To develop the Pharmacovigilance Guidelines for Clinical Application of Chinese Patent Medicines for Mucosal Administration in response to common problems， including insufficient safety information in package inserts， amplified medication risks in special populations， and non-standard clinical practices， thus establishing a risk management system tailored to the characteristics of Chinese patent medicines for mucosal administration. An approach combining qualitative and quantitative methods was adopted. In accordance with the Drug Administration Law of the People's Republic of China （2019 revision） and the GB/T 1.1—2020 standard， a systematic search was performed in the Chinese Pharmacopoeia （2020 edition）， the Catalog of Medicines Covered by Medical Insurance （2022 edition）， Chinese databases ［China Network of Knowledge Infrastructure （CNKI）， Wanfang Data （Wanfang）， and VIP journal resource integration service platform （VIP）］， and international databases （Cochrane Library， PubMed， and EMbase）. Guideline outlines were developed through questionnaire surveys， expert interviews， and the nominal group technique. The content of each item was formulated with full consideration of traditional Chinese medicine （TCM） incompatibility， as well as the conceptual connotations and extensions of pharmacovigilance. The results included 54 Chinese patent medicines for mucosal administration from the Chinese Pharmacopoeia （2020 edition） and 58 from the Catalog of Medicines Covered by Medical Insurance （2022 edition）. Safety-related items in the corresponding package inserts were collected， and 27 relevant publications were retrieved. Thirty experts from 24 institutions were mobilized for the drafting， and opinions from 61 external experts were solicited. A pharmacovigilance framework was established， covering the full chain of "monitoring， identification， assessment， and control". Based on seven anatomical sites， including nasal， ocular， and oral mucosa， a stratified monitoring system was constructed. The guideline proposed key recommendations on improving package insert sections such as "Adverse Reactions"， "Contraindications"， and "Precautions"， clinical procedure standardization in healthcare institutions， risk control， and dynamic pharmacovigilance. The Guideline provides evidence-based support tailored to the risk profile of Chinese patent medicines for mucosal administration， filling the current gap in international pharmacovigilance standards in this field， while offering technical support for safety management across the full life cycle of medicines for mucosal administration.

BackgroundPatients with depressive episode and schizophrenia have a high risk of suicide. The sleep electroencephalogram power spectral density characteristics of patients with depressive episode accompanied by suicidal behavior and those with schizophrenia may be different， but there is currently a lack of direct comparative studies on these two groups of patients. ObjectiveTo compare the sleep electroencephalogram power spectral density between depressive episode and schizophrenic patients with suicidal behavior， in order to provide references for exploring predictive indicators of suicidal behavior. MethodsFrom June 2018 to December 2020， 20 patients with depressive episode and 20 patients with schizophrenia who had committed suicide within the past month and were treated at the outpatient department of Shenzhen Kangning Hospital were selected. All of them met the diagnostic criteria for depressive episode or schizophrenia as defined in the International Classification of Diseases， tenth edition （ICD-10）. Using a random sampling method， 20 volunteers with matching gender and age to the patient groups were selected from the Cuiping community in Shenzhen as the control group. The subjective sleep of the patients was evaluated using the Insomnia Severity Index （ISI）， the Dysfunctional Belief and Attitude about Sleep （DBAS）， the Disturbing Dreams and Nightmare Severity Index （DDNSI）， and the Epworth Somnolence Scale （ESS）. The objective sleep of the patients was assessed using polysomnography. The sleep electroencephalogram was filtered and the power spectral density of the brain wave was analyzed and processed for all the subjects. The subjective and objective sleep conditions of the two patient groups were compared， and the sleep electroencephalogram power spectral density of the patient groups and the control group were also compared. ResultsA comparison of subjective and objective sleep conditions between patients with depressive episode accompanied by suicidal behavior and patients with schizophrenia accompanied by suicidal behavior showed no statistically significant differences （P>0.05）. Comparisons of sleep electroencephalogram power spectral density in the W stage （average power of α wave， total power of δ wave， average power of δ wave， average power of θ wave）， N1 stage （average power of β wave， total power of α wave， total power of δ wave）， N2 stage （total power of α wave， average power of α wave， total power of δ wave， average power of δ wave）， N3 stage （average power of α wave， average power of δ wave）， and R stage （total power of α wave， average power of α wave， total power of δ wave， average power of δ wave） between patients with depressive episode accompanied by suicidal behavior， patients with schizophrenia accompanied by suicidal behavior， and the control group showed statistically significant differences （P<0.05 or 0.01）. The total power of δ wave in the W stage and the average power of β wave and δ wave in the N1 stage were higher in two patient groups were higher than those of the control group. The total power of α wave and the average power of α wave in the N2 stage were lower than those of the control group， while the average power of δ wave was higher than that of the control group. The average power of α wave in the N3 stage of both patient groups were lower than that of the control group， while the average power of δ wave was higher than that of the control group. The total power and average power of α wave in the R stage were lower than those of the control group， while the total power and average power of δ wave were higher than those of the control group. All the differences were statistically significant. Patients with depressive episode accompanied by suicidal behavior had higher average powers of α wave， δ wave， and θ wave in the W stage compared with the control group， while the total power of α wave in the N1 stage was lower in the former group. All these differences were statistically significant （P<0.05）. ConclusionThe depressive episode patients accompanied by suicidal behavior have highly overlapping sleep electroencephalogram abnormal patterns with those of schizophrenia patients， mainly manifested as a general decrease in α wave power （N2， N3， R stage） and a general increase in δ wave power （W， N1， N2， N3， R stage） as well as β wave power in N1 stage. At the same time， patients with depressive episode accompanied by suicidal behavior also show specific changes， including an increase in the average power of α and θ waves during the wakefulness period （W stage）， and a decrease in the total power of α wave in N1 stage. ［Funded by Guangdong Province High-level Clinical Key Specialty （with supporting funds from Shenzhen City） （number， SZGSP013）； Shenzhen Key Medical Discipline （number， SZXK041）； Shenzhen Clinical Medicine Research Center Project （number， 20210617155253001）］

To develop the Pharmacovigilance Guidelines for Clinical Application of Chinese Patent Medicines for Mucosal Administration in response to common problems， including insufficient safety information in package inserts， amplified medication risks in special populations， and non-standard clinical practices， thus establishing a risk management system tailored to the characteristics of Chinese patent medicines for mucosal administration. An approach combining qualitative and quantitative methods was adopted. In accordance with the Drug Administration Law of the People's Republic of China （2019 revision） and the GB/T 1.1—2020 standard， a systematic search was performed in the Chinese Pharmacopoeia （2020 edition）， the Catalog of Medicines Covered by Medical Insurance （2022 edition）， Chinese databases ［China Network of Knowledge Infrastructure （CNKI）， Wanfang Data （Wanfang）， and VIP journal resource integration service platform （VIP）］， and international databases （Cochrane Library， PubMed， and EMbase）. Guideline outlines were developed through questionnaire surveys， expert interviews， and the nominal group technique. The content of each item was formulated with full consideration of traditional Chinese medicine （TCM） incompatibility， as well as the conceptual connotations and extensions of pharmacovigilance. The results included 54 Chinese patent medicines for mucosal administration from the Chinese Pharmacopoeia （2020 edition） and 58 from the Catalog of Medicines Covered by Medical Insurance （2022 edition）. Safety-related items in the corresponding package inserts were collected， and 27 relevant publications were retrieved. Thirty experts from 24 institutions were mobilized for the drafting， and opinions from 61 external experts were solicited. A pharmacovigilance framework was established， covering the full chain of "monitoring， identification， assessment， and control". Based on seven anatomical sites， including nasal， ocular， and oral mucosa， a stratified monitoring system was constructed. The guideline proposed key recommendations on improving package insert sections such as "Adverse Reactions"， "Contraindications"， and "Precautions"， clinical procedure standardization in healthcare institutions， risk control， and dynamic pharmacovigilance. The Guideline provides evidence-based support tailored to the risk profile of Chinese patent medicines for mucosal administration， filling the current gap in international pharmacovigilance standards in this field， while offering technical support for safety management across the full life cycle of medicines for mucosal administration.

Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

Objective To investigate the value of preoperative clinical data and computed tomography angiography (CTA) data in predicting perioperative mortality risk in patients with acute aortic dissection (AAD), and to construct a Nomogram prediction model. Methods A retrospective study was conducted on AAD patients treated at Affiliated Hospital of Zunyi Medical University from February 2013 to July 2023. Patients who died during the perioperative period were included in the death group, and those who improved during the same period were randomly selected as the non-death group using a random number table method. The first CTA data and preoperative clinical data within the perioperative period of the two groups were collected, and related risk factors were analyzed to screen out independent predictive factors for perioperative death. The Nomogram prediction model for perioperative mortality risk in AAD patients was constructed using the screened independent predictive factors, and the effect of the Nomogram was evaluated by calibration curves and area under the curve (AUC). Results A total of 270 AAD patients were included. There were 60 patients in the death group, including 42 males and 18 females with an average age of (56.89±13.42) years. There were 210 patients in the non-death group, including 163 males and 47 females with an average age of (56.15±13.77) years. Multivariate logistic regression analysis showed that type A AAD [OR=4.589, 95%CI (2.273, 9.267), P<0.001], irregular tear morphology [OR=2.054, 95%CI (1.025, 4.117), P=0.042], decreased hemoglobin [OR=0.983, 95%CI (0.971, 0.995), P=0.007], increased uric acid [OR=1.003, 95%CI (1.001, 1.005), P=0.004], and increased aspartate aminotransferase [OR=1.003, 95%CI (1.000, 1.006), P=0.035] were independent risk factors for perioperative death in AAD patients. The Nomogram prediction model constructed using the above risk factors had an AUC of 0.790 for predicting perioperative death, indicating good predictive performance. Conclusion Type A AAD, irregular tear morphology, decreased hemoglobin, increased uric acid, and increased aspartate aminotransferase are independent predictive factors for perioperative death in AAD patients. The Nomogram prediction model constructed using these factors can help assess the perioperative mortality risk of AAD patients.

Objective: Patients with atherosclerotic cardiovascular disease (ASCVD) following percutaneous coronary intervention (PCI) are classified as very-high-risk individuals in cardiovascular disease (CVD) risk stratification. The distribution pattern of traditional Chinese medicine (TCM) syndromes in this patient population, as well as its association with blood lipid profiles and clinical prognosis, remains unclear. The present prospective cohort study aims to investigate these correlations, thereby providing insights to enrich the research fields. Methods: We enrolled consecutive patients with ASCVD who underwent PCI at the Integrated Cardiology Unit of China-Japan Friendship Hospital between September 1, 2020 and December 31, 2022. Demographics and clinical characteristics, signs and symptoms defining each TCM syndrome, and fasting venous blood samples were collected at baseline and follow up or upon major adverse cardiovascular events (MACEs). We analyzed the correlation between TCM syndromes, blood lipid profiles, and MACEs, and developed a new joint prognostic model incorporating both TCM syndromes and blood lipids using logistic regression. The analyses were based on detailed baseline and one-year follow-up data. Results: A per-protocol analysis was performed on 586 patients with complete data ultimately. During the one-year follow-up, 174 patients (29.69%) experienced a MACE. We performed statistical analyses on comorbidities, medication, and biochemical indicators across groups defined by TCM syndrome differentiation. When comparing different TCM syndromes, no significant differences were found in age, body mass index (BMI), history of revascularization, comorbidities, family history of CVD, smoking or drinking, or statin intensity (P > 0.05). Patients with intertwined phlegm and blood stasis syndrome exhibited significantly higher levels of total cholesterol (TC, 5.27 ± 1.18 mmol/L, P < 0.001), triglyceride (TG, 1.96 ± 1.33 mmol/L, P = 0.008), low-density lipoprotein cholesterol (LDL-C, 3.35 ± 0.79 mmol/L, P < 0.001), and high-density lipoprotein cholesterol (HDL-C, 1.24 ± 0.81 mmol/L, P < 0.001) compared with those with other TCM syndromes combined. A multivariable logistic regression model was constructed to predict MACEs. The model included TCM syndrome type [with intertwined phlegm and blood stasis as a predictor, adjusted odds ratio (OR) = 1.413, 95% confidence interval (CI): 0.517 – 3.864, P = 0.501], age (adjusted OR = 0.97, 95% CI: 0.955 – 1.001, P = 0.057), male gender (adjusted OR = 0.698, 95% CI: 0.416 – 1.170, P = 0.173), TC (adjusted OR = 1.004, 95% CI: 0.513 – 1.965, P = 0.990), and LDL-C (adjusted OR = 5.825, 95% CI: 2.214 – 15.326, P < 0.001). This model demonstrated good discriminatory ability for MACEs in post-PCI ASCVD patients [the area under the receiver operating characteristic (ROC) curve (AUC) = 0.865, 95% CI: 0.816 – 0.914]. Conclusion The intertwined phlegm and blood stasis TCM syndrome is associated with a distinct atherogenic lipid profile characterized by elevated levels of TC and LDL-C. The prognostic model that incorporates this TCM syndrome type along with conventional lipid parameters (TC and LDL-C) shows good discriminatory ability for predicting MACEs in ASCVD patients after PCI, underscoring the potential clinical utility of integrating TCM syndrome differentiation into CVD risk assessment.

Objective To investigate the perioperative safety of patients with myasthenia gravis who take high doses of oral glucocorticoids. Methods A retrospective analysis was conducted on the clinical data of patients with myasthenia gravis who received oral glucocorticoids and underwent thoracoscopic thymectomy at the Department of Thoracic Surgery, the University of Hong Kong-Shenzhen Hospital from April 2013 to October 2019. Patients were divided into a high-dose steroid group and a medium-to-low dose steroid group based on the dosage of oral steroids, and the clinical data of the two groups were compared. Results A total of 102 patients were included, including 19 (18.62%) males and 83 (81.37%) females, with an average age of (32.25±9.83) years. There were 75 patients in the medium-to-low dose steroid group and 27 patients in the high-dose steroid group. All patients in both groups successfully completed the surgery without major intraoperative bleeding, conversion to open chest surgery, delayed extubation, severe infection, or perioperative death. The daily oral steroid dose for the high-dose steroid group was (35.81±4.29) mg, and for the medium-to-low dose steroid group it was (15.29±2.17) mg. There was no statistical difference in the operation time [(124.69±23.51) min vs. (117.89±21.46) min, P=0.172] and intraoperative blood loss [(21.19±3.48) mL vs. (20.56±3.41) mL, P=0.419] between the two groups. Postoperatively, 12 (11.76%) patients developed complications: one patient of myasthenic crisis (the medium-to-low dose steroid group), which was improved after short-term respiratory support and intravenous immunoglobulin treatment; 11 patients of respiratory/swallowing difficulties (9 in the medium-to-low dose steroid group and 2 in the high-dose steroid group), which were improved after anticholinergic treatment to reduce oral secretions and sputum suction, and the patients were discharged smoothly. There was no statistical difference in the incidence of postoperative complications between the two groups (P=0.637). Conclusion On the basis of good perioperative management, it is safe and feasible for patients with myasthenia gravis who take high dose of oral steroids to undergo thymectomy, and they have the same perioperative safety as patients with medium-to-low dose steroids.

Objective To evaluate the feasibility and safety of Remodeling+Ring (modified Yacoub) for patients with aortic root aneurysm. Methods The clinical data of patients who underwent modified Yacoub surgery at West China Hospital of Sichuan University from July 2020 to May 2023 were retrospectively analyzed. Results Four male patients were enrolled, with an average age of (47.3±10.3) years and body surface area of (1.9±0.2) m2. One patient had bicuspid aortic valve. Aortic valve regurgitation was mild in three patients and moderate in one patient. Preoperative New York Heart Association (NYHA) heart function was gradeⅠin one patient and gradeⅡin three patients. The maximum diameter of the aortic sinus was (59.3±8.1) mm. All four patients recovered and were discharged without a second thoracotomy. No postoperative complications such as brain injury, infection, respiratory failure or renal insufficiency occurred. During the follow-up of (17.0±13.1) months, two patients showed no regurgitation of the aortic valve, two patients exhibited mild regurgitation. Three patients had a heart function of gradeⅠ and one patient of gradeⅡ. Conclusion Modified Yacoub technique is safe and effective for patients with aortic root aneurysm.

ObjectiveTo investigate the epidemiological characteristics and influencing factors of depressive symptoms among middle school (junior, senior, and vocational high school) students in Yunnan Province, China, and to inform evidence-based intervention strategies for adolescent mental health. MethodsA cross-sectional survey was conducted between October and November 2023 using stratified random cluster sampling. Students from eight counties (districts) across four prefectures (cities) in Yunnan Province were included. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Multivariate logistic regression analysis was performed to examine factors associated with depressive symptoms, with stratified analyses conducted by gender, educational stage, and ethnicity. ResultsA total of 4 672 questionnaires were distributed, with 4 670 valid questionnaires retrieved, yielding a valid response rate of 99.96%. The surveyed participants were predominantly female students (50.81%), junior high school students (49.13%), ethnic minorities (52.78%), and urban residents (79.29%). The mean CES-D score for middle school students in Yunnan Province was (15.31±10.83). Female students had a significantly higher mean score (16.63±11.41) than male students (13.95±10.02) (P<0.001). Senior high school students had a significantly higher mean score (16.61±10.61) compared to both junior high school students (14.74±11.45) and vocational high school students (13.10±7.71) (all pairwise comparisons P<0.001). The prevalence of depressive symptoms among middle school students in Yunnan Province was 28.18%. The prevalence was significantly higher in females (34.09%) than in males (22.07%). By school type, the detection rate was highest among senior high school students (33.39%), followed by junior high school students (26.29%) and vocational high school students (17.27%) (P<0.05). Multivariate logistic regression analysis showed that female gender (OR=2.16, 95%CI: 1.86‒2.50), being in junior high school (OR=2.43, 95%CI: 1.84‒3.20) or senior high school (OR=2.27, 95%CI: 1.73‒2.98), not living with parents (OR=1.24, 95%CI: 1.07‒1.44), irregular breakfast consumption (OR=1.52, 95%CI: 1.33‒1.75), lack of moderate-to-vigorous physical activity (MVPA) (OR=1.69, 95%CI: 1.37‒2.09), sleep duration ≤5 h per night (OR=2.52, 95%CI: 2.02‒3.14) or 6‒7 h per night (OR=1.47, 95%CI: 1.25‒1.73), smoking (OR=1.86, 95%CI: 1.56‒2.23), and alcohol consumption (OR=1.81, 95%CI: 1.54‒2.13) were positively associated with depressive symptoms. In contrast, screen time ≤1 h (OR=0.71, 95%CI: 0.59‒0.86) was negatively associated with depressive symptoms. Stratified analyses showed that female students not living with parents (OR=1.29, 95%CI: 1.06‒1.58), senior high school students (OR=1.51, 95%CI: 1.21‒1.88), and Han Chinese students (OR=1.37, 95%CI: 1.11‒1.69) were more likely to experience depressive symptoms. Han Chinese students who smoked were also more likely to have depressive symptoms (OR=1.72, 95%CI: 1.34‒2.21). In contrast, male students with screen time ≤1 h (OR=0.71, 95%CI: 0.53‒0.95) and ethnic minority students (OR=0.74, 95%CI: 0.58‒0.95) were less likely to experience depressive symptoms. Regardless of gender, irregular breakfast consumption, lack of MVPA, sleep duration less than 8 h per night, smoking, and alcohol consumption were all positively associated with depressive symptoms (P<0.05). Among both junior and senior high school students, irregular breakfast consumption, lack of MVPA, smoking, and alcohol consumption were positively associated with depressive symptoms (all P<0.05), while screen time ≤1 h was negatively associated with depressive symptoms (all P<0.05). For junior high school students, engaging in 1‒2 days of MVPA per week, screen time more than 2 h per day, and sleep duration 6‒7 h per night were all positively associated with depressive symptoms (all P<0.05). Among junior high, senior high, and vocational high school students, sleep duration ≤5 h per night was positively associated with depressive symptoms (P<0.05). For both Han Chinese and ethnic minority students, irregular breakfast consumption, lack of MVPA, sleep duration less than 8 h per night, and alcohol consumption were all positively associated with depressive symptoms (all P<0.05). ConclusionThe prevalence of depressive symptoms among middle school students in Yunnan Province is comparable to that in central China and higher than that in northern regions. Prevention and control efforts should prioritize female students and those in junior and senior high school stages. Universal improvements in lifestyle behaviors among middle school students, such as regular breakfast consumption, MVPA, sufficient sleep (≥8 h), and abstinence from smoking and alcohol. Particular attention should be given to limiting excessive screen time among junior high school students and addressing the mental health needs of females not living with their parents, senior high school students, and Han Chinese students.

ObjectiveTo investigate the disruptive effects of perinatal exposure to the environmental endocrine disruptor bisphenol AF (BPAF) on hepatic lipid metabolism in prepubertal (postnatal day 21, PND21) male offspring rats, and to provide scientific evidence for assessing the obesogenic effect of BPAF. MethodsSprague-Dawley (SD) rats aged 8 weeks were used in this study. Pregnant rats were divided into BPAF dose groups (2, 10, 50 mg·kg⁻¹) and a vehicle control group (corn oil), with 6 confirmed pregnant females per group. Gavage administration started from gestational day 0 and continued until the end of lactation. At PND21, one male offspring per litter was randomly selected. Serum concentrations of glucose (GLU), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), leptin (LEP), free fatty acid (FFA), as well as oxidative stress markers superoxide dismutase (SOD) and malondialdehyde (MDA), were measured. Pathological changes in liver and adipose tissues were evaluated, and the expression levels of genes related to hepatic lipid metabolism were measured. ResultsCompared to the vehicle control group, the 50 mg·kg⁻¹ group showed significantly increased serum LEP and MDA levels in male offspring (P<0.05), and significant upregulation of hepatic lipoprotein lipase (Lpl), fatty acid synthetase (Fas), and peroxisome proliferator-activated receptor γ (Pparg) gene expression (P<0.05). The 2 mg·kg⁻¹ group exhibited a significant increase in adipocyte length (P<0.05), while the 50 mg·kg⁻¹ group showed significant increases in both adipocyte area and length (P<0.05). No significant abnormalities were observed in liver histopathological examination. ConclusionPerinatal exposure to 50 mg·kg⁻¹ BPAF induced adipocyte hypertrophy, elevated leptin levels, upregulation of lipid synthesis gene expression, and enhanced oxidative stress in prepubertal male offspring, suggesting that BPAF may exert environmental obesogenic effects by disrupting lipid metabolism pathways.