OBJECTIVE To analyze the selection and rationales of comparators for pharmaceutical enterprises in their medical insurance access application， so as to provide a reference for promoting communication and consensus between enterprises and medical insurance authorities in this process. METHODS The application materials for drugs outside the catalogue that passed formal review published by the National Healthcare Security Administration from 2021 to 2025 were extracted， and then content analysis was used to systematically sort out relevant information of the declared drugs and comparators； the specific situations and rationales of pharmaceutical enterprises’ selection of comparators were analyzed. RESULTS A total of 1 341 declared drug documents were collected. Data analysis showed that 1 035 （77.18%） were submitted with positive comparators and 306 （22.82%） used blank comparators； 58 drugs （4.33%） took combination therapy as the reference， and 5 drugs （0.37%） referred to non-pharmacological （or non-single pharmacological） treatment regimens. Among competitive drugs declared by multiple enterprises， 50.00% of the enterprises submitted different comparators. A total of 4 basic conditions and 39 additional conditions were extracted as the rationales for selecting positive comparators. For blank comparators， 12 drug-related factors， 2 administrative factors， and 1 other factor were identified. More than 10% of the drugs did not state the rationale for comparator selection， and over 44% of drugs using blank comparators provided only one justification. CONCLUSIONS Pharmaceutical enterprises mainly select comparators based on their own interests in the medical insurance access application， and there are deficiencies in the adequacy and standardization of their selection basis and reasoning. It is recommended that enterprises follow the principled requirements of medical insurance authorities， and fully and normatively explain the reasons for selecting comparators in combination with the characteristics of their own products. Meanwhile， it is advisable to change the current open-ended statement form of selection reasons into a closed-ended answering mode， so as to highlight the priority of selection， standardize the declaration behavior of enterprises， and reduce communication divergences between the two parties.

Objective:To establish a novel method for the early diagnosis of gastric cancer(GC)by screening for the microRNAs within tumor-specific exosomes in peripheral blood.Methods:The gene expression omnibus database was used to download the GSE148334 and GSE130654 datasets of GC exosomes,and differentially expressed RNAs were obtained according to logFC>1 or logFC<-1 and P<0.05.TargetScan and ENCORI databases were used to predict the regulatory relationship between mRNA,miRNA,and ln-cRNA,and Cytoscape software was used to construct a ceRNA network and identify hub genes for validation.A total of 27 patients with early-stage GC,25 healthy controls,and 25 patients with other types of cancer were enrolled,and the ultracentrifugation method was used to isolate exosomes in serum.RT-qPCR was performed for RNA in serum and exosome samples to analyze the expression of hub genes in each group.Results:Three hub genes were identified by the bioinformatics method,namely hsa-miR-105-5p,hsa-miR-219b-3p,and hsa-miR-889-3p,and RT-qPCR showed that the GC group had a significantly higher expression level of hsa-miR-219b-3p in serum and exosome samples than the healthy control group and the other cancer group(serum:4.050±2.697 vs.1.357±0.857/1.934±2.434,P<0.05;exosomes:2.525±1.518 vs.0.774±0.559/1.259±2.127,P<0.05),while there were no significant differences in the expression levels of hsa-miR-889-3p and hsa-miR-105-5p between the GC group and the other two groups(P>0.05).The re-ceiver operating characteristic(ROC)curve showed that hsa-miR-219b-3p in serum-derived exosomes had an area under the ROC curve of 0.896(95%CI=0.800-0.993),which was significantly better than the traditional tumor markers of carcinoembryonic antigen(P=0.015),CA19-9(P=0.021),and CA72-4(P=0.005),and there-fore,exosomal hsa-miR-219b-3p showed a better diagnostic efficacy in GC patients.Conclusion:This study shows that hsa-miR-219b-3p in serum-derived exosomes can be used as a potential marker for the early diagnosis of GC in clinical practice.

Objective:To analyze the differences in the clinical characteristics of patients with adenomyosis of different magnetic resonance imaging (MRI) types and the differences in treatment effects after the application of dienogest.Methods:A total of 176 patients with adenomyosis who were admitted to Peking University Third Hospital from June 2017 to February 2023 were included in the study, and all of them were clearly classified by pelvic MRI and treated with dienogest. The clinical characteristics and treatment of the patients were retrospectively collected, and the patients were divided into endogenous type, exogenous type and penetrating type by MRI. The differences in clinical symptoms, imaging features and treatment effect of patients with adenomyosis of different MRI types were analyzed.Results:(1) The percentages of patients with endogenous, exogenous, and penetrating types were 40.9% (72/176), 35.2% (62/176) and 23.9% (42/176), respectively. The proportion of dysmenorrhea in patients with endogenous type (90.3%, 65/72) was significantly lower than those of exogenous type (100.0%, 62/62) and penetrating type (97.6%, 41/42; χ2=7.853, P=0.020), while there was no significant difference between exogenous type and penetrating type ( P>0.05). There were no statistically significant differences in menarche time, menstrual cycle and menstrual period among the three types of patients (all P>0.05), there was also no statistically significant difference in the proportion of menstrual abnormalities (including heavy and irregular menstrual bleeding; P>0.05). The proportions of ovarian endometrioma and deep infiltrating endometriosis in exogenous and penetrating types were significantly higher than that in endogenous type (all P<0.05). (2) The pain scores of all patients were significantly lower than those before treatment (all P<0.001), the proportion of patients with exogenous type (62.9%, 39/62) who had complete remission after treatment was higher than those of endogenous type (49.2%, 32/65) and penetrating type (46.3%, 19/41), but there was no significant difference in pain relief (i.e. the variation in the pain scores) between the three types ( P>0.05). (3) Endogenous type ( OR=0.361, 95% CI: 0.147-0.883; P=0.026), failure to apply gonadotropin-releasing hormone agonist (GnRH-a) in advance ( OR=0.208, 95% CI: 0.083-0.518; P<0.001), cystic changes ( OR=2.671, 95% CI: 1.108-6.437; P=0.029) and abnormal menstruation ( OR=3.466, 95% CI: 1.464-8.209; P=0.005) were independent risk factors for irregular bleeding after dienogest treatment. Conclusions:(1) There are obvious differences in the clinical characteristics of patients with adenomyosis of different MRI types, and patients with exogenous and penetrating types are more likely to have dysmenorrhea symptoms. (2) Dienogest could significantly alleviate the symptoms of dysmenorrhea in patients with adenomyosis. (3) Endogenous type, failure to take GnRH-a in advance and associated menstrual abnormalities are independent risk factors for irregular bleeding after dienogest treatment.

OBJECTIVE To investigate the distribution and drug resistance of multidrug-resistant bacteria in the neonatal intensive care unit of a three-A children's hospital in Henan Province,and to provide reference for ational drug use in clinical practice.METHODS Clinical specimens from hospitalized newborns in neonatal intensive care unit from a three-A children's hospital from Jan.1,2019 to Dec.31,2023 were subjected to etiological exam-ination and drug sensitivity test,and to analyze the distribution and drug resistance of multidrug-resistant bacteri-a in hospitalized newborns.RESULTS During the 5-year period,1139 strains of multidrug-resistant bacteria were i-solated,including 229 gram-positive bacteria(20.11％)and 910 gram-negative bacteria(79.89％).There were 92 strains of methicillin-resistant Staphylococcus aureus(MRSA)(accounting for 8.08％),57 strains(accounting for 5.00％)of methicillin-resistant coagulase-negative Staphylococcus epidermidis and 28 strains(accounting for 2.46％)of methicillin-resistant coagulase-negative human Staphylococcus.370 strains(accounting for 32.48)of carbapenem-resistant Klebsiella pneumoniae(CRKP),268 strains(accounting for 23.53％)of extenspectrum β-lactamase-producing Escherichia coli and 85 strains(accounting for 7.46％)of K.pneumoniae,there were 767 sputum specimens(67.34％),160 blood specimens from peripheral intravenous puncture and central venous cath-eterization(PICC)(14.05％),63 bronchoalveolar lavage fluid specimens(5.53％),29 secretion specimens(eye and wound secretions)(2.54％),and 120 other specimens(10.54％).K.pneumoniae and E.coli producing su-per-broad spectrum β-lactamase,CRKP and MRSA were the main drug-resistant bacteria.CONCLUSION The sit-uation of drug resistance in neonatal intensive care unit is serious,therefore monitoring bacterial resistance should be strengthened according to the clinical laboratory results,and antibiotics should be applied rationally.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Multi-conjugate vaccine and polyvalent vaccine can reduce the number of vaccinations, improve vaccination efficiency, and provide wider protection against diseases, and can not only brings convenience to recipients but also reduce healthcare costs, making it a key focus in modern vaccine development. However, even if the components of the vaccine are derived from already approved monovalent vaccines, it must still be considered as a new vaccine and undergo randomized controlled clinical trials to evaluate their safety and efficacy in humans. Due to the inclusion of multiple antigens, clinical evaluation must consider the potential interactions between or among the components, as well as the impacts of adjuvants, preservatives, and other ingredients on the vaccines' safety and efficacy. These factors introduce certain specific challenges in the clinical evaluation of multi-conjugate vaccine and polyvalent vaccine. This article summarizes the key elements and methods of clinical study design for multi-conjugate vaccine and polyvalent vaccine in terms of safety, immunogenicity, and protective efficacy, and discuss the problems and challenges exisitng in vaccine clinical evaluation to provide reference for the standardization of clinical study design of multi-conjugate vaccine and polyvalent vaccine.

The impact of vaccines on public health and their effectiveness in controlling infectious diseases partly depends on their coverage rate, which refers to the proportion of individuals vaccinated within a specific population. Vaccination coverage is foundational data for vaccine immunization programs, a key parameter for evaluating and monitoring the implementation of vaccination plans, and an important data point in real-world post-market studies of vaccines. Additionally, research on vaccination coverage is becoming increasingly prevalent in vaccine evaluation, primarily used to establish the risk of disease incidence in populations with different vaccination coverage rates in order to assess the protective effectiveness of vaccines. This paper reviews the research methods used to assess vaccine coverage both domestically and internationally, as well as their applications in evaluating vaccine effectiveness. It also analyzes and compares the advantages and disadvantages of different research methods for measuring vaccination coverage and discusses the significance of monitoring and improving vaccine coverage rates. The goal is to promote research and application of vaccination coverage rates in China, providing a scientific basis for post-market vaccine studies and for local administrative departments to formulate immunization policies.

Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective To analyze the impact of medical guidance games combined with special-ized nursing on treatment compliance and clinical symptoms in preschool children with pneumonia.Methods A total of 113 preschool children with pneumonia admitted to Beijing Daxing District Peo-ple's Hospital from February 2023 to June 2024 were selected as research subjects and randomly di-vided into control group(n=56)and observation group(n=57).The control group received routine nursing,while the observation group received medical guidance games combined with specialized nursing on the basis of the control group.Treatment compliance,improvement time of clinical symp-toms,and psychological states were compared between the two groups.Results The total treatment compliance rate in the observation group was 98.2％,which was higher than 89.3％in the control group,and the difference was statistically significant(P＜0.05).The disappearance times of symp-toms such as cough,expectoration,dyspnea,and fever in the observation group were all shorter than those in the control group(P＜0.05).After intervention,the scores of the Children's Medical Fear Scale(CMFS)and the Screen for Child Anxiety Related Emotional Disorders(SCARED)in the ob-servation group were both lower than those in the control group(P＜0.05).Conclusion Medical guidance games combined with specialized nursing can improve treatment compliance in preschool children with pneumonia,shorten their recovery time,help alleviate negative emotions such as medi-cal fear and anxiety,and promote disease recovery.