Objective To investigate the safety and efficacy of novel bioabsorbable vascular scaffold(BVS)in the treatment of patients with complex coronary artery disease.Methods This was a retrospective,matched,single-center observational study.45 patients with coronary atherosclerotic cardiopathy received BVS treatment in the cardiovascular medicine department Department of the Affiliated Hospital of Guangdong Medical University from June 2020 to June 2021(BVS),and 45 patients treated with drug-eluting stents(DES)group were selected according to matching study requirements during the same period.Baseline,surgical,and follow-up data were compared between the two groups to evaluate safety and efficacy.The main measures of safety were:surgical time,intraoperative adverse events,etc.,and the end point of efficacy was target lesion failure(TLF),including cardiac death,target vessel myocardial infarction,and ischa-driven target lesion revascularization.Results A total of 90 patients were enrolled in this study,all of whom were followed up for at least 3 years.There were 20 cases of bifurcation lesions and 25 cases of diffuse long lesions in the two groups,and 50 cases of imaging were reviewed among the 90 patients.The proportion of stable coronary heart disease,history of diabetes,history of hypertension,history of smoking,pre-dilated balloon pressure and postoperative diastolic blood pressure in BVS group was higher than that in DES group,and the proportion of family history was lower than that in DES group(all P＜0.05).There were no statistically significant differences in the rates of cardiac death,target vessel myocardial infarction,and ischemia-driven revascularization of target lesions between the two groups(all P＞0.05).Binary Logistic regression model analysis showed that the diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis(OR 2.786,95％CI 1.096-7.081,P=0.031).Conclusions Compared with traditional DES,BVS implantation has consistent safety and efficacy in the treatment of complex coronary artery disease within 3 years.The diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis.

Objective:To carry out an overview of systematic reviews on interventions to prevent the recurrence of diabetic foot ulcer (DFU) patients.Methods:Systematic reviews or Meta-analysis on interventions to prevent DFU recurrence were electronically retrieved from databases such as China National Knowledge Infrastructure, WanFang Data, VIP, China Biology Medicine disc, Joanna Briggs Institute (JBI) Evidence-Based Healthcare Center Database, Cochrane Library, PubMed, Embase, CINAHL and Web of Science. The search period was from database establishment to April 20, 2023. Two researchers independently searched and screened literature, and extracted data, and used AMSTAR 2 software and the quality evaluation criteria for systematic review of JBI Evidence-Based Healthcare Center to evaluate the methodological quality of the included literature. GRADE evaluation system was used for quality assessment of outcome indicators (DFU recurrence rate, effectiveness of measures to prevent DFU recurrence) .Results:A total of 24 systematic reviews were included. Studies showed that monitoring and intervention of foot skin temperature, therapeutic shoes or insoles, comprehensive intervention measures, and specific surgical methods could reduce the recurrence rate of DFU, while foot self-care, foot exercise, health education, and psychological intervention had no statistical effect on preventing DFU recurrence. The methodological quality of systematic reviews was generally low. The reports of four articles were relatively complete, 18 articles had certain defects, and two articles had serious defects. The evaluation of evidence quality showed that there were three pieces of moderate-quality evidence, seven pieces of low-quality evidence, and 30 pieces of extremely low-quality evidence.Conclusions:Existing evidence suggests that foot skin temperature monitoring and intervention, therapeutic shoes or insoles, comprehensive intervention measures, and specific surgical methods (such as Achilles tendon lengthening, metatarsophalangeal joint replacement, metatarsal head resection and so on) have a positive impact on preventing DFU recurrence. Rigorous and high standard research is still needed to verify the controversial issues, so as to provide reliable evidence for future clinical practice and studies.

Aim To investigate the effects of hedysar-um polybotrys polysacchcaide(HPS)on gastric muco-sal inflammation of diabetic gastroparesis(DGP)rats and its possible mechanism.Methods A total of 62 male Wistar rats were randomly divided into the control group(12)and the modeling group(50).Except for the control group,the remaining rats were given multi-ple intraperitoneal injections of streptozotocin(25 mg ·kg-1 for three consecutive days)and irregular feed-ing of high-sugar and high-fat diet to replicate DGP model.The model rats were randomly divided into the model group(intragastatically purified water),low,medium and high dose HPS groups(50,100,200 mg ·kg-1·d-1)and the metformin group(90 mg· kg-1·d-1),respectively,and the control group was intragastrically treated with equal volume of purified water once a day for eight weeks.The pathological morphology of gastric mucosa was observed by HE stai-ning;the contents of TNF-α,IL-6,GAS and MTL in gastric mucosa were detected by ELISA.The expres-sion of JAK2 and STAT3mRNA in gastric mucosa was detected by RT-PCR.The levels of JAK2 and STAT3 proteins and their phosphorylation in gastric mucosa were detected by Western blot.Results Compared with the control group,the gastric mucosa of the model group showed a large number of inflammatory cells in-filtrated by HE staining.The contents of TNF-α and IL-6 significantly increased(P＜0.01),while the contents of GAS and MTL significantly decreased(P＜0.01).The mRNA expressions of JAK2 and STAT3 significantly increased(P＜0.05).p-JAK2and p-STAT3 significantly increased(P＜0.01).Compared with the model group,gastric mucosal inflammation was improved in each administration group.The con-tents of TNF-α and IL-6 decreased significantly,while the contents of GAS and MTL increased significantly.The mRNA expressions of JAK2 and STAT3 were sig-nificantly reduced.The expressions of p-JAK2 and p-STAT3 significantly decreased(P＜0.05).Conclu-sions HPS can improve gastric mucosal inflammation and repair gastric mucosal damage in rats,and its mechanism may be related to the regulation of JAK2/STAT3 signaling pathway.

Aim To design and synthesize a series of phenylacetamide derivatives with different substituted phenylacetic acid as raw materials,and to investigate the protective effects of the compound on the damage of pancreatic β cells induced by palmitate acid(PA).Methods Min6 cells were cultured and divided into B blank control group,PA treatment group and PA+compounds group.The viability of Min6 cells was de-tected by CCK-8.The protein expressions of TXNIP and NLRP3 were observed by Western blot.MDA con-tent and SOD activity were detected by MDA and SOD kit.The insulin secretion of Min6 islet cells was meas-ured with insulin ELISA kit.Results A total of 10 phenylacetamide derivatives were designed and synthe-sized.Their structures were confirmed by 1H NMR and ESI-MS.Pharmacological activity study showed that most of the compounds had protective effects on islet βcells,among which LY-6 and LY-8 had stronger pro-tective effects than PA model group,with the cell via-bility of 61.4％,and LY-6 had the highest cell activi-ty,reaching to 104.9％.Compared with PA group,the protein expression of TXNIP and NLRP3 decreased in LY-6 and LY-8 groups,MDA content decreased and SOD activity increased,and insulin secretion of Min6 cell increased.Conclusions LY-6 and LY-8 inhibit TXNIP expression and decrease the activation of NL-RP3 inflammasome,and decrease the production of MDA and increase SOD activity,and thus reducing is-let β cells apoptosis and increasing insulin secretion.Therefore,the compound LY-6 could serve as a poten-tial anti-diabetic new chemical entity.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Based on whole genome data, the identification and expression pattern analysis of the Atropa belladonna WRKY transcription factor family were conducted to provide a theoretical foundation for studying the biological functions and mechanisms of these transcription factors. In this study, bioinformatics methods were employed to identify members of the A. belladonna WRKY gene family and to predict their physicochemical properties, conserved motifs, promoter cis-acting elements, and chromosomal localization. Additionally, the expression patterns of the A. belladonna WRKY gene family under the regulation of environmental factors such as light quality and temperature were analyzed. The results revealed a total of 28 AbWRKY transcription factors, randomly distributed across 16 chromosomes, encoding 324-707 amino acids. Most AbWRKY proteins were acidic, unstable, and hydrophilic. Based on multiple sequence alignment and phylogenetic analysis, the WRKY gene family members were classified into two subfamilies. Conserved motif and domain analysis indicated that WRKY transcription factors in the same subfamily possessed conserved structural features. Promoter analysis predicted that the A. belladonna WRKY family contained light-responsive elements, hormone-responsive elements, and stress-responsive elements. Collinearity analysis showed that AbWRKY24 plays a crucial role in the expansion of the AbWRKY gene family. Then qRT-PCR results indicated that AbWRKY6, AbWRKY8, AbWRKY14, and AbWRKY24 responded to red light stress, while AbWRKY8, AbWRKY14, and AbWRKY24 responded to yellow light/low-temperature combined stress. AbWRKY6 and AbWRKY8 were significantly expressed in leaves and stems, AbWRKY27 and AbWRKY28 were significantly expressed in fibrous roots, and AbWRKY25 was significantly expressed in flowers. This study is the first to identify and analyze the WRKY gene family in A. belladonna and to examine its expression patterns under light and temperature regulation, laying a foundation for in-depth analysis and functional validation of the molecular mechanisms of A. belladonna WRKY transcription factors in responding to light quality and temperature environmental factors.
Transcription Factors/chemistry* ; Plant Proteins/metabolism* ; Phylogeny ; Gene Expression Regulation, Plant ; Light ; Temperature ; Atropa belladonna/metabolism* ; Multigene Family/genetics* ; Promoter Regions, Genetic/genetics* ; Sequence Alignment ; Amino Acid Sequence ; Genome, Plant/genetics*

This study aims to investigate the effect of Linggui Zhugan Decoction(LGZGD) on autophagy in the mouse model of chronic heart failure(CHF) induced by myocardial infarction(MI), as well as the regulatory effect of LGZGD on the hypoxia-inducible factor-1α(HIF-1α)/heme oxygenase-1(HO-1) signaling pathway, based on bioinformatics and animal experiments. The active ingredients and corresponding targets of LGZGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database, and GEO, GeneCards, and DisGeNET were searched for the disease targets. Cytoscape was used to establish a "drug-component-target" network. The protein-protein interaction(PPI) network analysis was performed on STRING. R language was used for Gene Ontology(GO) and Kyoto Encycloperfia of Genes and Genomes(KEGG) enrichment analyses. Molecular docking was adopted to validate the core targets. The mouse model of MI-induced CHF was established by surgical ligation of the left anterior descending coronary artery. The modeled mice were assigned into the sham, model, low-, medium-, and high-dose(2.34, 4.68, and 9.36 g·kg~(-1), respectively) LGZGD, and captopril(3.25 mg·kg~(-1)) groups. After continuous administration for 6 weeks, a Doppler ultrasound imaging system was used to examine the heart function indicators: left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), left ventricular end-systolic dimension(LVIDs), and left ventricular end-diastolic dimension(LVIDd). The myocardial tissue was stained with hematoxylin-eosin for the observation of morphological changes. The mRNA levels of microtubule-associated protein 1 light chain 3 beta(LC3B), Beclin1, p62, HIF-1α, and HO-1 in the myocardial tissue were determined by RT-qPCR. The protein levels of LC3B, beclin1, p62, autophagy-related protein 5(ATG5), HIF-1α, and HO-1 were determined by Western blot. The results showed that 103 active components of LGZGD, corresponding to 224 targets, were obtained. A total of 3 485 and 6 165 targets related to MI and CHF, respectively, were retrieved. The GSE16499 dataset obtained 3 263 differentially expressed genes. There were 31 common targets. The top 3 core active components were quercetin, naringenin, and 1-methoxyphaseollidin. The topology analysis results showed that the core targets were MAPK3, HMOX1(HO-1), MYC, ADRB2, PPARD, and HIF1A(HIF-1α). The molecular docking results showed strong binding between the core targets and the main active components of LGZGD. LGZGD significantly improved the heart function and alleviated the pathological changes in the myocardial tissue of mice. Western blot and RT-qPCR results showed that the HIF-1α/HO-1 signaling pathway and autophagy were activated in the model group. LGZGD up-regulated the levels of LC3B, Beclin1, ATG5, HIF-1α, and HO-1 while down-regulating the mRNA and protein levels of p62. In summary, LGZGD can enhance autophagy and improve the heart function in the mouse model of CHF after MI by upregulating the HIF-1α/HO-1 signaling pathway.
Animals ; Drugs, Chinese Herbal/chemistry* ; Myocardial Infarction/drug therapy* ; Heart Failure/physiopathology* ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Signal Transduction/drug effects* ; Male ; Computational Biology ; Heme Oxygenase-1/genetics* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Mice, Inbred C57BL ; Humans ; Chronic Disease ; Disease Models, Animal

Aim To investigate the effect of microinjection of EX527, a selective SIRT1 antagonist, into the ventrolateral orbital cortex (VLO) on morphine-induced conditioned place preference (CPP), and to explore the role of CREB/BDNF in it. Methods The cannulas were implanted bilaterally in the VLO of rats by brain stereotaxis surgery, and the model of morphine-induced CPP was established. The behavioral experiment consisted of four stages:habituation (d 1), pre-test (d 2-4), conditioning training (d 5-14) and test (d 15). At the stage of conditioning training, EX527 (1 μL, 5 g·L