The Pharmacovigilance Guidelines for Clinical Application of Traditional Chinese Medicine Injections （hereinafter referred to as the Guidelines） were released by the China Association of Chinese Medicine， with the standard number T/CACM 1563.4—2024. It is the first specialized guideline in China on the approach to pharmacovigilance activities for the clinical application of traditional Chinese medicine injections （TCMIs）. The Guidelines were jointly developed by the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， along with 30 experts in TCM pharmacovigilance， clinical practice （TCM， as well as integrated traditional Chinese and Western medicine），and evidence-based medicine from across the country. This publication filled the gap in standard documents in this field， both domestically and internationally. The Guidelines were formulated according to GB/T1.1—2020 Directives for standardization—Part 1： Rules for the structure and drafting of standardizing documents， the WHO Handbook for Guideline Development，and other methodological norms. Based on international norms，national laws and regulations，and scientific research results in the field of pharmacovigilance， methods adopted included expert interviews，literature research，nominal group technique， and Delphi method. Then， key points for pharmacovigilance for TCM injections were summarized and clarified in the four critical sections of "monitoring"，"identification"，"assessment"，and "control". The development process of the Guidelines included project initiation， international registration， expert interviews， literature search， and evaluation. Based on the research results of these steps，a draft was formed and revised through multiple rounds of in-group expert discussion and peer evaluations by 56 external experts. After revisions by the working group based on the feedback， the final version was formed. The Guidelines came into effect on January 8，2024，providing suggestions and reference norms for pharmacovigilance in the clinical application of TCMIs. To further promote the application and popularization of the Guidelines and help pharmacovigilance personnel better understand the development process，this study elucidates the background，methodological framework，and key development steps of the Guidelines.

The Pharmacovigilance Guidelines for Clinical Application of Traditional Chinese Medicine Injections （hereinafter referred to as the Guidelines） were released by the China Association of Chinese Medicine， with the standard number T/CACM 1563.4—2024. It is the first specialized guideline in China on the approach to pharmacovigilance activities for the clinical application of traditional Chinese medicine injections （TCMIs）. The Guidelines were jointly developed by the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， along with 30 experts in TCM pharmacovigilance， clinical practice （TCM， as well as integrated traditional Chinese and Western medicine），and evidence-based medicine from across the country. This publication filled the gap in standard documents in this field， both domestically and internationally. The Guidelines were formulated according to GB/T1.1—2020 Directives for standardization—Part 1： Rules for the structure and drafting of standardizing documents， the WHO Handbook for Guideline Development，and other methodological norms. Based on international norms，national laws and regulations，and scientific research results in the field of pharmacovigilance， methods adopted included expert interviews，literature research，nominal group technique， and Delphi method. Then， key points for pharmacovigilance for TCM injections were summarized and clarified in the four critical sections of "monitoring"，"identification"，"assessment"，and "control". The development process of the Guidelines included project initiation， international registration， expert interviews， literature search， and evaluation. Based on the research results of these steps，a draft was formed and revised through multiple rounds of in-group expert discussion and peer evaluations by 56 external experts. After revisions by the working group based on the feedback， the final version was formed. The Guidelines came into effect on January 8，2024，providing suggestions and reference norms for pharmacovigilance in the clinical application of TCMIs. To further promote the application and popularization of the Guidelines and help pharmacovigilance personnel better understand the development process，this study elucidates the background，methodological framework，and key development steps of the Guidelines.

Osteoarthritis （OA） and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan， a classic prescription in Tibetan medicine， have the functions of clearing heat， awakening the brain and opening orifices， relaxing tendons and promoting meridian circulation， and eliminating yellow water. Clinically， they are used to treat osteoarthritis， post-stroke sequelae， neuropathic pain， and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory， analgesic， and nerve-repairing effects. However， current research remains insufficient regarding the appropriate indications， timing， and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use， a panel of national experts， including clinical specialists， Tibetan medicine practitioners， pharmacologists， and methodologists， formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system， and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan， including therapeutic indications， dosage and administration， treatment duration， and medication safety. The consensus specifically addresses the clinical efficacy， appropriate timing of administration， dosage strategies， treatment cycles， and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke， reduce medication-related risks， and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine， with the standard number GS/CACM 369-2024.

Objective To investigate the association between the pattern of carotid artery calcification and the prognosis of patients with acute cerebral infarction after 3 months of treatment. Methods A total of 112 patients who were diagnosed with acute ischemic stroke （AIS） in our hospital from March 2021 to September 2022 were enrolled as subjects. CT angiography was performed within 24 hours after admission， and the carotid artery was assessed in terms of calcification pattern （no calcification， intimal calcification， and medial calcification） and calcification load （low and high calcification）. After 7 days of treatment， CT reexamination was performed to evaluate hemorrhagic transformation and infarct volume. The patients were followed up for 3 months， and according to the modified Rankin Scale （mRS） score， they were divided into good prognosis group （82 patients with an mRS score of <3 points） and poor prognosis group （30 patients with an mRS score of ≥3 points）. Results Compared with the good prognosis group， the poor prognosis group had a significantly higher proportion of patients with an age of ≥70 years， a mean systolic blood pressure of ≥165 mmHg， a fasting blood glucose level of ≥7.5 mmol/L， an NIHSS score of ≥12 on admission， intimal calcification， medial calcification， high calcification， hemorrhagic transformation， and an infarct volume of ≥50 mm3 （P<0.05）. The multivariate logistic regression analysis showed that NIHSS score ≥12 on admission， intimal calcification， hemorrhagic transformation， and infarct volume ≥50 mm3 were risk factors for poor prognosis （P<0.05）. Conclusion Intimal calcification of the carotid artery may be associated with the poor short-term prognosis of AIS patients， which can be used as a new noninvasive indicator for predicting prognosis.
Prognosis

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Objective:To establish the predictive model for major adverse cardiovascular events(MACE) following endovascular repair in elderly patients with abdominal aortic aneurysm(AAA).Methods:The clinical data and postoperative MACE were retrospectively collected from elderly patients with AAA who underwent their first endovascular aneurysm repair(EVAR)in Beijing Hospital and Tibet Autonomous Region People's Hospital between January 2016 and December 2023.Patients were randomly divided into training and validation cohorts at a ratio of 7∶3.Predictive models were using logistic regression, LASSO regression, random forest, linear discriminant analysis, na?ve Bayes, k-nearest neighbor algorithm, support vector machine, decision tree, and AdaBoost.Models were evaluated using receiver operating characteristic(ROC)curves.Results:A total of 171 elderly AAA patients were enrolled, aged 60 to 94 years(mean 73.0 ± 7.5 years), of whom 145 were male.MACE occurred after EVAR in 30 patients(17.5%). LASSO regression identified monocyte count, history of coronary artery disease, the ratio of maximum AAA diameter to body mass index(DBR), neutrophil-lymphocyte count ratio(NLR), and age as significant predictors, yielding an area under the ROC curve(AUC)of 0.816.Logistic regression achieved an AUC of 0.813 in the training cohort and 0.772 in the validation cohort.Among all models, AdaBoost demonstrated the best performance, with an AUC of 0.92 in the validation cohort.Conclusions:Age, monocyte count, DBR, NLR and creatinine could predict the occurrence of MACE after EVAR in AAA patients.The AdaBoost model provides the most accurate prediction of postoperative MACE.

County medical community serves as pivotal instruments for the hierarchical diagnostic and treatment system. Since their nationwide implementation in December 2023, there has been a pressing demand for governance theories to direct practical applications. Based on polycentric-collaborative governance theory, this study articulated a framework that modeled county medical community as accountable care organizations, anchored by a foundation of primary health care and a polycentric-collaborative governance structure. The framework encompassed critical dimensions, including problem orientation, diverse governance actors, multi-dimensional governance mechanisms, governance objectives, and evaluative metrics. This research also introduced 17 governance instruments, delineated 13 priority action fields, and pinpointed 5 potential reform areas, with a pronounced focus on bolstering governance capacity through value-based payment reforms and technological underpinnings of digital innovation. The framework′s viability and efficacy have been substantiated through a case study in Zhejiang Province. The framework presented herein could offer a comprehensive and systematic guide for county medical community practice, capturing the essence of the reform through a problem-oriented lens, fostering multi-actor involvement, and ensuring the harmonization of multi-dimensional governance mechanisms, thereby fortifying the reform′s systematic, integrative, and collaborative attributes.

Objective:To explore the therapeutic effect of anterior chamber puncture combined with laser peripheral iridectomy (LPI) on patients with acute primary angle closure glaucoma (PACG).Methods:A total of 85 patients (85 eyes) with acute PACG treated in the Qingdao Huangdao District Traditional Chinese Medicine Hospital from January 2019 to December 2022 were selected and divided into the study group (43 cases, treated with anterior chamber puncture combined with LPI) and the control group (42 cases, treated with drug antihypertensive combined with LPI) by random number table method. The best corrected visual acuity, intraocular pressure, corneal edema grade, central anterior chamber depth, angle opening range and postoperative complications were compared between the two groups.Results:Before surgery, there were no statistical differences in the best corrected visual acuity and intraocular pressure between the two groups ( P>0.05), and at 3, 6 and 12 months after surgery, the best corrected visual acuity and intraocular pressure in the two groups were significantly lower than those before surgery, and the study group were lower than those in the control group: (0.41 ± 0.09) logMAR vs. (0.47 ± 0.10) logMAR, (0.26 ± 0.05) logMAR vs. (0.31 ± 0.06) logMAR, (0.30 ± 0.07) logMAR vs. (0.34 ± 0.08) logMAR; (14.3 ± 3.6) mmHg(1 mmHg = 0.133 kPa) vs. (16.5 ± 3.2) mmHg, (15.0 ± 3.9) mmHg vs. (17.6 ± 3.6) mmHg, (17.4 ± 3.5) mmHg vs. (20.0 ± 3.8) mmHg, there were statistical differences ( P<0.05). Before surgery, there were no statistical differences between the two groups in central anterior chamber depth and angle opening range ( P>0.05), and at 3, 6 and 12 months after surgery, the central anterior chamber depth and angle opening range were higher in the both groups and the study group were higher than those in the control group: (2.94 ± 0.46) mm vs. (2.72 ± 0.45) mm, (3.01 ± 0.50) mm vs. (2.89 ± 0.48) mm, (2.93 ± 0.44)mm vs. (2.81 ± 0.47) mm; (244.0 ± 26.0)° vs. (236.1 ± 29.5)°, (256.5 ± 27.4)° vs. (248.3 ± 30.3)°, (250.7 ± 29.0)° vs. (241.5 ± 25.4)°, there were statistical differences ( P<0.05). There was no significant difference in preoperative corneal edema grade between the two groups ( P>0.05), and the corneal edema grade in the study group was lower than that in the control group at 3 d after operation, there was statistical difference ( P<0.05). The complication rate was 4.65%(2/43) in the study group and 14.29% (6/42) in the control group, there was no statistical difference ( χ2 = 2.31, P>0.05). Conclusions:The combination of anterior chamber puncture and LPI surgery is beneficial for controlling intraocular pressure, improving vision, and restoring anterior chamber depth in PACG patients, and its clinical efficacy is certain.

Objective To screen the key N6-methyladenosine(m6A)methylation related genes in renal clear cell carcinoma(ccRCC),and to study their expression and relationship with the prognosis,migration and invasion of renal clear cell carcinoma.Methods The RNA sequencing data and clinical data of ccRCC and ad-jacent tissues were downloaded from the Cancer Genome Atlas(TCGA)and GTEx(Genotype-Tissue Expres-sion).The expression profile and prognosis were analyzed with R 4.1.1,and the key genes were screened.Clinical specimens of 10 patients with ccRCC were collected.The mRNA and protein expressions were detec-ted by RT-qPCR and immunohistochemistry,respectively.In human ccRCC cell line RCC23,siRNA was used to knock down key genes,and CCK-8 was used to detect the survival rate of cells.Scratch test and Trans well test were used to detect the migration and invasion of cells,respectively.Results Among the 19 m6A methyl-ation related genes,only insulin-like growth factor 2 mRNA binding protein 3(IGF2BP3)was highly ex-pressed in cancer tissues,and the high expression was significantly positively correlated with poor prognosis.The high expression of IGF2BP3 was verified in clinical specimens by RT-qPCR and immunohistochemistry.After knockdown of IGF2BP3 by siRNA,the survival rate of RCC23 cells decreased significantly,and the mi-gration and invasion ability of cut cells decreased.Conclusion These results suggest that IGF2BP3 may be an effective biomarker and potential drug target for predicting the prognosis of patients with ccRCC.

Objective To investigate the influence of herbal compatibility on the chemical composition of Banxia Houpo Decoction(BHD)using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS)coupled with multivariate statistical analysis,and to evaluate the neuroprotective effects of key differential components against neuroinflammation and neuronal injury using cellular models.Methods(1)UPLC-MS analysis of chemical constituents in co-decoction and separated decoction(individual herbs decocted separately then combined)of Banxia Houpo Decoction,followed by orthogonal partial least squares-discriminant analysis(OPLS-DA)to identify differential components before and after herbal compatibility(2)BV2 microglia were stimulated with lipopolysaccharide(LPS)to establish a neuroinflammation model.Cell viability was assessed using the Cell Counting Kit 8(CCK-8)assay.Nitric oxide(NO)levels were measured by the Griess method,while TNF-α and IL-1β concentrations were quantified via enzyme-linked immunosorbent assay(ELISA).(3)SH-SY5Y neuronal cells were co-cultured with conditioned medium from LPS-stimulated BV2 cells(LPS-CM)to model neuronal injury.Cell viability was evaluated using the CCK-8 assay.Results UPLC-MS/OPLS-DA identified 11 differential components between compatibility methods,with honokiol and magnolol showing significant post-compatibility increases.In the neuroinflammation model,LPS stimulation elevated NO,TNF-α and IL-1 β levels in BV2 cells,which were suppressed by 5,10 μg/mL honokiol or magnolol.In the neuronal injury model,LPS-CM induced SH-SY5Y apoptosis,while 5,10 μg/mL honokiol or magnolol attenuated this damage.Conclusion Herbal compatibility significantly enhances honokiol and magnolol content in BHD.These components inhibit microglial inflammatory responses and neuronal apoptosis,suggesting their role as primary active constituents mediating BHD's neuroprotective effects.