Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

This study aimed to explore the anti-glioma effect of natural compound pterostilbene(PTE) through regulating pyroptosis and apoptosis pathways, and to analyze the possible anti-glioma pathways and targets of PTE by network pharmacology and molecular docking. In this study, the action targets of PTE and the glioma targets were obtained by network pharmacology to construct a target network and a protein-protein interaction(PPI) network to predict the possible action targets of PTE against glioma. Molecular docking was performed on the core targets by AutoDock and the action pathways of PTE against glioma were predicted by enrichment analysis. In addition, the effect of PTE on the viability of U87MG and GL261 glioma cells was detected by CCK-8 assay. Clone formation assay and cell scratching assay were used to explore the effect of different concentrations of PTE on the proliferation and migration, respectively of glioma cells. Hoechst staining was used to observe PTE-induced apoptosis in glioma cells. The changes in mitochondrial membrane potential were detected by JC-1 staining. The pyroptosis-inducing effect of PTE on glioma cells was observed by inverted microscopy and lactate dehydrogenase(LDH) assay. Hoechst 33342/PI dual staining assay was performed to detect the integrity of glioma cell membranes. The expressions of pyroptosis and apoptosis-related proteins in glioma cells after PTE induction were determined by Western blot. In this study, 37 anti-glioma targets of PTE were obtained, and enrichment analysis suggested that PTE exerted anti-glioma effects through various signaling pathways including cancer pathway, proteoglycan in cancer, PI3K/AKT pathway, and apoptosis regulatory pathway. Molecular docking revealed that PTE had good binding activity with the main targets. Compared with the control group, PTE significantly reduced the viability as well as the proliferation, migration and adhesion abilities of U87MG and GL261 cells; it induced the apoptosis of the two glioma cells and the decrease of mitochondrial membrane potential in U87MG cells, and the effects increased with the increase of drug concentration. Compared with the conditions in the control group, glioma cells in the PTE group had increased pyroptosis-specific appearance and gradually increased LDH release; the number of PI positive cells was significantly elevated with the increase of PTE concentration as revealed by Hoechst 33342/PI staining; the expression levels of apoptosis-related factors cleaved PARP1 and B-cell lymphoma-2(Bcl-2) associated X(BAX) in the PTE group were markedly up-regulated, while the expression level of Bcl-2 was markedly down-regulated; the activation levels of pyroptosis-related proteins cleaved caspase-3 and gasdermin E-N(GSDME-N) had a remarkable rise in the PTE group, while no significant changes were found in the activation levels of gasdermin D-N(GSDMD-N) and cleaved caspase-1. In summary, PTE plays an anti-glioma role by inhibiting cell viability, proliferation, and migration and activating the caspase-3/GSDME-mediated pyroptosis pathway and mitochondrial apoptosis pathway.
Pyroptosis ; Caspase 3/metabolism* ; Network Pharmacology ; Gasdermins ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism*

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.

Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

OBJECTIVE: To observe and compare the clinical outcomes between arthroscopic modified Mason-Allen repair and suture-bridge repair for medium-size rotator cuff tears. METHODS: From January 2017 to January 2018, 22 patients with medium-size rotator cuff tears underwent arthroscopic modified Mason-Allen repair. There were 9 males and 13 females with an average age of (57.14±10.26) years. From February 2018 to January 2019, 20 patients with medium-size rotator cuff tears underwent arthroscopic suture-bridge repair. There were 6 males and 14 females with an average age of (57.75±7.57) years. The preoperative and postoperative clinical function was assessed by American Shoulder and Elbow Surgeons (ASES) and Constant score system. The healing status of repaired rotator cuff was assessed using MRI. RESULTS: All patients were followed up, and the duration ranged from 24 to 33 months, with a mean of (26.38±2.29) months. In modified Mason-Allen group, AS###ES score and Constant score increased from (45.22±7.58) and (58.72±9.26) preoperatively to (96.89±3.49) and (93.18± 3.20) postoperatively. In suture-bridge group, ASES score and Constant score increased from(47.33±7.50) and (60.05±11.76) scores to (97.58±3.43) and (93.85±3.15). There were no significant differences in ASES score and Constant score between the two groups before and after operation. There were no significant differences in rotator cuff healing between the two groups. CONCLUSION Both arthroscopic modified Mason-Allen and suture-bridge repair for treatment of medium-size rotator cuff tears could obtain good clinical outcomes, and there were no significant differences in clinical outcomes between the two techniques.
Aged ; Arthroscopy ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Rotator Cuff/surgery* ; Rotator Cuff Injuries/surgery* ; Suture Techniques ; Sutures ; Treatment Outcome

OBJECTIVE To evaluate the clinical efficacy of Zishen Qinggan Formula through observing its effects on arterial function and inflammatory factors in patients with essential hypertension.METHODS 100 essential hypertension patients who meet the inclusion criteria were selected and randomly divided into the treatment group and the control group,50 cases in each group.The treatment group received ACEI/ARB+CCB standard treatment combined with Zishen Qinggan Formula,and the control group received ACEI/ARB+CCB drugs treatment.The course of treatment was 8 weeks.Changes of TCM syndrome scores,carotid intima-media thickness,UltraFast imaging pulse wave velocity (PWV),resistance index,inflammatory factors and safety indexes were compared before and after treatment.RESULTS ①TCM syndrome scores in both groups improved significantly after treatment,and that in the treatment group was better than the control group(P<0.01).② UltraFast imaging PWV of bilateral carotid arteries and resistance indexes in both groups improved after treatment (P<0.01),among which the treatment group was better than the control group(P<0.05).IMT of bilateral carotid arteries had no difference in two groups before and after treatment (P>0.05).③ Levels of serum CRP,IL6 and TNFα in both group improved after treatment (P<0.05),and that in the treatment group were better than the control group(P<0.01) ④ There was no significant difference in liver and kidney function in two groups before and after treatment(P>0.05).CONCLUSION In the aspect of improvement of arterial elasticity and inflammatory factors in patients with essential hypertension,western medicine ACEI/ARB+CCB basic therapy combined with Zishen Qinggan Formula is better than ACEI/ARB+CCB basic therapy alone.

BACKGROUNDNurr1 plays an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons, and it is a potential target for Parkinson's disease (PD). Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs), but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.

METHODSThe mRNA levels of Nurr1 in PBMC of four subgroups of 362 PD patients and 193 healthy controls (HCs) using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurr1 expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level.

RESULTSThe relative Nurr1 mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments (de novo) (P < 0.001) and HC groups (P < 0.010), respectively. Furthermore, the increase in Nurr1 mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurr1 mRNA expression level in PBMC. In vitro, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurr1 mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively (P < 0.001).

CONCLUSIONSDA agonists can induce Nurr1 expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.

Adult ; Aged ; Aged, 80 and over ; Dopamine Agonists ; therapeutic use ; Female ; Humans ; Leukocytes, Mononuclear ; drug effects ; metabolism ; Male ; Middle Aged ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; genetics ; Parkinson Disease ; drug therapy ; genetics ; RNA, Messenger ; genetics ; Young Adult

Inwardly rectifying potassium channels (Kir) are a special subset of potassium selective ion channels which pass potassium more easily into rather than out of the cell. These channels mediate a variety of cellular functions, including control of membrane resting potential, maintenance of potassium homeostasis and regulation of cellular metabolism. Given the existence of fifteen Kir genes in mammals, current genetic studies using mutant animals that lack a single channel may have missed many important physiological functions of these channels due to gene redundancy. This issue can be circumvented by using a simple model organism like Drosophila, whose genome encodes only 3 Kir proteins. The sophisticated genetic approaches of Drosophila may also provide powerful tools to identify additional regulation mechanisms of Kir channels. Here we provide an overview of the progress made in elucidating the function of Drosophila Kir channels. The knowledge of Drosophila Kir channels may lead us to uncover novel functions and regulation mechanisms of human Kir channels and help on pathological studies of related diseases.
Animals ; Drosophila ; physiology ; Membrane Potentials ; Potassium ; physiology ; Potassium Channels, Inwardly Rectifying ; physiology