Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

AIM:To investigate the optimal time of blood collection and the best concentration of Ganlong capsule(GLC)-containing serum for steatohepatitis.METHODS:Sixty C57BL/6J mice were gavaged with GLC at a dose of 90 mg/kg body weight,twice a day for 7 days.Control mice were administered the same volume of 0.9%saline.After 0.5,1,2 and 4 h from the last gavage,blood was collected to prepare GLC-containing serum.The LC-MS/MS was used to detect the inosine content of blank and drug-containing serum at different blood collection times to determine the optimal time.Subsequently,NCTC1469 cells stimulated with palmitic acid(PA)were treated with different concentrations of the GLC-containing serum.Nile Red staining was used to detect lipid droplet formation,and RT-qPCR was employed to as-sess the expression of intracellular fatty acid synthesis(Fabp1,Scd1)and fatty acid β-oxidation gene(Pparα).RE-SULTS:(1)LC-MS/MS detection revealed that the inosine concentration peaked 2 h after the last administration.(2)Nile red staining demonstrated that the GLC-containing serum exerted a dose-dependent decreasing trend of lipid droplets in hepatocytes induced by PA.(3)GLC-containing serum significantly downregulated the mRNA expression levels of lipo-genesis-genes(Fabp1 and Scd1)with a dose-dependent decreasing trend in the PA-induced NCTC1469 cells.The mRNA expression of genes associated with fatty acid β-oxidation(Pparα)were upregulated with a dose-dependent increasing trend.CONCLUSION:The 10%GLC-containing serum collected 2 hours after the last administration in mice has the best therapeutic effect for steatohepatitis.

The aim of this study was to evaluate the roles of interleukin (IL)-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury (SAKI). Methods: We enrolled 146 sepsis patients (84 non-SAKI and 62 SAKI patients) admitted to the emergency department from November 2020 to November 2021. Patients with SAKI were differentiated based on the severity of acute kidney injury. All clinical parameters were evaluated upon admission before administering antibiotic treatment. Inflammatory cytokines were assessed using flow cytometry and the Pylon 3D automated immunoassay system (ET Healthcare). In addition, a receiver operating characteristic (ROC) curve was utilized to determine the prognostic values of IL-17A in SAKI. Results: The levels of creatinine, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor alpha, C-reactive protein, and procalcitonin (PCT) were significantly higher in the SAKI group than in the non-SAKI group (p < 0.05). The level of IL-17A revealed significant differences among stages 1, 2, and 3 in SAKI patients (p < 0.05). The mean levels of PCT, IL-4, and IL-17A were significantly higher in the non-survival group than in the survival group in SAKI patients (p < 0.05). In addition, the area under the ROC curve of IL-17A was 0.811. Moreover, the IL-17A cutoff for differentiating survivors from non-survivors was 4.7 pg/mL, of which the sensitivity and specificity were 77.4% and 71.0%, respectively. Conclusion: Elevated levels of IL-17A could predict that SAKI patients are significantly prone to worsening kidney injury with higher mortality. The usefulness of IL-17A in treating SAKI requires further research.

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Objective To investigate the protective effects of left ventricular myocardial perfusion after delivery of acidic fibroblast growth factor (aFGF) in rats with diabetic cardiomyopathy (DCM) by using ultrasound‐targeted microbubble destruction ( UTMD ) with real‐time myocardial contrast echocardiography( RT‐MCE) . Methods Among 64 male SD rats ,52 rats were randomly selected and were induced DCM by streptozotocin through intraperitoneal injecting ,the other rats as normal control group . DCM rats were randomly divided into the DCM model group ,aFGF only group ,SonoVue‐aFGF group and the SonoVue‐aFGF+ UTMD group in this study . The aFGF only group rats were injected with aFGF solution through tail vein ,the SonoVue‐aFGF group were injected with SonoVue‐aFGF solution through tail vein and SonoVue‐aFGF+ UTMD group rats were injected with SonoVue‐aFGF solution through tail vein and using UTMD simultaneously . All rats underwent conventional echocardiography and RT‐MCE exams before and 4 weeks after intervention . Left ventricular ejection fraction ( LVEF) and left ventricular fraction shortening( LVFS ) were measured by conventional echocardiography . The plateau intensity ( A ) ,initial slope of the curve (β) and myocardial blood flow ( A ×β) of left ventricular anterior wall at the papillary muscle level were measured in left ventricular short‐axis view by RT‐MCE . Results Before intervention , LVEF and LVFS in the DCM model group ,aFGF only group ,SonoVue‐aFGF group and the SonoVue‐aFGF+UTMD group were significantly lower than in the normal control group ( P <0 .01) .During 4 weeks after intervention ,LVEF and LVFS in the aFGF only group ,SonoVue‐aFGF group and the SonoVue‐aFGF+UTMD group were slightly increased than those in the DCM model group ,but no statistically significant differences were found ( P > 0 .05) ,however A and A × β in the SonoVue‐aFGF+ UTMD group were significantly increased than those in the DCM model group( P < 0 .01) . Compared with the same group before intervention ,A and A ×βin the SonoVue‐aFGF+UTMD group were higher ( P <0 .05) and these in the DCM model group were lower during four weeks after intervention ( P < 0 .05) . Conclusions Acidic fibroblast growth factor delivered by using UTMD can improve the left ventricular myocardial perfusion in diabetic cardiomyopathy rats .

[ ABSTRACT] AIM:To explore the mechanisms of fluctuant high blood glucose-induced apoptosis of hepatocytes. METHODS:SD rats were randomly divided into normal control group ( N) , stable high blood glucose group ( S) , fluctu-ant high blood glucose group ( F) and insulin group ( I) .Diabetic rats were induced by intraperitoneal injection of strepto-zotocin (65 mg/kg) , and the fluctuant high blood glucose animal model was induced by intraperitoneal injection of ordinary insulin and glucose at different time points every day.The blood glucose fluctuation patterns of the animals in F group with-in 12 weeks were similar every day and no significant difference of the HbA1c concentration was observed compared with S group, indicating that the fluctuant hyperglycemia was successfully established in F group.The activity of superoxide dis-mutase ( SOD) and glutathione peroxidase ( GSH-Px) , and the content of malondialdehyde ( MDA) and nitric oxide ( NO) in the homogenate of the liver tissues were detected by colorimetry.The mRNA and protein levels of JNK, p-JNK, Bax and Bcl-2 were examined by RT-PCR and Western blot.RESULTS:After 12 weeks, the increases in the intakes of food and water, the urine output, and the abnormal liver function were observed in S group, I group and F group.Compared with N group, the MDA level was increased, the content of NO and the activity of SOD and GSH-Px were decreased, and up-regu-lation of JNK mRNA and p-JNK and Bax proteins, and down-regulation of Bcl-2 were also found in S group, I group and F group.The above effects were more obviously showed in F group.CONCLUSION:Oxidative stress activates JNK-MAPK signaling pathway, which is involved in fluctuant high glucose-induced apoptosis of hepatocytes.

Objective To discuss the effect of posterior quadrant disconnection surgery on temporoparietooccipital intractable epilepsy.Methods A retrospective review of clinical,neuropsychological,EEG,imaging and histopathological data of 3 patients with intractable epilepsy,admitted to and underwent posterior quadrant disconnection surgery in our hospital from February 2012 to October 2013,was performed.Results The clinical manifestations of 3 patients were simple partial seizures generalized seizures secondary to partial seizures and generalized tonic clonic seizures.MRI examination showed that 3 patients were porencephaly,white matter dysplasia,and gray matter heterotopia.Patients were treated with right posterior quadrant disconnection surgery after general anesthesia.Follow up of 32,12 and 29 months was respectively performed in these 3 patients.The seizure control result after surgery was Engel Ⅰ in 2 patients and Engel Ⅱ in one patient.There was no new prolonged neurological deficit or death.Conclusion Posterior quadrant disconnection surgery is an effective method for posterior quadrant intractable epilepsy,which results in similar excellent early seizure control as hemispherectomy.

Porcine interferon-alpha (pIFN-alpha) fermentative production by recombinant Pichia pastoris was carried out in a 10-L bioreactor to study its metabolism changes and effects on fermentation under different inducing strategies, by analyzing the change patterns of the corresponding metabolism and energy regeneration. The results show that the specific activities of alcohol oxidase (AOX), formaldehyde dehydrogenase (FLD) and formate dehydrogenase (FDH) largely increased when reducing temperature from 30 degrees C to 20 degrees C under pure methanol induction, leading significant enhancements in methanol metabolism, formaldehyde dissimilatory energy metabolism and pIFN-alpha antiviral activity. The highest pIFN-alpha antiviral activity reached 1.4 x 10(6) IU/mL, which was about 10-folds of that obtained under 30 degrees C induction. Using methanol/sorbitol co-feeding strategy at 30 degrees C, the major energy metabolism energizing pIFN-alpha synthesis shifted from formaldehyde dissimilatory energy metabolism pathway to TCA cycle, formaldehyde dissimilatory pathway was weakened and accumulation of toxic intermediate metabolite-formaldehyde was relieved, and methanol flux distribution towards to pIFN-alpha synthesis was enhanced. Under this condition, the highest pIFN-alpha antiviral activity reached 1.8 x 10(7) IU/mL which was about 100-folds of that obtained under pure methanol induction at 30 degrees C. More important, enhanced pIFN-alpha production with methanol/sorbitol co-feeding strategy could be implemented under mild conditions, which greatly reduced the fermentation costs and improved the entire fermentation performance.
Animals ; Energy Metabolism ; Fermentation ; Interferon-alpha ; biosynthesis ; genetics ; Methanol ; pharmacology ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; Sorbitol ; pharmacology ; Swine

Objective To explore the effects of oscillating blood glucose on apoptosis in renal tubular epithelial cells of diabetic rats and the role of oxidative stress.Methods Renal tubular epithelial cells (HK-2) were cultured in vitro with stable high glucose or oscillating high glucose,and MTF assay was applied to the neasurement of cell proliferation.Streptozotocin induced diabetic model was established with SD rats and the oscillating high blood glucose animal model was induced by intraperitoneal injection of insulin and glucose at different time points every.day.12 weeks later 24 h urine protein (24hUP),blood urea nitrogen (BUN),serum creatinine (Scr),superoxide dismutase (SOD), and malondialdehyde (MDA)were determined. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL),and immunohisto-chemistry was used to detect apoptosis associated gene Bax,Bcl-2,and NOX-4 expression in kidney.Changes in ultrastructure were observed.Results Oscillating high glucose may inhibit renal cells proliferation obviously when comparing with stable high glucose.In the rats with oscillating blood glucose rather than those with stable high blood glucose,there was a significant increase of BUN,Scr,24hUP,and MDA and a decrease of SOD[ (21.50 ± 1.72 vs 12.50 ± 1.85 )mmol/L,(97.51 ± 7.84 vs 82.12 ± 11.48 ) μmol/L,( 1.57 ± 0.09 vs 1.04 ± 0.12 ) mg/24 h,( 23.50 ± 1.87 vs 14.82 ± 2.96) nmol/ml,( 17.22 ± 1.12 vs 21.11 ± 1.80) U/ml,all P＜0.05 ] ; cell apoptosis was intensified with the up-regulation of Bax and NOX-4 protein expression and down-regulation of Bcl-2 in glomerular endothelial cells; and more severe pathological damages were observed.ConclusionComparing with stable high blood glucose,oscillating high blood glucose induces more apoptosis and less proliferation of renal tubular epithelial cells and the mechanism may be related to the increased oxidative stress.

Objective To compare the rapeutic effects of different acupoint combination applied with Rheumatoid Arthritis Cata-plasma on nuclear factor-? ? expression of CIA rats. Methods Induced arthritis rats back were endermic injected with type Ⅱ bovine collogen as animal models. There were five groups for comparison. NF-? ?, interleukin-1? (IL-1?) and tumor necrosis factor-? (TNF-?) of synovial cell clear supernatant liquid were observed. Results NF-? ?, IL-1? and TNF-? scores in therapy groups were steped down. The scores of systematic selection (distant and near coordination) of acupoints was the most close to normal group. Conclusion Rheumatoid Arthritis Cata-plasma can down-regulation the expression of nuclear factor-?? and correlated cell factor density of CIA rats synovial cell and repress positive feedback. Therapeutic effect of distant and near coordination of acupoints is better than distant selection and local selection of acupoints, probably by treating appearance and substance simultaneously to multitarget effect.