AlloReverse: multiscale understanding among hierarchical allosteric regulations.

Increasing data in allostery are requiring analysis of coupling relationships among different allosteric sites on a single protein. Here, based on our previous efforts on reversed allosteric communication theory, we have developed AlloReverse, a web server for multiscale analysis of multiple allosteric regulations. AlloReverse integrates protein dynamics and machine learning to discover allosteric residues, allosteric sites and regulation pathways. Especially, AlloReverse could reveal hierarchical relationships between different pathways and couplings among allosteric sites, offering a whole map of allostery. The web server shows a good performance in re-emerging known allostery. Moreover, we applied AlloReverse to explore global allostery on CDC42 and SIRT3. AlloReverse predicted novel allosteric sites and allosteric residues in both systems, and the functionality of sites was validated experimentally. It also suggests a possible scheme for combined therapy or bivalent drugs on SIRT3. Taken together, AlloReverse is a novel workflow providing a complete regulation map and is believed to aid target identification, drug design and understanding of biological mechanisms. AlloReverse is freely available to all users at https://mdl.shsmu.edu.cn/AlloReverse/ or http://www.allostery.net/AlloReverse/.

'Single-shot' pulmonary vein isolation using a novel lotos pulsed field ablation catheter: a pre-clinical evaluation of feasibility, safety, and 30-day efficacy.

AIMS: Pulsed field ablation (PFA) is emerging as a non-thermal, tissue-specific technique for pulmonary vein isolation (PVI) in atrial fibrillation therapy. This pre-clinical study aims to investigate the feasibility and safety of PVI using a novel PFA system including a nanosecond-scale PFA generator, a novel lotos PFA catheter, and a customized 12 Fr steerable sheath. METHODS AND RESULTS: A total of 11 Yorkshire swine were included in this study, with 4 in the acute cohort and 7 in the chronic cohort. Under general anaesthesia, transseptal puncture and pulmonary vein (PV) angiography was initially performed. The PFA catheter was navigated to position at the right and left PV antrum after the electroanatomic reconstruction of the left atrium. Biphasic PFA applications were performed on PVs in both the spindle-shaped and the lotos-shaped poses. Pulmonary vein isolation and PFA-associated safety were assessed 30 min after ablation in both cohorts and 30 days later in the chronic cohort. Detailed necropsy and histopathology were performed. Additional intracardiac echocardiography and coronary angiogram were evaluated for safety. All target PVs (n = 20) were successfully isolated on the first attempt. No spasm of coronary artery or microbubble was seen during the procedure. Eleven of 12 PVs (91.6%) remained in isolation at the 30-day invasive study. No evidence of PV stenosis was observed in any targets. However, transient diaphragm capture occurred in 17.6%. Histopathological examinations showed no evidence of collateral injury. CONCLUSION: This study provides scientific evidence demonstrating the safety and efficacy of the novel PFA catheter and system for single-shot PVI, which shows great potential.

Electrophysiological characteristics and long-term outcome of substrate-based catheter ablation for left posterior fascicular ventricular tachycardia targeting fragmented antegrade Purkinje potentials during sinus rhythm.

AIMS: The aim of this study was to investigate the electrophysiological characteristics and long-term outcome of patients undergoing substrate-based ablation of left posterior fascicular ventricular tachycardia (LPF-VT) guided by targeting of fragmented antegrade Purkinje potentials (FAPs) during sinus rhythm. METHODS AND RESULTS: This study retrospectively analysed 50 consecutive patients referred for ablation. Substrate mapping during sinus rhythm was performed to identify the FAP that was targeted by ablation. FAPs were recorded in 48 of 50 (96%) patients during sinus rhythm. The distribution of FAPs was located at the proximal segment of posterior septal left ventricle (LV) in two (4.2%) patients, middle segment in 33 (68.8%) patients, and distal segment in 13 (27.1%) patients. In 32 of 48 (66.7%) patients, the FAP displayed a continuous multicomponent fragmented electrogram, while a fragmented, split, and uncoupled electrogram was recorded in 16 (33.3%) patients. Entrainment attempts at FAP region were performed successfully in seven patients, demonstrating concealed fusion and the critical isthmus of LPF-VT. Catheter ablation targeting at the FAPs successfully terminated the LPF-VT in all 48 patients in whom they were seen. Left posterior fascicular (LPF) block occurred in four (8%) patients after ablation. During a median follow-up period of 61.2 ± 16.8 months, 47 of 50 (94%) patients remained free from recurrent LPF-VT. CONCLUSION: Ablation of LPF-VT targeting FAP during sinus rhythm results in excellent long-term clinical outcome. FAPs were commonly located at the middle segment of posterior septal LV. Region with FAPs during sinus rhythm was predictive of critical site for re-entry.

Muscle quality index and cardiovascular disease among US population-findings from NHANES 2011-2014.

BACKGROUND AND OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. However, current evidence on the association between muscle quality and CVD is limited. This study investigates the potential association between the muscle quality index (MQI) and the prevalence of CVD and CVD-related mortality. METHODS: Participants were selected from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Data on mortality and causes of death were obtained from the National Death Index (NDI) records through December 31, 2019. Statistical analysis used in this study, including weighted multivariable linear and logistic regression, cox regression and Kaplan-Meier (K-M) analysis, to estimate the association between MQI and all-cause mortality as well as CVD mortality. In addition, subgroup analysis was used to estimate the association between MQI and CVD subtypes, such as heart attack, coronary heart disease, angina, congestive heart failure, and stroke. RESULTS: A total of 5,053 participants were included in the final analysis. Weighted multivariable linear regression models revealed that a lower MQI.total level was independently associated with an increased risk of CVD development in model 3, with t value =-3.48, 95%CI: (-0.24, -0.06), P = 0.002. During 5,053 person-years of 6.92 years of follow-up, there were 29 deaths from CVD. Still, the association between MQI.total and CVD mortality, as well as all-cause mortality did not reach statistical significance in the fully adjusted model (HR = 0.58, 95% CI: 0.21-1.62, P = 0.30; HR = 0.91, 95% CI:0.65,1.28, P = 0.59, respectively). Subgroup analysis confirmed that MQI.total was negatively associated with congestive heart failure (OR = 0.35, 95% CI = 0.18,0.68, P = 0.01). CONCLUSION: This study highlights the potential of MQI as a measure of muscle quality, its negative correlation with congestive heart failure (CHF). However, MQI was not very useful for predicting the health outcomes such as CVD and mortality. Therefore, more attention should be paid to the early recognition of muscle weakness progression in CHF. Further studies are needed to explore more effective indicator to evaluate the association between muscle quality and health outcomes.

Prevalence of congenital heart disease among school children in Qinghai Province.

OBJECTIVES: This study aimed to investigate the prevalence of congenital heart disease (CHD) among school children in Qinghai province, a high-altitude region in China. METHODS: A cross-sectional study was conducted among school-aged children in 2019. All subjects completed a survey with a structure questionnaire and underwent CHD screening. CHD was screened by standard physical examination and further confirmed by echocardiography. Multivariate logistic regression were used to estimate the association of CHD prevalence with gender, nationality, and altitude. RESULTS: A total of 43,562 children aged 3-19 years participated in the study. The mean (SD) age was 11.2 (3.3) years. 49.7% were boys, and 80.0% were of Tibetan. CHD was identified in 293 children, with an overall prevalence of 6.73 ‰. Among them, 239 were unrecognized CHD, yielding a prevalence of 5.49 ‰. Atrial septal defect accounted for 51.9% of the CHD, followed by patent ductus arteriosus (31.1%), ventricular septal defect (9.9%). The CHD prevalence was significantly higher in female (8 ‰), Han race (18 ‰), children lived in Qumalai county (13 ‰), and children lived in a higher altitude (13 ‰). Female had greater prevalence of total CHD, atrial septal defect, and patent ductus arteriosus, but insignificant difference was observed in ventricular septal defect prvalence than male. In multivariable logistic regression analyses, female (OR, 1.48; 95% CI, 1.17-1.87, P = 0.001), Han population (OR, 3.28; 95% CI, 1.67-6.42, P = 0.001), and higher altitudes (OR, 2.28; 95% CI, 1.74-3.00, P < 0.001) were shown to be independently association with CHD prevalence. CONCLUSIONS: The prevalence of CHD in Qinghai province was 6.73 ‰. Altitude elevation, female, and Han population were independently association with CHD prevalence.

CircPUM1 promotes hepatocellular carcinoma progression through the miR-1208/MAP3K2 axis.

Hepatocellular carcinoma (HCC) is a common disease with a significant mortality, and there is no effective treatment for advanced patients. Growing evidence indicates that circRNAs are closely related to HCC progression, may be used as biomarkers and targets for the diagnosis and treatment of HCC. Recent researches have shown that circPUM1 may play an oncogene role in a variety of human cancers, but its role in HCC development has not been reported. Our study found that circPUM1 could promote the proliferation, migration and invasion of HCC cells in vitro. In addition, in vivo studies showed that circPUM1 could increase the development of HCC tumours and regulate the expression of EMT-related proteins. Furthermore, we demonstrated that circPUM1 could promote the development of HCC by up-regulating the expression of MAP3K2 via sponging miR-1208. Our study suggested that circPUM1 may be a potential therapeutic target for HCC.

Epidemiological and phylogenetic analysis of canine kobuviruses in Tangshan, China.

Canine kobuviruses (CaKoV) have been found in healthy and diarrheic dogs as well as asymptomatic wild carnivores in various countries. In order to investigate the prevalence and evolution of CaKoV in Tangshan, China, 82 dog fecal samples from pet hospitals in Tangshan were subjected to RT-PCR targeting a segment of the 3D gene of CaKoV. Using this method, we identified CaKoV in 14 samples (17.07%, 14/82). Of the CaKoV-positive samples, 78.57% (11/14) and 50% (7/14) were positive for canine parvovirus and canine coronavirus, respectively. The nucleotide sequences of the 14 strains 96.6%-100% identical to each other and 77.6%-99.2% identical to representative sequences from the NCBI GenBank database. We also amplified the 14 VP1 gene sequences and found that they were 93.3%-99.6% identical to each other and 73.3%-97.8% identical to representative sequences from the NCBI GenBank database. Phylogenetic analysis revealed that the 14 CaKoV strains from Tangshan are closely related to those identified in China and Thailand and display less similarity to those found in Africa, the United States, and Europe. Our data suggest that CaKoV circulated in young pet dogs in Tangshan and displays a high co-infection rate with CCoV and CPV. However, the relationship between the three viruses and their roles in the host requires further investigation.

Novel Strategy for Predicting Conduction Abnormalities During Transcatheter Closure of Perimembranous Ventricular Septal Defect in Adults.

BACKGROUND: In this study we evaluated the feasibility and efficacy of predicting conduction system abnormalities under 3-dimensional (3D) electroanatomic mapping guidance during transcatheter closure of perimembranous ventricular septal defects (pmVSDs) in adults.Methods and Results:The distribution of the His-Purkinje system (HPS) close to the margins of pmVSDs in the left ventricle was identified using 3D electroanatomic mapping and near-field HPS was further confirmed by different pacing protocols. Of the 20 patients in the study, 17 (85%) were successfully treated by transcatheter intervention. The minimum distance between the margins of the pmVSD and near-field HPS, as measured by 3D electroanatomic mapping, ranged from 1.3 to 3.9 mm (mean [± SD] 2.5±0.7 mm). Five patients with a minimum distance <2 mm had a higher risk (3/5; 60%) for adverse arrhythmic events, whereas patients with a distance >2 mm were at a much lower risk (1/15; 6.7%) of procedure-related conduction block (P=0.032). No other adverse events were recorded during the follow-up period (median 30 months). CONCLUSIONS: A minimum distance between the pmVSD and near-field HPS <2 mm was associated with a relatively high risk of closure-related conduction block. 3D electroanatomic mapping may be helpful in guiding decision making for transcatheter closure and reduce the incidence of adverse arrhythmic events.

Genetic Variants on SCN5A, KCNQ1, and KCNH2 in Patients with Ventricular Arrhythmias during Acute Myocardial Infarction in a Chinese Population.

OBJECTIVE: Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. About half of sudden deaths from AMI are mainly because of malignant ventricular arrhythmias (VA) after AMI. The sodium channel gene SCN5A and potassium channel genes KCNQ1 and KCNH2 have been widely reported to be genetic risk factors for arrhythmia including Brugada syndrome and long QT syndrome (LQTS). A few studies reported the association of SCN5A variant with ventricular tachycardia (VT)/ventricular fibrillation (VF) complicating AMI. However, little is known about the role of KCNQ1 and KCNH2 in AMI with VA (AMI_VA). This study focuses on investigating the potential variants on SCN5A, KCNQ1, and KCNH2 contributing to AMI with VA in a Chinese population. MATERIALS AND METHODS: In total, 139 patients with AMI_VA, and 337 patients with AMI only, were included. Thirty exonic sites were selected to be screened. Sanger sequencing was used to detect variants. A subsequent association study was also performed between AMI_VA and AMI. RESULTS: Twelve variants [5 on KCNH2(NM_000238.3), 3 on KCNQ1(NM_000218.2), and 4 on SCN5A(NM_198056.2)] were identified in AMI_VA patients. Only 5 (KCNH2: c.2690A>C; KCNQ1: c.1927G>A, c.1343delC; SCN5A: c.1673A>G, c.3578G>A) of them are missense variants. Two (KCNQ1: c.1343delC and SCN5A: c.3578G>A) of the missense variants were predicted to be clinically pathogenic. All these variants were further genotyped in an AMI without VA group. The association study identified a statistically significant difference in genotype frequency of KCNH2: c.1539C>T and KCNH2: c.1467C>T between the AMI and AMI_VA groups. Moreover, 2 rare variants (KCNQ1: c.1944C>T and SCN5A: c.3621C>T) showed an elevated allelic frequency (more than 1.5-fold) in the AMI_VA group when compared to the AMI group. CONCLUSION: Twelve variants (predicting from benign/VUS to pathogenic) were identified on KCNH2, KCNQ1, and SCN5A in patients with AMI_VA. Genotype frequency comparison between AMI_VA and AMI identified 2 significant common variants on KCNH2. Meanwhile, the allelic frequency of 2 rare variants on KCNQ1 and SCN5A, respectively, were identified to be enriched in AMI_VA, although there was no statistical significance. The present study suggests that the ion-channel genes KCNH2, KCNQ1, and SCN5A may contribute to the pathogenesis of VA during AMI.

[Effects of Renshenjian Decoction on blood and urine metabonomics in type 2 diabetes rats based on ~1H-NMR].

Proton nuclear magnetic resonance(~1H-NMR) is used to investigate the effect of Renshenjian Decoction on serum and urine metabolism of type 2 diabetic rats with insulin resistance induced by high-sugar and high-fat diet combined with low-dose streptozotocin(STZ). After the successful establishment of the insulin resistance model of type 2 diabetes, administration for 35 days, the serum and urine of rats were taken. Once the ~1H-NMR data have been collected and processed, PCA and OPLS-DA were used to analyze them. The results show that: compared with the blank group, the contents of methionine, taurine, α-glucose and ß-glucose in the serum of the model group increased significantly(P<0.001), while the contents of 3-hydroxybutyric acid, lactic acid and unsaturated fatty acids decreased significantly(P<0.01). In the model group, the contents of trimethylamine oxide, glycine, α-glucose, ß-glucose, taurine and phosphocholine in urine increased significantly(P<0.05), while the contents of creatine, lactic acid, acetic acid and citric acid decreased significantly(P<0.05). Compared with the model group, the contents of 3-hydroxybutyric acid and unsaturated fatty acids in serum of rats in the treatment group increased significantly(P<0.05), while the contents of taurine, α-glucose and ß-glucose decreased significantly(P<0.01). In the treatment group, the contents of lactic acid, taurine and creatine in urine increased significantly(P<0.05), while the contents of trimethylamine oxide, glycine, α-glucose, ß-glucose and phosphocholine decreased significantly(P<0.01). The results show that Renshenjian Decoction can regulate metabolic disorder and promote the metabolic phenotype to return to the normal range. It displayed therapeutic effect on type 2 diabetic rats with insulin resistance and provided a certain scientific basis for the biological basic research of Renshenjian Decoction by improving insulin resistance in diabetes mellitus.

Interleukin 8 and Pentaxin (C-Reactive Protein) as Potential New Biomarkers of Bovine Tuberculosis.

Bovine tuberculosis (bTB) is caused by Mycobacterium bovis During the early stage of infection, greater than 15% of M. bovis-infected cattle shed mycobacteria through nasal secretions, which can be detected by nested PCR. To compare the differences in the protein profiles of M. bovis-infected cattle that were nested PCR positive (bTBPCR-P) and M. bovis-infected cattle that were nested PCR negative (bTBPCR-N) and to screen for biomarkers that will facilitate the early and accurate detection of bTB, we investigated the protein expression profiles of serum and bovine purified protein derivative (PPD-B)-stimulated plasma among bTBPCR-P (n = 20), bTBPCR-N (n = 20), and uninfected cattle (NC; n = 20) by iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (iTRAQ-2D LC-MS/MS). After comprehensive analysis, we selected 15 putative differentially expressed serum proteins and 15 plasma proteins for validation by parallel reaction monitoring (PRM) with the same cohort used in the iTRAQ analysis. Four serum and five PPD-B-stimulated proteins were confirmed in follow-up enzyme-linked immunosorbent assays. PPD-B-stimulated interleukin 8 (IL-8) displayed the potential to differentiate M. bovis-infected cattle from NC, with an area under the curve (AUC) value of 0.9662, while PPD-B-stimulated C-reactive protein (CRP) displayed the potential to differentiate bTBPCR-P from bTBPCR-N, with an AUC value of 1.00. Finally, double-blind testing with 244 cattle indicated that the PPD-B-stimulated IL-8 test exhibited good agreement with traditional tests (κ > 0.877) with a >90% relative sensitivity and a >98% relative specificity; the PPD-B-stimulated CRP test displayed good agreement with nested PCR (κ = 0.9117), with an observed 94% relative sensitivity and 97% relative specificity. Therefore, the PPD-B-stimulated IL-8 and CRP tests could be used to detect bTB and to differentiate bTBPCR-P from bTBPCR-N.

Association between elevated blood glucose level and non-valvular atrial fibrillation: a report from the Guangzhou heart study.

BACKGROUND: To estimate the prevalence of elevated blood glucose level (EBG, including type 2 diabetes mellitus and impaired fasting glucose), and its association with non-valvular atrial fibrillation (NVAF) in Guangzhou, China. METHODS: The population-based follow-up Guangzhou Heart Study collected baseline data from July 2015 to August 2017 among 12,013 permanent residents aged > 35 from 4 Guangzhou districts. Two streets (Dadong and Baiyun) in the Yuexiu District, and one street (Xiaoguwei) and two towns (Xinzao and Nancun) in the Panyu District were chosen as representative of urban and rural areas, respectively. Each participant completed a comprehensive questionnaire, and underwent physical examination, blood sample collection for laboratory testing, electrocardiography, and other evaluations. Multivariable logistic regression analyses were used to estimate the independent association between hyperglycemia and NVAF prevalence. RESULTS: The prevalence of EBG in overall study population was 29.9%. Compared with residents without EBG, the odds ratio (OR) for AF among residents with EBG was significantly higher (1.94, 95% confidence interval [CI]: 1.40-2.70, P <  0.001), even after multivariate adjustment for metabolic abnormalities (OR = 1.60, 95% CI: 1.14-2.25, P = 0.007), and driven by women (OR = 1.80, 95% CI: 1.12-2.91, P = 0.016). CONCLUSIONS: In Guangzhou, China, prevalence of EBG is high among residents aged > 35 years and associated with a multivariate adjusted increase in prevalence of NVAF overall and in women.

Mid-term outcomes of concomitant left atrial appendage closure and catheter ablation for non-valvular atrial fibrillation: a multicenter registry.

To investigate the safety and midterm outcome of concomitant left atrial appendage (LAA) closure and catheter ablation (CA) as a one-stage hybrid procedure for non-valvular atrial fibrillation (AF) in a multicenter registry. A total of 50 consecutive patients with symptomatic drug-resistant non-valvular AF with CHA2DS2-VASc score ≥ 2 and contraindications for antithrombotic therapy were included in the prospectively established LAA closure registry, and underwent concomitant LAA closure (48 for WATCHMAN and 2 for ACP) and CA procedure (40 for radiofrequency and 10 for cryoballoon CA). Two cardiac tamponades, one peripheral vascular complications and one mild air embolism were observed during perioperative period. After mean follow-up of 20.2 ± 11.5 months, 18 (36%) patients presented with atrial arrhythmia relapse and 45 (91.8%) patients presented with complete sealing; furthermore, there were two transient ischemic attacks and one ischemic stroke under an off-oral anticoagulant situation, respectively. Concomitant CA and LAA closure as a one-stage hybrid procedure might be feasible and potentially decrease costs in patients with symptomatic non-valvular AF with high stroke risk and contraindication to antithrombotic treatment, and as safe as LAA closure procedure only during the perioperative period. However, it was necessary to further validate the mid-term safety.

Scalable Rhodium(III)-Catalyzed Aryl C-H Phosphorylation Enabled by Anodic Oxidation Induced Reductive Elimination.

Transition metal catalyzed C-H phosphorylation remains an unsolved challenge. Reported methods are generally limited in scope and require stoichiometric silver salts as oxidants. Reported here is an electrochemically driven RhIII -catalyzed aryl C-H phosphorylation reaction that proceeds through H2 evolution, obviating the need for stoichiometric metal oxidants. The method is compatible with a variety of aryl C-H and P-H coupling partners and particularly useful for synthesizing triarylphosphine oxides from diarylphosphine oxides, which are often difficult coupling partners for transition metal catalyzed C-H phosphorylation reactions. Experimental results suggest that the mechanism responsible for the C-P bond formation involves an oxidation-induced reductive elimination process.

Genomic sequence and virulence of a novel NADC30-like porcine reproductive and respiratory syndrome virus isolate from the Hebei province of China.

Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of porcine reproductive and respiratory syndrome (PRRS), which results in immense economic losses in the swine industry. Outbreaks of disease caused by NADC30-like PRRSV are of great concern in China. Here, a novel variant, NADC30-like PRRSV strain HB17A, was analyzed and its pathogenicity in pigs was examined. The full-length genome sequence of HB17A shared 83.6-95.1% nucleotide similarity with NADC30-like and NADC30 PRRSV without any gene insertions, but with a unique 2-amino acid deletion in Nsp2. A phylogenetic analysis showed that HB17A clustered with NADC30 strains. Different degrees of variation in the signal peptide, transmembrane region (TM), primary neutralizing epitope (PNE), non-neutral epitopes, and N-glycosylation sites were observed in GP5. Challenge experiments showed that HB17A infection resulted in persistent fever, moderate respiratory clinical signs, low levels of viremia and viral loads in serum, and mild gross and microscopic lung lesions. Moreover, IFN-γ, IL-6, and IL-10 cytokine levels were significantly elevated in serum, but the levels of IFN-α and IL-2 were similar to those of the negative controls. HB17A was less pathogenic but was secreted longer in nasal discharge than HP-PRRSV FZ06A. Our findings indicate that HB17A is a novel NADC30-like strain with certain deletions and mutations but with no evidence of genomic recombination. This strain exhibits intermediate virulence in pigs. This research will be help define the evolutionary characteristics of Chinese NADC30-like PRRSV.

[Effects of Renshenjian decoction on pancreatic metabonomic profiles in insulin resistance rats based on ¹H-NMR metabonomics].

Pancreas metabonomic profiles of the type 2 diabetic rats' induced by streptozotocin(STZ) and high-sugar, high fat diet on the treatment of Renshenjian decoction(RSJD) after 8 weeks were investigated.In this study, 48 Rats were randomly divided into four groups: normal control (NC), Pathological model (PM), Renshenjian decoction(RSJD 3.76 g·kg⁻¹) and glimepiride control (GC 0.04 mg·kg⁻¹). They are induced insulin resistance model of type 2 diabetes mellitus by streptozotocin(STZ) after 4 weeks' high-sugar, high fat diet except for NC. After sucessful modeling, they are given intragastric administration respectively with same amount of saline, RSJD and glimepiride in 4 weeks. At the end of the 8th week, the pancreatic tissue of rats in each group was collected, and the ¹H-NMR spectrum was collected after being treated by certain method, and analyzed by principal component analysis (PCA). Compared with NC's rats, we found PM's a significant elevation in the level of leucine/isoleucine, valine, lactic acid, creatine but reduction in the level of inose and less obvious changes in the level of creatine, cholic acid, taurine in pancreatic extract. After having been recieved RSJD, reduction level in leucine/isoleucine, valine, alanine, creatine, choline, taurine are also found in pancreatic extract of RSJD's rats, together with the increase of creatinine and tryptophan levels. The results showed that RSJD could regulate the level of amino acids in pancreas of IR rats, promoting a recovery in the process of metabolism. It's helpful to simulate the metabolic changes of IR rats via ¹H-NMR for a further understanding to study the mechanism how RSJD treat IR rats.

[Network Pharmacological Studies of Puerariae Radix in Improving Insulin Resistance].

Objective: To investigate the active components and potential mechanism of Puerariae Radix in improving insulin resistance by using network pharmacological method. Methods: Key target proteins related with insulin resistance were selected based on molecular docking technology, and then took the selected components with 31 target proteins of four pathways for docking. Meanwhile, component-target proteins network was established to network analysis by software Cytoscape 3. 2. 1. Results: 19 compounds had close interactions with four pathways such as AMPK. There were 13 compositions can verify through literature, which revealing that active ingredients and potential molecular mechanism of Puerariae Radix in improving insulin resistance, preliminarily. Conclusion: The network pharmacological method is helpful to explore the possible active components in Puerariae Radix and elucidate the mechanism.

Genetic characterization of porcine kobuvirus and detection of coinfecting pathogens in diarrheic pigs in Jiangsu Province, China.

In this study, 396 samples from diarrheic pigs on 46 pig farms in Jiangsu Province, China, were analyzed by RT-PCR. One-hundred eighty-one pigs from 37 farms tested positive for porcine kobuvirus (PKV). Phylogenetic analysis of the 3D gene from 19 isolates showed sequence homology of 88.0 %-100 % and 69.4 %-100 % for nucleotides and amino acids, respectively, while similarity to isolates of other kobuviruses was 69.6 %-78.8 % and 27.8 %-56.9 %, respectively. One-hundred eighty-five samples contained two or more pathogens, and 31/68 PKV-positive samples tested positive for other diarrheic pathogens, confirming the existence of PKV infection and coinfection.

A case report of right bundle branch block and junctional beats during ablation at the right ventricle outflow tract: metallic occluder's unanticipated effect.

Background: Previously, ablation at the outflow tract was considered to be safe and rarely affected the His-Purkinje system due to their spatial distance. However, we have reported a case of right bundle branch block (RBBB) and junctional beats that were recorded during radiofrequency catheter ablation in a patient who had a history of peri-membranous ventricular septal defect (pmVSD) closure and the implantation of a metallic occluder. Case summary: A 16-year-old girl with a metallic occluder for peri-membranous ventricular septum defect underwent an ablation procedure for premature ventricular complexes. During the ablation at the right ventricular outflow tract (RVOT), RBBB and junctional beats were recorded. His bundle potentials and the high-frequency potential generated by electrical interference were observed when mapping the margin of the occluder. To ensure safety, we attempted ablation at the right coronary cusp in the left ventricular outflow tract, which eventually proved to be successful, presenting an alternative ablation strategy. Conclusion: This is a rare report of RBBB and junctional beats observed during ablation at RVOT in a patient with pmVSD and a metallic occluder. The observed damage to the His-Purkinje system may be attributed to uncontrolled radiofrequency energy heating up caused by the metallic device. This case emphasizes the importance of thorough electroanatomic and activation mapping prior to starting the ablation procedure, especially in complicated cases. Furthermore, it suggests that ablation at a relatively remote position is both feasible and relatively safe for patients with occluder devices.

Bone Marrow Mesenchymal Stem Cell Extracellular Vesicle-derived miR-27b- 3p activates the Wnt/Β-catenin Pathway by Targeting SMAD4 and Aggravates Hepatic Ischemia-reperfusion Injury.

BACKGROUND: To investigate the roles of extracellular vesicles (EVs) secreted from bone marrow mesenchymal stem cells (BMSCs) and miR-27 (highly expressed in BMSC EVs) in hepatic ischemia‒ reperfusion injury (HIRI). APPROACHES AND RESULTS: We constructed a HIRI mouse model and pretreated it with an injection of agomir-miR-27-3p, agomir-NC, BMSC-EVs or control normal PBS into the abdominal cavity. Compared with the HIRI group, HIRI mice preinjected with BMSC-EVs had significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated liver necrosis (P<0.05). However, compared with HIRI+NC mice, HIRI+miR-27b mice had significantly increased ALT and AST levels, aggravated liver necrosis, and increased apoptosis-related protein expression (P<0.05). The proliferation and apoptosis of AML-12 cells transfected with miR-27 were significantly higher than the proliferation and apoptosis of AML-12 cells in the mimic NC group (P<0.01) after hypoxia induction. SMAD4 was proven to be a miR-27 target gene. Furthermore, compared to HIRI+NC mice, HIRI+miR-27 mice displayed extremely reduced SMAD4 expression and increased levels of wnt1, ß-catenin, c-Myc, and Cyclin D1. CONCLUSION: Our findings reveal the role and mechanism of miR-27 in HIRI and provide novel insights for the prevention and treatment of HIRI; for example, EVs derived from BMSCs transfected with antimiR- 27 might demonstrate better protection against HIRI.