Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To investigate whether Lingbao Huxin Pill (LBHX) protects against acute myocardial infarction (AMI) at the infarct border zone (IBZ) of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1 (SIRT1)-mediated forkhead box protein O1 (FOXO1) and nuclear factor-κ B (NF-κ B) signaling pathways. METHODS: Six-week-old Wistar rats with normal diet were randomized into the sham, the model, Betaloc (0.9 mg/kg daily), LBHX-L (0.45 mg/kg daily), LBHX-M (0.9 mg/kg daily), LBHX-H (1.8 mg/kg daily), and LBHX+EX527 (0.9 mg/kg daily) groups according to the method of random number table, 13 in each group. In this study, left anterior descending coronary artery (LADCA) ligation was performed to induce an AMI model in rats. The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was conducted to assess cardiomyocyte apoptosis in the IBZ. The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain, Masson and hematoxylineosin (HE) staining assays. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1 β, and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays (ELISAs). The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR (RT-qPCR). The protein expressions of SIRT1, FOXO1, SOD2, BAX and NF- κ B p65 were detected by Western blot analysis. RESULTS: The ligation of the LADCA successfully induced an AMI model. The LBHX pretreatment reduced the infarct size in the AMI rats (P<0.01). The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ. Further, the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue (P<0.05), myocardial interstitial collagen deposition (P<0.05) and inflammation at the IBZ. The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that the LBHX pretreatment upregulated the protein levels of SIRT1, FOXO1 and SOD2 (P<0.05) and downregulated NF- κ B p65 and BAX expressions (P<0.05). The RT-qPCR results showed that LBHX increased the SIRT1 mRNA and FOXO1 mRNA levels (P<0.05). These protective effects, including inhibiting apoptosis and alleviating inflammation in the IBZ, were partially abolished by EX527, an inhibitor of SIRT1. CONCLUSION LBHX could protect against AMI by suppressing apoptosis and inflammation in AMI rats and the SIRT1-mediated FOXO1 and NF- κ B signaling pathways were involved in the cardioprotection effect of LBHX.
Animals ; Apoptosis ; Drugs, Chinese Herbal ; Inflammation/metabolism* ; Myocardial Infarction/pathology* ; NF-kappa B/metabolism* ; Nerve Tissue Proteins ; Rats ; Rats, Wistar ; Sirtuin 1/genetics*

WNT signaling plays an important role in cardiac development, but abnormal activity is often associated with cardiac hypertrophy, myocardial infarction, remodeling, and heart failure. The effect of WNT signaling on regulation of atrial natriuretic peptide (ANP) secretion is unclear. Therefore, the purpose of this study was to investigate the effect of Wnt agonist 1 (Wnta1) on ANP secretion and mechanical dynamics in beating rat atria. Wnta1 treatment significantly increased atrial ANP secretion and pulse pressure; these effects were blocked by U73122, an antagonist of phospholipase C. U73122 also abolished the effects of Wnta1-mediated upregulation of protein kinase C (PKC) β and γ expression, and the PKC antagonist Go 6983 eliminated Wnta1-induced secretion of ANP. In addition, Wnta1 upregulated levels of phospho-transforming growth factor-β activated kinase 1 (p-TAK1), TAK1 banding 1 (TAB1) and phospho-activating transcription factor 2 (p-ATF2); these effects were blocked by both U73122 and Go 6983. Wnta1-induced ATF2 was abrogated by inhibition of TAK1. Furthermore, Wnta1 upregulated the expression of T cell factor (TCF) 3, TCF4, and lymphoid enhancer factor 1 (LEF1), and these effects were blocked by U73122 and Go 6983. Tak1 inhibition abolished the Wnta1-induced expression of TCF3, TCF4, and LEF1 and Wnta1-mediated ANP secretion and changes in mechanical dynamics. These results suggest that Wnta1 increased the secretion of ANP and mechanical dynamics in beating rat atria by activation of PKC–TAK1–ATF2–TCF3/LEF1 and TCF4/LEF1 signaling mainly via the WNT/Ca2+ pathway. It is also suggested that WNT–ANP signaling is implicated in cardiac physiology and pathophysiology.

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 µM) and BQ788 (0.3 µM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 µM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 µM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxiaactivated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 µM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 µM) and LY294002 (10.0 µM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 µM) and BQ788 (0.3 µM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 µM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 µM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxiaactivated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 µM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 µM) and LY294002 (10.0 µM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

Objective: To explore the medication compliance for secondary prevention drugs and long-term prognosis of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) between hospitals in different regions of China. Methods: The Optimal Antiplatelet Therapy for Chinese Patients with Coronary Artery Disease (OPT-CAD) study was a prospective, multi-center and registered study. Patients diagnosed as ACS and underwent PCI in OPT-CAD study were selected. Taking the Yangtze River as the dividing line between the south and the north of China, these patients were divided into two groups according to the hospitals where the patients visited, namely the southerns region group (n=1 958) and the northerns region group (n=5 091). In order to reduce selection bias and potential confounding factors, the patients in the two groups were matched by the tendency score, and the patients in the two groups were matched by the 1: 1 nearest match method according to the tendency score. The main endpoint of this study was the major adverse cardiovascular and cerebrovascular events (MACCE) occurring within 5 years after discharge, namely the composite endpoint of cardiac death, myocardial infarction, and/or ischemic stroke. Secondary endpoints were all-cause death, cardiac death, myocardial infarction, ischemic stroke, and type 2, 3, and 5 bleeding events defined by the Academic Research Consortium on Hemorrhage (BARC) within 5 years. The secondary preventive drugs was recorded, including antiplatelet drugs, statins, beta blockers, angiotensin converting enzyme inhibitors/angiotensinⅡreceptor blockers (ACEI/ARB), etc. Before and after the matching, the secondary preventive medication and the incidence of clinical events of the two groups were compared. Results: A total of 7 049 ACS patients, including 1 958 patients in the southern region group and 5 091 patients in the northern region group were enrolled in this study. There were 5 319 males (37.9%), and the aged was (60.7±6.7) years. After propensity score matching, there were 1 324 cases in each group. Before matching, in the northern region group, the proportion of smoking, hypertension and diabetes, previous history (myocardial infarction, PCI and stroke) and family history of coronary heart disease were higher (all P<0.05). The proportion of complex lesions, diffuse lesions, small vessel lesions and thrombotic lesions in the northern region group was higher than that in the southern region group (all P<0.05). Sixty months after discharge, the antiplatelet patterns were quite different between patients in the northern and southern region group (P<0.001). The proportion of clopidogrel monotherapy in the southern region group was higher than that in the northern region group (9.8% (130/1324) vs. 1.1% (14/1324)), while the proportion of aspirin monotherapy in the northern region group was higher than that in the southern region group (67.4% (893/1324) vs. 46.5% (616/1324)). As for the use of other secondary prophylactic drugs, the proportion of patients in southern region group receiving beta blockers (24.5% (325/1324) vs. 16.8% (222/1324), P<0.001) and ACEI/ARB (19.4% (257/1324) vs. 10.0% (133/1324), P<0.001) was higher than that in northern region group. After matching, the incidence of MACCE (8.4%(111/1 324) vs.6.2% (82/1 324), P=0.030) and BARC 2, 3 and 5 bleeding (6.0% (80/1 324) vs. 4.0% (53/1 324), P=0.020) was higher in patients in northern region group. Conclusions: ACS patients who undergo PCI in northern area hospital is at higher prevalence of comorbidities and complicated coronary artery lesions compared to patients in the southern area hospital, and the drug compliance is worse than that in southern area, and the prognosis is also relatively poor.
Acute Coronary Syndrome/drug therapy* ; Aged ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; China ; Humans ; Male ; Medication Adherence ; Middle Aged ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; Prospective Studies ; Secondary Prevention ; Treatment Outcome

Objective To understand the genotypes and nucleotide polymorphisms of Echinococcus granulosus metacestode from humans and sheep in Tianjun region,Qinghai Province. Methods The specific primers were designed according to the cox1 and nad1 genes of E.granulosus mitochondrial genome sequences accessed by GenBank.The primers were used to detect the cyst samples from 16 sheep and 2 humans infected with E.granulosus in Tianjun region of Qinghai Province by PCR,then the PCR amplification products were sequenced,the genotypes and nucleotide polymorphisms of the cox1 and nad1 genes were analyzed.Results The 18 isolated samples all belonged to E.granulosus G1 genotype.Among all the isolates,9 haplotypes ex-isted in the cox1 gene with 16 nucleotide mutation sites,and there were 0 to 5 nucleotide differences with the highest variation rate of 0.31%,whereas 7 haplotypes occurred with 15 nucleotide mutation sites,and there were 1 to 8 nucleotide differences with the highest variation rate of 0.89% for the nad1 gene.Conclusions The epidemic genotype of E.granulosus is G1 in hu-mans and sheep in Tianjun region of Qinghai Province,and the nucleotide polymorphisms of the cox1 gene were more abundant than those of the nad1 gene,and the resolution of the nucleotide polymorphisms of cox1 gene is higher than that of the nad1 gene used in E.granulosus isolates.

Microspheres (MS) are an excellent transarterial chemoembolization carrier for cancer treatment. Then the Bletilla striata polysaccharide (BSP) that was isolated from the rattan of Bletilla striata was used as skeleton material, and the matrine (ME) loaded Bletilla striata polysaccharide microspheres (ME-BSPMS) were prepared by emulsify-chemical crosslinking method. ME-BSPMS was characterized for appearance shape, particle size, drug loading, swelling ratio, suspension property, drug entrapment condition and in vitro release characteristics. The results showed that the ME-BSPMS appeared as round spherical and smooth shape by SEM, with an average size of (85 ±7) μm. ME-BSPMS with a good suspension in physiological saline and the swelling ratio could reach upwards of (53 ±4.2)% in 20 minutes, also with a large amount of drug loading of (30.12 ±3.25)%. The results of DSC scanning indicate that good compatibility exists between the ME and BSP, and the ME could be embedded fully in the matrix of the ME-BSPMS. The accumulation drug release from ME-BSPMS was (25.38 ±1.57)% at 12 h, this suggests that the ME-BSPMS has a good sustained release effect. These results indicate that the ME-BSPMS may be a promising transarterial chemoembolization carrier for cancer treatment.

OBJECTIVETo investigate the relationship between NK cell count/activity and acute graft-versus-host disease (aGVHD) in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSA total of 26 patients who had undergone allo-HSCT from January to July 2015 were enrolled in this study. The NK cell count/activity in the peripheral blood of recipients on day 30 after allo-HSCT were monitored by using 4-color flow cytometry. The incidence of aGVHD in patients was evaluated by clinical manifestation combinating with related pathologic indicators, and the relationship between NK cell count/activity and aGVHD were analyzed.

RESULTSIn the aGVHD group and the no-aGVHD group, the NK cell count and activity on days 30 after allo-HSCT were 655±216 cells/µl vs 1169±372 cells/µl(P=0.002) and 7.3±3.6% vs 9.0±3.6% (P=0.008). In the II-IV grade aGVHD group and the 0-I grade aGVHD group, the NK cell count/activity were 617±220 cells/µl vs 1081±399 cells/µl (P=0.001) and 4.2±1.7% vs 8.3±3.5%(P=0.001). As compared with the 0-I grade aGVHD group, patients in the II-IV grade aGVHD group had higher relapse rate (57% vs 5%)(P=0.010) , lower 1-year progression-free survival(PFS) rate (43% vs 84%)(P=0.010).

CONCLUSIONNK cell count/activity on day 30 after allo-HSCT were closely relates with aGVHD, which may be a potential marker for aGVHD and can provide a new target for aGVHD therapy.