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.

Monkeypox,caused by the monkeypox virus(MPXV),is a zoonotic infectious disease characterized clinically by fever,rash,and lymphadenopathy.In September 2024,the outbreak of a novel MPXV Clade Ib variant in the Democratic Republic of the Congo was designated by the World Health Organization as a public health emergency of international concern,highlighting deficiencies in current prevention and control systems.Although modified attenuated smallpox vaccines exhibit cross-protective efficacy against MPXV infection,their adverse effects still limit clinical applications.Further-more,the therapeutic efficacy of tecovirimat—the FDA emergency-authorized antiviral drug for Smallpox—is limited.Recent studies have shown that tecovirimat does not significantly improve lesion healing time or reduce overall mortality in patients infected with MPXV CladeⅠ.Monoclonal antibodies,which neutralize viral activity by targeting critical membrane proteins,have emerged as a pivotal strategy to overcome current therapeutic bottlenecks by integrating therapeutic,diagnostic and prophylactic functions.This article reviews the epidemiological and virological characteristics of MPXV,along with functional characteristics of MPXV major membrane proteins,including A29L,A35R,B6R,E8L,M1R and H3L,focusing on the research progress in monoclonal antibodies against these key targets.Their protective effects in vitro/in vivo are explored while such as strategies monoclonal antibody combina-tion therapy are recommended to enhance efficacy and overcome drug resistance.

Objective To investigate the diagnostic and prognostic value of serum leucine-rich alpha-2-glycoprotein 1(LRG1)and dipeptidyl peptidase 4(DPP4)levels in patients with acute cerebral watershed infarction(ACWI).Methods Selected 150 ACWI patients treated in the Baoding Second Central Hospital from January 2022 to December 2023 as the study subjects(ACWI group),and another 120 volunteers who underwent physical examinations were regarded as the control group.According to the prognosis of ACWI patients,they were separated into a good prognosis group(n=98)and a poor prognosis group(n=52).ELISA was used to detect serum LRG1,DPP4 and carcinoembryonic amtigen(CEA)levels,a biochemical analyzer was used to detect levels of albumin(ALB),adenosine deaminase(ADA),creatinine(Cre).Multivariate logistic regression was applied to analyze the influencing factors of poor prognosis in ACWI patients.Spearman correlation analysis of LRG1 and DPP4 levels with NIHSS and mRS scores in the ACWI group.The ROC curve was applied to analyze the diagnostic value of LRG1 and DPP4 levels for the occurrence of ACWI and prognosis,and Z-test was used to compare the differences in AUC.Results The serum LRG1(56.03±16.11pg/ml)and DPP4(9.90±3.25ng/L)levels in ACWI patients were higher than those in the control group(41.78±12.54pg/ml,7.34±2.32ng/L),the differences were statistically significant(t=7.951,7.272,all P＜0.001).ACWI patients with poor prognosis had higher National Institute of Health Stroke Scale NIHSS scores,mRS scores,larger infarct proportion,LRG1 and DPP4 levels than those with good prognosis(t/χ2=3.258～17.208),but had lower ALB levels than those with good prognosis(t=3.143),the differences were statistically significant(all P＜0.001).Multivariate logistic regression analysis showed that large area infarction,increased NIHSS score,mRS score,LRG1 and DPP4 levels were independent risk factors for poor prognosis in ACWI patients(Wald χ2=4.358～6.000,all P<0.05),while elevated ALB was an independent protective factor for poor prognosis in ACWI patients(Wald χ2=4.535,P<0.05).Spearman correlation analysis showed a positive correlation between serum LRG1 and DPP4 levels in ACWI patients(r=0.446,P<0.001).ROC curve analysis showed that the AUC(95%CI)for diagnosing ACWI with serum LRG1 and DPP4 were 0.788(0.734～0.835)and 0.790(0.736～0.837),respectively,while the AUC(95%CI)for combined diagnosis was 0.922(0.883～0.951),which was better than individual diagnosis(Z=5.798,5.612,all P<0.05).The AUC(95%CI)of LRG1 and DPP4 in diagnosing ACWI patients with poor prognosis was 0.796(0.722～0.857)and 0.800(0.727～0.861),respectively,and the AUC(95%CI)of combined diagnosis was 0.924(0.869～0.961),which was better than their respective individual diagnoses(Z=2.891,4.222,all P<0.05).Conclusion LRG1 and DPP4 levels are higher in the serum of ACWI patients and higher in patients with poor prognosis.The two levels are positively correlated,and the combination has a certain value in diagnosing the occurrence of ACWI and poor prognosis,which provides a theoretical basis for clinical diagnosis.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

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.

An automatic epileptic seizure detection model based on multi-channel recurrence plots and SE-VGG16 is proposed to enhance the accuracy of automatic detection of epileptic seizures.Firstly,triaxial accelerometer is used to collect patients'motion signals as a substitute of electroencephalogram signals,and these signals are converted into two-dimensional images through recurrence plots and then subjected to multi-channel fusion for generating multi-channel recurrence plots.Subsequently,squeeze-and-excitation module is employed to improve VGG16,which enhances the network's adaptability to different channels and enables precise classification.Experimental results show that the proposed model achieves the best performance across all indicators,attaining an accuracy of 99.3%,precision of 99.2%,recall rate of 98.9%,and F1-score of 99.0%.This model significantly boosts the accuracy and applicability of epileptic seizure detection,expands the potential of wearable devices for epileptic seizure monitoring in non-clinical settings,and provides a new technical pathway for epilepsy management and research.

Objective:To explore the relationship between insomnia, depression, sense of meaning in life and suicidal behavior among college students.Methods:A cross-sectional survey was conducted among 7 260 college students at a university in Hebei Province from September to November 2024. The insomnia severity index (ISI), patient health questionnaire(PHQ-9), meaning in life questionnaire(MLQ), and suicide behavior questionnaire-revised (SBQ-R) were used for assessment. Structural equation modeling test was conducted by Mplus 8.0 to test the mediating effect of depression and the moderating effect of sense of meaning in life.Results:(1) The scores of insomnia (6.00 (4.00, 8.00)), depression (2.50 (0, 2.00)), and suicidal behavior (4.00 (3.00, 4.00)) were significantly and positively correlated with each other ( r=0.51-0.66, all P<0.01). The sense of meaning in life (47.80 (39.00, 58.00)) was negatively correlated with insomnia, depression, and suicidal behavior ( r=-0.04--0.22, all P<0.01). (2) Insomnia could positively predict suicidal behavior among college students ( β= 0.15, P<0.01). (3) Depression played a partial mediating role between insomnia and suicidal behavior, with a mediating effect value of 0.40 (95% CI= 0.37-0.43), accounting for 72.73%(0.40/0.55) of the total effect. Conclusion:Depression plays a partial mediating role between insomnia and suicidal behavior among college students. The sense of meaning in life can moderate the impact of insomnia on depression and suicidal behavior.

Objective To establish a method for the simultaneous determination of 16 cephalosporin antibiotics of the fourth generation in whole blood by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),including representative drugs such as cefalexin,cefuroxime axetil,cefetamet pivoxil,ceftizoxime,cefodizime,cefteram pivoxil,cefpodoxime proxetil,cefditoren pivoxil,cefminox sodium,cefoperazone,cefpirome,cefoxitin,cefamandole nafate,cefquinome sulfate,cefpiramide,and ceftiofur.Methods Whole blood was pretreated with acetonitrile for protein precipitation and then determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry.The liquid phase used a Hypersil GOLD? C18 column(2.1 mm ×100 mm,1.9 μm).The organic phase was 0.1％formic acid methanol solution,and the aqueous phase was 0.1％formic acid aqueous solution(containing 10 mmol/mL ammonium formate)for gradient elution.Detection was performed in electrospray positive ionization mode with selected reaction monitoring(SRM).Results The 16 drugs showed good linearity within their respective concentration ranges,with R2 values all greater than 0.99.Limits of detection for cefminox sodium and cefpiramide were 50 and 20 ng/mL,respectively,and for the remaining 14 drugs were all lower than 5 ng/mL.The relative standard deviations(RSDs)of intra-day and inter-day precisions at four spiked concentrations for the 16 drugs were all no higher than 10％(n=5).Accuracy ranged within±15％for mosg drugs,except for cefamandole nafate,ceftiofur,and cefetamet pivoxil at the lower limit of quantification,which showed accuracy within±20％.Extraction recoveries exceeded 80％for all compounds.Conclusion This method has high detection sensitivity,rapid speed,and good repeatability for the simultaneously determination of 16 cephalosporin antibiotics in whole blood.