BACKGROUND:BCR/ABL gene is a specific gene of Ph chromosome-positive acute lymphoblastic leukemia,and its expression level has become a sensitive indicator for monitoring minimal residual disease before and after allogeneic hematopoietic stem cell transplantation.However,whether the expression level of BCR/ABL gene before transplantation affects the efficacy of transplantation and how to guide the early intervention of relapse with tyrosine kinase inhibitors after transplantation is still inconclusive.OBJECTIVE:To explore the relationship between BCR/ABL gene expression and recurrence in patients with Ph chromosome positive acute lymphoblastic leukemia before and after related and allogeneic hematopoietic stem cell transplantation.METHODS:Twenty-four patients with Ph chromosome positive acute lymphoblastic leukemia who achieved complete hematological remission and underwent allogeneic hematopoietic stem cell transplantation were selected at the Affiliated Hospital of North China University of Science and Technology between January 2015 and December 2022.Real time fluorescence quantitative polymerase chain reaction was used to dynamically detect the expression levels of BCR/ABL genes during treatment,representing minimal residual disease.Based on BCR/ABL gene expression,tyrosine kinase inhibitors combined with chemotherapy was administered before transplantation to select the timing of allogeneic hematopoietic stem cell transplantation.After transplantation,the disease status was evaluated to guide the use of tyrosine kinase inhibitors,and an early intervention plan for recurrence was developed.RESULTS AND CONCLUSION:Follow-up was until December 2023,with a median follow-up time of 49(12-82)months.There were 8 cases of hematological recurrence,with a median recurrence time of 14(8-39)months and a cumulative recurrence rate of 33％(8/24).Univariate analysis showed that recurrence after allogeneic hematopoietic stem cell transplantation was not significantly correlated with gender,age,extramedullary complications,time from diagnosis to transplantation,HLA typing,acute graft-versus-host disease,and chronic graft-versus-host disease(P＞0.05).There was a significant correlation between the relief treatment course and minimal residual disease levels before transplantation.The second hematology completely resolution and positive minimal residual disease before transplantation had a higher hematological recurrence rate(P＜0.05).The 3-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 27％,63％,and 74％;the 5-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 38％,57％,and 74％,respectively.It is concluded that Ph chromosome positive acute lymphoblastic leukemia patients with BCR/ABL gene positive before transplantation have a higher recurrence rate.BCR/ABL gene expression after transplantation can guide the application of tyrosine kinase inhibitors and serve as a basis for early intervention in recurrence.

BACKGROUND:BCR/ABL gene is a specific gene of Ph chromosome-positive acute lymphoblastic leukemia,and its expression level has become a sensitive indicator for monitoring minimal residual disease before and after allogeneic hematopoietic stem cell transplantation.However,whether the expression level of BCR/ABL gene before transplantation affects the efficacy of transplantation and how to guide the early intervention of relapse with tyrosine kinase inhibitors after transplantation is still inconclusive.OBJECTIVE:To explore the relationship between BCR/ABL gene expression and recurrence in patients with Ph chromosome positive acute lymphoblastic leukemia before and after related and allogeneic hematopoietic stem cell transplantation.METHODS:Twenty-four patients with Ph chromosome positive acute lymphoblastic leukemia who achieved complete hematological remission and underwent allogeneic hematopoietic stem cell transplantation were selected at the Affiliated Hospital of North China University of Science and Technology between January 2015 and December 2022.Real time fluorescence quantitative polymerase chain reaction was used to dynamically detect the expression levels of BCR/ABL genes during treatment,representing minimal residual disease.Based on BCR/ABL gene expression,tyrosine kinase inhibitors combined with chemotherapy was administered before transplantation to select the timing of allogeneic hematopoietic stem cell transplantation.After transplantation,the disease status was evaluated to guide the use of tyrosine kinase inhibitors,and an early intervention plan for recurrence was developed.RESULTS AND CONCLUSION:Follow-up was until December 2023,with a median follow-up time of 49(12-82)months.There were 8 cases of hematological recurrence,with a median recurrence time of 14(8-39)months and a cumulative recurrence rate of 33％(8/24).Univariate analysis showed that recurrence after allogeneic hematopoietic stem cell transplantation was not significantly correlated with gender,age,extramedullary complications,time from diagnosis to transplantation,HLA typing,acute graft-versus-host disease,and chronic graft-versus-host disease(P＞0.05).There was a significant correlation between the relief treatment course and minimal residual disease levels before transplantation.The second hematology completely resolution and positive minimal residual disease before transplantation had a higher hematological recurrence rate(P＜0.05).The 3-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 27％,63％,and 74％;the 5-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 38％,57％,and 74％,respectively.It is concluded that Ph chromosome positive acute lymphoblastic leukemia patients with BCR/ABL gene positive before transplantation have a higher recurrence rate.BCR/ABL gene expression after transplantation can guide the application of tyrosine kinase inhibitors and serve as a basis for early intervention in recurrence.

To analyze the disease burden of acute lymphoid leukemia(ALL) and its changing trends in China and globally from 1990 to 2021, aiming to provide a theoretical basis for disease prevention, treatment, and policy formulation.

OBJECTIVE To establish a quality control method for Jinbei oral liquid based on multi-wavelength switching high performance liquid chromatography （HPLC） fingerprint， chemical pattern recognition and multi-index content determination. METHODS A total of 15 batches of Jinbei oral liquid were used as test samples. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （ Version 2012 ） was adopted to establish multi-wavelength switching HPLC fingerprints， followed by chromatographic peak identification and similarity evaluation. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were applied to conduct chemical pattern recognition on the 15 batches of samples. The multi-wavelength switching HPLC method was used to simultaneously determine the contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianoli c acid B and wogonoside in samples. RESULTS A total of 25 common peaks were calibrated in the fingerprints of 15 batches of Jinbei oral liquid， among which 7 common peaks were unambiguously identified. The similarity of all samples was higher than 0.960. Chemical pattern recognition results showed that samples S1-S8 were clustered into group 1， and samples S9-S15 were clustered into group 2. Baicalin， wogonoside， neochlorogenic acid， chlorogenic acid and salvianolic acid B were identified as the differential quality markers. The average contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianolic acid B and wogonoside in 15 batches of Jinbei oral liquid were 0.213 7， 0.085 3， 0.104 9， 0.287 3， 0.420 1， 0.062 1， 0.176 0 mg/mL， respectively. CONCLUSIONS The established quality control method for Jinbei oral liquid combining multi-wavelength switching HPLC fingerprint， chemical pattern recognition and multi-index content determination is stable and reliable， which can provide a reference for the formulation of quality standards of this preparation.

OBJECTIVE To establish a quality control method for Jinbei oral liquid based on multi-wavelength switching high performance liquid chromatography （HPLC） fingerprint， chemical pattern recognition and multi-index content determination. METHODS A total of 15 batches of Jinbei oral liquid were used as test samples. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （ Version 2012 ） was adopted to establish multi-wavelength switching HPLC fingerprints， followed by chromatographic peak identification and similarity evaluation. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were applied to conduct chemical pattern recognition on the 15 batches of samples. The multi-wavelength switching HPLC method was used to simultaneously determine the contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianoli c acid B and wogonoside in samples. RESULTS A total of 25 common peaks were calibrated in the fingerprints of 15 batches of Jinbei oral liquid， among which 7 common peaks were unambiguously identified. The similarity of all samples was higher than 0.960. Chemical pattern recognition results showed that samples S1-S8 were clustered into group 1， and samples S9-S15 were clustered into group 2. Baicalin， wogonoside， neochlorogenic acid， chlorogenic acid and salvianolic acid B were identified as the differential quality markers. The average contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， forsythoside A， baicalin， salvianolic acid B and wogonoside in 15 batches of Jinbei oral liquid were 0.213 7， 0.085 3， 0.104 9， 0.287 3， 0.420 1， 0.062 1， 0.176 0 mg/mL， respectively. CONCLUSIONS The established quality control method for Jinbei oral liquid combining multi-wavelength switching HPLC fingerprint， chemical pattern recognition and multi-index content determination is stable and reliable， which can provide a reference for the formulation of quality standards of this preparation.

ObjectiveTo systematically identify the main chemical components of Linggui Zhugan granules （LGZGG）， and to explore the pharmacodynamic substance basis for the treatment of metabolic dysfunction-associated steatohepatitis （MASH）. MethodsThe chemical components of LGZGG were systematically analyzed by ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）. The protein-protein interaction （PPI） network and "compound prescription-disease-component-target" network were constructed by network target analysis to predict the potential pharmacodynamic substances and core targets of LGZGG in the treatment of MASH. The potential pharmacodynamic substances were enriched by macroporous adsorption resin， and the chemical composition of the LGZGG-50% ethanol elution fraction （LGZGG-50） was analyzed by UPLC-Q-TOF-MS/MS. The mouse model of MASH was established by feeding a high-fat， high-cholesterol， and high-fructose diet for 12 weeks. Mice were randomly allocated into normal， model， positive drug （MGL-3196， 1 mg·kg^-1）， LGZGG （crude drug， 34 g·kg^-1·d^-1）， LGZGG-50 （crude drug， 34 g·kg^-1·d^-1） groups. The levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in the serum were measured， and the pathological changes in the liver tissue were observed by hematoxylin-eosin （HE） and Sirius red staining. The in vivo efficacy of LGZGG and LGZGG-50 in the treatment of MASH was evaluated on the basis of the findings. The expression levels of adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， silent information regulator 2-related enzyme 1 （SIRT1）， peroxisome proliferator-activated receptor α （PPARα）， and carnitine palmitoyltransferase 1A （CPT1A） in the liver tissue were determined by Western blot to verify the regulatory effects of core targets. ResultsA total of 83 chemical components were identified from LGZGG， including 20 flavonoids， 13 terpenoids， 17 organic acids， 7 amino acids， 11 glycosides， 3 nucleosides， 3 aromatics， 3 alkaloids， 2 phenylpropanoids， 2 sugars， 1 nucleic acid， and 1 steroid. A total of 134 common targets were obtained by network target analysis. The core targets included SIRT1， PPARα， nuclear factor-kappa B subunit 1 （NF-κB1）， and interleukin-6 （IL-6）. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis revealed that the targets were mainly enriched in the AMPK， PPAR and other signaling pathways. The topological analysis of the "compound prescription-disease-component-target" network showed that the potential pharmacodynamic substances of LGZGG against MASH were flavonoids and terpenoids. The relative content of flavonoids and terpenes in LGZGG-50 were 74.00% and 62.41% in positive and negative ion modes， respectively， indicating that LGZGG-50 effectively enriched total flavonoids and total terpenoids. The results of in vivo efficacy showed that compared with the model group， LGZGG and LGZGG-50 reducef the body weight， liver weight， serum TG， GLU， and ALT levels of MASH mice （P<0.05，P<0.01）， and LGZGG additionally increased the HDL-C level （P<0.01）. Both groups alleviated the pathological damage in the liver tissue. The results of Western blot showed that compared with the model group， the protein levels of p-AMPK/AMPK， SIRT1， PPARα， and CPT1A were up-regulated in the LGZGG group （P<0.05，P<0.01）， and those of p-AMPK/AMPK and CPT1A were up-regulated in the LGZGG-50 group （P<0.01）. ConclusionLGZGG ameliorates MASH， with the main pharmacodynamic substances being flavonoids and terpenoids. The mechanism may be related to the regulation of AMPK/SIRT1/PPARα signaling pathway， improvement of lipid metabolism， and alleviation of pathological damage in the liver tissue.

ObjectiveTo evaluate the efficacy of immediate postoperative oral administration of 2 mg estradiol/estradiol dydrogesterone tablets in reducing secondary surgery for retainedproducts of conception（RPOC）， preventing intrauterine adhesions（IUA）， and promoting endometrial repair following induced abortion. MethodsA retrospective analysis was conducted on 494 patients who underwent induced abortion. The control group （n=214） received conventional postoperative treatment with antibiotics and Yimucao granules， while the observation group （n=280） received immediate administration of estradiol/dydrogesterone tablets （each tablet contains 2 mg of estradiol），combined with antibiotics and Yimucao granules. The two groups were compared for the secondary surgery rate for RPOC， incidence of IUA， endometrial thickness at 2 weeks postoperatively， duration of postoperative vaginal bleeding， time to menstrual resumption， incidence of reduced menstrual volume after resumption， and postoperative complications （pelvic infection， intrauterine fluid accumulation）. ResultsThe observation group showed a lower rate of secondary surgery for RPOC compared to the control group （0.4% vs 2.3%）， but the difference was not statistically significant （P=0.13， Fisher’s exact test）. The observation group also had a significantly lower incidence of IUA （P<0.05）， greater postoperative endometrial thickness at 2 weeks （P<0.05）， and significantly shorter duration of postoperative vaginal bleeding and time to menstrual resumption. The incidence of reduced menstrual volume postoperatively and complications （pelvic infection， intrauterine fluid accumulation） were also significantly lower in the observation group （all P<0.05）. ConclusionImmediate oral administration of estradiol/dydrogesterone tablets after induced abortion significantly prevents intrauterine adhesions， shortens postoperative vaginal bleeding duration， promotes endometrial repair， improves menstrual recovery， and potentially reduces the risk of secondary surgery for retained products of conception.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

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.