Objective To explore the expression of junctophilin 2(JP2)and fibroblast growth factor 23(FGF23)in a rabbit model of atrial fibrillation mediated-cardiomyopathy(AMC).Methods Rabbit models of atrial fibrillation(AF)were developed through rapid atrial stimulation and then divided into three groups:control group(pacemak-ers implanted without pacing,n=6),AF group(pacing with ejection fraction decrease＜10％,n=5),and AMC group(pacing with ejection fraction decrease≥10％,n=6).Echocardiography was performed to detect left ventric-ular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD)and left ventricular ejection fraction(LVEF).JP2 and FGF23 were detected by ELISA method.Western blot and RT-qPCR were conducted to detect protein and mRNA expression of JP2 and FGF23.Results Left atrial diameter,right atrial diameter and right ventricular diameter increased and LVEF decreased in the AMC group as compared with the control group.AMC group had lower LVEF and larger aorta and right ventricle diameter.Compared with the control group,the ex-pression of FGF23(P＜0.001)and JP2(P＜0.01)in left atrial cardiomyocytes was significantly increased in the AF group,while the expression of JP2 was decreased in the AMC group(P＜0.001).AMC group had lower expression of JP2 and FGF23 compared with AF group.Compared to the control group,plasma concentration of JP2 and FGF23 increased in the AF group and FGF23 plasma concentration increased in the AMC group.Plasma concentration of FGF23 and JP2 was lower in AMC group than that in AF group.Conclusions FGF23 expression increased and JP2 expression decreased as found in the rabbit AMC model.

Objective:To explore the expression of family with sequence similarity 83 member A (FAM83A) in colorectal cancer, and the effect of FAM83A knockdown on the proliferation of colorectal cancer cells and the related mechanism.Methods:The expression of FAM83A in the tissues of 102 patients with colorectal cancer and its adjacent tissues was detected by immunohistochemistry. HCT116 cells were divided into experimental group and control group. The experimental group cells were transfected with FAM83A-siRNA plasmid, and the control group cells were transfected with MOCK-siRNA plasmid. The mRNA content of FAM83A in each group was detected by fluorescence quantitative PCR. The expressions of FAM83A, P13K, p-AKT and p-mTOR in each group were detected by Western blot. CCK8 assay and clonogenesis assay were used to detect cell proliferation.Results:The positive rate of FAM83A in colorectal cancer patients was 88.23% (90 cases /102 cases), and the expression rate of FAM83A in paracancer tissues was 10.78% (11 cases /102 cases). The expression rate of Fam83a in colorectal cancer tissues was significantly higher than that in paracancer tissues, with statistical significance ( P<0.001). After siRNA transfection, the mRNA expression levels of FAM83A in HCT116 cells of the experimental group and control group were 1.23±0.20 and 0.43±0.12, respectively, and the protein expression levels of FAM83A were 1.19±0.11 and 0.23±0.08, respectively. The expression levels of P13K were 1.21±0.17 and 0.28±0.09, the expression levels of p-AKT were 1.35±0.23 and 0.57±0.18, and the expression levels of p-mTOR were 1.48±0.20 and 1.05±0.14. The expression of P13K, p-Akt and p-mTOR was down-regulated (all P<0.05). The absorbance of HCT116 cells in the experimental group and the control group was 1.09±0.22 and 2.21±0.27, respectively. The cloning rate of HCT116 cells in the experimental group and the control group was 21.6%±2.4% and 62.7%±4.1%, respectively. The proliferation ability of HCT116 cells in the experimental group decreased significantly ( P<0.05) . Conclusions:The expression of FAM83A is significantly increased in colorectal cancer tissues, which may be related to the malignant degree of colorectal cancer. FAM83A affects the proliferation of colorectal cancer cells through the P13K/AKT/mTOR signaling pathway.

Objectives:To investigate whether circumferential pulmonary vein isolation(CPVI)combined with additional ablation reduces the recurrence rate of atrial fibrillation(AF)compared with CPVI alone. Methods:A literature search was conducted using the databases CNKI,Wanfang Data,VIP,Chinese Biomedical Literature Database,PubMed,Embase,the Cochrane Library.Randomized controlled studies that met the standards in recent ten years were screened,and the relevant literature contents were meta-analyzed by Review Manager 5.3 software.The comparison results of CPVI alone with CPVI combined with the additional ablation strategies in the recurrence of AF were summarized. Results:A total of 21 literatures were included with 3 357 patients,of whom 1 580 underwent CPVI alone and 1 777 underwent CPVI combined with additional site ablation.The follow-up time was more than 1 year.Meta-analysis showed that there was no significant difference between CPVI alone and CPVI combined ablation strategies in reducing AF recurrence(OR=0.86,95%CI:0.73-1.01,P=0.06).Subgroup analysis based on additional ablation site,AF type,left atrial diameter,and AF diagnosis time showed that only in the small left atrial diameter subgroup,CPVI combined with additional ablation further reduced the recurrence rate of AF(OR=0.68,95%CI:0.47-0.98,P=0.04). Conclusions:The ablation strategy of CPVI combined with additional sites could not reduce the recurrence rate of AF compared with CPVI alone.

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

SGLT2 inhibitors currently have clear benefits in the treatment of heart failure whether combined with diabetes or not. Ventricular remodeling after myocardial infarction leads to the occurrence and development of heart failure, and eventually leads to death. There are relatively few studies on SGLT2 inhibitors in patients with myocardial infarction. The purpose of this article is to review the research progress of SGLT2 inhibitors application before and after myocardial infarction.

AIM: To explore the protective effect and mechanism of dexmedetomidine on intestinal mucosal barrier injury in septic rats. METHODS: Forty eight SD rats were randomly divided into four groups (n=12): sham operation group (sham group), sepsis group (sepsis group), sepsis + dexmedetomidine group (DEX group), and sepsis + DEX + HIF-1ɑ inhibitor Bay87-2243 (Bay87-2243 group). Sepsis model was established by cecal ligation and perforation (CLP). The rats in both DEX and Bay87-2243 groups were given 30 μg/kg of DEX intraperitoneally 30 minutes before CLP and 2 hours after CLP; while the rats in Bay87-2243 group received oral gavage of Bay87-2243 (9 mg/kg) for 3 days before CLP. The other groups were intraperitoneally injected and orally with the same amount of normal saline. The HIF-1ɑ and the tight junction protein (tight junction protein, TJs) was detected by western blot; the plasma concentrations of diamine oxidase (DAO), intestinal fatty acid binding protein (FABP2) and D-lactic acid (D-LAC) were detected by ELISA; the morphological changes of intestinal mucosa were detected by HE staining. RESULTS: DEX significantly increased the expression level of HIF-1ɑ (P<0.05) on intestinal mucosa in rats with sepsis injury (P<0.05), thus ameliorated intestinal mucosal pathological injury, reduced Chiu's score (P<0.05), decreased intestinal mucosal permeability (P<0.05), and up-regulated TJs protein expression (P<0.05). Moreover, effect on sepsis induced intestinal mucosal injury of DEX was reversed by HIF-1ɑ Bay87-2243. CONCLUSION: DEX could protect against sepsis-induced intestinal mucosal injury by up-regulating HIF-1ɑ expression in rats.

AIM: To investigate the effect and mechanism of hypoxia inducible factor-1α on intestinal mucosal barrier in sepsis. METHODS: SD rats were randomly divided into 4 groups: sham group, sepsis group, sepsis+HIF-1α stimulant (sepsis+DMOG group), sepsis+HIF-1α inhibitor (sepsis+Bay87-2243 group), 6 rats in each group. Sepsis model was established by cecal ligation and perforation (CLP). The levels of inflammatory markers IL-1β, IL-6, TNF-α, oxidative stress markers MDA and antioxidant factors SOD and CAT were detected by ELISA and the expression of HIF-1α in intestinal mucosa was detected by Western blot. The pathological damage of intestinal mucosa was detected by HE staining. RESULTS: Inflammatory factors, oxidative stress factors and HIF-1α were significantly up-regulated in septic rats (P<0.05). The contents of IL-1β, IL-6, TNF-α and MDA in plasma were significantly decreased by intraperitoneal injection of DMOG (P<0.05); the levels of SOD and CAT in plasma were increased (P<0.05), HIF-1α was up-regulated (P<0.05), and the pathological damage of intestinal mucosa was alleviated, with decreased Chiu's score (P<0.05). Oral administration of Bay87-2243 gave the opposite result. CONCLUSION: HIF-1α has a protective effect on intestinal mucosal injury in sepsis. The mechanism may be related to the alleviation of inflammatory response and inhibition of oxidative stress.

ObjectivecircRNAs play an important role in tumor development, but the relationship between circRNAs and hepatocellular carcinoma remains to be further explored. The present study aimed to bioinformatically analyze the target gene of microRNA-1. Another aim was to screen circRNAs that are associated with target genes and differentially expressed in hepatocellular carcinoma cells, as well as provide theoretical basis for clinical screening of molecular markers and targeted therapies related to hepatocellular carcinoma.MethodsThe miRNA related database used for the prediction of microRNA-1 target genes, and the bioinformatic analysis of the target genes of microRNA-1 involved functional enrichment analysis and signal transduction pathway enrichment. Then, the circRNAs, which are related to the downstream target genes of microRNA-1, are screened through the circRNA database.ResultsThe number of microRNA-1 target genes was 230 in miRNA related database. Through GO analysis, it was found that the target genes of microRNA-1 had a strong tendency in regulation, and were mainly enriched in three aspects: biological function, biological process and cell localization.The target genes of microRNA-1 are involved in the function of proteins, regulation of biosynthesis, cofactor binding, enzyme regulation and other biological processes. Predicted target genes of miRNA-1 were significantly enriched in cancer signaling pathways, hepatitis B occurrence, endocytosis and splicing pathways. Further, 21 circRNAs related to the target gene of microRNA-1 were found in three circRNA databases, wherein hsa_circ_0004651 was highly expressed in hepatocellular carcinoma cell line HepG2 and its pavent gene was hnRNPD.ConclusionMicroRNA-1 influence the occurrence of hepatocellular carcinoma development through the regulation of protein and enzyme. Hsa_circ_0004651 may affect the development of hepatocellular carcinoma with microRNA-1 and its parental gene hnRNPD.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective: To investigate the early diagnosis and treatment for burn complicated with severe paroxysmal sympathetic hyperactivity (PSH). Methods: Medical records of patients with burn complicated with severe PSH, admitted to our department from April 2016 to March 2019 and meeting the inclusion criteria were analyzed retrospectively. There were 4 males and 1 female, aged 17 months to 39 years, with an average of (21±16) years. During occurrence of PSH, the vital signs of patients were routinely monitored and oxygen were given. Other treatment included central venous catheterization and infusion of electrolyte solution, infusion of plasma according to patients′ condition, use of opioid analgesics and benzodiazepine sedatives, physical cooling and drug cooling, and establishment or maintenance of artificial airway and use of ventilator. Heart rate was controlled below 120 beats per minute in adults and 140 beats per minute in children with comprehensive treatment dominated by analgesia and sedation. Besides, single or multiple vasoactive agents, even in large doses were used to maintain normal blood pressure of patients. The occurrence characteristics, time, and treatment outcome of PSH were analyzed. Results: PSH happened rapidly, with a sharp increase in several minutes to dozens of minutes. Five patients were with symptoms such as high body temperature, shortness of breath, very fast heart rate, normal or elevated systolic blood pressure, hyperhidrosis, and dystonia at the onset. The symptoms occurred simultaneously or successively. According to the Clinical Feature Scale, the above-mentioned 6 indexes achieved the highest score of 3 points except of systolic blood pressure. Four patients showed dilated pupils and impaired consciousness. Among the patients, PSH occurred in the acute exudation stage in 3 patients, in the fluid reabsorption stage in 1 patient, and in the late repair stage in 1 patient. PSH of patients lasted for 3 hours to 12 days. The symptoms of 4 patients were effectively controlled, and 1 patient died of deterioration. No PSH occurred in the cured patients during follow-up of 3 to 14 months. Conclusions Burn complicated with PSH can occur at any time before wound repair and in patients with different injury conditions. The causes of PSH include sudden burn, persistent pain, fright and fear, strange environment, low blood volume, and other adverse stimuli, and PSH is more likely to occur in children with underdeveloped brain function. Intravenous infusion of analgesics sedatives, physical therapy and medication to lower body temperature, stabilizing blood pressure and respiration are effective measures to treat PSH. PSH should be distinguished from the common complications of burns, such as sepsis, cerebral edema, hyperpyretic convulsion, transfusion response, stress disorder, etc.