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Background As revealed by previous studies, the head shaking tilt suppression test (HSTST) is associated with the vestibular cerebellum-mediated central storage mechanism and the video head impulse test (vHIT) is crucial for the diagnosis of peripheral vestibular diseases. Objective To explore the clinical application value of HSTST and vHIT in vestibular migraine (VM) and Meniere's disease (MD) . Methods Patients presenting with vertigo or dizziness as the primary complaint and diagnosed with VM and MD were selected from the Neurology Department of the Second People's Hospital of Guiyang from July 2021 to December 2022. After collecting their medical history and performing bedside examinations, pure tone audiometry test was conducted on those with hearing impairment. All patients completed vestibular function tests, including head shaking test (HST), HSTST, caloric test, and vHIT, were performed, followed by calculating the tilt suppression index (TSI). Then the Clinical features and examination results of VM and MD patients with HST positive were compared, and the ROC curve of TSI was plotted to distinguish between the two groups of patients. Results Among the 50 VM patients involved in the study, 22 (44.0%) were HST positive, including 19 (86.4%) exhibiting horizontal nystagmus and 3 (13.6%) showing vertical nystagmus. Among the 45 MD patients, 23 (51.1%) were HST positive, all of whom were horizontal nystagmus. The analysis of the patients with HST positive showed that the female to male ratio in VM and MD patients was 4.5∶1 and 1∶1.3, respectively. The prevalence of family history of headaches was higher in VM patients compared to MD patients (P

Abstract Obesity is a serious global health issue. Emerging evidence indicates that the gut microbiota may contribute to the development of obesity, possibly by instigating inflammatory processes. The objective of this research is to conduct a comparative analysis of the gut microbiota composition in obese and normal-weight Uygur adults, while examining the associations with adipocyte-related factors and dietary variables. According to the inclusion and exclusion criteria, twenty-seven Uygur adults with obesity and twenty Uygur adults with normal-weight were recruited from a local community. Anthropometric measurements and blood samples were collected. Gut microbiota composition was analyzed using 16 S rRNA gene sequencing. Adipocyte-related factors were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed to compare the gut microbiota composition between the two groups and to identify correlations between gut microbiota and adipocyte-related factors. Compared with the normal-weight group, the obese group exhibited a marked reduction in both diversity and richness of the gut microbiota, alongside a decrease in Ruminococcaceae_UCG_014, Coprococcus_2, and Parabacteroides, and an increase in Megamonas and Lachnoclostridium, implying a potential link to the development of obesity. Individuals with obesity were found to have higher Leptin (LEP), Interleukin-6 (IL-6), and C-reactive protein (CRP) than normal-weight individuals. Obese Uygur adults exhibited a gut microbiota characterized by diminished diversity and richness relative to normal-weight individuals. Parabacteroides, Megamonas, and Lachnoclostridium may play an important role in the development of obesity in Uygur population. Underlying mechanisms need further investigation.

Background With the continuous development of society and technological innovations, the average life expectancy of human beings has gradually increased, leading to the gradual increase in the number of perimenopausal women. This trend poses a serious challenge to the management of perimenopausal health in the community. Objective To understand the health characteristics and health needs of perimenopausal women in the community, explore the relationship between the two, and provide evidence to support the development and improvement of perimenopausal health management in community health service organisations. Methods Perimenopausal women (n=260) who attended or were accompanied to the Huamu Community Health Service Centre and its subordinate stations in Pudong New Area, Shanghai, from February to March 2023 were selected as study subjects. Questionnaires were used to collect information on the health characteristics of the study subjects (related to physiological stage, social characteristics, disease status, lifestyle, and quality of life), their knowledge of menopause and attitudes toward treatment, as well as their needs for knowledge related to menopause and preventive health care for menopausal diseases. Results Fifty percent (130/260) of perimenopausal women had a current history of chronic disease, 51.9% (135/260) of perimenopausal women had a past history of chronic disease, 73.8% (192/260) of perimenopausal women had fair/poor quality of sleep, 33.5% (87/260) of perimenopausal women did little exercise. 58.5% (152/260) of perimenopausal women were completely unaware or had only heard of menopause, 41.9% (109/260) of perimenopausal women had a negative attitude towards menopause treatment, 45.0% (117/126) of perimenopausal women needed menopause-related knowledge, and 66.6% (173/260) of perimenopausal women needed preventive health care for menopausal diseases. The results of ordered multicategorical Logistic regression analyses showed that literacy, the number of menopausal symptoms in the last 3 monthss, and attitudes toward menopause treatment were the factors influencing perimenopausal women's need for menopause-related knowledge (P

Objective To study the effects of different pellet feed hardness on the growth and reproduction, feed utilization rate, and environmental dust in laboratory mice. Methods One hundred of fifty 50 3-week-old SPF-grade C57BL/6JGpt and 150 ICR laboratory mice were randomly divided into three groups, with an equal number of males and females. They were fed diets with different hardness of 18.62 kg, 23.15 kg, and 27.89 kg. Body weight, feed utilization rate, and dust levels in cages were recorded and calculated for mice aged 3-10 weeks. Forty-five 6-week-old male mice and ninety 4-week-old female mice from each strain were randomly divided into three groups and fed pellet feeds with three different hardness levels. After 2 weeks of adaptation to the same hardness feed, the mice were paired at a 1∶2 male-to-female ratio and monitored for reproductive data for 3 months. Results At the age of 4 weeks, the body weight of male C57BL/6JGpt mice in 23.15 kg group was significantly higher than that in the 18.62 kg and 27.89 kg groups (P0.05). For both strains, feed utilization rate for males was higher than that for females across different feed hardness groups at all weeks of age (P0.05). However, the monthly production index of C57BL/6JGpt mice first increased and then decreased with the increase of feed hardness, while that of ICR mice increased with increasing feed hardness, though these differences were not statistically significant (P>0.05). Conclusion Different strains and genders had different tolerance to feed hardness. C57BL/6JGpt mice are more adapted to lower hardness feeds, while ICR mice are better suited to slightly higher hardness feeds.

Carnosine dipeptidase 1 (CNDP1), an enzyme integral to the hydrolysis of dipeptides containing histidine, plays an indispensable role in myriad physiological processes, including hydrolysis of proteins, maturation of specific biochemical functionalities within proteins, tissue regeneration, and regulation of cell cycle. However, the implications of CNDP1 in oncogenesis and its prognostic value are not yet fully elucidated. Initially, we procured the GSE40367 dataset from the Gene Expression Omnibus and established a protein–protein interaction network. Thereafter, we conducted functional and pathway enrichment analyses utilizing GO, KEGG, and GSEA. Moreover, we undertook an association analysis concerning the expression of CNDP1 with immune infiltration, along with survival analysis across various cancers and specifically in hepatocellular carcinoma (HCC). Our study uncovered a total of 2,248 differentially expressed genes, with a down-regulation of CNDP1 in HCC and other cancers. Our explorations into the relationship between CNDP1 and immune infiltration disclosed a negative correlation between CNDP1 expression and the presence of immune cells in HCC. Survival analyses revealed that diminished expression of CNDP1 correlates with an adverse prognosis in HCC and several other types of cancer. These observations intimate that CNDP1 holds promise as a novel prognostic biomarker for both pan-cancer and HCC.

The pathogenesis of cognitive impairment (CI) in coronary artery disease (CAD) patients is still unclear and numerous influence factors could affect the CI status. The current studies suggest that sleep quality and behavior pattern are significant influence factors associated with CAD susceptibility.

Objective To analyze the clinical and genetic characteristics of three children with congenital heart defects， dysmorphic facial features and intellectual developmental disorders（CHDFIDD）. Methods Three children presenting with CHDFIDD were enrolled. Genomic DNA was extracted from peripheral venous blood of the children and their parents. Whole-exome sequencing（WES） was performed using chip-capture high-throughput sequencing technology. Suspected causative mutations were verified by Sanger sequencing and bioinformatic analysis. Using “CDK13 gene” and “CDK13-related diseases” as search terms， literatures of CNKI and Wanfang database were retrieved until February 2024. Using “CDK13”， “CDK13-related disorder” and “CHDFIDD” as search terms， literatures from the establishment of PubMed database untio February 2024 was retrieved， and the relevant literature was reviewed. Results WES revealed heterozygous variants of the CDK13 gene in three children， including c.2572 C>T （p.Leu858Phe）， c.2579 G>A （p.Arg860Gln）， and c.2602C>T （p.Arg868Trp）， which were verified as de novo variants by Sanger sequencing.Combined with the clinical phenotype， all 3 children were diagnosed with CHDFIDD. However， the possibility that one of the affected children’s parents was a germline chimera for the mutation could not be excluded. According to the ACMG guidelines， all three mutation sites were classified as likely pathogenic. A total of 14 studies consisting of 108 cases were retrieved. Among them， c.2572C>T has not been reported. Conclusions The de novo variants of the CDK13 gene may be the genetic cause of developmental delay/intellectual disability in these three children. The findings in the present study expand the spectrum of CDK13 gene mutations， providing reference for the diagnosis of CHDFIDD.

ObjectiveTo explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death （YNSUD）, to provide the experimental basis for prevention and treatment of YNSUD.MethodsFour kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 （CCK-8）. The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase （LDH） Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope.ResultsSpecies identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts.ConclusionThe extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

Objective To explore the intervention mechanism of puerarin(PUR) on the inflammatory response of vascular endothelial cells with KKAy mouse models.Methods C57bL/6j mice were used as the control group. KKAy mice were randomly divided into diabetes group, metformin hydrochloride(MH)and puerarin(PUR) group with 10 in each. The indexes of glucose metabolism in each group were recorded. The contents of tumor necrosis factor-α (TNF-α), interferon-γ(IFN-γ), transforming growth factor-β1(TGF-β1), interleukin-1 (IL-1) and vascular endothelial growth factor (VEGF) were detected by ELISA; TUNEL method was used to detect apoptosis in vascular tissue; mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were detected by RT-qPCR and Western blot. Results Compared with the control group, the indexes of glucose metabolism and apoptosis in diabetes group increased significantly; The contents of TNF-α, IFN-γ, TGF-β1, IL-1 and VEGF in serum changed significantly (P＜0.05) and the mRNA and protein expressions of VCAM-1 and ICAM-1 in vascular tissue increased significantly(P＜0.05). Compared with diabetes group, MH group and PUR group significantly improved glucose metabolism and cell apoptosis; TNF-α, IFN-γ, TGF-β1, IL-1 and VEGF decreased significantly (P＜0.05); The mRNA and protein expressions of VCAM-1 and ICAM-1 were all significantly improved(P＜0.05). Conclusions PUR can effectively inhibit the expression of vascular endothelial inflammatory factors, VCAM-1 and ICAM-1 adhesion molecules in KKAy mice, and alleviate the vascular endothelial injury found in diabetes mice.

Background Population aging is getting worse in our country. Family doctor contract service plays an important role in boosting the construction of hierarchical diagnosis and treatment system and establishing a reasonable and orderly medical order. Current research about family doctor contract service policy mainly focus on qualitative evaluation, and there are few researchers use tools to quantitatively evaluate each individual representative policy. Objective This study aims to quantitatively evaluate the pros and cons of six Chinese central government policies about family doctor contract service, thus, proposing strategies and measures to promote the high-quality development of our country's family doctor contract service, and helping the construction of healthy China. Methods We searched Peking University's PKULAW.com and websites of some relevant ministries of the State Council of China from January 1, 2015 to April 30, 2022. The key word was "family doctor". The software ROSTCM 6.0 was used for text mining. Based on the results, this study selected central government policies about family doctor contract services, then used the PMC index model to quantitatively evaluate these policies. Results This study included thirty-two policies based on inclusion and exclusion criteria. The top five high-frequency keywords in the field of family doctor services are "contract service" (n=274) , "health" (n=272) , "medical" (n=264) , "family doctor" (n=225) , and "contract" (n=180) . They were marked as P1-P6, respectively. In terms of methods and other aspects, the scores of each dimension are relatively high. The results of quantitative evaluation showed that the ranking of policies is P1>P3>P2>P6>P4>P5. Three policies were rated as excellent, the other three were rated as acceptable. The scores were relatively high in the policy content, policy nature, policy evaluation, policy field and policy role. Conclusion Our country's family doctor contract service policy had a relatively broad content and is relatively mature. It is suggested to pay attention to the combination of long-term, medium-term and short-term validity of the policies, improve incentive approaches from multiple perspectives, enhance the sense of professional honor of family doctors, and use a variety of policy tools and policy action.

Objective To explore the role of miR-499 targeting TGF-α mRNA protein in regulating the migration and apoptosis of human osteosarcoma cell line Saos2 and its pathogenesis. Methods The expression differences of miR-499 and TGF-α in osteosarcoma tissues were detected by RT-qPCR. Double luciferase reporter gene assay was used to detect the targeting relationship between miR-499 and TGF-α. Transwell cell assay and TUNEL apoptosis assay were used to detect the migration and apoptosis of Saos2 cells. A nude mouse xenograft model of osteosarcoma was constructed to detect the regulatory mechanism of miR-499/TGF-α axis in vivo. Results In osteosarcoma, miR-499 expression was decreased (P＜0.01) but TGF-α mRNA expression was increased(P＜0.01). miR-499 negatively regulated TGF-α mRNA protein expression (P＜0.01). Transfection of miR-499 simulacrum inhibited the migration and promoted apoptosis of Saos2 cells (P＜0.01), while TGF-α promoted the migration and inhibited apoptosis of Saos2 cells (P＜0.01). miR-499 inhibited the carcinogenic effect of TGF-α. Conclusions miR-499 inhibits the biological function of osteosarcoma cell line Saos2 by inhibiting at TGF-α mRNA protein level which suggests that miR-499 may inhibit the development of osteosarcoma.

Traditional Chinese Drugs has proven to have unique merits in treating chronic atrophic gastritis (CAG) , but needs to be verified further by high-quality large-sample clinical studies. We detailed the technique essentials of clinical trial protocol design and assessment for CAG treated with Traditional Chinese Drugs, which may be used as a methodological reference for clinical trial protocol design for CAG treated using Traditional Chinese Drugs, promoting the quality improvement of relevant studies. Then we discussed the essentials of relevant clinical trial protocol design, especially the selection of outcome indicators, in accordance with the attributes of Traditional Chinese Drugs, and features and actual needs of such trials, providing ideas for comprehensive evaluation of efficacy of Traditional Chinese Drugs in treating CAG.

Objective To observe the effects of 5-azacytidine(5-Aza)-induced bone marrow mesenchymal stem cells(BM-MSCs) transplantation on the myocardial infarction area, the expression of related cytokines and potassium channels in rats. Methods Rats were randomly divided into control group, model group, blank control group, BM-MSCs group and 5-Aza-BM-MSCs group. Coronary artery ligation was used to develope a model of myocardial infarction, and cell transplantation was performed using a 4-point injection method. HE staining was used to observe the pathology of infarct myocardium, and the expression of caspase-3, beclin-2, VEGF, PGI2, superoxide dismutase (SOD), IL-3, IL-6 and TNF-α in infarct areas were detected by immunohistochemistry. The Kv1.2 and Kv1.5 proteins expressions of potassium channels were detected by Western blot. Results 1)Compared with the control group, the area of myocardial infarction and the expression level of caspase-3, beclin-2, VEFG, PGI2, IL-3, IL-6 and TNF-α in the model group all significantly increased (P＜0.05). However, the expression level of Kv1.2 and Kv1.5 were reduced (P＜0.05). 2)Compared with the model group, the area of myocardial infarction and caspase-3, beclin-2, and IL-3, IL-6 and TNF-α expression level significantly reduced both in the BM-MSCs group and the 5-Aza-BM-MSCs group (P＜0.05), Kv1.5, VEGF, PGI2, and SOD expression level increased(P＜0.05); Kv1.2 in BM-MSCs group decreased, but increased in 5-Aza-BM-MSCs group (P＜0.05). 3)Compared with the BM-MSCs group, the area of myocardial infarction and the expression of caspase-3 and IL-6 decreased in the 5-Aza-BM-MSCs group (P＜0.05), Kv1.2, VEGF and SOD expression level increased (P＜0.05). Conclusions 5-Aza-BM-MSCs more effectively reduces inflammatory response and apoptosis, promotes neovascularization, improves myocardial antioxidant capacity, reduces myocardial infarction area, and promotes the expression of potassium ion channel Kv1.2 protein as compare to single BM-MSCs transplantation.

Objective To investigate the effects of the main compositions of Astragalus on testicular Leydig cells and their synthesis of estradiol(E2), P450arom under TGF-β1 induction. Methods Leydig cells were divided into three groups: control group, model group and Chinese herbal medicine intervention group. Results Compared with the control group, Leydig cells in the model group showed abnormal morphology and less cells(P＜0.01).TGF-β1 significantly inhibited the synthesis of E2 and P450arom by Leydig cells (P＜0.05). Total Astragalus flavone, total Astragalus saponin and total astragalus polysaccharide all resulted in pathological changes of Leydig cells induced by TGF-β1. Compared with the model group, the number of cells increased significantly (P＜0.01) and all of them alleviated the inhibitory effect of TGF-β 1 on the synthesis of E2 in Leydig cells induced by TGF-β1, and the effect of concentration of 20 mg/L total saponin of Astragalus was the most significant. Conclusions Total Astragalus saponin is the most effective component in Astragalus to exert TGF-β1 inhibitory effect on E2 synthesis by Leydig cells.

Coronavirus disease 2019 (COVID-19) emerged in China in late 2019, which was manifested as fever, cough, dyspnea, normal level of white blood cells, decreased blood lymphocytes, and pulmonary opacities on CT scans. National Health Commission of the People's Republic of China has revised the recommendations on COVID-19 seven times, but there are still many challenges in the diagnosis and management of COVID-19. The radiological findings in a proportion of patients revealed diffuse interstitial opacities, mimicking interstitial pneumonia. Thus it is essential to differentiate the COVID-19 from the acute and progressive diffuse interstitial lung diseases in order to avoid misdiagnosis or overdiagnosis. Therefore, our study compared COVID-19 with interstitial pneumonia and tried to explore the differential diagnostic algorithm.

Objective The efficacy of the two teaching methods for EBUS-TBNA was evaluated by comparing the learning curve, diagnostic accuracy, and specimen acquisition for genotyping by operators and so to find a better one for training pulmonologists. Methods The first fifty patients of each operator learning EBUS-TBNA between January 2015 and June 2019 in a single center were retrospective collected and grouped by the operators training methods. The diagnosis, genotyping and clinical characters were reviewed. Results A total of 442 patients were collected and reviewed. There were two training groups: a conventional training group (232 cases) and a simulator assistant training group (210 cases). There was no statistical difference in the diagnostic yield between the groups of trainees. However, specimen from lung cancer patients in simulator training group were more adequate for gene testing than in conventional training group (86.8% vs 71.2%, P＜0.05). By comparing the learning curve among the groups, it was found that the trainees in stimulator assistant training group needed less minimum number of operations to achieved proficiency than in conventional training group. Conclusions Simulation-based training is demonstrated to be more efficient in improving the bronchoscopists'skill in terms of getting sufficient specimen for gene testing. Simulation-based training may also shorten the time needed for bronchoscopists'training and can be applied in the EBUS-TBNA training course.

Background: Evaluating clinical outcome prior to concurrent chemoradiotherapy remains challenging for oesophageal squamous cell carcinoma (OSCC) as traditional prognostic markers are assessed at the completion of treatment. Herein, we investigated the potential of using sub-region radiomics as a novel tumour biomarker in predicting overall survival of OSCC patients treated by concurrent chemoradiotherapy. Methods: Independent patient cohorts from two hospitals were included for training (n = 87) and validation (n = 46). Radiomics features were extracted from sub-regions clustered from patients' tumour regions using K-means method. The LASSO regression for ‘Cox’ method was used for feature selection. The survival prediction model was constructed based on the sub-region radiomics features using the Cox proportional hazards model. The clinical and biological significance of radiomics features were assessed by correlation analysis of clinical characteristics and copy number alterations(CNAs) in the validation dataset. Findings: The overall survival prediction model combining with seven sub-regional radiomics features was constructed. The C-indexes of the proposed model were 0.729 (0.656–0.801, 95% CI) and 0.705 (0.628–0.782, 95%CI) in the training and validation cohorts, respectively. The 3-year survival receiver operating characteristic (ROC) curve showed an area under the ROC curve of 0.811 (0.670–0.952, 95%CI) in training and 0.805 (0.638–0.973, 95%CI) in validation. The correlation analysis showed a significant correlation between radiomics features and CNAs. Interpretation: The proposed sub-regional radiomics model could predict the overall survival risk for patients with OSCC treated by definitive concurrent chemoradiotherapy. Fund: This work was supported by the Zhejiang Provincial Foundation for Natural Sciences, National Natural Science Foundation of China. Keywords: Oesophageal cancer, Radiomics, Prognostic model, Radiation therapy, Imaging

The gingival recession in the population has a high incidence, which leads to the root surface exposure, tooth sensitivity, and serious impact on the appearance. At present, the gold standard surgery for clinical treatment of gingival recession is the coronal advanced flap + subepithelial connective tissue graft, which can significantly improve the gingival recession. However, there is a big problem in the treatment of the donor site. Now there are a lot of materials which are used to replace the subepithelial connective tissue. In this article, we review the substituted materials of the subepithelial connective tissue.

In this study, human globular adiponectin-glucagon-like peptide-1 analog (gAd-GLP-1-A) fusion protein was expressed and its glucose-lowering effect was measured in vivo. We constructed a prokaryotic expression vector PET28a-gAd-GLP-1-A and transformed the vector into Escherichia coli BL21 (DE3). A recombinant fusion protein of about 25KD was expressed from BL21 (DE3) cells after isopropylthio-β-D-galactoside induction. This protein was N-terminal His-tagged gAd-GLP-1-A fusion protein. Most of the protein was expressed in inclusion body. The fusion protein in inclusion body was purified by using High-Affinity Nickel Iminodiacetic Acid Resin and refolded in urea gradient refolding buffer. The refolded protein was incubated with enterokinase to remove the N-terminal His-tag. The fusion protein without His-tag is gAd-GLP-1-A fusion protein, which exhibited significant glucose-lowering effect in diabetic mice.

Abstract Genetic data are now widely available. There is, however, an apparent lack of concerted effort to produce software systems for statistical analysis of genetic data compared with other fields of statistics. It is often a tremendous task for end-users to tailor them for particular data, especially when genetic data are analysed in conjunction with a large number of covariates. Here, R http://www.r-project.org, a free, flexible and platform-independent environment for statistical modelling and graphics is explored as an integrated system for genetic data analysis. An overview of some packages currently available for analysis of genetic data is given. This is followed by examples of package development and practical applications. With clear advantages in data management, graphics, statistical analysis, programming, internet capability and use of available codes, it is a feasible, although challenging, task to develop it into an integrated platform for genetic analysis; this will require the joint efforts of many researchers.

Activation of the cholinergic anti-inflammatory pathway, which relies on the α7nAchR (alpha 7 nicotinic acetylcholine receptor), has been shown to decrease proinflammatory cytokines. This relieves inflammatory responses and improves the prognosis of patients with experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, pancreatitis, arthritis and other inflammatory syndromes. However, whether the cholinergic anti-inflammatory pathway has an effect on acute viral myocarditis has not been investigated. Here, we studied the effects of the cholinergic anti-inflammatory pathway on acute viral myocarditis.In a coxsackievirus B3 murine myocarditis model (Balb/c), nicotine and methyllycaconitine were used to stimulate and block the cholinergic anti-inflammatory pathway, respectively. Relevant signal pathways were studied to compare their effects on myocarditis, survival rate, histopathological changes, ultrastructural changes, and cytokine levels. Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-α and IL-6. Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and upregulated the expression of TNF-α and IL-6. In addition, levels of the signaling protein phosphorylated STAT3 were higher in the nicotine group and lower in the methyllycaconitine group compared with the untreated myocarditis group.These results show that nicotine protects mice from CVB3-induced viral myocarditis and that methyllycaconitine aggravates viral myocarditis in mice. Because nicotine is a α7nAchR agonist and methyllycaconitine is a α7nAchR antagonist, we conclude that α7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-α and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-α and IL-6, aggravating viral myocarditis.

BACKGROUND: Several previous reports have revealed that idiopathic ventricular arrhythmias (VAs), including premature ventricular contractions (PVCs) and ventricular tachycardias (IVTs), can originate from endocardial mitral annulus (ENDO MA). However, these data are limited to ENDO MA VAs, and little is known about the electrocardiographic (ECG) characteristics and the efficacy of radiofrequency catheter ablation (RFCA) via the coronary venous system for the VAs arising from the epicardial MA (EPI MA). METHODOLOGY/PRINCIPAL FINDINGS: Characteristics of body surface electrocardiogram and electrophysiologic recordings were analyzed in 21 patients with symptomatic PVCs/IVTs originating from the vicinity of MA. Among 597 patients with PVCs/IVTs, the incidence of VAs originating from the ENDO and EPI MA was 3.52% (21 cases). Eleven (52%) from the ENDO MA, and 10 (48%) from the EPI MA. There were different characteristics of ECG of PVCs/VT originating from the ENDO and EPI MA. The prolonged pseudodelta wave time and intrinsicoid deflection time in lead V2 and the precordial maximum deflection index reliably differentiated EPI MA VAs from ENDO MA VAs with high sensitivity and specificity. Successful RFCA in 18 patients could be achieved (85.7% acute procedural success). CONCLUSIONS/SIGNIFICANCE: ECG characteristics of PVCs/VTs originating from the different portions of the MA are different, and can help regionalize the origin of these arrhythmias. RFCA within the coronary venous system was relatively effective and safe for the PVCs/IVTs and should be seen as an alternative approach, when the MA PVCs/IVTs could not be eliminated by RFCA from the endocardium.