natural vaginal delivery and breastfeeding favor the development of a strong immune system in infants, and the immune response of infants to vaccines is closely related to their immune system. This large prospective cohort study aimed to explore the effects of delivery and feeding mode on infant's immune response to hepatitis B vaccine (HepB). Methods: A total of 1,254 infants who completed the whole course of HepB immunization and whose parents were both HBsAg negative were enrolled from infants born in Jinchang City during 2018-2019 by cluster sampling method. Results: Twenty (1.59%) of the 1,254 infants were nonresponders to HepB. Among the other 1,234 infants, 10.05% (124/1,234), 81.69% (1,008/1,234) and 8.27% (102/1,234) of infants had low, medium, and high responses to HepB, respectively. Logistic regression analysis showed that cesarean section (OR: 8.58, 95% CI: 3.11-23.65, p<0.001) and birth weight <3.18 kg (OR: 5.58, 95% CI: 1.89-16.51, p=0.002) were independent risk factors for infant nonresponse to HepB, and cesarean section (OR: 7.63, 95% CI: 4.64-12.56, p<0.001), formula feeding (OR: 4.91, 95% CI: 1.47-16.45, p=0.001), maternal anti-HBs negativity (OR: 27.2, 95% CI: 10.67-69.35, p<0.001), paternal non-response history of HepB (OR: 7.86, 95% CI: 2.22-27.82, p=0.014) and birth weight <3.22 kg (OR: 4.00, 95% CI: 2.43-6.59, p<0.001) were independent risk factors for infant low response to HepB. In cases where birth weight and genetic factors are unmodifiable and maternal anti-HBs effects are controversial, it makes sense to enhance infant response by changing delivery and feeding patterns. Conclusions: Natural vaginal delivery and breastfeeding are beneficial to the infant's immune response to HepB.

Adults in Northwest China experienced the largest outbreak of Japanese encephalitis in history 10 years after the Japanese encephalitis vaccine was included in the national immunization program: A retrospective epidemiological study.

Mainland China included Japanese encephalitis (JE) vaccine in the national immunization program in 2008 to control the JE epidemic. However, Gansu province in Western China experienced the largest JE outbreak since 1958 in 2018. We conducted a retrospective epidemiological study to explore the causes of this outbreak. We found that adults aged ≥20 years (especially those in rural areas) were the main JE cases in Gansu Province, with a significant increase in the JE incidence in older adults aged ≥60 years in 2017 and 2018. In addition, JE outbreaks in Gansu Province were mainly located in the southeastern region, while the temperature and precipitation in Gansu Province were gradually increasing in recent years, which made the JE epidemic areas in Gansu Province gradually spread to the western of Gansu Province. We also found that adults aged ≥20 years in Gansu Province had lower JE antibody positivity than children and infants, and the antibody positivity rate decreased with age. In the summer of 2017 and 2018, the density of mosquitoes (mainly the Culex tritaeniorhynchus) in Gansu Province was significantly higher than in other years, and the genotype of JEV was mainly Genotype-G1. Therefore, in the future JE control in Gansu Province, we need to strengthen JE vaccination for adults. Moreover, strengthening mosquito surveillance can provide early warning of JE outbreaks and the spread of epidemic areas in Gansu Province. At the same time, strengthening JE antibody surveillance is also necessary for JE control.

Immediate and long-term changes in the epidemiology, infection spectrum, and clinical characteristics of viral and bacterial respiratory infections in Western China after the COVID-19 outbreak: a modeling study.

BACKGROUND: The impact of COVID-19 on the epidemiology, clinical characteristics, and infection spectrum of viral and bacterial respiratory infections in Western China is unknown. METHODS: We conducted an interrupted time series analysis based on surveillance of acute respiratory infections (ARI) in Western China to supplement the available data. RESULTS: The positive rates of influenza virus, Streptococcus pneumoniae, and viral and bacterial coinfections decreased, but parainfluenza virus, respiratory syncytial virus, human adenovirus, human rhinovirus, human bocavirus, non-typeable Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae infections increased after the onset of the COVID-19 epidemic. The positive rate for viral infection in outpatients and children aged <5 years increased, but the positive rates of bacterial infection and viral and bacterial coinfections decreased, and the proportion patients with clinical symptoms of ARI decreased after the onset of the COVID-19 epidemic. Non-pharmacological interventions reduced the positive rates of viral and bacterial infections in the short term but did not have a long-term limiting effect. Moreover, the proportion of ARI patients with severe clinical symptoms (dyspnea and pleural effusion) increased in the short term after COVID-19, but in the long-term, it decreased. CONCLUSIONS: The epidemiology, clinical characteristics, and infection spectrum of viral and bacterial infections in Western China have changed, and children will be a high-risk group for ARI after the COVID-19 epidemic. In addition, the reluctance of ARI patients with mild clinical symptoms to seek medical care after COVID-19 should be considered. In the post-COVID-19 era, we need to strengthen the surveillance of respiratory pathogens.

Safety of primary immunization using inactivated SARS-CoV-2 vaccine (CoronaVac®) among population aged 3 years and older in a large-scale use: A multi-center open-label study in China.

OBJECTIVE: To evaluate the safety of primary immunization using CoronaVac® among population aged 3 years and above in a large-scale use. METHOD: A multi-center open-label study was carried out in 11 provinces of China. Individuals aged 3 years and older who had no history of COVID-19 vaccination or had received only one dose of CoronaVac® were enrolled in this study. Adults and elderly with or without underlying medical conditions(UMCs) were also recruited. Eligible participants received one or two doses of CoronaVac® with an interval of 28 days. Demographic information, vaccination and the occurrence of adverse events were recorded by participants or guardians using data collection system designed for this study. All adverse events occurred within 6 months after the second dose of vaccination were collected. The incidence of adverse events that cannot be ruled out as being caused by the vaccine were calculated to assess the safety of CoronaVac®. This study is registered with ClinicalTrials. Gov (NCT04911790 and NCT04992208). RESULTS: A total of 162,691 participants have been included in this study and 89.50 % had finished primary immunization. Among adults and elderly, people with UMCs accounted for 25.85 %, with the top five disease being hypertension, diabetes, chronic gastritis, coronary heart disease(CHD) and kidney stone. The overall incidence of adverse reactions (ARs) within 6 months after the second vaccination was 2.70 %, with incidence for children and adolescents, adults, and elderly being 2.03 %, 3.46 %, and 1.90 %, respectively. Most ARs were mild (grade 1). Pain at the injection sites, fatigue, induration/swelling, and headache were the most common symptoms, occurring in 1.64 %, 0.46 %, 0.31 % and 0.24 %, respectively. No serious adverse events related to vaccines were reported. No adverse events of special interest (AESIs) were identified. For children and adolescents, children aged 3-5 years had the highest incidence of ARs of 3.29 %. The incidence of ARs among those aged 18 years and older with and without UMCs were 2.81 % and 2.99 %, respectively, with no statistical significance between two groups(P = 0.089). And people with coronary heart disease had higher AR incidence compared to those with other UMCs, but the most common symptoms was pain at the injection site. CONCLUSION: CoronaVac® is safe in a large-scale use and shows well-tolerance for children and adolescents and people with underlying medical conditions. Further studies need to be conducted to explore the relation of ARs incidence to age or different kinds of UMCs.

In Vivo Metabolites of Panaxadiol Inhibit HepG-2 Cell Proliferation by Inducing G1 Arrest and ROS-Mediated Apoptosis.

In this study, 10 metabolites were obtained by collecting and extracting fecal samples after oral administration of panaxadiol (PD). Of these 10 metabolites, M7 (3ß,21ß,22α-hydroxy-24-norolean-12-ene), M8 (21ß,22α-hydroxy-24-norolean-12-ene-3-one), M9 (3ß,30α-hydroxy-24-norolean-22,30-epoxy-12-ene), and M10 (3ß,21ß-hydroxy-24-norolean-12-ene) were new compounds. MTT screening of the isolated compounds revealed that the inhibitions of cancer cells by M2, M4, M7, M8, and M10 were significantly stronger than that by the mother drug M0, with the activity of M2 being the most significant. Further, we investigated the anticancer mechanism of M2. The results showed that M2 significantly increased the level of ROS in cells; regulated the expressions of Bax, Bcl-2, and Cyt-C through the mitochondrial pathway; triggered the caspase cascade; and induced apoptosis. M2 could also induce G1 phase arrest and significantly regulate cell cycle-related proteins. In conclusion, the experimental results provide data for further study on the metabolic mechanism of PD in vivo and the potential of developing new anti-cancer drugs.

Effect of different vaccine strategies for the control of Japanese encephalitis in mainland China from 1961 to 2020: A quantitative analysis.

BACKGROUND: We aimed to quantify the impact of each vaccine strategy (including the P3-inactivated vaccine strategy [1968-1987], the SA 14-14-2 live-attenuated vaccine strategy [1988-2007], and the Expanded Program on Immunization [EPI, 2008-2020]) on the incidence of Japanese encephalitis (JE) in regions with different economic development levels. METHODS: The JE incidence in mainland China from 1961 to 2020 was summarized by year, then modeled and analyzed using an interrupted time series analysis. RESULTS: After the P3-inactivated vaccine was used, the JE incidence in Eastern China, Central China, Western China and Northeast China in 1968 decreased by 39.80 % (IRR = 0.602, P < 0.001), 7.80 % (IRR = 0.922, P < 0.001), 10.80 % (IRR = 0.892, P < 0.001) and 31.90 % (IRR = 0.681, P < 0.001); the slope/trend of the JE incidence from 1968 to 1987 decreased by 30.80 % (IRR = 0.692, P < 0.001), 29.30 % (IRR = 0.707, P < 0.001), 33.00 % (IRR = 0.670, P < 0.001) and 41.20 % (IRR = 0.588, P < 0.001). After the SA 14-14-2 live-attenuated vaccine was used, the JE incidence in Eastern China and Northeast China in 1988 decreased by 2.60 % (IRR = 0.974, P = 0.009) and 14.70 % (IRR = 0.853, P < 0.001); the slope/trend of the JE incidence in Eastern China and Central China from 1988 to 2007 decreased by 4.60 % (IRR = 0.954, P < 0.001) and 4.70 % (IRR = 0.953, P < 0.001). After the EPI was implemented, the JE incidence in Eastern China, Central China and Western China in 2008 decreased by 10.50 % (IRR = 0.895, P = 0.013), 18.00 % (IRR = 0.820, P < 0.001) and 24.20 % (IRR = 0.758, P < 0.001), the slope/trend of the JE incidence in Eastern China from 2008 to 2020 decreased by 17.80 % (IRR = 0.822, P < 0.001). CONCLUSIONS: Each vaccine strategy has different effects on the JE incidence in regions with different economic development. Additionally, some economically underdeveloped regions have gradually become the main areas of the JE outbreak. Therefore, mainland China should provide economic assistance to areas with low economic development and improve JE vaccination plans in the future to control the epidemic of JE.

Accuracy of hepatitis B disease surveillance, Gannan prefecture, Gansu province, China; 2017.

Hepatitis B is a major global public health threat. According to China's National Notifiable Disease Reporting System (NNDRS), Gannan Tibetan Autonomous Prefecture (Gannan) had the highest incidence of hepatitis B in Gansu Province during 2004 to 2016. We evaluated NNDRS hepatitis B case reports from Gannan to determine accuracy of diagnosis and to understand factors associated with inaccuracy. We reviewed medical records with hepatitis B diagnosis hospitalized in seven county hospitals in Gannan between January 1, 2016 and July 31, 2017. Using national "Classification and Diagnostic Procedures for Hepatitis B," we independently reclassified the diagnoses. We determined the positive predictive value (PPV) of reported hepatitis B cases. We investigate clinicians' understanding of the diagnostic and reporting criteria for hepatitis B by questionnaire. We reviewed and re-categorized 400 inpatients reported. Sixteen cases had been reported as acute hepatitis B, but on re-categorization, none were acute hepatitis B cases. PPVs for chronic hepatitis B and unclassified hepatitis B cases were 66% and 15% respectively; 327 (82%) of the reported hepatitis B cases were inaccurately classified; 261 were carriers, 59 were reported previously, and 7 did not have hepatitis B. The actual incidence of hepatitis B in Gannan in 2016 was estimated to be 19/100,000, significantly below the reported incidence of 106/100,000. Among reported cases, 81% had been tested for Alanine aminotransferase, 52% for hepatitis C antibody, 80% with liver ultrasound, 32% for hepatitis A antibody, and 7% for hepatitis B virus (HBV) DNA. Not all cases were tested for anti-HBc IgM or hepatitis E antibody or had a liver biopsy. In the knowledge test, 56% of clinicians accurately diagnosed three simulated cases of acute hepatitis B, and 17% correctly diagnosed two simulated cases chronic hepatitis B; 22% knew that "a client with only HBsAg positivity need not be reported." The falsely high incidence in Gannan was due to diagnostic and reporting inaccuracies. We recommend that clinicians and laboratorians receive additional training in hepatitis B diagnostic criteria and reporting standards, including appropriate use of IgM anti-HBc tests. Hepatitis B surveillance data should be periodically reviewed and evaluated for accuracy.

Gypensapogenin I Ameliorates Isoproterenol (ISO)-Induced Myocardial Damage through Regulating the TLR4/NF-κB/NLRP3 Pathway.

Myocardial fibrosis (MF) is a common pathological feature of many heart diseases and seriously threatens the normal activity of the heart. Jiaogulan (Gynostemma pentaphyllum) tea is a functional food that is commercially available worldwide. Gypensapogenin I (Gyp I), which is a novel dammarane-type saponin, was obtained from the hydrolysates of total gypenosides. It has been reported to exert a beneficial anti-inflammatory effect. In our study, we attempted to investigate the efficiency and possible molecular mechanism of Gyp I in cardiac injury treatment induced by ISO. In vitro, Gyp I was found to increase the survival rate of H9c2 cells and inhibit apoptosis. Combined with molecular docking and Western blot analysis, Gyp I was confirmed to regulate the TLR4/NF-κB/NLRP3 signaling pathway. In vivo, C57BL6 mice were subcutaneously injected with 10 mg/kg ISO to induce heart failure. Mice were given a gavage of Gyp I (10, 20, or 40 mg/kg/d for three weeks). Pathological alterations, fibrosis-, inflammation-, and apoptosis-related molecules were examined. By means of cardiac function detection, biochemical index analysis, QRT-PCR monitoring, histopathological staining, immunohistochemistry, and Western blot analysis, it was elucidated that Gyp I could improve cardiac dysfunction, alleviate collagen deposition, and reduce myocardial fibrosis (MF). In summary, we reported for the first time that Gyp I showed good myocardial protective activity in vitro and in vivo, and its mechanism was related to the TLR4/NF-κB/NLRP3 signaling pathway.

Gypensapogenin H suppresses tumor growth and cell migration in triple-negative breast cancer by regulating PI3K/AKT/NF-κB/MMP-9 signaling pathway.

Due to its aggressiveness and high metastasis rates, triple-negative breast cancer (TNBC) is a ubiquitous and deadly disease for the majority of women globally. Gypensapogenin H (GH) is a novel dammarane-type triterpene isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. Our previous work demonstrated that GH promoted apoptosis in TNBC. In the present study, xenograft TNBC models (xenotransplantation of MDA-MB-231 cells in nude mice) were used to evaluate the efficacy of GH in vivo. We preliminarily predicted the mechanism of GH inhibiting breast cancer tumors at the gene level through transcriptome screening. Through western blot analysis of tumor tissue, we found that GH could inhibit tumor proliferation and migration by regulating the PI3K/AKT/NF-κB/MMP-9 signaling pathway in vivo. We also analyzedthe results at the cell level in vitro, which were consistent with those in vivo. In summary, GH inhibited TNBC growth in vivo and suppressed TNBC cell migration in vitro. Our findings could help understand the mechanism of action of GH and suggest that GH would be a promising agent for TNBC therapy.

Impact of the expanded program on immunization on the incidence of Japanese encephalitis in different regions of Mainland China: An interrupt time series analysis.

In 2008, Mainland China included the Japanese encephalitis (JE) vaccine in the Expanded Program on Immunization (EPI) to control the JE epidemic. However, Northwest China experienced the largest JE outbreak since 1994 in 2018, and the effects of the EPI in different regions are unclear. Therefore, we used an interrupted time series design to evaluate the effects of the EPI in different regions. In this study, ß1 and ß1+ß3 represented the slope or trend of the JE incidence before and after the EPI, respectively; ß2 was the level change of the JE incidence immediately after the EPI; ß3 represented the slope change of the JE incidence before and after the EPI. We found that the JE incidence in all regions showed a decreasing trend before the EPI (ß1<0.000, P<0.05). The JE incidence in Mainland China (ß2=-7.669, P<0.05), East China (ß2=-9.791, P<0.05), Central China (ß2=-10.695, P<0.05), South China (ß2=-6.551, P<0.05) and Southwest China (ß2=-2.216, P<0.05) decreased by 7.669/100,000, 9.791/100,000, 10.695/100,000, 6.551/100,000 and 2.216/100,000 immediately after the EPI, and the EPI had short-term effects on the JE incidence in these regions. The slope of the JE incidence in Mainland China (ß3=0.272, P<0.05), East China (ß3=0.337, P<0.05), Central China (ß3=0.381, P<0.05), South China (ß3=0.254, P<0.05) and Southwest China (ß3=0.081, P<0.05) increased by 0.272, 0.337, 0.381, 0.254 and 0.081 after the EPI, and the EPI had long-term effects on the JE incidence in these regions. The JE incidence in many regions (excluding North China) showed a decreasing trend after the EPI (ß1+ß3 <0.000). Northwest China (GDP from 2008 to 2020 ranked last in Mainland China) and Southwest China (GDP from 2008 to 2020 ranked fifth in Mainland China), with underdeveloped economy, used to be low-epidemic regions of JE, but they have become high-epidemic regions in recent years. Economic development may contribute to the geographic variations in the effects of the EPI. Therefore, it is significant for JE control in Mainland China to increase support for underdeveloped regions and adjust the vaccine strategy according to the new epidemic situation of JE.

Gypensapogenin I Suppresses Cell Proliferation in Triple-Negative Breast Cancer Via Triggering the Closure of AKT/GSK3ß/ß-Catenin and Notch-1 Signaling Pathways.

Jiaogulan (Gynostemma pentaphyllum) tea is a functional food that is commercially available worldwide. Gypensapogenin I (Gyp I), which is a natural damarane-type saponin, was obtained from the hydrolysates of total gypenosides. The present research was performed to investigate the potential antiproliferation effect of Gyp I in MDA-MB-231 cells and the underlying mechanisms. Here, we found that Gyp I attenuated survival, inhibited proliferation, and induced apoptosis in MDA-MB-231 cells. Target prediction by binding molecule docking and western blot assays confirmed the mechanism by which Gyp I inhibited the proliferation of breast cancer cells via the AKT/GSK3ß/ß-catenin signaling pathway. We also showed that Gyp I exhibited superior in vivo efficacy that was dose dependent. Tumor tissue transcriptome analysis indicated that Gyp I could decrease the expression levels of NOTCH1 and HES1, which was in contrast to the effect on MAML and NUMBL, indicating that our compound hindered the activation of the Notch-1 signaling pathway. In summary, we report for the first time that Gyp I shows excellent anti-breast cancer activity in vivo and in vitro and that its pathway of action is related to the AKT/GSK3ß/ß-catenin and Notch-1 signaling pathways. Therefore, Jiaogulan tea can not only be used as a health food but also possesses the possibility to treat triple-negative breast cancer (TNBC).