To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

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 explore the ArcCHECK system-based methods for dose verification of ultra-long target for cervical cancer VMAT so as to assure the precision of cervical cancer radiotherapy.Methods A total of 33 patients with ultra-long target(target length≥26 cm)admitted to some hospital for cervical cancer VMAT from 2021 to 2023 were selected retrospectively,and radiotherapy plans were designed for the patients with VMAT technology and verified dosimetrically with different methods.Firstly,the dose distribution data were collected respectively at 5 and 8 cm away from the center of the ArcCHECK system along the bed exit direction,and enrolled into Group Test 1 and Test 2 respectively.Then the ArcCHECK system was flipped 180°,and the dose distribution data were acquired at 8 cm away from the center along the bed exit direction and included into Group Test 3.Dose merging between Group Test 2 and Test 3 with the Merge function was carried out to obtain the dose distribution data which were divided into Group Test 4.The monitor units of Group Test 1,2 and 4 were summarized,and difference analyses were performed on the length of the target area,detection point and irradiation time.Group Test 1,2 and 4 were compared in terms of γ pass rate,normalized dose deviation,confidence limit(CL)of pass rate and acceptance rate(γ pass rate≥95%and γ pass rate≥90%).Spearman's correlation coefficient was used to correlate the parameters such as maximum transverse diameter,length,volume and monitor unit of the target area and expected execution time of the plan.SPSS 19.0 software was used for statistical analysis.Results Group Test 1,2 and 4 had the monitor unit being(758.76±107.63)MU,and had statistically significant differences in length of the target area,detection point and irradiation time(P<0.01).In Group Test 4 γ pass rate under 2%/2 mm criterion did not reach 90%,and in Group Test 1 and 2 γ pass rates under 3%/3 mm and 3%/2 mm criteria both amounted to 95%.Group Test 1,2 and 4 had statistically significant differences in γ pass rate and normalized dose deviation(all P<0.05).In Group Test 1 there were more than 90%of the verification results where γ pass rate≥95%and more than 95%where γ pass rate≥90%under 3%/3 mm criterion.The monitor unit was positively correlated with the maximum transverse diameter,length and volume of the target area,respectively(0.337≤r≤0.568,P<0.05),and the expected execution time of the plan was positively correlated with the volume and monitor unit of the target area,respectively(0.457≤r≤0.517,P<0.01).Conclusion The dose verification method with the target at 5 cm away from the center along the bed exit direction can be applied clinically with high feasibility to the dose verification during the radiotherapy of the cervical cancer VMAT patients with ultra-long target,with the safety of the verification devices ensured effectively.

Objective:To investigate expression and clinical significance of T cell activation related membrane molecules in infertility patients with polycystic ovary syndrome(PCOS).Methods:A total of 80 PCOS infertility patients who visited Second Affiliated Hospital of Hainan Medical College from January 2020 to June 2021 were selected as observation group,and 80 cases of women who underwent physical examination at same time were selected as control group.Expressions of membrane molecules related to T cell acti-vation in peripheral blood of patients between two groups were compared.Patients with PCOS infertility were divided into pregnant group[66(82.5％)]and non pregnant group[14(17.5％)]according to different prognosis.General clinical data,peripheral blood inflammatory factors and T cell activation related membrane molecules expressions were compared between two groups,focusing on correlation between T cell activation related membrane molecules expressions and prognosis of PCOS infertility patients,ROC curve and decision-making curve of T cell activation related membrane molecule expressions were drawn to predict prognosis of PCOS infer-tility patients,whose prediction efficiency and net profitability were further analyzed.Pearson correlation analysis was used to explore correlation between T cell activation related membrane molecules expressions and clinical characteristics of PCOS infertility patients.Results:CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients in observation group were significantly higher than control group(P<0.05).Total testosterone(T),TNF-α,IFN-γ,CD4+CD45+T and CD4+CD63+T cells expressions of patients in non pregnancy group were significantly higher than pregnancy group(P<0.05).Multivariate Logistic regression analysis showed that CD4+CD45+T and CD4+CD63+T cells were independent predictors of prognosis of PCOS infertility patients(P<0.05),ROC analysis showed that AUC of CD4+CD45+T cells predicting prognosis of PCOS infertility patients was 0.756(0.721～0.826),and the best diag-nostic cut-off point was 48.1％,AUC of CD4+CD63+T cells was 0.746(0.711～0.834),and the best cut-off point for diagnosis was 31.2％,while AUC of CD4+CD45+T and CD4+CD63+T cells combination was 0.948(0.897～0.986).Decision curve analysis showed that combined prediction of CD4+CD45+T and CD4+CD63+T cells was higher than a single indicator.Correlation analysis showed that CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood of patients with PCOS infertility was related to T,TNF-α,insulin resistance index(HOMA-IR),IFN-γ,IL-2 and IL-10(P<0.05).Conclusion:The higher the CD4+CD45+T and CD4+CD63+T cells expressions in peripheral blood,the worse the prognosis of patients with PCOS infertility.

Objective To investigate the effects of varying pulse intervals in the programmed intermittent epidural bolus(PIEB)mode on labor analgesia in primiparous and multiparous women,and to evaluate the differ-ences in analgesic outcomes between these two groups.Methods A total of 60 primiparous and 60 multiparous women who met the inclusion criteria were recruited and randomly allocated into two groups:a 45-minute pulse interval group(P45 group,n=30)and a 60-minute pulse interval group(P60 group,n=30).Epidural labor anal-gesia was initiated when cervical dilation reached 1～3 cm.The programmed intermittent epidural bolus(PIEB)mode was started 45 minutes after analgesia commencement in the P45 group and 60 minutes after analgesia com-mencement in the P60 group.Each pulse delivered 10 ml of a solution containing 0.08%ropivacaine and 0.5 μg/ml sufentanil.Pain scores were assessed using the Visual Analog Scale(VAS)at five specific time points:baseline(t0),1 hour post-analgesia initiation(t1),2 hours post-analgesia initiation(t2),full cervical dilation(t3),and delivery(t4).Secondary outcomes included Bromage scores,the number of patient-controlled analgesia(PCA)button presses,total drug consumption,and adverse reactions.Results In primiparous women,the VAS score at t1 was significantly lower in the P45 group compared to the P60 group(P<0.05),whereas no significant differences were observed in VAS scores between the two groups at t2—t4.The median PCA press count was also significantly lower in the P45 group than in the P60 group(P<0.05).However,there were no significant differences between the groups in terms of total drug consumption,Bromage scores,or the incidence of adverse events(P>0.05).In multiparous women,no significant differences were found in VAS scores,Bromage scores,or PCA press counts between the P45 and P60 groups at any time point(P>0.05).Conversely,total drug consumption was significantly higher in the P45 group compared to the P60 group(P<0.05).Conclusions For primiparous women,a 45-minute pulse interval in the PIEB mode not only provides superior labor analgesia but also significantly reduces the frequency of PCA presses without escalating the risk or severity of motor block or adverse events.For multiparous women,the pulse interval does not substantially influence the effectiveness of labor analgesia.These findings contribute valuable new evidence for refining clinical labor analgesia protocols.

Objective:To quantitatively evaluate the level of the three medical linkage in China from 2009 to 2022,explore the influencing factors and driving paths of the three medical linkage in China,and provide a new perspective for promoting the development of the three medical linkage.Methods:An optimized coupling coordination degree model was used to calculate the coupling coordination degree between the trinity healthcare systems and different binary systems within the systems in 31 provinces of China(excluding Hong Kong,Macao and Taiwan),and the Fuzzy-set Qualitative Comparative Analysis method was used to explore the condition configurations of multi-factor-driven three medical linkage.Results:From 2009 to 2022,the coupling coordination degree between the trinity healthcare systems in each province of China generally showed an increasing trend year by year.Among the binary systems,the overall coordinated development situation between the medical and medical insurance systems was the best and the regional development was the most balanced.The coupling coordination degree gap between the trinity healthcare system and the internal binary systems among provinces gradually widened,and the multi-polarization trend intensified.The paths to promote high-level three medical linkage can be summarized into two types:internal and external balanced development type(H1)and government-led type(H2,H3),among which the H1 path with per capita GDP and health expenditure as core conditions was the most common.Conclusion:It is suggested to enhance institutional and technological innovation,and integrate resources through a cross-departmental collaboration mechanism and digital technology.Provinces should select high-level optimization paths by leveraging regional endowments to narrow the regional development gap.Meanwhile,under the impetus of high-level policies,the protection and supervision system continues to improve,thereby promoting the three medical linkage.

BACKGROUND:Studies have found that inhibition of tumor necrosis factor receptor-associated factor 6 improves myocardial function and promotes myocardial autophagy in sepsis,but the specific mechanism is not clear.OBJECTIVE:To explore the effect of inhibiting tumor necrosis factor receptor-associated factor 6-regulated mTORC1/ULK1 autophagy signaling pathway on myocardial injury in sepsis mice.METHODS:Thirty male Kunming mice were randomly divided into sham operation group,cecal ligation and puncture group(model group),model+tumor necrosis factor receptor-associated factor 6 specific inhibitor C25-140(model+C)group,model+C25-140+autophagy inhibitor 3-methyladenine(model+C+3-MA)group,and model+C25-140+mTORC1-specific agonist MHY1485(model+C+M)group.The cecum of mice in the sham operation group was not ligated or punctured.The mice in the other groups underwent cecum ligation and puncture to establish the mouse sepsis model.C25-140,3-methyladenine,and MHY1485 were intraperitoneally injected 0.5 hours after surgery according to the grouping.Myocardial tissue was obtained 24 hours after surgery.Hematoxylin-eosin staining was used to evaluate myocardial inflammatory lesions.Transmission electron microscopy was used to observe the changes in the autophagic bodies and mitochondrial microstructures of myocardial cells.TUNEL assay was used to detect myocardial cell apoptosis.PCR was used to detect the relative expression of tumor necrosis factor receptor-associated factor 6 mRNA.Western blot assay was used to detect the expression of related proteins.RESULTS AND CONCLUSION:(1)Compared with sham operation group,myocardial inflammatory cell infiltration and fibrous edema were observed in the model group.The mitochondria of the cells were obviously swollen,and autophagosomes were occasionally seen;cardiomyocyte apoptosis increased significantly;the expression of tumor necrosis factor receptor-associated factor 6,phosphorylated nuclear factor κB P65/P65,p-mTOR/mTOR,p-ULK1/ULK1,P62 and Bax protein increased,and the expression of Bcl2 protein decreased(P＜0.05).(2)Compared with the model group,myocardial inflammation and fibrous edema were alleviated in the model+C group.Myocardial mitochondrial swelling was reduced and autophagosomes increased;cardiomyocyte apoptosis decreased;the expression of phosphorylated nuclear factor κB P65/nuclear factor-κB P65,p-mTOR/mTOR,p-ULK1/ULK1,P62,and Bax protein decreased,while the Beclin-1 and Bcl2 protein increased(P＜0.05).(3)Compared with the model+C group,myocardial autophagosomes decreased and myocardial mitochondrial swelling was more obvious in the model+C+3-MA group.Myocardial inflammation was aggravated;myocardial cell apoptosis increased;the expression of phosphorylated nuclear factor κB P65/nuclear factor κB P65,P62,and Bax protein increased,and the Beclin-1 and Bcl2 protein decreased(P＜0.05).(4)Compared with the model+C group,the expression of p-mTOR/mTOR and p-ULK1/ULK1 in the model+C+M group increased,and the Beclin-1 and microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ protein expression decreased(P＜0.05).It is concluded that inhibition of tumor necrosis factor receptor-associated factor 6 regulates mTORC1/ULK1 autophagy signal to promote myocardial autophagy and participate in the protection of myocardial injury in sepsis.

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 This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.