The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

ObjectiveTo evaluate the clinical efficacy and safety of acupuncture in treating severe Bell's palsy and to explore its potential mechanism by investigating the effect on serum levels of glial cell line-derived neurotrophic factor （GDNF） and nerve growth factor （NGF）. MethodsA randomized， subject-blinded， sham-acupuncture controlled trial was conducted. A total of 130 patients with severe Bell's palsy were randomly allocated into a treatment group or a control group at a 1∶1 ratio. Both groups received conventional western medicine. In addition， the treatment group received acupuncture， while the control group received sham acupuncture， with each session lasting 30 minutes. The treatment course lasted 8 weeks for both groups， followed by a follow-up assessment at week 12. The primary outcome was the proportion of patients achieving House-Brackmann （H-B） grade Ⅱ or lower at week 8. Secondary outcomes included Sunnybrook facial grading system scores at week 0， 4， 8， and 12， the time to satisfactory recovery（the time required to achieve H-B grade≤Ⅱ）， distribution of H-B grades and facial disability index （FDI） scores including the physical function subscale （FDIP） and social/well-being function subscale （FDIS） scores at week 0， 4， 8， and 12， and serum GDNF and NGF levels at week 0， 4， and 8. Adverse events and participants' self-assessments of treatment efficacy were also recorded. ResultsA total of 122 participants completed the study， including 62 in the treatment group and 60 in the control group. An intention-to-treat （ITT） analysis was performed， and missing data were handled using the last observation carried forward （LOCF） method. The proportion of patients achieving H-B grade ≤grade Ⅱ at week 8 was 78.5% （51/65） in the treatment group， significantly higher than 49.2% （32/65） in the control group （P＜0.05）. The Sunnybrook scores， FDIP and FDIS scores increased， while H-B grades decreased at week 4， 8， and 12 in both groups compared to week 0； moreover， improvements in all outcome measures were significantly greater in the treatment group than in the control group （P＜0.05）. The median time to satisfactory recovery was 6 weeks （95%CI： 5.697-6.303） in the treatment group， significantly shorter than 12 weeks （95%CI： 8.314-15.686） in the control group （P＜0.05）. Serum levels of GDNF and NGF were significantly higher in the treatment group at weeks 4 and 8 （P＜0.05）. No serious acupuncture-related adverse events occurred in either group. Adverse events were reported in 5 patients （7.69%） in the treatment group and 4 patients （6.15%） in the control group， with no statistically significant difference between groups （P＞0.05）. Patients' self-assessment of treatment efficacy after 8 weeks treatment was significantly better in the treatment group （P＜0.05）. ConclusionAcupuncture can effectively improve facial nerve function and shorten recovery time in patients with severe Bell's palsy， with a favorable safety profile. The therapeutic mechanism may be associated with the upregulation of serum GDNF and NGF levels.

Objective:We aimed to explore the effect of exercise on cardiac function and APJ system in old mice.Meth-ods:Male C57/BL6 mice were divided into young group(n=30),old control group(n=30),old continuous moderate-intensity training(CMIT)group(n=30),and old high-intensity interval training(HIIT)group(n=30).Mice in the CMIT group and HIIT group underwent 8-week exercise intervention,respectively.Mice in the young group and old con-trol group were placed on stationary treadmill simultaneously.The heart function parameters were measured,and the ex-pression of APJ/Apelin in myocardium and circulating Apelin/Elabela were compared among above-mentioned groups.Results:Compared yo mice in old control group,those in the CMIT group and HIIT group had significant higher left ven-tricular ejection fraction[(67.74±6.18)％,(70.69±7.43)％vs.(61.17±4.78)％]and left ventricular fractional short-ening[(33.07±4.29)％,(33.37±5.57)％vs.(28.05±3.61)％](P＜0.05 or＜0.01);and significant lower Tei index[(0.78±0.09),(0.78±0.12)vs.(0.88±0.08)]and left ventricular posterior wall thickness at diastole[(1.01±0.09)mm,(1.02±0.10)mm vs.(1.19±0.14)mm](P＜0.05all).Compared to mice in old control group,those in the HIIT group had significant higher mitral valve E/A ratio[(1.63±0.11)vs.(1.42±0.18),P=0.043].Compared to mice in old control group,those in the HIIT group had significant higher expressions of APJ and Apelin in myocardium,as well as the levels of Apelin[(1186.23±393.74)pg/ml vs.(413.17±80.81)pg/ml]and Elabela[(5.38±2.76)ng/ml vs.(1.57±0.60)ng/ml]in the serum(P＜0.05 or＜0.01).Conclusion:Long-term exercise initiated late in life could im-prove heart function of mice.The APJ-Apelin/Elabela system may be involved in the exercise-mediated improvement of cardiac aging.

Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.

Objective:To examine the relationship between college students'core self-evaluation and academic burnout,and to provide empirical support for intervention strategies.Methods:A two-point longitudinal study was conducted with 245 medical students over a period of 18 months(T1:May 2023,T2:November 2024)to assess participants'core self-evaluation level using the Core Self-Evaluation Scale(CSES),and the overall burnout level u-sing the Academic Study Burnout Inventory(ASBI).Cross-lagged panel model was applied to examine the bidirec-tional causal relationship.Results:The cross-lagged results showed that core self-evaluation score in T1 negatively predicted academic burnout score inT2(β=-0.21,P＜0.01),and academic burnout score in T1 also negatively predicted core self-evaluation score in T2(β=-0.20,P＜0.05).Conclusion:Core self-evaluations and academic burnout exhibit a reciprocal predictive relationship over time.

Objective:To investigate the dynamic characteristics of human papillomavirus (HPV) genomic integration during cervical lesion progression and the clinical value of HPV integration detection in stratify HPV-positive women, and to explore its molecular mechanisms in cervical carcinogenesis.Methods:A prospective cohort study was designed to enroll high-risk HPV (HR-HPV) positive women who underwent cervical cancer screening in Drum Tower Hospital Affiliated to Nanjing University Medical School and Nanjing Maternity and Child Health Care Hospital from July 2022 to July 2024. Cervical exfoliated cells samples were collected, and HPV whole genome targeted capture and high-throughput sequencing technology were used. The HPV integration patterns, host gene functional region distribution and pathway enrichment characteristics of 157 samples with different cervical lesions grades were analyzed, including 31 cases of normal cervix, 40 cases of cervical intraepithelial neoplasia (CIN) Ⅰ, 32 cases of CIN Ⅱ, 42 cases of CIN Ⅲ, and 12 cases of cervical cancer.Results:HR-HPV integration was detected in 80.2% (126/157) of the 157 HR-HPV positive samples. The incidence of HR-HPV integration in cervical cancer patients was 12/12, which was higher than that in normal women (77%, 24/31). The incidence of HPV16 integration was significantly higher in high-grade lesions, and the incidence of HPV16 integration was 43% (18/42) in CIN Ⅲ patients and 8/12 in cervical cancer patients ( P<0.001). A total of 14 438 integration events were detected in 126 samples with HPV integration. The integration sites were mainly distributed in the host intergenic region (51.0%, 7 359/14 438) and intronic region (38.1%, 5 494/14 438), and the integration frequency of viral L1 gene was the highest (28.4%, 4 498/16 781). Functional enrichment analysis showed that HPV integration-related host genes were significantly enriched in transport of small molecules,cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway, and purine ribonucleotide biosynthetic process, which synergistically drove carcinogenesis through multiple mechanisms. Conclusions:HPV integration events are significantly associated with the progression of cervical lesions. HPV integrated detection based on cervical exfoliated cells is expected to optimize the current screening strategy, reduce excessive intervention of HPV positive women and facilitate their accurate triage management.

Objective:To investigate the trends in detection, treatment, and outcomes of rifampicin-resistant tuberculosis (TB) in Jiangsu Province from 2013 to 2023, assess the effectiveness of control policies and measures for drug-resistant TB, and provide evidence for better control of drug-resistant TB.Methods:Data and indicators related to the screening, diagnosis, treatment, and outcomes of rifampicin-resistant TB in Jiangsu Province from 2013 to 2023 were obtained from the Tuberculosis Management Information System. The Joinpoint regression method was employed to analyze the trends over this period, and annual percent change (APC) and average annual percent change (AAPC) were calculated. A comparative analysis was also conducted to evaluate the changes before and after implementing relevant policies and measures.Results:From 2013 to 2023, the number of registered rifampicin-resistant TB patients in Jiangsu Province showed a consistent upward trend (APC=AAPC=1.45%, P=0.035). The screening rates for drug resistance among new TB patients in high-risk groups and the proportion of molecular biological testing for drug resistance all exhibited increasing trends, with a notable turning point occurring in 2018. The trend of the treatment enrollment rate for rifampicin-resistant TB patients experienced a significant shift in 2020, showing a marked increase from 2013 to 2020 (APC=12.91%, P=0.008). The treatment success rate of rifampicin-resistant TB patients also showed a significant upward trend after a turning point in 2020 (APC=9.94%, P=0.004). Conclusion:From 2013 to 2023, significant progress was seen in preventing and treating rifampicin-resistant TB in Jiangsu Province, with relevant policies and measures proving to be highly effective.

Objective:To compare the safety, number of lymph nodes removed, rate of lymph node metastasis, and prognosis between proximal gastrectomy (PG) and total gastrectomy (TG) in patients with Siewert types II and III adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, clinical data of patients diagnosed with adenocarcinoma of the esophagogastric junction at Changzhi People's Hospital, affiliated with Changzhi Medical College, between December 2019 and November 2022, were collected. Patients who had received neoadjuvant therapy, had multiple malignant lesions in the stomach, had concomitant malignancies in other organs, had incomplete clinical data, or had been lost to follow-up were excluded. The study cohort comprised 308 patients, 99 in the PG group and 209 in the TG group. To reduce confounding bias, propensity score matching was performed, matching patients for age, sex, body mass index, tumor diameter, and pathological stage in a 1:1 ratio, resulting in 73 patients in each group. The primary outcomes assessed were operative details, number of lymph nodes dissected, rate of lymph node metastasis, postoperative complications, duration of hospital stay, and follow-up and survival outcomes.Results:The PG group had a significantly shorter median operative time than did the TG group (250 vs. 280 minutes, Z = -4.970, P<0.001), with fewer cases of intraoperative blood loss >100 mL (30.1%[22/73] vs. 46.6%[34/73], χ2=4.171, P=0.041), and a smaller number of lymph nodes removed (median 33 vs. 46, Z =-4.774, P<0.001); all of these differences are statistically significant (all P<0.05). Differences between the two groups in postoperative hospital stay and postoperative complications were not statistically significant (both P>0.05). Furthermore, no statistically significant differences were found between the PG and TG groups in the number of lymph nodes dissected or the lymph node metastasis rates at stations No. 1, No. 2, No. 3, No. 4sa, No. 4sb, and No. 7 (all P> 0.05). Among the 209 patients in the TG group, analysis of risk factors for metastasis to distal perigastric lymph nodes (No.4d, No.5, and No.6) showed that patients with tumor diameters ≤4 cm and T1–T3 stage disease had significantly lower rates of metastasis to these lymph nodes than did patients with tumor diameters >4 cm and/or T4 stage disease (0/78 vs. 12/131 [9.2%]); these differences are statistically significant ( P=0.014). The median duration of follow-up for the entire cohort was 26 months. The 3-year overall survival rates for the PG and TG groups were 62.5% and 63.3%, respectively; this difference is not statistically significant (χ 2=0.330, P = 0.565). Multivariate analysis showed that older age ( P = 0.035) and advanced pathological stage ( P = 0.018) were significant independent risk factors that affected overall survival in patients with Siewert type II and III adenocarcinoma of the esophagogastric junction. Conclusions:PG is safe and feasible for patients with Siewert types II and III adenocarcinoma of the esophagogastric junction. The number of lymph nodes dissected and metastasis status were similar in the TG and PG groups.

Trophoblast cells serve as the foundation for placental development. We analyzed published multiomics sequencing data and found that trophoblast cells highly expressed RRS1 compared to primitive endoderm and epiblast. We used HTR-8/SVneo cells for further investigation, and Western blot and immunofluorescence staining confirmed that HTR-8/SVneo cells highly expressed RRS1. RRS1 was successfully knocked down in HTR-8/SVneo cells using siRNA. Using IncuCyte S3 live-cell analysis system based on continuous live-cell imaging and real-time data, we observed that proliferation, migration, and invasion abilities were all significantly decreased in RRS1-knockdown cells. RNA-seq revealed that knockdown of RRS1 affected the gene transcription, and upregulated pathways in extracellular matrix organization, DNA damage response, and intrinsic apoptotic signaling, downregulated pathways in embryo implantation, trophoblast cell migration, and wound healing. Differentially expressed genes were enriched in diseases related to placental development. Consistent with these findings, human chorionic villus samples collected from spontaneous abortion cases exhibited significantly reduced RRS1 expression compared to normal controls. Our results highlight the functional importance of RRS1 in human trophoblasts and suggest that its deficiency contributes to early pregnancy loss.
Humans ; Trophoblasts/physiology* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Female ; Pregnancy ; Abortion, Spontaneous/metabolism* ; Cell Line ; Placentation/genetics*

Alzheimer's disease (AD), a progressive dementia, is one of the most common neurodegenerative diseases. Clinical trial results of amyloid-β (Aβ) and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing. There are currently no effective strategies for slowing the progression of AD. Herein, we spotlight the dysregulation of lipid metabolism, particularly the elevation of ceramides (Cers), as a critical yet underexplored facet of AD pathogenesis. Our study delineates the role of Cers in promoting microglial pyroptosis, a form of programmed cell death distinct from apoptosis and necroptosis, characterized by cellular swelling, and membrane rupture mediated by the NLRP3 inflammasome pathway. Utilizing both in vivo experiments with amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and in vitro assays with BV-2 microglial cells, we investigate the activation of microglial pyroptosis by Cers and its inhibition by icariin (ICA), a flavonoid with known antioxidant and anti-inflammatory properties. Our findings reveal a significant increase in Cers levels and pyroptosis markers (NOD-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, gasdermin D (gasdermin D (GSDMD)), and interleukin-18 (IL-18)) in the brains of AD model mice, indicating a direct involvement of Cers in AD pathology through the induction of microglial pyroptosis. Conversely, ICA treatment effectively reduces these pyroptotic markers and Cer levels, thereby attenuating microglial pyroptosis and suggesting a novel therapeutic mechanism of action against AD. This study not only advances our understanding of the pathogenic role of Cers in AD but also introduces ICA as a promising candidate for AD therapy, capable of mitigating neuroinflammation and pyroptosis through the cyclooxygenase-2 (COX-2)-NLRP3 inflammasome-gasdermin D (GSDMD) axis. Our results pave the way for further exploration of Cer metabolism disorders in neurodegenerative diseases and highlight the therapeutic potential of targeting microglial pyroptosis in AD.