Repeat expansion diseases(REDs) are a group of genetic disorders caused by the pathological expansion of specific short tandem repeats(STRs) in genomic DNA. They are characterized by significant clinical and genetic heterogeneity. Owing to the complexity of their pathogenesis, effective treatments remain elusive. With the in-depth analysis of the pathogenesis of these diseases, along with the development and innovation of targeting tools in recent years, targeted therapy strategies have become a research hotspot, and some antisense oligonucleotide drugs have entered the clinical trial stage. This article aims to review the latest advances in basic research and clinical trial outcomes of targeted therapy at the DNA, RNA and protein levels. Currently, this field still faces key bottlenecks including a high risk of off-target effects, low delivery efficiency, and challenges in clinical translation. Future efforts should focus on the optimization and refinement of targeting tools and delivery vectors, as well as multilevel collaborative combination therapeutic strategies.Combined with precise clinical classification and staging, this will promote the fundamental transformation of REDs treatment from symptomatic supportive care to etiological intervention.

Objective To investigate the perioperative management of antithrombotic drugs in patients undergoing non-cardiac surgery.Methods Patients on long-term antithrombotic drugs who underwent non-cardiac surgery in our hospital were included.Through interviews with patients and physicians,perioperative antithrombotic medication regimens were reviewed and compared with the"Multidisciplinary Expert Consensus on Perioperative Management of Antithrombotic Therapy"to evaluate compliance with consensus and analyze influencing factors.Results A total of 372 patients were included in the analysis.Among them,355 patients were on long-term antiplatelet therapy alone,and 17 were on long-term oral anticoagulantion.364(97.8％)discontinued antithrombotic medications prior to surgery.109 patients(29.3％)received low molecular weight heparin(LMWH)bridging therapy.Among the 355 patients on antiplatelet therapy,108(30.4％)had discontinuation durations consistent with the consensus recommendations,while 186(52.4％)discontinued medications for longer periods.Postoperatively,the average hospital stay for antiplatelet therapy patients was 6.64 days,with only 37(10.4％)resuming therapy during hospitalization.The average hospital stay for patients on anticoagulants was 9.94 days,with only 2(11.8％)resuming therapy during hospitalization.Regarding perioperative risk assessment,only 40(10.8％)of patients underwent additional internal medical evaluation for thromboembolic risk after medication discontinuation,with the remainder assessed soly by surgeons.Coronary heart disease was an independent risk factor associated with internal medical evaluation(OR 2.851,95％CI 1.160-7.011,P=0.022).For bleeding risk assessment,surgeons evaluations aligned with the consensus in 68.0％of cases,but surgeons tended to underestimate risk compared to the consensus.Conclusions In this single-center study,perioperative antithrombotic management showed low compliance with expert consensus,characterized by prolonged preoperative medication discontinuation,high rates of LMWH bridging,and low postoperative in-hospital resumption of therapy.A robust multidisciplinary collaboration system should be established to enhance comprehensive patient assessment.

Objective:To investigate the relationship between fibroblast growth factor receptor-2(FGFR2)gene polymorphisms and the risk of breast cancer and its protein expression in Han women from Heilongjiang,China.Meth-ods:Using the Snapshot technique for multiplex single nucleotide polymorphism genotyping,the polymorphisms rs3135718 and rs1219648 of FGFR2 were analyzed in 747 breast cancer patients and 716 healthy controls.Logistic re-gression was used to examine the association between these genotypes and breast cancer susceptibility.In a subset of 338 cases,immunohistochemistry was performed to assess FGFR2 protein expression,and chi-square tests was used to analyze the relationship between polymorphisms and protein expression.Results:The genotype frequencies of FGFR2 rs3135718 and rs1219648 showed significant differences between the breast cancer and control group.Logistic regression revealed that,for rs3135718,the CT,CC,and CT+CC genotypes were associated with increased breast cancer risk compared to the TT genotype(OR=1.280,95%CI:1.003-1.633;OR=1.500,95%CI:1.112-2.023;OR=1.341,95%CI:1.066-1.688).For rs1219648,the GA,GG,and GA+GG genotypes were significantly associated with higher breast cancer risk compared to the AA genotype(OR=1.352,95%CI:1.063-1.719;OR=1.826,95%CI:1.361-2.504;OR=1.475,95%CI:1.175-1.852).However,no significant association was found between FGFR2 rs3135718 and rs1219648 polymorphisms and FGFR2 protein expression(χ2=0.052,P=0.820;χ2=0.117,P=0.732).Conclusion:FGFR2 gene poly-morphisms rs3135718 and rs1219648 are significantly associated with breast cancer susceptibility in Han women from Heilongjiang,China,but these polymorphisms do not show a clear relationship with FGFR2 protein expression.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective:To investigate the relationship between fibroblast growth factor receptor-2(FGFR2)gene polymorphisms and the risk of breast cancer and its protein expression in Han women from Heilongjiang,China.Meth-ods:Using the Snapshot technique for multiplex single nucleotide polymorphism genotyping,the polymorphisms rs3135718 and rs1219648 of FGFR2 were analyzed in 747 breast cancer patients and 716 healthy controls.Logistic re-gression was used to examine the association between these genotypes and breast cancer susceptibility.In a subset of 338 cases,immunohistochemistry was performed to assess FGFR2 protein expression,and chi-square tests was used to analyze the relationship between polymorphisms and protein expression.Results:The genotype frequencies of FGFR2 rs3135718 and rs1219648 showed significant differences between the breast cancer and control group.Logistic regression revealed that,for rs3135718,the CT,CC,and CT+CC genotypes were associated with increased breast cancer risk compared to the TT genotype(OR=1.280,95%CI:1.003-1.633;OR=1.500,95%CI:1.112-2.023;OR=1.341,95%CI:1.066-1.688).For rs1219648,the GA,GG,and GA+GG genotypes were significantly associated with higher breast cancer risk compared to the AA genotype(OR=1.352,95%CI:1.063-1.719;OR=1.826,95%CI:1.361-2.504;OR=1.475,95%CI:1.175-1.852).However,no significant association was found between FGFR2 rs3135718 and rs1219648 polymorphisms and FGFR2 protein expression(χ2=0.052,P=0.820;χ2=0.117,P=0.732).Conclusion:FGFR2 gene poly-morphisms rs3135718 and rs1219648 are significantly associated with breast cancer susceptibility in Han women from Heilongjiang,China,but these polymorphisms do not show a clear relationship with FGFR2 protein expression.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

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 investigate the perioperative management of antithrombotic drugs in patients undergoing non-cardiac surgery.Methods Patients on long-term antithrombotic drugs who underwent non-cardiac surgery in our hospital were included.Through interviews with patients and physicians,perioperative antithrombotic medication regimens were reviewed and compared with the"Multidisciplinary Expert Consensus on Perioperative Management of Antithrombotic Therapy"to evaluate compliance with consensus and analyze influencing factors.Results A total of 372 patients were included in the analysis.Among them,355 patients were on long-term antiplatelet therapy alone,and 17 were on long-term oral anticoagulantion.364(97.8％)discontinued antithrombotic medications prior to surgery.109 patients(29.3％)received low molecular weight heparin(LMWH)bridging therapy.Among the 355 patients on antiplatelet therapy,108(30.4％)had discontinuation durations consistent with the consensus recommendations,while 186(52.4％)discontinued medications for longer periods.Postoperatively,the average hospital stay for antiplatelet therapy patients was 6.64 days,with only 37(10.4％)resuming therapy during hospitalization.The average hospital stay for patients on anticoagulants was 9.94 days,with only 2(11.8％)resuming therapy during hospitalization.Regarding perioperative risk assessment,only 40(10.8％)of patients underwent additional internal medical evaluation for thromboembolic risk after medication discontinuation,with the remainder assessed soly by surgeons.Coronary heart disease was an independent risk factor associated with internal medical evaluation(OR 2.851,95％CI 1.160-7.011,P=0.022).For bleeding risk assessment,surgeons evaluations aligned with the consensus in 68.0％of cases,but surgeons tended to underestimate risk compared to the consensus.Conclusions In this single-center study,perioperative antithrombotic management showed low compliance with expert consensus,characterized by prolonged preoperative medication discontinuation,high rates of LMWH bridging,and low postoperative in-hospital resumption of therapy.A robust multidisciplinary collaboration system should be established to enhance comprehensive patient assessment.