To standardize the clinical application of oral Chinese patent medicines （CPMs）， and address the safety issues arising from their dosage form characteristics， irrational clinical use， and the lack of targeted pharmacovigilance systems， the China Association of Chinese Medicine organized the formulation and release of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines， aiming to inform the safe clinical use of oral CPMs and related pharmacovigilance work. According to the principles of GB/T1.1—2020 and the Drug Administration Law of the People's Republic of China （2019 revision）， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， led a drafting group comprising 18 institutions. After multiple rounds of expert interviews， literature retrieval， evidence screening， and extensive solicitation of opinions， the Guidelines were registered internationally. Systematic standardization focused on safety monitoring， risk identification， assessment， control， and other aspects. The Guidelines clarified the characteristics of oral CPMs in terms of safety monitoring， known risks， and potential risks， compared to non-oral CPMs. Then， risk control measures were proposed， including medication in special populations and irrational medication. As a special guideline for pharmacovigilance in the clinical application of oral CPMs， the Guidelines systematically construct a technical system in line with the characteristics of traditional Chinese medicine （TCM）， which is essential for improving the clinical safety management of oral CPMs and provides an important reference for medical institutions， pharmaceutical manufacturers， and regulatory authorities.

To standardize the clinical application of oral Chinese patent medicines （CPMs）， and address the safety issues arising from their dosage form characteristics， irrational clinical use， and the lack of targeted pharmacovigilance systems， the China Association of Chinese Medicine organized the formulation and release of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines， aiming to inform the safe clinical use of oral CPMs and related pharmacovigilance work. According to the principles of GB/T1.1—2020 and the Drug Administration Law of the People's Republic of China （2019 revision）， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， led a drafting group comprising 18 institutions. After multiple rounds of expert interviews， literature retrieval， evidence screening， and extensive solicitation of opinions， the Guidelines were registered internationally. Systematic standardization focused on safety monitoring， risk identification， assessment， control， and other aspects. The Guidelines clarified the characteristics of oral CPMs in terms of safety monitoring， known risks， and potential risks， compared to non-oral CPMs. Then， risk control measures were proposed， including medication in special populations and irrational medication. As a special guideline for pharmacovigilance in the clinical application of oral CPMs， the Guidelines systematically construct a technical system in line with the characteristics of traditional Chinese medicine （TCM）， which is essential for improving the clinical safety management of oral CPMs and provides an important reference for medical institutions， pharmaceutical manufacturers， and regulatory authorities.

BACKGROUND:Type 2 diabetes mellitus impairs renal function,and studies have shown that exercise interventions can protect the kidneys.Irisin can protect renal function in diabetic nephropathy patients by restoring autophagy through inhibition of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway. OBJECTIVE:To explore whether exercise can restore autophagy and ameliorate renal injury by inhibiting over-activation of the renal PI3K/Akt/mTOR signaling pathway,as well as to analyze the differences in the effects of different modalities of exercise. METHODS:Six-week-old Sprague-Dawley rats were randomly divided into a blank control group(normal rats)and a diabetic group,and then the diabetic group was randomly divided into a diabetic model group,a moderate-intensity continuous exercise group,and a high-intensity intermittent exercise group after successful modeling using high-fat,high-sugar feeding plus intraperitoneal administration of low-dose 1%streptozotocin(30 mg/kg).The two exercise groups were subjected to 8 weeks of exercise intervention with different exercise intensities.The fasting blood glucose concentration was detected by glucose oxidase method,glycated hemoglobin levels was measured using a kit,serum insulin concentration was detected by Elisa method,and insulin resistance index was calculated.Gene expression of PI3K,AKT,mTOR,Beclin-1,podocin,and nephrin was detected by RT-PCR.Protein expression of mTOR and autophagy marker proteins LC3-1,LC3-2,and Beclin-1 was detected by western blot RESULTS AND CONCLUSION:Fasting blood glucose and glycosylated hemoglobin levels were highly significantly increased,insulin resistance levels were significantly increased,and insulin levels were significantly decreased in type 2 diabetic rats.Both exercises resulted in highly significant decreases in fasting blood glucose and glycosylated hemoglobin levels,significant decreases in insulin resistance levels and significant increases in insulin levels in type 2 diabetic rats.Insulin levels were significantly higher in the high-intensity intermittent exercise group compared with the moderate-intensity continuous exercise group.The expression of podocin and nephrind genes was significantly reduced in type 2 diabetic rats and two different forms of exercise significantly the gene expression.There was a further trend toward an increase in gene expression of podocyte-associated proteins in the moderate-intensity continuous exercise group compared with the high-intensity intermittent exercise group,but there was no significant difference.The mRNA and protein expression of PI3K,AKT and mTORC1 in kidney tissues of type 2 diabetic rats were significantly increased,and the expression of autophagy marker proteins Beclin-1 and LC3-2 and LC3-2/LC3-1 were significantly decreased.Both different forms of exercise significantly decreased the mRNA and protein expression of PI3K,AKT,and mTORC1,and significantly increased the autophagy marker proteins Beclin-1,LC3-2,and LC3-2/LC3-1 in renal tissues.Compared with the moderate-intensity continuous exercise group,there was a trend toward further decreases in mRNA expression of PI3K,AKT,and mTORC1 and protein expression of mTOR,and a trend toward further elevation of Beclin-1,LC3-2,and LC3-2/LC3-1 in the high-intensity intermittent exercise group,but only Beclin-1 showed a significant difference between groups.In summary,renal podocyte injury in type 2 diabetes mellitus with suppressed autophagy is closely related to aberrant activation of the PI3K/AKT/mTORC1 signaling pathway.Both moderate-intensity continuous exercise and high-intensity intermittent exercise can protect the diabetic kidney,reduce podocyte damage,and restore renal podocyte autophagy,which may be achieved by inhibiting the excessive activation of the PI3K/AKT/mTOR signaling pathway.High-intensity intermittent exercise shows a trend toward more favorable restoration of autophagy compared with moderate-intensity continuous exercise,but with a slight decrease in podocyte protein expression.

Congenital heart disease(CHD)is the leading cause of mortality associated with birth defects.Whole-genome sequencing and whole-exome sequencing technologies have resulted in major advancements in our understanding of the genetics of CHD,and cell and animal models have emerged as reliable options for investigating the specific genetic mechanisms and factors underlying CHD.Human induced pluripotent stem cells(iPSCs)offer a novel approach for studying CHD by generating patient-specific iPSC-derived cardiomyocytes for related research.In addition,CRISPR-Cas9 gene editing tools enable the introduction or correction of variant genes in iPSCs,thus facilitating a more comprehensive exploration of variant pathogenicity and the molecular basis of CHD.This review considers the progress in understanding the genetic basis of CHD using genome sequencing,and explores how gene editing techniques and patient iPSCs contribute to this progress.We highlight the significance of combining these two approaches for disease research,providing valuable insights for clinical investigations on the mechanisms responsible for CHD.

With the rapid development of artificial intelligence(AI),how to digitize the teaching of Medical Immunology is a new challenge posed by the times and education.This study is based on the advanced teaching model of Medical Immunology,which includes lectures-PAD class-flipped classrooms-expert lecture.By introducing knowledge mapping and AI teaching assistant into the entire learning process,the students not only deepen their understanding of the knowledge system of Medical Immunology,but also ex-ercise their ability to apply immunological knowledge to solve practical clinical problems,enhance their self-learning ability,expres-sion ability,communication ability,on-site performance ability,and cultivate a spirit of unity,cooperation,and exploration.The practice of empowering Medical Immunology teaching with digital intelligence achieves the integration of theory and application,the linkage between in class and out of class teaching,the connection between commonalities and individualities,and the union of abili-ties and qualities in Medical Immunology teaching.It also provides practical basis for exploring the implementation path of digital intel-ligence empowerment in Medical Immunology teaching.

Objective The aim of this study was to explore the effects of changes in the estrogen receptor alpha 36(ER-α36)expression on the proliferation and membrane-initiated estrogen signaling in glioblastoma U251 cells.Methods The expression and localization of ER-α36 and EGFR glioblastoma U87 cells and U251 cells were determined by immunofluorescence,qRT-PCR and Western blot.The effect of upregulating ER-α 36 on U251 cell proliferation and estrogen signaling pathway activity by low con-centrations of 100 pmol/L icariin isomer(SNG162)was detected by MTT assay and Western blot.Results ER-α36 and EGFR were co-expressed in the cell membrane of glioblastoma.Compared with DMSO(control group),the expression ER-α36(P<0.01)and EG-FR increased in U251 cells treated with SNG162(P<0.05);Further experments also found that low concentrations of SNG162 in-creased the expression of cycle related proteins-cyclin D1,cyclin B,cyclin E and CDK4(P<0.01),and enhanced the proliferative a-bility of U251 cells(P<0.05).Conclusion The low concentration of SNG162 upregulates the expression of ER-α36,activates the estrogen-mediated ERK1/2 MAPK,p38 MAPK,and EGFR/Src signaling pathways,promotes glioblastoma proliferation,and activates the membrane initialized estrogen signaling pathway.

Objective To investigate the spatiotemporal expression pattern of metabotropic glutamate receptor 4(mGluR4)in the mouse cochlear basilar membrane and its dynamic changes during postnatal development until hair cell synaptic maturation.Methods Ten healthy 3-month-old C57BL/6L wild-type mice(5 males,5 females,25～35 g)were bred to obtain offspring.Cochlear samples from postnatal days 1～30(P1～P30)were analyzed.Frequency-specific auditory brainstem response(ABR)thresholds were measured at 45.2,32.0,22.6,16.0,11.3,8.0,5.6,and 4.0 kHz in P12,P14,P16,P21,and P30 mice.Immunofluorescence assay combined with confocal laser scanning microscopy was used to scan cochlear whole-mount preparations.Spatiotemporal co-localization profiling of mGluR4 and synaptic markers Ctbp2 and Snap25 was observed,and quantitative comparisons of fluorescent puncta density were performed.Results ABR testing revealed undifferentiated waveforms in all P12 mice,while 70%of P14 mice exhibited well-defined Wave I.In P14,P16,P21 and P30,mice undergoing ABR testing,50%failed to exhibit ABR waveforms when stimulated by 45.2 kHz tones,and 87.5%showed no response to 32.0 kHz stimuli.Auditory response thresholds for other frequencies progressively decreased with increasing postnatal age.Immunolocalization demonstrated stronger mGluR4 expression in inner hair cells(IHCs)versus outer hair cells(OHCs).Distinct mGluR4 puncta were observed at IHC presynaptic active zones(co-localized with Snap25)as early as P11,but showed minimal overlap with CtBP2-labeled ribbons.Quantitative analysis revealed significantly higher mGluR4 puncta density at P30 compared to P14 synapses(P<0.05).Conclusion Postnatal upregulation of mGluR4 at IHC synaptic regions correlates with functional maturation.These findings suggest mGluR4 may modulate vesicular exocytosis regulation and exert pharmacological inhibition on glutamate release,potentially influencing synaptic plasticity during auditory pathway refinement.

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.

Objective:To understand the clinical manifestations, laboratory characteristics, and treatment of Staphylococcus aureus ( Sa) infection in children, and explore the predictive value of lymphocyte count, neutrophil to lymphocyte ratio(NLR), and high-sensitivity C-reactive protein to albumin ratio(CAR) in patient with secondary bloodstream infection(BSI). Methods:A retrospective analysis was conducted on 72 children with Sa infection admitted to the Nanchong Hospital of Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2020 to April 2024. Clinical data including basic information, drug resistance, antibiotic treatment were collected. Differences in laboratory test results and inflammatory indicators were analyzed. The influencing factors of Staphylococcus aureus bacteraemia(SAB) in pediatric patients were analyzed using univariate/multivariate Logistic regression and correlation analysis. The predictive value was analyzed by receiver operating characteristic curve (ROC) and area under curve (AUC). Results:Seventy-two patients were selected, of whom 60 (83.33%) had skin and soft tissue infections (SSTIs), mainly community-associated Staphylococcus aureus(CA-SA)(50 cases), including 16 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) cases (32.00%, 16/50). The detection rate of MRSA was 37.50% (27/72). The resistance rates of Sa to penicillin, clindamycin, and erythromycin were 97.22%(70/72), 69.44%(50/72), and 69.44%(50/72), respectively. Compared with the SSTIs group, the levels of lymphocyte count in children with bone and joint infections were significantly lower, while NLR and CAR levels were higher ( P<0.05). Fourteen patients had secondary SAB. In the secondary SAB group, lymphocyte counts were lower, while inflammatory indicators (NLR, CAR), and D-dimer were higher. CAR and NLR are positively correlated with the occurrence of bloodstream infections ( P<0.05). CAR ( OR=4.866, 95% CI: 1.37-17.25) and NLR ( OR=1.293, 95% CI: 1.032-1.620) were independent risk factors for secondary bloodstream infection, and ROC curve results showed that the combination of the two indicators had a higher sensitivity (0.929) and AUC (0.909) than individual testing. After undergoing effective treatment, the levels of CAR and NLR in the children in the secondary SAB group were significantly reduced. Wound infection patients underwent debridement treatment in 38 cases (52.78%, 38/72), while antibiotic treatment still primarily used first- and second-generation cephalosporins. For patients with secondary bloodstream infection, vancomycin was the first choice. Conclusions:Children′s wound infections with Sa primarily involve skin and soft tissue infections, commonly seen in CA-SA. NLR and CAR are independent risk factors for children with secondary bloodstream infection, and their combined detection has certain value for early diagnosis.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.