OBJECTIVE To explore the intervention mechanism of Bushen anzhi decoction （BSAZD） in rats with insomnia induced by kidney failing to store spirit. METHODS A total of 36 SD rats were randomly divided into normal group （normal saline）， model group （normal saline）， eszopiclone group （positive control group， 0.27 mg/kg）， and low-， medium- and high-dose BSAZD groups （5.85， 11.70， 23.40 g/kg）， with 6 rats in each group. Except for the normal group， rats in the remaining groups were subjected to combined administration of D-galactose and DL-4-chlorophenylalanine to establish the rat model of insomnia due to kidney failing to store spirit. After successful modeling， corresponding liquid medicine or normal saline was intragastrically administered once daily for 14 consecutive days. After the last administration， behavioral indicators and hippocampal histopathological morphology of rats were detected. Untargeted metabolomics was adopted to screen serum differential metabolites and enrich relevant signaling pathways. RESULTS Compared with the model group， the high-dose BSAZD group exhibited significantly increased open arm entries ， open arm time and sleep time （ P ＜0.05）， accompanied by markedly decreased closed arm entries， closed arm time and sleep latency （ P ＜0.05）. Hippocampal neurons in the high-dose BSAZD group were arranged regularly， and the size， morphology and location of cell nuclei were nearly normal. Untargeted metabolomics analysis identified oxidized glutathione， glutamate and other differential metabolites in serum of rats in the high-dose BSAZD group； these differential metabolites were mainly enriched in GABAergic synapse， glutamatergic synapse， cAMP signaling pathway and 2-oxocarboxylic acid metabolism pathway. CONCLUSIONS BSAZD can improve sleep quality， relieve anxiety-like behaviors in rats with insomnia due to kidney failing to store spirit. Its therapeutic mechanism may be associated with regulating GABAergic and glutamatergic synaptic pathways to restore neurotransmitter balance and further alleviate oxidative stress injury， modulating the cAMP signaling pathway to facilitate neural repair， and intervening the 2-oxocarboxylic acid metabolism pathway to optimize energy supply.

OBJECTIVE To explore the intervention mechanism of Bushen anzhi decoction （BSAZD） in rats with insomnia induced by kidney failing to store spirit. METHODS A total of 36 SD rats were randomly divided into normal group （normal saline）， model group （normal saline）， eszopiclone group （positive control group， 0.27 mg/kg）， and low-， medium- and high-dose BSAZD groups （5.85， 11.70， 23.40 g/kg）， with 6 rats in each group. Except for the normal group， rats in the remaining groups were subjected to combined administration of D-galactose and DL-4-chlorophenylalanine to establish the rat model of insomnia due to kidney failing to store spirit. After successful modeling， corresponding liquid medicine or normal saline was intragastrically administered once daily for 14 consecutive days. After the last administration， behavioral indicators and hippocampal histopathological morphology of rats were detected. Untargeted metabolomics was adopted to screen serum differential metabolites and enrich relevant signaling pathways. RESULTS Compared with the model group， the high-dose BSAZD group exhibited significantly increased open arm entries ， open arm time and sleep time （ P ＜0.05）， accompanied by markedly decreased closed arm entries， closed arm time and sleep latency （ P ＜0.05）. Hippocampal neurons in the high-dose BSAZD group were arranged regularly， and the size， morphology and location of cell nuclei were nearly normal. Untargeted metabolomics analysis identified oxidized glutathione， glutamate and other differential metabolites in serum of rats in the high-dose BSAZD group； these differential metabolites were mainly enriched in GABAergic synapse， glutamatergic synapse， cAMP signaling pathway and 2-oxocarboxylic acid metabolism pathway. CONCLUSIONS BSAZD can improve sleep quality， relieve anxiety-like behaviors in rats with insomnia due to kidney failing to store spirit. Its therapeutic mechanism may be associated with regulating GABAergic and glutamatergic synaptic pathways to restore neurotransmitter balance and further alleviate oxidative stress injury， modulating the cAMP signaling pathway to facilitate neural repair， and intervening the 2-oxocarboxylic acid metabolism pathway to optimize energy supply.

OBJECTIVE To investigate the cognition， attitudes， and current practices of Chinese physicians regarding biosimilars and their clinical switching， so as to provide a basis for the rational clinical application of biosimilars in China and the improvement of related policies.METHODS A national cross-sectional online questionnaire survey was conducted in 2025. Quota sampling was adopted， with quotas based on physicians’ sex， city tier， and specialty. Questionnaire invitations were distributed to licensed physicians， and physicians who had prescribed monoclonal antibody biosimilars were included for analysis. The questionnaire covered their familiarity with biosimilars， attitudes， clinical switching practices， and reasons. Data were processed using reliability and validity tests， dispersion analysis， and cross-tabulation analysis.RESULTS The questionnaire scale showed good reliability and validity， with Cronbach’s α coefficient ＞0.7 and KMO value ＞0.6. A total of 2 071 survey invitations were distributed， and 300 valid questionnaires were returned， with an effective response rate of 14.5%. Among the respondents， 75.3% had prescribed 3-5 types of monoclonal antibody biosimilars； only 35.3% were aware that China currently has no clear regulatory provisions on biosimilar switching； 46.3% and 47.3% of respondents believed that there was no difference in safety and efficacy， respectively， between biosimilars and originator products； 63.0% of respondents were concerned about the immunogenicity risk of long-term switching between originator drugs and biosimilars. A total of 92.3% of respondents had experience with biosimilar switching， 87.7% of which involved switching from originator products to biosimilars， and 28.2% of respondents had completed three or more switches in the same patient. Among the primary reasons for switching， non-medical factors accounted for 57.4%， higher than medical factors at 42.6%； “lower treatment cost after switching” was the most important reason for switching； 95.3% of respondents believed that informed consent should be obtained from patients before switching.CONCLUSIONS The surveyed physicians had basic knowledge of biosimilars， but their understanding of the relevant regulations of the national drug regulatory authority was insufficient. Although most physicians were concerned about the risks of non-medical switching， clinical switching was mostly driven by non-medical factors. It is recommended to strengthen policy education for medical professionals and standardize clinical switching behavior. The National Medical Products Administration should also promptly improve the interchangeability review standards and post-marketing surveillance system for biosimilars, so as to promote the rational use of biosimilars.

OBJECTIVE To evaluate the clinical efficacy and safety of eravacycline in intensive care unit （ICU） patients with carbapenem-resistant Acinetobacter baumannii （CRAB） and/or carbapenem-resistant Klebsiella pneumoniae （CRKP） pneumonia.METHODS Clinical data of patients with CRAB and/or CRKP pneumonia who were admitted to the ICU of Peking Union Medical College Hospital， Chinese Academy of Medical Sciences， and received eravacycline treatment from July 2023 to November 2024 were collected. The 28-day all-cause mortality rate， clinical failure rate， 28-day ICU-free days among surviving patients， 28-day mechanical ventilation-free days among surviving patients， microbiological clearance， and adverse reactions were recorded.RESULTS A total of 37 patients were included. Among the 37 patients， 11 （29.73%） experienced clinical failure， and the 28-day all-cause mortality rate was 18.92% （7/37）. The 28-day ICU-free days among surviving patients were （14.60±10.61） days， and the 28-day mechanical ventilation-free days among surviving patients were （24.55±4.29） days. Microbiological clearance was achieved in 12 patients （32.43%）， and the mean time to conversion was （10.58±12.05） days. Adverse reactions occurred in 5 patients （13.51%）， including 2 cases of elevated liver enzymes， 2 cases of coagulopathy， and 1 case of drug hypersensitivity syndrome.CONCLUSIONS Eravacycline can effectively control systemic bacterial infection and inflammatory response in ICU patients with pneumonia caused by CRAB and/or CRKP. However， patients with underlying liver disease or receiving multiple antibacterial agents should be alert to elevated liver enzymes， coagulation abnormalities， and the rare drug hypersensitivity syndrome.

ObjectiveTo explore the process and guidelines for ethical review in decentralized drug clinical trials， promote clinical trial progress， and ensure drug development progress. MethodsThe key points of the ethical review were summarized by studying the relevant laws and regulations on decentralized drug clinical trials， analyzing the advantages and challenges of decentralized drug clinical trials， and combining the experience of the ethics committee of the institution in reviewing decentralized drug clinical trials. ResultsRelevant laws and regulations were the basis for the ethical review， and the ethics committee should adopt appropriate review methods based on regulations and hospital ethical standard operating procedures. The ethics committee should focus on the feasibility， applicability， and rationality， the adequacy of informed consent， the protection of rights and interests and privacy of subjects， as well as the qualification and standard operating procedures of electronic platforms for conducting decentralized drug clinical trials. ConclusionDecentralized drug clinical trials are in their early stages and urgently require guidance from relevant laws and regulations. Ethical review is also constantly being refined through exploration. It is necessary to supervise the implementation of responsibilities by all parties， pay attention to the rights and interests of subjects， and gradually promote the implementation of decentralized drug clinical trials.

OBJECTIVE: To report the blood group antigen and antibody specificity identification methods for a patient with high-frequency antibodies, and the process of finding and providing compatible blood for the patient. METHODS: A patient sent from the Blood Transfusion Department of Shanxi Provincial People's Hospital to Blood Transfusion Technology Research Laboratory of Taiyuan Blood Center in November 2022 was selected for the study. Classical serological methods were used to determine the patient's blood type, screen for unexpected antibodies, identify antibodies, and perform crossmatching. High-frequency antibody identification was carried out using red blood cells treated with various enzymes. Blood group genotyping was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF) and Sanger sequencing. Multiple strategies were employed to address the patient's blood source problem. The study was approved by the Medical Ethics Committee of Taiyuan Blood Center [Ethics No. 2024 Ethics Review No.(2)]. RESULTS: The patient's blood type was B, RhD positive. Initial screening of the patient's serum with multiple screening cells and antibody identification cells in saline medium was negative, but positive in antiglobulin medium. The patient's serum showed varying reaction intensities with red blood cells treated with different enzymes. MALDI-TOF mass spectrometry and Sanger sequencing revealed a homozygous nonsense variant c.376C>T (p.Gln126Ter) in the ABCG2 gene, resulting in the Jr(a-) phenotype. During family donor selection, the patient's son was found to have a heterozygous variant c.376C>T (p.Gln126Ter), and another heterozygous variant c.421C>A (p.Gln141Lys), which predicted a Jr(a+w) phenotype. Crossmatch tests confirmed the compatibility of blood from the patient's son, which was used to address the urgent blood requirement. Later, rare blood from a Jr(a-) donor from the Guangzhou Blood Center was used for the patient's ongoing treatment, saving the patient's life. CONCLUSION Combining classic serological testing with blood group gene typing techniques successfully identified the rare Jr(a-) blood type and high-frequency anti-Jra antibodies. Enzyme-treated red blood cell identification methods confirmed the presence of anti-Jra antibodies. By searching within the family and seeking help from other blood centers, compatible blood was found. This approach may provide insights for resolving similar complex blood matching problems in the future.
Humans ; Blood Grouping and Crossmatching/methods* ; Blood Group Antigens/immunology* ; Blood Transfusion ; Male ; Isoantibodies/blood* ; Female ; Genotype

OBJECTIVE: To explore the regulatory mechanisms underlying the weak expression of ABO blood group antigens due to variants in the non-coding regions of the ABO gene. METHODS: From June 2014 to October 2023, a total of 29 samples from the Taiyuan Blood Center and local hospitals, which were serologically identified as having weak ABO antigen expression without detectable coding region mutations, were selected for this study. Full-length ABO gene sequencing was performed using third-generation long-read sequencing technology (Pacific Biosciences) to obtain complete haplotype sequences of the ABO gene. Variants in the non-coding regions were compared and identified to infer their regulatory effects on weak antigen expression. The procedures followed in this study were in accordance with the ethical standards of the World Medical Association's Declaration of Helsinki (2013 revision). The Medical Ethics Committee of Taiyuan Blood Center has granted an exemption from ethical review. RESULTS: 18 bp deletions in the -35 to -18 region of the promoter were identified in 7 samples. Variants in intron 1 (+5.8 kb) were detected in 7 samples, including ABO*A (28+5792_5793delCT (1 case) and ABO*B (28+5793T>C) located in the GATA binding region; ABO*B (28+5808C>T) (1 case) in the E-box region; and ABO*B (28+5875C>T) (4 cases) in the RUNX1 binding region. Nucleotide variants at splice sites were detected in 2 samples, namely ABO*B (C.98+1G>A) and ABO*B (C.204-2A>C). CONCLUSION Variants in the non-coding regulatory sequences of the ABO gene are a significant factor contributing to weak ABO antigen expression. In clinical ABO sequencing, it is essential to screen not only the conventional coding regions but also the flanking sequences, introns, and splice sites of the ABO gene to facilitate precise blood transfusion.
ABO Blood-Group System/genetics* ; Humans ; Alleles ; Promoter Regions, Genetic ; Haplotypes ; Introns

Objective:To investigate the role of reactive astrocytes expressing aromatase(ARO)in the penumbra during ischemic stroke.Methods:A mouse model of middle cerebral artery occlusion(MCAO/R)was prepared using the suture method.Western blot and immunofluorescence staining were used to observe the expression of ARO in the penumbra after ischemia reperfusion.We generated a glial fibrillary acidic protein promoter-driven aromatase knock-out(GFAP-ARO-KO)mouse model in vivo.Neurologic impairment scores,rotarod test,grip strength test and adhesive removal test on the plantar surface of the paw were performed after MCAO/R modeling.Results:In wild type mice,the expression of ARO was significantly increased in astrocytes in the penumbra after MCAO/R(P<0.01).Compared to the control group,the expression of ARO in the GFAP-ARO-KO group was significantly reduced in astrocytes in the penumbra after MCAO/R.And loss of ARO increased cerebral infarction volume and aggravated sensorimotor impair-ment.Conclusion:After ischemic stroke,reactive astrocytes in the penumbra highly express ARO and play a protective role in post-ischemia reperfusion injury.

Objective:To analyze the impact of stressful life events on the social activity participation of middle-aged and elderly adults in China, providing a scientific basis for improving their quality of life.Methods:This study was conducted in January 2024.Data were derived from the China health and retirement longitudinal study (CHARLS) conducted from 2011 to 2020. SPSS 25.0 software was used for statistical analysis.Ordered Logistic regression analysis was employed to explore the association between stressful life events experienced over the past decade and the level of social activity participation, with stratified analysis by age, gender, and place of residence.Results:A total of 10 838 middle-aged and elderly adults were included in this study. The proportions of individuals with no social activity participation, low social activity participation, and high social activity participation were 52.07%(5 643/10 838), 24.21%(2 624/10 838), and 23.72%(2 571/10 838), respectively. After adjusting for sociodemographic characteristics and health-related behaviors, individuals who experienced stressful life events were 15.2% less likely to participate in social activities compared to those who did not ( RR=0.848, 95% CI=0.786-0.915).Stratified analysis revealed that the decrease in the likelihood of social activity participation following stressful life events was significantly greater in urban residents than that in rural residents ( Pinteraction=0.004). Conclusion:Experiencing stressful life events over the past decade may reduce the level of social activity participation among middle-aged and elderly adults. It is recommended to strengthen psychological counseling for this population and encourage active social engagement.

Objective To investigate the intervention effect of cordycepin on DCM rats and its reg-ulative effect on of AKT/GSK3β signaling pathway.Methods A total of 80 male SD rats were randomly divided into model group,cordycepin group,AKT inhibitor group and cordycepin+AKT inhibitor group,with 20 rats in each group.After the establishment of DCM model,corre-sponding intervention was given to each group.Another 20 healthy rats served as control group.Cardiac function indicators(LVEF,LVFS,LVESD,LVEDD),levels of IL-6,IL-1β,TNF-α,SOD,GSH-Px and MAD,and expression of AKT/GSK3β signaling pathway related proteins were de-termined and compared among the groups blotting.Results The model group had significantly lower LVEF and LVFS,decreased myocardial SOD and GSH-Px contents,and declined p-AKT/AKT and p-GSK3β/GSK3β,but increased LVESD and LVEDD and myocardial IL-6,IL-1β,TNF-αand MAD expression levels when compared with the control group(P＜0.05).Cordycepin treat-ment obtained increased LVEF and LVFS and myocardial tissue SOD,GSH-Px,Bcl-2,p-AKT/AKT and p-GSK3β/GSK3β protein expressions,and decreased LVESD and LVEDD and myocar-dial expression of IL-6,IL-1β,TNF-α,MAD and Bax than the model group(P＜0.05),while AKT inhibitor reversed all the changes induced by modelling(P＜0.05).Combination of cordycepin+AKT inhibitor resulted in lower LVEF,LVFS and myocardial SOD,GSH-Px,Bcl-2,p-AKT/AKT,p-GSK3β/GSK3β protein levels,and increased LVESD,LVEDD and expressions of IL-6,IL-1β,TNF-α,MAD and Bax protein in myocardial tissue when compared with cordycepin group(P＜0.05).And the combination also resulted in increases in LVEF and LVFS[(61.29±5.61)％vs(39.28±4.12)％,(39.05±3.43)％vs(24.47±2.73)％,P＜0.05]and decreases in LVESD and LVEDD(4.36±0.48 mm vs 6.97±0.69 mm,6.07±0.61 mm vs 9.02±0.85mm,P＜0.05)when compared with AKT inhibitor group.Conclusion Cordycepin improves cardiac function,myocar-dial injury,inflammation and oxidative stress in DCM rats probably by activating AKT/GSK3βsignaling pathway,and inhibits the apoptosis of cardiomyocyte.