Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To investigate the clinical significance of monitoring SIL::TAL1 fusion transcripts in the evaluation of treatment response and prognosis of children with T-acute lymphoblastic leukemia (T-ALL).Methods:A retrospective cohort study was conducted to analyze the clinical data of 46 newly diagnosed pediatric T-ALL with SIL::TAL1 fusion transcripts treated at Beijing Children′s Hospital Capital Medical University from November 2004 to December 2022. The SIL::TAL1 fusion transcripts were quantitatively detected at the initial diagnosis (TP0) and early stage of induction therapy (TP1), at the end of induction remission therapy (TP2), before consolidation therapy (TP3) and subsequent treatment. Patients were divided into negative and positive groups on SIL::TAL1 fusion transcripts level, differences of clinical features and survival among groups at TP0 to TP3 were analyzed. The χ2 test or Fisher exact test or Mann-Whitney U test was used to compare the clinical difference. Survival analysis was estimated by Kaplan-Meier method with Log-Rank testing. Multivariate analysis was conducted by Cox proportional hazards models. Results:Among the 46 children with SIL::TAL1 fusion transcripts, 36 were males and 10 were females, with the onset age of 6.8 (3.4, 9.5) years. The negative rates of SIL::TAL1 fusion transcripts for TP1,TP2, TP3, before delayed intensification Ⅰ treatment (TP4), before maintenance therapy (TP5) were 36% (13/36), 78% (32/41), 76% (32/42), 15/16, and 12/12, respectively. No significant difference was found on clinical features and prednisone response between groups at TP0-TP3 (all P>0.05). The 5-year events free survival (EFS) rate of patients classified as negative (32 cases) and positive (9 cases) groups at TP2 was (78±8)% and (33±16)%, respectively ( χ2=9.86, P=0.002), the 5-year overall survival (OS) rate was (81±7)% and (44±17)%, respectively ( χ2=6.40, P=0.011). The 5-year EFS rate of patients classified as negative (32 cases) and positive (10 cases) groups at TP3 was (78±8)% and (30±15)%, respectively ( χ2=13.04, P<0.001) and the 5-year OS rate was (84±6)% and (30±15)%, respectively ( χ2=15.95, P<0.001). Cox multivariate regression showed that positive of SIL::TAL1 transcript at TP3 was adverse independent prognostic factors for EFS and OS (EFS: HR=6.70, 95% CI 2.01-22.35, P=0.002; OS: HR=10.73, 95% CI 2.50-46.09, P=0.001). Conclusions:Monitoring SIL::TAL1 fusion transcripts can reflect the clinical treatment response. The level of SIL::TAL1 fusion transcripts at early period can predict long-term outcomes of these patients.

Objective To compare the differences of endoscopic ultrasound (EUS)-guided non-invasive measurement of portal venous pressure and EUS-guided portal pressure gradient(EUS-PPG) in measurement of portal venous pressure on animals and their correlation. Methods Twenty-four miniature pigs were selected and fed with carbon tetrachloride and phenobarbital sodium combined with high-fat,low-protein and low-choline diet for 16 weeks to establish a liver cirrhotic portal hypertension model. The changes of biochemical indexes of liver function and liver pathology in the experimental pigs were observed to evaluate whether the model was successful. After the model was successfully established,the hemodynamic parameters of the portal venous trunk were measured non-invasively under EUS guidance,including portal venous blood flow and splenic artery pulsatility index,thereby calculating portal venous pressure. Then,taking EUS-PPG,the portal vein,hepatic vein,and inferior vena cava were punctured with an 18G puncture needle under general anesthesia guided by the translinear endoscopic ultrasound,and the PPG was calculated through the central venous pressure monitoring system.The Pearson correlation analysis,Kappa test,ICC intraclass correlation coefficient and Bland-Altman plot were used for consistency analysis. Results All the 24 pigs survived 16 weeks after modeling.The serum levels of alanine transaminase (ALT),aspartate transaminase (AST),albumin (ALB),globulin (GLB),total bilirubin (TBIL) and indirect bilirubin (IBIL)after modeling were higher than those before modeling(P<0.05). HE staining and Sirius red staining showed abnormal liver morphology and increased collagen fibers after modeling,suggesting that the experimental pig model of liver cirrhotic portal hypertension was successfully established. The results of EUS-guided non-invasive measurement of portal venous pressure showed that the mean splenic artery pulsatility index was (2.03±0.68),the mean portal vein flow was (17.27±4.31)cm/s,and the mean portal venous pressure was (15.97±3.65)mmHg. The measurement results of the mean portal venous pressure,hepatic venous pres-sure and PPG of EUS-PPG were (20.68±4.71)mmHg,(4.07±2.14)mmHg and (16.38±4.28)mmHg respectively. Pearson correlation analysis showed that there was a significant positive correlation between the portal venous pressures measured by the two methods (r=0.902,P<0.001);the consistency tests of Kappa test and ICC intraclass correlation coefficient showed that the measurement results of the two methods were highly consistent (Kappa=0.699,P<0.001;ICC=0.945);Bland-Altman plot analysis showed that most of the points fell within 95％ limits of agreement. Conclusion EUS-guided non-invasive measurement of portal venous pressure has a high correlation and consistency with the measurement results by EUS-PPG,which has high success rate,and accurate reflection of portal venous pressure,with low cost and good safety.

Objective To elucidate the pharmacokinetic characteristics and primary metabolic pathways of anthocyanins in vivo,as well as the endogenous metabolites exhibiting sensitive responses to bilberry extract intervention in rats by LC-MS/MS technology,following oral administration of bilberry extract.Methods Multi-component pharmacokinetic technology was employed to study the systemic exposure characteristics of anthocyanins in blood,the metabolic product profile,and the dynamic concentration changes of anthocyanins and their metabolites in plasma after oral administration of bilberry extract to rats.Metabolomics technology was used to analyze changes in endogenous metabolites at the time point when most anthocyanins reached their peak plasma concentration.Results After administration of European cranberry extract,a total of 18 anthocyanin parent compounds and 14 metabolites were detected in rat plasma.Glucuronidation was identified as the primary metabolic pathway.The time to reach peak concentration(Tmax)for most parent compounds ranged from 15 to 60 minutes.Moreover,30 minutes after oral dosing with the cranberry extract,the levels of various endogenous acyl-carnitines,fatty acids,and lysophosphatidylcholines in the blood decreased.The plasma exposure of most anthocyanin components and their metabolites showed a highly linear correlation with the administered dose(R2>0.9).Conclusion This study clarified the main pharmacokinetic characteristics and metabolic pathways of anthocyanins from bilberry extract in rats,as well as the potential impact on various endogenous metabolites.It provides data support for effectively exploring the pharmacodynamic material basis and mechanism of action of bilberry extract.

Objective: To investigate the impact of milk and egg supplementation on body composition and bone mineral density of rural primary school students in Yunnan Province, so as to provide a reference for developing targeted nutritional intervention strategies. Methods: In December 2023, a cluster sampling method was adopted to select students from grades one to three in four primary schools each from Jinggu and Shidian countys of Yunnan Province, as the intervention group (662 students). Additionally, two boarding primary schools were selected from each county based on the principle of matching scale and student numbers as the control group (455 students). Starting from April 2023, the intervention group received 200 mL milk and 50 g eggs during the break on school days for 8 months, while the control group maintained their usual diet behavior. Body composition was measured by using bioelectrical impedance analysis, and distal radial bone mineral density was assessed via dual energy X-ray absorptiometry in April and December 2023. The intervention effects were analyzed by using a difference in-differences approach. Results: The final measurements of body fat percentage, skeletal muscle mass and fat free mass of the intervention group and the control group of primary school students were significantly higher than the baseline values, and the net effect of milk and egg intervention on these body composition indicators was not statistically significant ( P >0.05, both before and after adjustment). In contrast, bone mineral density increased significantly by 0.02 g/cm 2 in the intervention group. The net intervention effect on bone mineral density was statistically significant ( β=0.02, 95%CI =0.00-0.04), and remained significant after model adjustment ( β=0.02, 95%CI =0.00-0.04) (both P < 0.05). Subgroup analysis showed statistically significant effects of the intervention among girls ( β=0.02, 95%CI =0.00-0.04), day students ( β=0.04, 95%CI =0.01-0.07), and students with normal nutritional status ( β=0.02, 95%CI =0.00-0.04) (all P <0.05). No significant effect of milk and egg supplementation was observed on body composition indicators (all P <0.05). Conclusions Milk and egg supplementation can improve bone mineral density among rural primary school students in Yunnan Province. It is recommended that rural school aged children should increase intake of milk and eggs to support growth and development.

Objective:To investigate the clinical significance of monitoring SIL::TAL1 fusion transcripts in the evaluation of treatment response and prognosis of children with T-acute lymphoblastic leukemia (T-ALL).Methods:A retrospective cohort study was conducted to analyze the clinical data of 46 newly diagnosed pediatric T-ALL with SIL::TAL1 fusion transcripts treated at Beijing Children′s Hospital Capital Medical University from November 2004 to December 2022. The SIL::TAL1 fusion transcripts were quantitatively detected at the initial diagnosis (TP0) and early stage of induction therapy (TP1), at the end of induction remission therapy (TP2), before consolidation therapy (TP3) and subsequent treatment. Patients were divided into negative and positive groups on SIL::TAL1 fusion transcripts level, differences of clinical features and survival among groups at TP0 to TP3 were analyzed. The χ2 test or Fisher exact test or Mann-Whitney U test was used to compare the clinical difference. Survival analysis was estimated by Kaplan-Meier method with Log-Rank testing. Multivariate analysis was conducted by Cox proportional hazards models. Results:Among the 46 children with SIL::TAL1 fusion transcripts, 36 were males and 10 were females, with the onset age of 6.8 (3.4, 9.5) years. The negative rates of SIL::TAL1 fusion transcripts for TP1,TP2, TP3, before delayed intensification Ⅰ treatment (TP4), before maintenance therapy (TP5) were 36% (13/36), 78% (32/41), 76% (32/42), 15/16, and 12/12, respectively. No significant difference was found on clinical features and prednisone response between groups at TP0-TP3 (all P>0.05). The 5-year events free survival (EFS) rate of patients classified as negative (32 cases) and positive (9 cases) groups at TP2 was (78±8)% and (33±16)%, respectively ( χ2=9.86, P=0.002), the 5-year overall survival (OS) rate was (81±7)% and (44±17)%, respectively ( χ2=6.40, P=0.011). The 5-year EFS rate of patients classified as negative (32 cases) and positive (10 cases) groups at TP3 was (78±8)% and (30±15)%, respectively ( χ2=13.04, P<0.001) and the 5-year OS rate was (84±6)% and (30±15)%, respectively ( χ2=15.95, P<0.001). Cox multivariate regression showed that positive of SIL::TAL1 transcript at TP3 was adverse independent prognostic factors for EFS and OS (EFS: HR=6.70, 95% CI 2.01-22.35, P=0.002; OS: HR=10.73, 95% CI 2.50-46.09, P=0.001). Conclusions:Monitoring SIL::TAL1 fusion transcripts can reflect the clinical treatment response. The level of SIL::TAL1 fusion transcripts at early period can predict long-term outcomes of these patients.

OBJECTIVE: To compare the efficacy and safety of intravenous colistin sulfate combined with nebulized inhalation versus intravenous monotherapy for pulmonary infections caused by carbapenem-resistant organism (CRO). METHODS: A multicenter retrospective cohort study was conducted. Clinical data were collected from patients admitted to the intensive care unit (ICU) of 10 tertiary class-A hospitals in Henan Province between July 2021 and May 2023, who received colistin sulfate for CRO pulmonary infections. Data included baseline characteristics, inflammatory markers [white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), C-reactive protein (CRP)], renal function indicators [serum creatinine (SCr), blood urea nitrogen (BUN)], life support measures, anti-infection regimens, clinical efficacy, microbiological clearance rate, and prognostic outcomes. Patients were divided into two groups: intravenous group (colistin sulfate monotherapy via intravenous infusion) and combination group ((intravenous infusion combined with nebulized inhalation of colistin sulfate). Changes in parameters before and after treatment were analyzed. RESULTS: A total of 137 patients with CRO pulmonary infections were enrolled, including 89 in the intravenous group and 48 in the combination group. Baseline characteristics, life support measures, daily colistin dose, and combination regimens (most commonly colistin sulfate plus carbapenems in both groups) showed no significant differences between two groups. The combination group exhibited higher clinical efficacy [77.1% (37/48) vs. 59.6% (52/89)] and microbiological clearance rate [60.4% (29/48) vs. 39.3% (35/89)], both P < 0.05. Pre-treatment inflammatory and renal parameters showed no significant differences between two groups. Post-treatment, the combination group showed significantly lower WBC and CRP [WBC (×10⁹/L): 8.2±0.5 vs. 10.9±0.6, CRP (mg/L): 14.0 (5.7, 26.6) vs. 52.1 (24.4, 109.6), both P < 0.05], whereas NEU, PCT, SCr, and BUN levels showed no significant between two groups. ICU length of stay was shorter in the combination group [days: 16 (10, 25) vs. 21 (14, 29), P < 0.05], although mechanical ventilation duration and total hospitalization showed no significant differences between two groups. CONCLUSIONS Intravenous colistin sulfate combined with nebulized inhalation improved clinical efficacy and microbiological clearance in CRO pulmonary infections with an acceptable safety profile.
Humans ; Colistin/therapeutic use* ; Retrospective Studies ; Administration, Inhalation ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/pharmacology* ; Male ; Female ; Middle Aged ; Gram-Negative Bacteria/drug effects* ; Aged ; Treatment Outcome ; Respiratory Tract Infections/drug therapy*