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.

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.

AIM:Clopidogrel and aspirin are com-monly used drugs for the secondary prevention of cerebrovascular disease.Due to drug resistance,their preventive effect is often affected.This article explores the clinical value of clopidogrel and aspirin pharmacogenetic genetic testing in the secondary prevention of ischemic stroke.METHODS:220 pa-tients with mild ischemic stroke or TIA admitted to our hospital from 2021.7 to 2022.9 were included and randomly divided into individualized treatment group and clopidogrel conventional treatment group(control group).The patients were followed up for one year to observe stroke recurrence and hemorrhagic events.RESULTS:(1)Compared with the control group,the recurrence rate of ischemic stroke in the individualized treatment group after 1-year follow-up was slightly lower(5.82％vs.7.92％,P＞0.05),the risk of cerebral hemorrhage was simi-lar,but the risk of other occurrences was increased(6.79％vs.0.99％,P＜0.05).(2)COX regression analy-sis showed that ESRS(HR 2.576,95％CI 1.226-5.413,P=0.013)and history of hypertension(HR 5.517,95％CI 1.624-18.737,P=0.006)were associated with recurrence of ischemic stroke,independent of anti-thrombotic regimen(HR 0.918,95％CI 0.291-2.894,P=0.883).CONCLUSION:Aspirin GPIBA,PTGS1,and ITGB3 gene polymorphisms have limited signifi-cance in guiding antiplatelet medication.Selecting aspirin maintenance therapy for clopidogrel CYP2C19*2*3 allele carriers cannot significantly re-duce the risk of recurrence of minor ischemic stroke and may increase other bleeding risks.COX regression analysis shows that ESRS and history of hypertension are independent risk factors for stroke recurrence.

Abstract OBJECTIVE Linezolid(LZD) is a synthetic oxazolidone antibacterial drug that has activity against most Gram positive bacteria. LZD is widely used in pediatric patients, and its common adverse reactions include gastrointestinal reactions and bone marrow suppression, etc. In recent years, LZD-induced hyperlactatemia has gradually attracted attention. LZD-induced hyperlactatemia can exacerbate the condition of pediatric patients and is associated with high mortality rates in children. However, there is currently a lack of data on the risk factors for LZD-induced hyperlactatemia in pediatric patients. METHODS Therefore, this paper collected and retrospectively analyzed the information of hospitalized pediatric patients who received LZD treatment at the Children's Hospital of Chongqing Medical University from October 2012 to February 2023, including demographic characteristics of pediatric patients and clinical treatment related records, etc. According to the inclusion and exclusion criteria, this paper identified whether the included pediatric patients had developed hyperlactatemia and evaluated the causal relationship between LZD and hyperlactatemia using the Naranjo's Scale. The risk factors were analyzed using univariate and multivariate logistic regression, and the dose-response relationship between risk factors and LZD-induced hyperlactatemia was further analyzed using a restricted cubic spline(RCS) model. RESULTS A total of 331 pediatric patients were included, of which 145 pediatric patients(43.8%) developed LZD-induced hyperlactatemia, including 122 cases of mild hyperlactatemia and 23 cases of severe hyperlactatemia; the causal relationship score of LZD-induced hyperlactatemia was “possibly related” in 87 cases(60.0%) and “highly likely related” in 58 cases(40.0%). The median age of pediatric patients was 3(0.92, 9) years old, with 55.29% males, 25.38% patients with liver disease, 8.76% pediatric patients with kidney disease, and 36.56% pediatric patients with cardiovascular disease; the median number of treatment days for pediatric patients receiving LZD was 13(8, 22) d, with pediatric patients with hyperlactatemia having a longer median number of LZD treatment days than those without hyperlactatemia[16(10, 28) vs 11(7, 18)]; 41.09% of pediatric patients used P-glycoprotein inducers in combination, with more pediatric patients(57.4%) experiencing hyperlactatemia; 53.47% of pediatric patients used P-glycoprotein inhibitors in combination; the median values of lactic acid baseline, creatinine baseline, and baseline estimated glomerular filtration rate(eGFR) were 0.92(0.80, 0.92)mmol·L-1, 26(18.25, 34.90) μmol·L-1, 179.97(137.23, 222.70)mL·min-1·(1.73 m)-2, respectively. Multivariate logistic regression analysis showed that pediatric patients received longer LZD treatment duration(OR=1.026, P=0.004), and the combination of P-glycoprotein inducers(OR=2.023, P=0.004), higher lactic acid baseline levels(OR=2.408, P=0.022), and lower eGFR(OR=0.997, P=0.047) were independent risk factors for LZD-induced hyperlactatemia. The RCS model showed that as the number of days of LZD treatment increases, the risk of LZD-induced hyperlactatemia increased nonlinearly(P-non-linear=0.041); when the lactic acid baseline value was -1, the risk of LZD-induced hyperlactatemia dramatically increased as the lactic acid baseline value increased, when it was >0.92 mmol·L-1, the risk of LZD-induced hyperlactatemia slowly increased as the lactic acid baseline value increased(P-non-linear=0.013). CONCLUSION This study explores for the first time the risk factors of LZD-induced hyperlactatemia in pediatric patients, including the impact of the interaction between LZD and drugs that affect mitochondrial function, P-glycoprotein inducers, and P-glycoprotein inhibitors on hyperlactatemia. RCS models are used to analyze the dose-response relationships between LZD treatment days, lactic acid baseline values, and the occurrence of LZD-induced hyperlactatemia. When LZD is combined with P-glycoprotein inducers(mainly isoniazid, rifampicin, and ethambutol), the risk of LZD-induced hyperlactatemia increases, and its related mechanisms still need further research. In addition, pediatric patients with renal insufficiency may need to adjust the LZD dosage appropriately to avoid the occurrence of hyperlactatemia. In conclusion, when pediatric patients receive LZD treatment, attention should be paid to risk factors such as lactic acid baseline value, duration of LZD use, combined use of P-glycoprotein inducers, and renal dysfunction, in order to prevent the occurrence of LZD-induced hyperlactatemia based on the pediatric patient's treatment needs.

This paper is based on the theory of"internal diseases will be presented externally"in Traditional Chinese Medicine, combined with the idea of syndrome differentiation and grasping the main symptoms, and proposes the concept of"virtual special disease". It is extracted from ancient books and expert experience, and it is believed that it is widespread and can be tested by clinical practice. The application of virtual syndrome to diagnosis can achieve the purpose of simplifying the complexity TCM syndrome differentiation. On the one hand, it provides a new exploration for enriching the TCM syndrome differentiation system; on the other hand, it provides new ideas for supplementing the biological research of syndromes and developing the diagnosis of integrated traditional Chinese and Western medicine.

AIM:To investigate the effects of survivin inhibitor YM155 {4,9-dihydro-1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(2-pyrazinylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazolium bromide} on the apoptosis, mito-chondrial membrane potential (Δψm) and cytochrome C (Cyt C) of retinoblastoma Y79 cells, and to analyze the mitochon-drial mechanisms of apoptosis .METHODS:Y79 cells were cultured in vitro and treated with YM155 at concentrations of 0, 0.5, 1, 2, 4 and 8 nmol/L.The cells in control group were treated without YM 155.The proliferation of Y79 cells were measured by CCK-8 assay and bromodeoxyuridine ( BrdU) labeling assay .Y79 cells were randomly divided into 4 groups:control group ( with equal volume of RPMI-1640 nutrient medium ) , positive control group ( 10 nmol/L topotecan ) , low-dose (1 nmol/L) YM155 group and high-dose (2 nmol/L) YM155 group.The effects of YM155 on the apoptosis, the changes of Δψm , the mitochondrial distribution and the protein level of Cyt C in the Y 79 cells were evaluated by flow cytom-etry with Annexin V-FITC/PI staining, JC-1 staining, immunofluorescence analysis and Western blot , respectively.RE-SULTS:Compared with control group , YM155 significantly inhibited the proliferation of Y 79 cells and induced apoptosis (P<0.05).YM155 significantly reduced Δψm of the Y79 cells, promoted Cyt C which released from mitochondria to the cytosol and reduced the protein level of Cyt C in the mitochondria (P<0.05).CONCLUSION:YM155 inhibits Y79 cell proliferation and induces apoptosis , and the possible mechanisms may be involved in the mitochondrium-mediated apoptotic pathway .

OBJECTIVE: To explore the repair effects of bone marrow mesenchymal stem cells( BMSCs) on hematopoietic injury induced by benzene poisoning in mice. METHODS: Five specific pathogen free healthy male Kunming mice were selected to obtain BMSCs through bone marrow attachment culturing method. The Kunming mice were randomly divided into poisoning group and BMSCs transplantation group,18 mice in each group,after the benzene poisoning model was established by subcutaneous multi-point injection of benzene and oil mixture 3 times/week,10 weeks continuously. Each group was injected through tail vein with 250. 0 μL 0. 9% sodium chloride solution or 250. 0 μL BMSCs suspension( cell density 2 × 109/L) once per week for 4 weeks,respectively. The control group( 10 mice) was not given any treatment.Mice were euthanized 2 weeks after treatment. The blood routine examination was conducted. Nucleated cells in bone marrow were observed after Giemsa staining. The clones of hemopoietic progenitor cells were counted and the levels of serum interferon-γ( IFN-γ) were examined using enzyme-linked immune sorbent assay. RESULTS: The mouse model of chronic benzene poisoning was established successfully. After the BMSCs transplantation treatment,the white blood cell count,platelet count,red blood cell count,hemoglobin level and bone marrow nucleated cell as well as granulocyte-macrophage colony forming unit( CFU-GM) in benzene poisoning group were significantly decreased compared with control group( P <0. 01),while those indexes of BMSCs treatment group were higher than that of benzene poisoning group( P < 0. 05). The counts of platelet,red blood cell,bone marrow nucleated cell and CFU-GM in BMSCs treatment group were significantly lower than that of control group( P < 0. 05). The level of serum IFN-γ in benzene poisoning group was higher than that of control group( P < 0. 01),and serum IFN-γ level in BMSCs treatment group was lower than that of benzene poisoning group( P < 0. 01). There was no significant difference of IFN-γ level in BMSCs treatment group compared with control group( P > 0. 05). CONCLUSION: BMSCs have repair effects on hematopoietic system injury caused by benzene poisoning.

Objective To observe the clinical effect of Qiye Shenan tablet combined with sumatriptan in the treatment of middle-aged and elderly patients with chronic migraine.MethodsA total of 124 elderly patients with chronic migraine treated in our hospital from July 2015 to December 2015 were selected.The patients were divided into two groups according to the principle of randomization, with 62 cases in each group.The control group was treated with sumatriptan, The observation group was treated with Qiye Shenan tablet on this basis.The curative effect of the two groups, the relevant indicators and adverse reactions were analyzed.ResultsThe effective rate was 95.16% in the observation group, which was higher than that in the control group (80.65%, P<0.05).After treatment, the VAS score and the main symptom scores of the observation group were (1.86±0.42,3.48±0.59), respectively, which were lower than those in the control group (3.19±0.50,5.06±0.64) (P<0.05).The level of nitric oxide (NO) in the observation group was (33.04±3.86)μmol/L, which was lower than that in the control group (40.92±4.28)μmol/L(P<0.05).The adverse reaction rate was 11.29% in the observation group, which was lower than that in the control group (17.74%), but there was no significant difference between the two groups.ConclusionQiye Shenan tablet can improve the therapeutic effect of chronic migraine in the elderly, reduce the pain of the patients and improve the related symptoms, and the safety of medication.

Objective To explore the influencing factors of late diagnosis for newly diagnosed HIV/AIDS positive patients in Guangxi in 2015.Methods The CD4 + T lymphocytes count which was first detection for newly diagnosed HIV/AIDS positive patients in Guangxi during 2015 was collected.Data were statistically analyzed.Results We collected 8 586 newly diagnosed HIV/AIDS whose median CD4+ T lymphocytes counts was 237.5 cells/μl,and 43.12％ of them had less than 200 cells/μl.Gender,age,occupation,marriage,nation,education,route of transmission,types of testing and region had effects on late HIV diagnosis(all P ＜ 0.05).Logistic analysis found that risk factors associated with the late diagnosis of HIV were male(OR =1.851,95％ CI:1.673-2.048),migrant worker (OR =1.387,95％ CI:1.242-1.549),education below middle and secondary school(OR =1.619,95％ CI:1.400-1.873),currently married(OR =1.207,95％ CI:1.075-1.354),divorced or widowed(OR =1.508,95％ CI:1.309-1.738).Voluntary testing was a protective factor.Conclusions The prevalence the late diagnosis of HIV was high in Guangxi in 2015,it is crucial for related departments to enhance the testing and screening effort for HIV/AIDS.

Objective To systematically review the effects of hospital-community integrated management mode in diabetes mellitus. Methods To comprehensively search the database including CNKI, Taiwan Airiti library, WanFang Data, WeiPu Data and PubMed, we manually searched the relevant references of literature for the RCTs on hospital-community integrated management mode in diabetes mellitus, and Meta-analysis was used by software Revman 5. 2, and making descriptive analysis of the outcomes which could not be merged. Results A total of 15 RCTs were included involving 3 in English and 12 in Chinese, and 7 studies with high-quality and 8 of them with low-quality. According to the 11 evaluation focused outcomes indexes, the result of Meta-analysis showed that compared with conventional management, the hospital-community integration mode could effectively improve patients′ biochemical indicators such as glycated hemoglobin (HbA1c)[MD= -0. 39, 95%CI(-0. 56, -0. 22),P<0. 001], fasting plasma glucose[MD=-0. 75, 95%CI (-1. 16, -0. 33),P<0. 001], triglycerides[MD= -0. 36, 95%CI ( -0. 63, -0. 10), P=0.007], high-density lipoprotein (HDL-C)[MD =0. 09, 95%CI (0. 04, 0. 14), P <0. 001], low density lipoprotein (LDL-C)[MD= -0. 15, 95%CI (-0. 23, -0. 06),P=0. 001], but there was no effect on total cholesterol[MD= -0. 27, 95%CI (-0. 58, 0. 03),P=0. 080]. At the same time, the descriptive analysis presented that the model could improve patients′ awareness rate of diabetes health knowledge and promote the correct behavior of medication and regular exercise, in addition it could increase the score of life quality and reduce medical expenses. Conclusions Diabetes hospital-community integrated management can effectively improve the level of blood glucose and blood lipids, reduce the occurrence and development of related complications and provide a reliable basis for the management of diabetic patients. There is a positive impact to improve the patients′ behavior and quality of life, but it requires more randomized controlled studies to be analyzed and verified.