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Background: Type 2 diabetes mellitus (T2DM) is a serious metabolic syndrome with high mortality and disability rates globally, which usually caused by unhealthy dietary patterns. Cinnamomum camphora leaf is a traditional Chinese medicinal herb used for attenuating hyperglycemia and digestive disorder, and high level of lignans has been found in C. camphora leaf., Purpose: This study aimed to examine the chemical composition of lignans extracted from C. camphora leaf (LCCL), and illustrate its therapeutic effect and mechanism on T2DM and its concomitant glycolipid metabolic disorder., Methods: The components of LCCL were separated and purified by silica gel and macroporous adsorption resin, and were distinguished through LC/MS and NMR. The antioxidant activity of LCCL was determined by free radical scavenging assay in vitro; the hypoglycemic and hypolipidemic abilities were evaluated by α-glucosidase, α-amylase and pancreatic lipase inhibition trials, respectively. T2DM model mice were established by high-sugar and high-fat (HSHF) feed together with streptozotocin (STZ) infection, and then grouped to assess the effect of LCCL treatment. Hematoxylin-eosin (H&E), Periodic Acid-Schiff (PAS) and oil red O staining were employed to analyze the histopathology. qRT-PCR assay, 16S rRNA analysis, and western blot were conducted to illuminate the anti-diabetic mechanism of LCCL., Results: 6 sesamin lignans were identifed from LCCL. The in vitro assays showed strong inhibitive abilities of LCCL with low IC50 on DPPH (33.68 ± 0.54 μg/ml),O 2 - (39.25 ± 0.61 μg/ml), OH• (45.72 ± 0.72 μg/ml), α-glucosidase (0.82 ± 0.14 mg/ml), α-amylase (0.86 ± 0.11 mg/ml) and pancreatic lipase (0.91 ± 0.12 mg/ml). LCCL treatment (100, 200 and 400 g kg -1mg kg -1 ) gradually decreased the fasting blood glucose (FBG) and fasting insulin (FINS), improved the glucose and insulin tolerance, down-regulated the homeostasis model assessment insulin resistance (HOMA-IR) indexes, alleviated the hepatic inflammatory response and oxidative stress, promoted the glycogen storage and depleted the fat accumulation in the liver. Besides, LCCL administration alleviated the glycolipid metabolism disorder in T2DM mice with a gut microbiota dependent manner, that significantly increased biodiversity, altered the composition of gut microbiota and increased the proportion of Lactobacillus., Conclusion: The lignan-rich extract of C. camphor leaf (LCCL), containing at least 6 lignans compounds, displayed promising antioxidant, hypoglycemic and hypolipidemic activities. The treatment of LCCL alleviated the glycolipid metabolism disorder in T2DM mice with a gut microbiota dependent manner. These finding suggested that LCCL should be further investigated to develop its complementary therapeutic effect on T2DM., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Aortic aneurysm and dissection (AAD) are severe vascular diseases with high mortality rates. However, the causal relationship between serum uric acid levels and the occurrence of AAD remains a subject of controversy. To address this issue, we conducted a two-sample Mendelian randomization (MR) analysis to investigate whether there is a causal association between these factors. We obtained single-nucleotide polymorphisms (SNPs) data related to serum uric acid levels from the FinnGen study and data on AAD from the UK Biobank. Various two-sample MR methods, including inverse variance weighted (IVW) analysis, MR-Egger regression analysis, weighted median analysis, and contamination mixture method, were employed to assess the causal relationship between serum uric acid and the risk of AAD. Sensitivity analysis was conducted to evaluate the stability and reliability of the results. The findings revealed a positive association between serum uric acid levels and the risk of aortic aneurysm (AA) (odds ratio [OR] = 1.200, 95 % confidence interval [CI]: 1.020-1.400, P = 0.0239). However, no significant correlation was observed between serum uric acid levels and the occurrence of aortic dissection (AD) (OR = 0.893, 95 % CI = 0.602-1.326, P = 0.576). Our study, which employed MR analysis, identified a positive association between serum uric acid levels and the risk of AA. However, we did not observe a significant correlation with AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 The Authors. Published by Elsevier B.V.)

Background/aims: Functional dyspepsia (FD) overlapping with other gastrointestinal disorders are quite common. The characteristics of FD overlap in Chinese population with latest Rome IV criteria were unclear. This large-scale outpatient-based study assessed the characteristics of FD overlap in South China., Methods: Consecutive FD patients visited the Gastroenterology Clinic at 2 tertiary medical centers in Hangzhou, China who fulfilled the Rome IV criteria were enrolled. Complete questionnaires related to the gastrointestinal symptoms (Rome IV criteria), Reflux Disease Questionnaire, anxiety and depression, quality of sleep and life, and demographic information were collected., Results: Among the total of 3281 FD patients, 50.69% overlapped with gastroesophageal reflux disease, 21.46% overlapped with irritable bowel syndrome, 6.03% overlapped with functional constipation. FD overlap had higher proportion of single/divorced/widowed rate, high education level, being employed, drinking, night shift, unhealthy dietary habit than FD only ( P < 0.05). They had higher frequency of consultation and economic burden, as well as lower scores in quality of life ( P < 0.001). Multivariate logistic regression showed that increasing age, female, low body mass index, history of gastroenteritis, anxiety, depression, and poor sleep quality were independent risk factors for FD overlap., Conclusions: FD overlap was quite common in China with high economic burden and poor quality of life, FD patients with history of gastroenteritis, anxiety, depression, and poor sleep quality were more likely to have overlap disorders. Awareness of the physical and psychosocial stressors in overlapping condition would help optimize the management of FD overlap in clinical practice.

The data of 115 patients with nasopharyngeal masses (78 males and 37 females) aged between 12 and 78 years at the Sun Yat-sen University Cancer Center from May 2022 to July 2023 were retrospectively reviewed, including 70 cases of nasopharyngeal carcinoma and 45 cases of benign hyperplasia. The mean, median, and percentiles (10 th , 25 th , 75 th , and 90 th ) of the apparent diffusion coefficient (ADC) histogram derived from multiplexed sensitivity encoding diffusion-weighted imaging (MUSE-DWI) of the benign hyperplasia group were significantly higher than those of the nasopharyngeal carcinoma group (all P <0.05). Conversely, the kurtosis and skewness of benign hyperplasia group were significantly lower than those of the nasopharyngeal carcinoma group (both P <0.05). The area under receiver operating characteristic (ROC) curve of the combined ADC histogram parameters was 0.812 (95% CI : 0.732-0.892), and the sensitivity, specificity and accuracy were 92.86%, 57.78% and 79.13%, respectively. The current study indicates ADC histogram parameters derived MUSE-DWI exhibit significant discriminatory value between nasopharyngeal carcinoma and benign hyperplasia.

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1 -/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Objective: To systematically collect and evaluate the health economics research of Human papilloma virus(HPV) vaccination population expansion to men, and to provide evidence for optimizing HPV vaccine immunization strategies. Methods: Health economics research studies on male HPV vaccination published in databases including PubMed, Web of Science, CNKI, and Wanfang Database from January 2010 to September 2022 were collected according to the systematic evaluation research design. The quality of the studies was assessed using the health economics evaluation reporting standards (2022 edition) (CHEERS 2022), with full score of 28. The results of the studies were reviewed and analyzed systematically. Results: A total of 21 studies complies with the criteria were included, all of which was foreign research. The average CHEERS score of the literatures was 25.71 points, range from 23 to 28 points. 85.71% (12/14) studies of the gender-neutral population showed that including male in HPV vaccination were more consistent with the cost effectiveness than female vaccination alone under certain conditions (target at adolescents of 10 to 15 years old or adults under 26 years old). 80.00% (4/5) of the studies target at ordinary men only were proved that male vaccination with HPV vaccine was in line with the cost-effectiveness. 2 studies targeting men who have sex with men (MSM) were both concluded that it met the cost-effectiveness. In addition, the results of 2 gender-neutral population studies and 1 study on men alone showed that extending HPV vaccination to men did not conform to cost effectiveness. The main reasons for the non-cost-effectiveness included the high price of vaccines and the age of vaccination. Conclusion: The quality of the health economics evaluation studies on expanding HPV vaccination to the male population is high. Vaccination targeting adolescents and young men as well as special groups (such as MSM) are likely to be cost-effective, and vaccinations for other groups are still need further evaluated. It is recommended that relevant research should be conducted to provide evidence for expanding the scope of HPV vaccination to men in China.

Objective: To analyze the willingness of receiving influenza vaccine and its influencing factors among health care workers (HCWs) in Yangtze River Delta region from 2020 to 2021. Methods: Convenient sampling method was adopted. From July 2020 to March 2021, 76 hospitals in Jiangsu, Zhejiang, Anhui and Shanghai provinces were selected according to the hospital level and job position, and a questionnaire survey was conducted on the willingness of receiving influenza vaccination. Logistic regression model was used to analyze the influencing factors of vaccination intention. Results: A total of 1 332 HCWs were investigated, with a ratio of male to female about 1∶3.2, and the length of working years was (15.07±9.75) years. A total of 614 HCWs had received influenza vaccine in 2019, with a vaccination rate of 46.09%. About 63.21% (842/1 332) of HCWs were willing to be vaccinated with influenza vaccine. The results of binary logistic regression analysis showed that the willingness of receiving influenza vaccine among HCWs in primary hospitals was higher than that in secondary hospitals ( OR =0.573) and tertiary hospitals ( OR =0.357). The willingness of HCWs who had received influenza vaccine in 2019 was higher than that of HCWs who had not received influenza vaccine ( OR =0.226) and had unknown history of influenza vaccination ( OR =0.228). The willingness of HCWs in departments of prevention, health care and infection was higher than that in departments of pre-examination, outpatient, emergency, pediatrics and respiratory ( OR =1.670). Conclusion: The willingness of receiving influenza vaccination among HCWs in Yangtze River Delta region is high, but it is still lower than that in developed countries. It is necessary to strengthen publicity and education to improve the influenza immunization level of HCWs.

Background: Tumor necrosis factor alpha-induced protein 2 (TNFAIP2), a TNFα-inducible gene, appears to participate in inflammation, immune response, hematopoiesis, and carcinogenesis. However, the potential role of TNFAIP2 in the development of acute myeloid leukemia (AML) remains unknow yet. Therefore, we aimed to study the biological role of TNFAIP2 in leukemogenesis., Methods: TNFAIP2 mRNA level, prognostic value, co-expressed genes, differentially expressed genes, DNA methylation, and functional enrichment analysis in AML patients were explored via multiple public databases, including UALCAN, GTEx portal, Timer 2.0, LinkedOmics, SMART, MethSurv, Metascape, GSEA and String databases. Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Beat AML database were used to determine the associations between TNFAIP2 expression and various clinical or genetic parameters of AML patients. Moreover, the biological functions of TNFAIP2 in AML were investigated through in vitro experiments., Results: By large-scale data mining, our study indicated that TNFAIP2 was differentially expressed across different normal and tumor tissues. TNFAIP2 expression was significantly increased in AML, particularly in French-American-British (FAB) classification M4/M5 patients, compared with corresponding control tissues. Overexpression of TNFAIP2 was an independent poor prognostic factor of overall survival (OS) and was associated with unfavorable cytogenetic risk and gene mutations in AML patients. DNA hypermethylation of TNFAIP2 at gene body linked to upregulation of TNFAIP2 and inferior OS in AML. Functional enrichment analysis indicated immunomodulation function and inflammation response of TNFAIP2 in leukemogenesis. Finally, the suppression of TNFAIP resulted in inhibition of proliferation by altering cell-cycle progression and increase of cell death by promoting early and late apoptosis in THP-1 and U937AML cells., Conclusion: Collectively, the oncogenic TNFAIP2 can function as a novel biomarker and prognostic factor in AML patients. The immunoregulation function of TNFAIP2 warrants further validation in AML., (© 2022. The Author(s).)

Background: Localized senile pruritus is a continued health problem for the elderly. This study aimed to evaluate the efficacy and safety of artemether emulsion on localized senile pruritus., Methods: Sixty patients diagnosed with senile pruritus were randomized into the artemether emulsion (1%) group or emulsion base group in a 1:1 ratio (the artemether group vs the control group). The patients used artemether emulsion or emulsion base for pruritus twice daily for 2 weeks. The pruritus visual analog scale (VAS) and the rate of adverse events were evaluated in week 0 and week 2., Results: The VAS scores in week 2 after treatment decreased significantly compared with those before treatment in both groups (P < .05). After treatment, patients receiving the artemether emulsion had significantly lower mean VAS scores compared to those who received the emulsion base (1.21 ± 1.64 vs 3.67 ± 2.97, P < .05). When the VAS scores were compared between the 2 groups before treatment, the effective rate of the artemether group was significantly higher than that of the control group (χ2 = 55, P < .05) in week 2 after treatment. Besides, no adverse events occurred in both groups., Conclusions: Both artemether emulsion and emulsion base were effective in treating localized senile pruritus, and artemether emulsion was superior to emulsion base., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis in Asia and the Western Pacific, which mainly invades central nervous system. Vaccination is the most important strategy to prevent JE. Currently, both live attenuated Japanese encephalitis vaccines (JE-L) and inactivated vaccines (JE-I) are in use. Due to the supply of vaccines and the personal choice of recipients, there will be a demand for interchangeable immunization of these two vaccines. However, relevant research is limited. By reviewing domestic and foreign research evidence, this article summarizes the current situation of the interchangeable use of JE-L and JE-I, and makes recommendations when the interchangeable immunization is in urgent need, so as to provide reference for practical vaccination and policymaking in China.

Objective: To analyze the epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019. Methods: The data of hepatitis A incidence in Zhejiang Province from 2010 to 2019 were collected from the infectious disease surveillance system of China Information System for Disease Control and Prevention. ArcGIS 10.7 software was used for spatial autocorrelation analysis. SaTScan 9.6 software was used for spatiotemporal scanning analysis. SPSS 25.0 software was used for additional analysis. Results: Zhejiang Province has reported 5 465 cases of hepatitis A in 2010-2019 years, with an average annual incidence rate of 1.00/100 000, and periodicity and seasonality are not obvious. The incidence of male was higher than that of female ( P =0.023), and the highest incidence rate was 50-59 years old. Spatial autocorrelation analysis showed that there was a positive spatial correlation between the incidence of hepatitis A in Zhejiang Province from 2010 to 2017, with the weakest correlation in 2010 (Moran's I =0.103, Z =1.769, P =0.049), and the strongest correlation in 2016 (Moran's I =0.328, Z =4.979, P =0.001). Spatiotemporal scanning analysis showed that there was spatial aggregation of hepatitis A in Zhejiang Province from 2010 to 2019, with a total of three aggregation areas identified. Among them, the mostly aggregation area was concentrated in Xiangshan county of Ningbo city, which covered 10 counties (cities and districts), including Ninghai county and Yinzhou district, and appeared from January 1 to June 30, 2012. Conclusion: The incidence level of hepatitis A in Zhejiang Province shows a stable fluctuation trend from 2010 to 2019, and the seasonal regularity is not obvious. The population group aged 50-59 years old is the key population. There is spatial aggregation in the epidemic situation of hepatitis A. Targeted prevention and control measures of hepatitis A should be done based on the law of spatiotemporal aggregation and local incidence.

Estimating the actual real-world effectiveness of the vaccine is an essential part of the post-marketing evaluation. This regression discontinuity design (RDD) using observational data is designed to quantify the effect of an intervention when eligibility for the intervention is based on a defined cutoff as age, making it suited to estimate vaccine effects. This approach can avoid the high cost and ethical issues; overcome difficulties in the organization and practice process in randomized controlled trials, which leads to a higher level of causal inference evidence and more realistic results. Here, we describe key features of RDD in general, and then specific scenarios, with examples, to illustrate that RDD are an essential tool for advancing our understanding of vaccine effects.

Influenza is an infectious respiratory disease caused by the influenza viruses. Older people, infants and people with underlying medical conditions could have a higher risk of severe influenza symptoms and complications. The co-infection of Coronavirus Diseases 2019 (COVID-19) with influenza viruses could lead to the complication of prevention, diagnosis, control, treatment, and recovery of COVID-19. Influenza vaccine and COVID-19 vaccine overlapped in target populations, vaccination time, and inoculation units. Although there was insufficient evidence on the immunogenicity and safety of co-administration of influenza vaccine and COVID-19 vaccine, World Health Organization and some countries recommended co-administration of inactivated influenza vaccine and COVID-19 vaccine. This review summarized domestic and international vaccination policies and research progress, and put forward corresponding suggestions in order to provide scientific support for the formulation of vaccination strategy on seasonal influenza vaccine and COVID-19 vaccine.

Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. Lactobacillus johnsonii ( L. johnsonii ), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage L. johnsonii could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in Il10 -/- mice. We identified this subset of immune cells activated by L. johnsonii as CD206 + macrophages IL-10 . Mechanistically, L. johnsonii supplementation enhanced the mobilization of CD206 + macrophages IL-10 through the activation of STAT3 in vivo and in vitro . In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of L. johnsonii by macrophages. Clinically, there was positive correlation between the abundance of L. johnsonii and the expression level of MRC1, IL10 and TLR1/2 in UC tissues. L. johnsonii could activate native macrophages into CD206 + macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. L. johnsonii may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.

Inborn errors of metabolism, also known as inherited metabolic diseases (IMDs), are related to genetic mutations and cause corresponding biochemical metabolic disorder of newborns and even sudden infant death. Timely detection and diagnosis of IMDs are of great significance for improving survival of newborns. Here we propose a strategy for simultaneously detecting six types of IMDs via combining GC-MS technique with the random forest algorithm (RF). Clinical urine samples from IMD and healthy patients are analyzed using GC-MS for acquiring metabolomics data. Then, the RF model is established as a multi-classification tool for the GC-MS data. Compared with the models built by artificial neural network and support vector machine, the results demonstrated the RF model has superior performance of high specificity, sensitivity, precision, accuracy, and matthews correlation coefficients on identifying all six types of IMDs and normal samples. The proposed strategy can afford a useful method for reliable and effective identification of multiple IMDs in clinical diagnosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy and safety of artemether emulsion treating patients with mild-to-moderate acne vulgaris., Methods: A total of 73 (randomized 1:1) patients were externally administered either artemether emulsion (1%) or fusidic acid emulsion (5g: 0.1g) twice daily for 12 weeks. Efficacy and safety evaluations were performed at weeks 0 and 12 by Global acne Grading System (GAGS), the number of acne and papule, as well as the rate of clinical respond., Results: After 12 weeks, patients randomized to the artemether emulsion group received artemether emulsion had significantly lower GAGS scores (5.08 ± 1.99 versus 13.75 ± 4.87, p  < .001) compared to patients who received fusidic acid emulsion. Patients in the artemether emulsion group had comparable baseline acne scores (11.11 ± 3.73 versus 10.75 ± 4.66, p  = .626) and papule score (16.11 ± 5.58 versus 17.03 ± 6.34, p  = .356), but significantly lower acne score (3.00 ± 1.55 versus 9.08 ± 4.90, p  < .001) and comparable papule score (2.81 ± 1.61 versus 12.69 ± 5.45, p  < .001) compared to the fusidic acid emulsion group at 12 weeks. No major adverse events were noted in either treatment group through 12 weeks., Conclusions: Artemether emulsion had better effect in improving mild-to-moderate AV compared to fusidic acid emulsion with barely AEs.

Vascular calcification (VC) in macrovascular and peripheral blood vessels is one of the main factors leading to diabetes mellitus (DM) and death. Apart from the induction of vascular calcification, advanced glycation end products (AGEs) have also been reported to modulate autophagy and apoptosis in DM. Autophagy plays a role in maintaining the stabilization of the external and internal microenvironment. This process is vital for regulating arteriosclerosis. However, the internal mechanisms of this pathogenic process are still unclear. Besides, the relationship among autophagy, apoptosis, and calcification in HASMCs upon AGEs exposure has not been reported in detail. In this study, we established a calcification model of SMC through the intervention of AGEs. It was found that the calcification was upregulated in AGEs treated HASMCs when autophagy and apoptosis were activated. In the country, AGEs-activated calcification and apoptosis were suppressed in Atg7 knockout cells or pretreated with wortmannin (WM), an autophagy inhibitor. These results provide new insights to conduct further investigations on the potential clinical applications for autophagy inhibitors in the treatment of diabetes-related vascular calcification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 He, Qu, Kwan Law, Qiu, Han, Ricardo de Seabra Rodrigues Dias, Liu, Zhang, Wu, Wu, Fai Mok, Cheng, He and Wai Wong.)

Since the founding of the People's Republic of China in 1949, China's vaccination work has been making remarkable achievements. However, under the state of emergency, such as major infectious disease outbreaks, major natural disasters, vaccine-related events, large-scale population entry at the border, vaccination services confront many challenges, and the emergency plan for vaccination services in most areas is still in the exploratory stage. Based on the experience at home and abroad, combined with China's relevant policies, technical guidelines and evidence, this study provides suggestions for vaccination services in aforementioned emergency events, in order to standardize the development and implementation of vaccination services under the state of emergency in China.

Objectives: To investigate the prevalence of cough and its influencing factors in community children under 5 years old. Methods: From October to December 2019, we selected 3 102 community children under the age of 5 from 50 natural villages/residential communities in 14 towns/streets of Yiwu, Zhejiang Province, using multi-stage random sampling method. A face-to-face and on-site questionnaire survey was conducted among child caregivers to collect demographic data and information about children's cough in the last 1 month. Multiple logistic regression model was used to analyze children's cough and the influencing factors of different cough states. Results: Multivariate logistic regression model analysis results showed that compared with 0-1 year old, dispersed, caregivers with education level below high school, families with 1 child under 5 years old, Cough risk was higher in 1-2, 2-3, 3-4 years old, nurseries, caregivers with education level of high school or above, and families with more than 2 children under 5 years old. OR ( 95% CI) values were 1.52(1.19-1.92), 1.65(1.29-2.10), 1.86(1.36-2.54), 2.59(1.99-3.38), 1.48(1.26-1.74) and 1.35(1.13-1.62), respectively. Further analysis of the influencing factors of different states of cough, multivariate logistic regression model analysis results showed that preschool status, the number of children under 5 years old in the family and the education level of caregivers were the influencing factors of acute, prolonged and chronic cough. Age was only an influencing factor of acute and persistent cough. Conclusions: The disease burden of cough in children under 5 years old community was heavy, and the cough was related to children's age, education level of caregivers, number of children under 5 years old in the family and childcare status.

Objective: To evaluate the immunogenicity and safety of concomitant inoculation of Measles and Rubella Combined Live-attenuated Japanese encephalitis vaccine. Methods: Healthy children aged 8 months in selected cities in Zhejiang Province were randomly assigned to the MR and JVE-L combined vaccination group (the experimental group), and the MR single vaccination group (the control group) was taken before the exemption and 6 weeks after the exemption. Peripheral venous blood 1 ml was used as serum antibody test for measles and rubella, and the levels of measles and rubella antibodies before and after vaccination were evaluated. The safety of combined vaccination was evaluated. Measles and rubella IgG antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Data were double-entry with Epidata and statistical analysis was performed using Epi Info epidemiological statistical analysis software. Results: The results showed that no severe adverse event occurred in two groups, clinical reactions in each inoculation group were mild.The seroconversion rate of measles antibody and rubella antibody were 96.43% and 88.49% in the experimental group after vaccination, the geometrical mean concentrations(GMC) of measles antibody was 1 526.45 mIU/ml and the GMC of rubella antibody was 47.70 mIU/ml after concomitant inoculation; the seroconversion rate of measles antibody and rubella antibody were 97.62% and 86.11% in the control group, the GMC of Measles antibody was 1 392.28 mIU/ml and the GMC of Rubella antibody was 45.72 mIU/ml after MV inoculation. No difference were detected in two groups of seroconversion rate of measles antibody and rubella antibody and GMC after vaccination. Conclusion: The immunogenicity and safety is equivalent when MR and JVE-L were simultaneous inoculation.

Intestinal fungi are critical for modulating host immune homeostasis and underlying mechanisms remain unclear. We show that dendritic cell (DC)-specific deficiency of casitas B-lineage lymphoma (c-Cbl) renders mice susceptible to dextran sodium sulfate (DSS)-induced colitis. Mechanistically, we identify that c-Cbl functions downstream of Dectin-2 and Dectin-3 to mediate the ubiquitination and degradation of noncanonical nuclear factor κB subunit RelB. Thus, c-Cbl deficiency in DCs promotes α-mannan-induced activation of RelB, which suppresses p65-mediated transcription of an anti-inflammatory cytokine gene, il10 , thereby aggravating DSS-induced colitis. Moreover, suppressing fungal growth with fluconazole or inhibition of RelB activation in vivo attenuates colitis in mice with DC-specific deletion of c-Cbl. We also demonstrate an interaction between c-Cbl and c-Abl tyrosine kinase and find that treatment with DPH, a c-Abl agonist, synergistically increases fungi-induced c-Cbl activation to restrict colitis. Together, these findings unravel a previously unidentified fungi-induced c-Cbl/RelB axis that sustains intestinal homeostasis and protects against intestinal inflammation., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Bladder cancer (BCa) is an aggressive malignancy because of its distant metastasis and high recurrence rate. Circular RNAs (circRNAs) exert critical regulatory functions in cancer progression. However, the expression patterns and roles of circRNAs in BCa have not been well investigated. In this study, we first screened circRNA expression profiles using a circRNA microarray of paired BCa and normal tissues, and the expression of circST6GALNAC6 was confirmed by qRT-PCR and fluorescence in situ hybridization (FISH). MTT, colony formation and Transwell assays were performed to measure cell proliferation, migration and invasion. We investigated the regulatory effect of circST6GALNAC6 on miRNA and its target genes to explore the potential regulatory mechanisms of circST6GALNAC6 by chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), MS2-tagged RNA affinity purification (MS2-TRAP), immunofluorescence (IF) and dual luciferase activity assays. A nude mouse xenograft model was used to examine the functions of circST6GALNAC6/STMN1 in tumour metastasis in vivo. We found that 881 circRNAs were significantly dysregulated in BCa tissues compared to normal tissues. circST6GALNAC6(hsa&#95;circ&#95;0088708) was downregulated in BCa tissues and cells. Overexpression of circST6GALNAC6 effectively inhibited the cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and suppressed BCa metastasis in vivo. Mechanistically, we showed that the SP1 transcription factor, which binds to the circST6GALNAC6 mRNA transcript, activates circST6GALNAC6 transcription. Next, we verified that circST6GALNAC6 serves as a sponge that directly binds miR-200a-3p to regulate stathmin (STMN1) expression. Furthermore, we found that STMN1 is involved in circST6GALNAC6/miR-200a-3p axis-regulated BCa EMT and metastasis. Thus, our findings indicate an important underlying mechanism in BCa metastasis by which SP1-induced circST6GALNAC6 sponges miR-200a-3p to promote STMN1/EMT signalling. This mechanism could provide pivotal potential prognostic biomarkers and therapeutic targets for BCa.

Objective: To explore whether Panax notoginseng saponins (PNS) exhibits heart protective effect in myocardial infarction (MI) rats and to identify the potential signaling pathways involved., Methods: MI rats induced by ligating the left anterior descending (LAD) coronary artery were assigned to sham coronary artery ligation or coronary artery ligation. Totally 36 Sprague-Dawley rats were randomly divided into sham group (distilled water, n=9), MI group (distilled water, n=9), PNS group (PNS, 40 mg/kg daily, n=9) and fosinopril group (FIP, 1.2 mg/kg daily, n=9) according to a random number table. The left ventricular morphology and function were conducted by echocardiography. Histological alterations were evaluated by the stainings of HE and Masson. The serum levels of C reactive protein (CRP), tumor necrosis factor α (TNF-α), growth differentiation factor-15 (GDF-15) and the ratio of metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1) were determined by ELISA. The levels of activating transcription factor 3 (ATF3), mitogen-activated protein kinase kinase 3 (MAP2K3), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylation of p38 MAPK (p-p38 MAPK), transforming growth factor-β (TGF-β1), collagen I, nuclear factor kappa B p65 (NFκB p65), phosphorylation of NFκB p65 (p-NFκB p65), and phosphorylation of inhibitory kappa Bα (p-Iκ Bα) in hearts were measured by Western blot and immunohistochemical staining, respectively., Results: PNS improved cardiac function and fibrosis in MI rats (P<0.05). The serum levels of CRP, TNF-α, GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats. The expressions of TGF-β1, collagen I, MAP2K3, p38 MAPK, p-p38 MAPK, NFκB p65, p-NFκB p65, and p-IκBα were down-regulated, while ATF3 increased with the treatment of PNS (P<0.05)., Conclusions: PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2K3/p38 MAPK and NFκB signaling pathways. These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.

Purpose: The gross tumor volume (GTV) could be an independent prognostic factor for unresectable locally advanced non-small cell lung cancer (LANSCLC). We aimed to develop and validate a novel integrated GTV-TNM stratification system to supplement LANSCLC sub-staging in patients treated with concurrent chemoradiotherapy (CCRT)., Methods: We performed a retrospective review of 340 patients with unresectable LANSCLC receiving definitive CCRT. All included patients were divided into two randomized cohorts. Then the Kaplan-Meier method and Cox regression were calculated to access the prognostic value of the integrated GTV-TNM stratification system, which was further validated by the area under the receiver operating characteristic curve (AUC) score and F1-score., Results: The optimal outcome-based GTV cut-off values (70 and 180 cm 3 ) of the modeling cohort were used to determine each patient's integrated GTV-TNM stratum in the whole cohort. Our results indicated that a lower integrated GTV-TNM stratum could had better overall survival and progression-free survival (all P < 0.001), which was recognized as an independent prognostic factor. Also, its prognostic value was robust in both the modeling and validation cohorts. Furthermore, the prognostic validity of the integrated GTV-TNM stratification system was validated by significantly improved AUC score (0.636 vs. 0.570, P = 0.027) and F1-score (0.655 vs. 0.615, P < 0.001), compared with TNM stage., Conclusions: We proposed a novel integrated GTV-TNM stratification system to supplement unresectable LANSCLC sub-staging due to its prognostic value independent of TNM stage and other clinical characteristics, suggesting that it could be considered in individual treatment decision-making process.

Background: Shifts have occurred in the epidemiological characteristics of Japanese encephalitis (JE), extending from the molecular level to the population level. The aim of this study was to investigate the seroprevalence of JE neutralizing antibodies in healthy populations from different age groups in Zhejiang Province, and to conduct mosquito monitoring to evaluate the infection rate of Japanese encephalitis virus (JEV) among vectors, as well as the molecular characteristics of the E gene of isolated JEV strains., Methodology/principal Findings: A total of 1190 sera samples were screened by a microseroneutralization test, including 429 infants (28d-11m) and 761 participants (2y-82y). For those under 1 year old, the geometric mean titers (GMTs) of the JE neutralizing antibody was 9.49 at birth and significantly declined as the age of month increased (r = -0.225, P<0.001). For those above 1-year old, seropositive proportions were higher in subjects aged 1-3 years old as well as ≥25 years old (65%-75%), and relatively lower in subjects aged between 4-25 years old (22%-55%). Four or more years after the 2nd dose of JEV-L (first dose administered at 8 months and the second at 2 years of age), the seropositive proportion decreased to 32.5%, and GMTs decreased to 8.08. A total of 87,201 mosquitoes were collected from livestock sheds in 6 surveillance sites during 2015-2018, from which 139 E gene sequences were successfully amplified. The annual infection rate according to bias-corrected maximum likelihood estimation of JEV in Culex tritaeniorhynchus was 1.56, 2.36, 5.65 and 1.77 per 1000, respectively. JEV strains isolated during 2015-2018 all belonged to Genotype I. The E gene of amplified 139 samples differed from the JEV-L vaccine strain at fourteen amino acid residues, including the eight key residues related to virulence and virus attenuation. No divergence was observed at the sites related to antigenicity., Conclusions/significance: Zhejiang Province was at a high risk of JE exposure due to relatively lower neutralizing antibody levels among the younger-aged population and higher infection rates of JEV in mosquitoes. Continuous, timely and full coverage of JE vaccination are essential, as well as the separation of human living areas and livestock shed areas. In addition, annual mosquito surveillance and periodic antibody level monitoring are important for providing evidence for improvement in JE vaccines and immunization schedules., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study aimed to evaluate the efficacy and safety of Qidong Yixin (QY) oral liquid in the treatment of viral myocarditis (VMC)., Methods: We searched seven databases for randomized clinical trials on QY for treating VMC. The retrieval period was from database establishment to December 31, 2019. Cochrane risk of bias tool in the Cochrane Handbook was used to assess the methodological quality. Review Manager (RevMan) 5.3 was used to analyze the results., Results: We included 19 studies comprising 2,608 patients, albeit with low methodological quality. Our meta-analysis revealed that combination therapy with QY and western medicine was more effective than western medicine alone (QY vs other Chinese patent medicines: RR = 1.37, 95% Cl: 1.23∼1.52, P < 0.00001; QY + coenzyme Q10 + routine treatment vs coenzyme Q10 + routine treatment: RR = 1.20, 95% Cl: 1.14∼1.27, P < 0.00001; QY + trimetazidine + acyclovir vs trimetazidine + acyclovir: RR = 1.59, 95% Cl: 1.38∼1.83, P < 0.00001; QY + routine treatment vs routine treatment: RR = 1.09, 95% Cl: 1.03∼1.15, P < 0.003). A study on posttreatment myocardial enzyme levels revealed that QY with western medicine downregulated creatine kinase isoenzyme (CK-MB) (QY + antiviral treatment + routine treatment vs antiviral treatment + routine treatment group: MD = -11.28, 95% CI: -13.33∼-9.22, P < 0.00001; QY + routine treatment vs routine treatment: MD = -4.96, 95% CI: -5.56∼-4.32, P < 0.00001), creatine kinase (CK) (MD = -32.10, 95% CI: -35.63∼-28.57, P < 0.00001), and lactate dehydrogenase (LDH) (QY + antiviral treatment + routine treatment vs antiviral treatment + routine treatment: MD = -48.76 95% CI: -58.18∼-39.33, P < 0.00001; QY + routine treatment vs routine treatment: MD = -23.52, 95% CI: -30.10-16.94, P < 0.00001) rather than western medicine alone, with no evidence of aspartate aminotransferase (AST) downregulation on treatment with QY with western medicine (MD = 2.88, 95% CI: -0.95∼6.71, P < 0.00001) in patients. Two studies reported adverse events, indicating that QY is relatively safe., Conclusion: Although QY may have potential advantages in treating VMC, they remain unclear owing to the poor methodological quality of most studies. Larger, multicenter, high-quality randomized controlled trials are required to verify the effectiveness of QY., Competing Interests: All authors declare no conflicts of interest., (Copyright © 2020 Jun Hu et al.)

Ischemic heart disease has became the world's most common deadly disease, and coronary heart disease(CHD) is the most common type of ischemic heart disease. The pathological mechanism of CHD has not been fully elucidated. In recent years, scientific studies have found that gut micro-biota are closely related to the occurrence and development of CHD, and CHD could be intervened by regulating gut micro-biota because of the correlation between CHD and intermediate metabolite of gut micro-biota. Current intervention strategies mainly include probiotics supplementation, reduction of TMAO and increase of SCFAs, which can achieve the effect of stabilizing plaques, and controlling blood pressure, blood lipids, blood glucose and obesity. Traditional Chinese medicine(TCM) has the multi-component and multi-target effects, which is correlated to its role in the prevention and treatment of CHD. This paper summarizes the domestic and foreign researches on the effect of TCM in attenuating CHD and its main risk factors by regulating gut micro-biota. The article aims to explore the correlation between gut micro-biota and CHD, and propose three main intervention strategies. Furthermore, the research progress of TCM on CHD, hypertension, dyslipidemia, hyperglycemia and obesity is reviewed by the categories of Chinese medicine monomer and compound, in the hope to provide more theoretical basis for TCM therapy on CHD and guidance for further studies in this field.

Vascular calcification is a major complication of cardiovascular disease and chronic renal failure. Autophagy help to maintain a stable internal and external environment that is important for modulating arteriosclerosis, but its pathogenic mechanism is far from clear. Here, we aimed to identify the bioactive compounds from traditional Chinese medicines (TCM) that exhibit an anti-arteriosclerosis effect. In β-glycerophosphate (β-GP)-stimulated human aortic smooth muscle cells (HASMCs), the calcium level was increased and the expression of the calcification-related proteins OPG, OPN, Runx2, and BMP2 were all up-regulated, followed by autophagy induction and apoptosis. Meanwhile, we further revealed that β-GP induced apoptosis of human osteoblasts and promoted differentiation of osteoblasts through Wnt/β-catenin signaling. Bavachin, a natural compound from Psoralea corylifolia , dose-dependently reduced the level of intracellular calcium and the expression of calcification-related proteins OPG, OPN, Runx2 and BMP2, thus inhibiting cell apoptosis. In addition, bavachin increased LC3-II and beclin1 expression, along with intracellular LC3-II puncta formation, which autophagy induction is Atg7-dependent and is regulated by suppression of mTOR signaling. Furthermore, addition of autophagy inhibitor, wortmannin (WM) attenuated the inhibitory effect of bavachin on β-GP-induced calcification and apoptosis in HASMCs. Collectively, the present study revealed that bavachin protects HASMCs against apoptosis and calcification by activation of the Atg7/mTOR-autophagy pathway and suppression of the β-catenin signaling, our findings provide a potential clinical application for bavachin in the therapy of cardiovascular disease., (Copyright © 2019 He, Law, Zhang, Qiu, Qu, Wu, Han, Song, Zheng, Liu, He and Wong.)

Objective: To assess the efficacy and safety of artemether emulsion in patients with papulopustular rosacea. Methods: A total of 130 (randomized 1:1) were externally administered either artemether emulsion (1%) or metronidazole emulsion (3%) twice daily for 4 weeks with an open-label 8-week follow-up. The primary endpoints included the proportion of patients who achieved clinical effective responses, as well as erythema and papule and pustule score at week 4. Results: Numerically more patients achieved an effective response at week 4 with artemether emulsion (87.1%) than metronidazole emulsion (80.0%) ( p  > .05). Patients with artemether emulsion had comparable baseline erythema score (2.45 ± 0.67 versus 2.42 ± 0.70, p  = .809) and papule and pustule score (2.11 ± 0.96 versus 2.32 ± 0.83, p  = .264), but significantly lower papule and pustule score (0.21 ± 0.52 versus 0.42 ± 0.83, p  = .001) and comparable erythema score (0.53 ± 0.88 versus 0.62 ± 0.88, p  = .999) compared to patients with metronidazole emulsion at week 4. There was a significantly higher proportion of patients with metronidazole emulsion relapse compared to metronidazole emulsion during the open-label 8-week follow-up period (21.6% versus 2.4%, p  < .01). Conclusions: Artemether emulsion improved papulopustular rosacea in the metronidazole emulsion group as early as 4 weeks, but its beneficial effect was maintained through the 8-week follow-up period compared to metronidazole emulsion.

Background: Bladder cancer is one of the most frequent urologic tumours in the world. MicroRNA-200c (miR-200c) has been considered a regulator of tumour angiogenesis. Akt2/mTOR was considered a regulator of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α). However, the mechanism by which miR-200c regulates bladder cancer angiogenesis remains unknown., Methods: Western blotting and qRT-PCR were used to detect the expression of protein and mRNA, respectively. Cell proliferation, migration and invasion were detected using MTT, wound-healing and transwell assays, respectively. A dual luciferase reporter assay was used to identify the binding site between miR-200c and Akt2. A tube formation assay was also applied to detect the angiogenesis ability., Results: Significantly higher expression levels of HIF-1α and VEGF and lower levels of miR-200c were observed in three types of bladder cancer cell lines. Transfection with the miR-200c mimic markedly inhibited cell viability, angiogenesis, and the expression of VEGF and HIF-1α. Overexpression of miR-200c remarkably suppressed the expression of Akt2, and the binding site between them was identified. Knockdown of Akt2 remarkably decreased the expression of VEGF and HIF-1α by regulating mTOR. miR-200c influenced the expression of VEGF and HIF-1α through the Akt2/mTOR signalling pathway and further regulated angiogenesis in bladder cancer cells., Conclusions: We proved that miR-200c could suppress HIF-1α/VEGF expression in bladder cancer cells and inhibit angiogenesis, and these regulations were achieved by targeting Akt2/mTOR. This study may provide new insight into the prevention and treatment of bladder cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.10.23). The authors have no conflicts of interest to declare., (2019 Translational Cancer Research. All rights reserved.)

Objective: To investigate the effect of triptolide on the excursion of Tc and Th cells in peripheral blood of systemic lupus erythematosus (SLE) BALB/c-un nude mice induced by pristane., Methods: Eighteen female BALB/c-un nude mice were randomly divided into blank, SLE and triptolide group, each with 6 mice by random table method. Group SLE and group triptolide were established by single intraperitoneal injection of pristane, and blank group was used as blank control group. SLE model was established by single intraperitoneal injection. Triptolide group was fed with triptolide at the dose of 5 mg/(kg·d), and the blank group and SLE group were fed normally. Blood samples were collected from the caudal vein before treatment and 1, 3 and 6 months after treatment respectively. Fluorescence labeled flow cytometry was used to delect Tc and Th lymphocyte subsets at different stages of treatment., Results: After treatment for 3 and 6 moths, the percentages of Tcl, Thl cells and CD8 + , Tcl/Tc2, Thl/Th2 and CD4 + /CD8 + all decreased in the group of triptolide, and the percentage of CD4 + , Tc2 and Th2 cells increased (P＜0.05)., Conclusion: The mechanism of triptolide in the treatment of SLE may be related with the excursion of Tc and Th cells to Tcl and Tc2 to maintain the relative homeostasis of Tc and Th cells at different stage, thus affecting the immune response and the inflammatory reaction.

The pro-apoptotic proteins BAX and BAK are critical regulatory factors constituting the apoptosis machinery. Downregulated expression of BAX and BAK in human colorectal cancer lead to chemotherapeutic failure and poor survival rate in patients. In this study, isogenic DLD-1 colon cancer cells and the BAX and BAK double knockout counterpart were used as the cellular model to investigate the role of BAX/BAK-associated signaling network and the corresponding downstream effects in the development of drug resistance. Our data suggested that DLD-1 colon cancer cells with BAX / BAK double-knockout were selectively resistant to a panel of FDA-approved drugs (27 out of 66), including etoposide. PCR array analysis for the transcriptional profiling of genes related to human cancer drug resistance validated the altered level of 12 genes (3 upregulated and 9 downregulated) in DLD-1 colon cancer cells lack of BAX and BAK expression. Amongst these genes, XPC responsible for DNA repairment and cellular respiration demonstrated the highest tolerance towards etoposide treatment accompanying upregulated glycolysis as revealed by metabolic stress assay in DLD-1 colon cancer cells deficient with XPC . Collectively, our findings provide insight into the search of novel therapeutic strategies and pharmacological targets to against cancer drug resistance genetically associated with BAX , BAK , and XPC , for improving the therapy of colorectal cancer via the glycolytic pathway.

Long noncoding RNAs (lncRNAs) play crucial roles in the development of human cancers. LncRNA small nucleolar RNA host gene 20 (SNHG20) has been reported to be an oncogene in several cancers, whereas the specific role of SNHG20 in glioblastoma is unclear. In this study, we found that SNHG20 was significantly upregulated in glioblastoma tissues and cell lines. Survival analysis suggested that high expression of SNHG20 indicated the low overall survival rate of glioblastoma patients. Subsequently, gain or loss-of-function assays were carried out to examine the effect of SNHG20 on glioblastoma cell proliferation and apoptosis. We found that SNHG20 knockdown obviously suppressed cell proliferation, increased cell apoptosis and impaired stem properties, while SNHG20 overexpression led to the opposite results. In vivo experiment demonstrated that knockdown of SNHG20 efficiently suppressed cell growth in vivo. Furthermore, western blotting demonstrated that the PI3K/Akt/mTOR signaling pathway was activated by SNHG20 in glioblastoma cells. At last, rescue assays validated that PI3K/Akt/mTOR signaling pathway involved in the glioblastoma progression mediated by SNHG20. Taken together, this study revealed that SNHG20 regulated PI3K/Akt/mTOR signaling pathway to promote tumorigenesis and stemness of glioblastoma.

Objective: To evaluate the cost-benefit and cost-effectiveness of current strategy for preventing mother-to-child transmission (PMTCT) of hepatitis B virus. Methods: A decision tree model with the Markov process was developed and simulated over the lifetime of a birth cohort in Zhejiang Province in 2016. The current PMTCT strategy was compared with universal vaccination and non-vaccination. Costs were assessed from social perspective. Benefits were the savings from reduced costs associated with disease and effectiveness were measured by quality-adjusted of life-years (QALY) gained. The net present value (NPV), cost-benefit ratio (BCR) and incremental cost-effectiveness ratio (ICER) were calculated. Univariate and Probabilistic Sensitivity Analyses (PSA) were performed to assess parameter uncertainties. The parameters of costs and utilities value of hepatitis B-related disease came from the results of the field survey, which were obtained by face-to-face questionnaire survey combined with inpatient medical records, including eight county and municipal hospitals in Jinhua, Jiaxing and Taizhou. A total of 626 outpatients and 523 inpatient patients were investigated. The annual total costs of infection was calculated by combining the costs of outpatient and inpatient. Results: The PMTCT strategy showed a net-gain as 38 323.78 CNY per person, with BCR as 21.10, which was higher than 36 357.80 CNY per person and 13.58 respectively of universal vaccination. Compared with universal vaccination, the PMTCT strategy would save 2 787.07 CNY per additional QALY gained for every person, indicating that PMTCT would be cost-saving. The most important parameters that could affect BCR and ICER were the vaccine coverage rate and costs of hepatitis B related diseases respectively. The PSA showed the PMTCT strategy was preferable as it would gain more QALY and save costs. Conclusions: The PMTCT strategy appeared as highly cost-beneficial and highly cost-effective. High vaccination rate was a key factor of high economic value.

In this study, reduction-sensitive self-assembled polymer nanoparticles based on poly (lactic-co-glycolic acid) (PLGA) and chondroitin sulfate A (CSA) were developed and characterized. PLGA was conjugated with CSA via a disulfide linkage (PLGA-ss-CSA). The critical micelle concentration (CMC) of PLGA-ss-CSA conjugate is 3.5 µg/mL. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the nanoparticles (PLGA-ss-CSA/DOX) with high loading efficiency of 15.1%. The cumulative release of DOX from reduction-sensitive nanoparticles was only 34.8% over 96 h in phosphate buffered saline (PBS, pH 7.4). However, in the presence of 20 mM glutathione-containing PBS environment, DOX release was notably accelerated and almost complete from the reduction-sensitive nanoparticles up to 96 h. Moreover, efficient intracellular DOX release of PLGA-ss-CSA/DOX nanoparticles was confirmed by CLSM assay in A549 cells. In vitro cytotoxicity study showed that the half inhibitory concentrations of PLGA-ss-CSA/DOX nanoparticles and free DOX against A549 cells were 1.141 and 1.825 µg/mL, respectively. Therefore, PLGA-ss-CSA/DOX nanoparticles enhanced the cytotoxicity of DOX in vitro. These results suggested that PLGA-ss-CSA nanoparticles could be a promising carrier for drug delivery.

Isoalantolactone (IAL) is a sesquiterpene lactone extracted from roots of Inula helenium L and has shown anti-inflammatory effects. In this study we investigated the therapeutic effects of IAL on acute lung injury (ALI) and elucidated the mechanisms underlying its anti-inflammation potential in vitro and in vivo. Treatment with lipopolysaccharide (LPS, 100 ng/mL) drastically stimulated production of inflammatory mediators such as NO, TNF-α, IL-1β, and IL-6 in mouse bone marrow-derived macrophages (BMDMs), which was dose-dependently suppressed by pretreatment with IAL (2.5, 5, 10, 20 μM). We further revealed that IAL suppressed LPS-induced NF-κB, ERK, and Akt activation. Moreover, the downregulation of non-degradable K63-linked polyubiquitination of TRAF6, an upstream transcription factor of NF-κB, contributed to the anti-inflammatory effects of IAL. ALI was induced in mice by intratracheal injection of LPS (5 mg/kg). Administration of IAL (20 mg/kg, i.p.) significantly suppressed pulmonary pathological changes, neutrophil infiltration, pulmonary permeability, and pro-inflammatory cytokine expression. Our results demonstrate that IAL is a potential therapeutic reagent against inflammation and ALI.

Berberine presents therapeutic ability for various central nervous system disorders, including Alzheimer's disease and cerebral ischemia. The present study investigated the role of berberine in nerve regeneration and analyzed the potential mechanism mediated by berberine in hippocampal pyramidal neurons. Reverse transcription‑quantitative poylmerase chain reaction, western blot, TUNEL assay and immunofluorescence were used to analyze the therapeutic effects of berberine on nerve regeneration. Berberine treatment increased growth and viability of hippocampal pyramidal neurons. Berberine treatment inhibited apoptosis of hippocampal pyramidal neurons and increased apoptosis regulator Bcl‑2 and Bcl‑w expression. Neuroinflammation of tumor necrosis factor α, interleukin (IL)1β, IL6 levels and autophagy‑related proteins microtubule‑associated proteins 1A/1B light chain 3B, autophagy related 16 like 1 and autophagy related 7 were downregulated by berberine treatment in hippocampal pyramidal neurons. Notably, study has found that berberine increased insulin-like growth factor receptor (IGFR) and decreased c‑Jun N‑terminal kinase (JNK) and protein kinase B (AKT) expression in hippocampal pyramidal neurons. IGFR antagonist abolished berberine‑increased growth of hippocampal pyramidal neurons. In conclusion, these results indicate that berberine can promote nerve regeneration through IGFR‑mediated JNK‑AKT signal pathway.

The stromal and immune cells that form the tumor microenvironment serve a key role in the aggressiveness of tumors. Current tumor-centric interpretations of cancer transcriptome data ignore the roles of stromal and immune cells. The aim of the present study was to investigate the clinical utility of stromal and immune cells in tissue-based transcriptome data. The 'Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data' (ESTIMATE) algorithm was used to probe diverse cancer datasets and the fraction of stromal and immune cells in tumor tissues was scored. The association between the ESTIMATE scores and patient survival data was asessed; it was indicated that the two scores have implications for patient survival, metastasis and recurrence. Analysis of a colorectal cancer progression dataset revealed that decreased levels immune cells could serve an important role in cancer progression. The results of the present study indicated that trasncriptome-derived stromal and immune scores may be a useful indicator of cancer prognosis.

Objective: To investigate the epidemiological characteristics of measles outbreak caused by genotype D8 virus in Pinghu city of Zhejiang province, and provide evidence for the control of the outbreak. Methods: The measles outbreak data were collected through National Measles Surveillance System. The outpatient records and admission records were checked, field investigation and outbreak response were conducted. Blood samples in acute phase and swab specimens were collected from the patients for laboratory testing, including serology test, RNA extraction and amplification, measles virus isolation and genotype identification. Software SPSS 17.0 and Excel 2016 were used for data analysis. Results: A total of 10 confirmed measles cases were reported in Pinghu city, and 8 cases were aged >40 years. Six blood samples were collected, in which 5 were measles D8 virus positive and 1 was negative in measles virus detection. There were epidemiological links among 10 cases which occurred in a factory, a hospital and a family at the same time. There was no statistical difference in symptoms among cases caused by D8 virus and H1a virus. After the emergent measles vaccination, the measles outbreak was effectively controlled. Conclusion: Untimely response due to the uneasy detection of measles cases in the early stage, nosocomial infection and weak barrier of measles immunity in adults might be the main reasons for this outbreak. Measles vaccination is effective in the prevention of measles D8 virus infection. It is necessary to strengthen measles genotype monitoring for the tracing of infection source and control of outbreaks.

Non-small-cell lung cancer (NSCLC) accounts for most lung cancer cases. Therapeutic interventions integrating the use of different agents that focus on different targets are needed to overcome this set of diseases. The proteasome system has been demonstrated clinically as a potent therapeutic target for haematological cancers. However, promising preclinical data in solid tumors are yet to be confirmed in clinics. Herein, the combinational use of Bortezomib (BZM) and 2-aminoethoxydiphenylborane (2-APB) toward NSCLC cells was studied. We confirmed that BZM-triggered cytoprotective autophagy that may counteract with the cytotoxic effects of the drug per se. 2-APB was selected from screening of a commercial natural compounds library, which potentiated BZM-induced cytotoxicity. Such an enhancement effect was associated with 2-APB-mediated autophagy inhibition. In addition, we revealed that 2-APB suppressed calcium-induced autophagy in H1975 and A549 NSCLC cells. Interestingly, BZM [0.3 mg/kg/3 days] combined with 2-APB [2 mg/kg/day] significantly inhibited both primary (around 47% tumor growth) and metastatic Lewis lung carcinoma after a 20-day treatment. Our results suggested that BZM and 2-APB combination therapy can potentially be developed as a novel formulation for lung cancer treatment.

For the characteristics of high stability， high conservation between species， and tissue specificity， circular RNA(circRNA) has been expected to become a new molecular biomarker for the clinical diagnosis， treatment and prognosis， and the potential target for targeted therapy. Study on the traditional Chinese medicine(TCM) syndrome includes not only the macro indexes collected by using four traditional methods of diagnosis， but also contains some micro information that can not be achieved by using the four traditional diagnosis methods. The questions such as how to deal with the relationship between the holistic concept of TCM and micro research， and how to solve the contradiction between the fuzziness of syndrome description and the accuracy of microscopic research， need to be considered before the micro research in TCM syndrome. circRNA as a new field of understanding human disease， may provide some ideas for the TCM syndrome research due to its characteristics. Overall， it is necessary to pay attention to explore the molecular level with same syndrome in different diseases and reveal the connotation and essence of syndromes by understanding of circRNA., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome have been implicated in the initiation or progression of atherosclerosis. Recent research showed that irisin, a newly discovered adipomiokine, alleviates endothelial dysfunction in type 2 diabetes partially via reducing oxidative/nitrative stresses, suggesting that irisin may be a promising candidate for the treatment of vascular complications of diabetes. However, the association between irisin and NLRP3 inflammasome in the pathogenesis of atherosclerosis remains unclear. In the present study, we cultured human umbilical vein endothelial cells (HUVECs) in advanced glycation end products (AGEs) medium; exogenous irisin (0.01, 0.1, 1 μg/ml) were used as an intervention reagent. siRNA and adenoviral vector were constructed to realize silencing and over-expression of NLRP3 gene. Our data showed that irisin significantly reversed AGEs-induced oxidative stress and NLRP3 inflammasome signaling activation (p < 0.05), and increased the endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production in a dose-dependent manner (p < 0.05). siRNA-mediated knockdown NLRP3 facilitated the irisin-mediated anti-inflammatory and antiatherogenic effects (p < 0.05). However, these irisin-mediated effects were reversed by over-expression NLRP3 (p < 0.05). Taken together, our results reveal that irisin alleviates AGEs-induced inflammation and endothelial dysfunction via inhibiting ROS-NLRP3 inflammasome signaling, suggest a likely mechanism for irisin-induced therapeutic effect in vascular complications of diabetes.

Protostemonine (PSN) is the main anti-inflammatory alkaloid extracted from the roots of Stemona sessilifolia (known as "Baibu" in traditional Chinese medicine). Here, we reported the inhibitory effects of PSN on lipopolysaccharide (LPS)-induced macrophage activation in vitro and LPS-induced acute lung injury in mice. Macrophage cell line RAW264.7 cells and mouse bone marrow-derived macrophages (BMDMs) were treated with PSN (1, 3, 10, 30 and 100 μmol/L) for 0.5 h and then challenged with LPS (0.1 μg/mL) for 24 h. Pretreatment with PSN significantly inhibited LPS-induced phosphorylation of MAPKs and AKT, iNOS expression and NO production in the macrophages. C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) to induce acute lung injury (ALI). The mice were subsequently treated with PSN (10 mg/kg, ip) at 4 and 24 h after LPS challenge. PSN administration significantly attenuated LPS-induced inflammatory cell infiltration, reduced pro-inflammatory cytokine (TNF-α, IL-1β and IL-6) production and eliminated LPS-mediated lung edema. Furthermore, PSN administration significantly inhibited LPS-induced pulmonary MPO activity. Meanwhile, LPS-induced phosphorylation of p38 MAPK, iNOS expression and NO production in the lungs were also suppressed. The results demonstrate that PSN effectively attenuates LPS-induced inflammatory responses in vitro and in vivo; the beneficial effects are associated with the decreased phosphorylation of MAPK and AKT and the reduced expression of pro-inflammatory mediators, such as iNOS, NO and cytokines. These data suggest that PSN may be a potential therapeutic agent in the treatment of ALI.

Aim: To determine whether fructo-oligosaccharide (FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids (SCFA) in an irritable bowel syndrome (IBS) mouse model., Methods: Mice were randomly assigned to daily oral gavage of saline solution with or without FOS (8 g/kg body weight) for 14 d. Mice were further assigned to receive either daily one-hour water avoidance stress (WAS) or sham-WAS for the first 10 d. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was evaluated. Gas chromatography, real-time reverse transcription PCR, and immunohistochemistry assays were used to quantify cecal concentrations of SCFA, intestinal cytokine expression, and number of intestinal mast cells per high-power field (HPF), respectively., Results: Mice subjected to WAS exhibited visceral hypersensitivity and low-grade inflammation. Among mice subjected to WAS, FOS increased visceral hypersensitivity and led to higher cecal concentrations of acetic acid (2.49 ± 0.63 mmol/L vs 1.49 ± 0.72 mmol/L, P < 0.05), propionic acid (0.48 ± 0.09 mmol/L vs 0.36 ± 0.05 mmol/L, P < 0.01), butyric acid (0.28 ± 0.09 mmol/L vs 0.19 ± 0.003 mmol/L, P < 0.05), as well as total SCFA (3.62 ± 0.87 mmol/L vs 2.27 ± 0.75 mmol/L, P < 0.01) compared to saline administration. FOS also increased ileal interleukin (IL)-23 mRNA (4.71 ± 4.16 vs 1.00 ± 0.99, P < 0.05) and colonic IL-1β mRNA (2.15 ± 1.68 vs 0.88 ± 0.53, P < 0.05) expressions as well as increased mean mast cell counts in the ileum (12.3 ± 2.6 per HPF vs 8.3 ± 3.6 per HPF, P < 0.05) and colon (6.3 ± 3.2 per HPF vs 3.4 ± 1.2 per HPF, P < 0.05) compared to saline administration in mice subjected to WAS. No difference in visceral sensitivity, intestinal inflammation, or cecal SCFA levels was detected with or without FOS administration in mice subjected to sham-WAS., Conclusion: FOS administration intensifies visceral hypersensitivity and gut inflammation in stress-induced IBS mice, but not in the control mice, and is also associated with increased intestinal SCFA production., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest related to this study.

Aim: To compare the effect of University of Wisconsin (UW) solution with or without metformin, an AMP-activated protein kinase (AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion (HMP)., Methods: Eighteen young (4 mo old) and 18 aged (17 mo old) healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group (UWP), and UW solution with metformin perfusion group (MUWP). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-α) in the perfused liquid were tested. The expression levels of AMPK and endothelial nitric oxide synthase (eNOS) in liver sinusoidal endothelial cells were also examined. Additionally, microscopic evaluation of the harvested perfused liver tissue samples was done., Results: AST, ALT, LDH, IL-18 and TNF-α levels in the young and aged liver-perfused liquid were, respectively, significantly lower in the MUWP group than in the UWP group ( P < 0.05), but no significant differences were found between the young and aged MUWP groups. Metformin increased the expression of AMPK and eNOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-eNOS mediated pathway. Histological examination revealed that in the MUWP group, the extent of liver cells and tissue damage was significantly reduced compared with the UWP group., Conclusion: The addition of metformin to the UW preservative solution for ex vivo HMP can reduce rat liver injury during cold ischemia, with significant protective effects on livers, especially of aged rats., Competing Interests: Conflict-of-interest statement: All the authors declare no conflict of interest related to this publication.