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.

As a patented characteristic medicine of Yi ethnic minority， Pingxuan capsules have the effects of nourishing the liver and kidney， pacifying the liver， and subduing Yang. With the main indications of dizziness， headache， palpitations， tinnitus， insomnia， dreaminess， waist and knee soreness caused by liver-kidney deficiency and liver Yang upward disturbance， Pingxuan capsules are widely used in the treatment of posterior circulation ischemic vertigo， vestibular migraine， benign paroxysmal positional vertigo. However， the current knowledge is limited regarding the efficacy， syndrome differentiation， and safety of this medicine. On the basis of summarizing the experience of clinicians and the existing evidence， this study invites clinical experts of traditional Chinese and Western medicine， pharmaceutical experts， and methodological experts from relevant fields across China to conduct evidence-based evaluation of Pingxuan capsules. The evaluation follows the Specifications for the Development of Clinical Expert Consensus on Chinese Patent Medicines issued by the Standardization Office of the China Association of Chinese Medicine， and reaches 5 recommendations and 16 consensus suggestions. The consensus clarifies the clinical applications， efficacy， dose， course of treatment， combination of medicines， precautions， and contraindications of Pingxuan capsules in the treatment of vertigo and explains the safety of clinical application. This consensus is applicable to clinicians （traditional Chinese medicine， Western medicine， and integrated traditional Chinese and Western medicine） and pharmacists in tertiary hospitals， secondary hospitals， and community-level medical and health institutions across China， providing a reference for the rational use of Pingxuan capsules in the treatment of vertigo. It is hoped that the promotion of this consensus can facilitate the rational use of drugs in clinical practice， reduce the risk of drug use， and give full play to the advantages of Pingxuan capsules in the treatment of vertigo diseases. This consensus has been reviewed and published by the China Association of Chinese Medicine， with the number GS/CACM330-2023.

Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE^-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.

Objective To discuss the effects of the"twelve needles for hands and feet"acupuncture on the brain response mechanism and acupoint specificity in hemiplegic patients after ischemic stroke using fMRI.Methods Totally 43 inpatients from Dongzhimen Hospital of Beijing University of Chinese Medicine from December 2018 to March 2023 were included.The included patients were randomly divided into a true acupoint group of 23 cases and a fake acupoint group of 20 cases using the random number table method for clinical scale evaluation and magnetic resonance scanning.The true acupoint group received"twelve needles for hands and feet"acupuncture;the fake acupoint group was treated with acupuncture by opening 1 inch next to the meridian point,once a day,for consecutive 10 d.Intervention completed,excluding subjects who fell out during the intervention process,had unsatisfactory MRI data quality and had incomplete clinical scales,and conducting data processing and analysis.Bilateral anterior central gyrus(PreCG),amygdala(AMYG),caudate nucleus(CAU),putamen lenticularis(PUT),pallidus lenticularis(PAL)and thalamus(THA)were selected as regions of interest(ROI),and the changes in Granger causality(GC)and differences in scale scores between the two groups before and after treatment were compared.Results After intervention in the true acupoint group,the GC of CAU.R → PreCG.R,AMYG.R → PAL.R was stronger than before intervention,and the GC of THA.L→PAL.L,AMYG.R→THA.R in the true acupoint group was weaker than before intervention(P<0.05);after intervention with fake acupoints,the GC of AMYG.R→PUT.L in the false acupoint group was stronger than before intervention,and the GC of THA.L→PreCG.R,AMYG.L→CAU.L was weaker than before intervention(P<0.05);the GC of THA.R→PAL.L before intervention was stronger than false acupoint group,the GC of CAU.L→PreCG.R,PUT.L→PreCG.R before intervention was weaker than fake acupoint group(P<0.05);the GC of CAU.R→PreCG.R,THA.L→PreCG.R,AMYG.R→CAU.L,THA.L→PAL.R,AMYG.L→THA.L after intervention in the true acupoint group was stronger than the false acupoint group,and the GC of AMYG.R→AMYG.L after intervention in the true acupoint group was weaker than the fake acupoint group(P<0.05).Conclusion"Twelve needles for hands and feet"acupuncture can stimulate preferential compensation of the right motor circuit,bilateral basal ganglia remodeling,and balance regulation of excitatory inhibitory effects on the thalamus in patients with radiation-induced coronary stroke,thereby improving the degree of motor dysfunction and neurological deficits;acupuncture at acupoints stimulates brain activity more than at non-acupoints,indicating acupoint specificity.

Objective:To investigate the efficacy of a decellularized extracellular matrix (dECM)-quaternized chitosan (QCS)-gelatin (Gel) composite scaffold loaded with growth factors in repairing diabetic foot wounds in a rat model.Methods:A dECM-QCS-Gel composite scaffold (referred to as GDQ scaffold) was fabricated using a 3D bioprinter. Forty 8-week-old male Sprague-Dawley (SD) rats were selected to establish a diabetic foot wound model with a diameter of approximately 1 cm. Based on the treatment methods for diabetic foot wounds, the rats were divided into five groups: Control group (no treatment), Exosome group (wound covered with exosome suspension), Exosome+GDQ group (wound covered with GDQ scaffold loaded with exosome suspension), GDQ group (wound covered with GDQ scaffold alone), and Growth factor+GDQ group (wound covered with GDQ scaffold loaded with recombinant human basic fibroblast growth factor suspension). The wound healing rate was measured. Histological analysis was performed by HE staining and Masson staining. ELISA kits were used to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 in wound tissues from each group. Protein expression levels of MIP-1 and MIP-2 genes were also assessed.Results:The wound healing rate of the growth factor+GDQ group on the 21st d was 94.89%±1.21%, which was higher than that of the exosome+GDQ group ( P<0.05). With increasing repair time, the expression levels of TNF-α, IL-1β and IL-6 in each group all decreased, while IL-10 increased in all groups ( P<0.05). Among them, the exosome+GDQ group (TNF-α: 46.54±1.26 pg/ml, IL-1β: 225.79±7.29 pg/ml, IL-6: 142.81±4.02 pg/ml and IL-10: 117.36±0.95 pg/ml, P<0.001) and the growth factor+GDQ group (TNF-α : 40.01±1.64 pg/ml, IL-1β: 209.15±2.98 pg/ml, IL-6: 138.50±2.61 pg/ml and IL-10: 127.66±1.23 pg/ml, P<0.05); The levels of TNF-α and IL-1β in the exosome+GDQ group were both lower than those in the exosome+GDQ group ( P<0.05), and IL-10 was higher than that in the exosome+GDQ group ( P<0.05). On the 7th d the control group showed the highest expression levels of MIP-1α and MIP-2. All other groups had lower levels, with the growth factor+GDQ group showing the lowest among them. On the 21st d, the inflammatory protein expression in the growth factor+GDQ group had further decreased and remained lower than in all other experimental groups. Conclusions:The GDQ composite scaffold, when combined with bioactive factors, can synergistically reduce inflammation in diabetic foot wounds and promote wound healing. The scaffold loaded with basic fibroblast growth factor demonstrated superior therapeutic efficacy compared to the scaffold loaded with exosomes.

Objective:To establish reference values for clot waveform analysis (CWA) and analyze their diagnostic efficacy in distinguishing acquired hemophilia A (AHA) and lupus anticoagulant (LA)-positive patients.Methods:Case-Control Study. A total of 391 healthy individuals(260 males and 131 females) with a mean age of 45.53±14.85 years were enrolled at Nanyang central Hospital between January 6, 2023 and October 10, 2024. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were measured to establish reference ranges for the CWA parameters, including maximal reaction velocity (Min1), maximal reaction acceleration (Min2), and maximal reaction deceleration (Max2). A total of 158 definitively diagnosed AHA and LA-positive patients (mean age:42.46±14.83 years), including 34 AHA patients and 124 LA-positive patients, were recruited. The Mann Whitney U test was used to analyze the differences in the CWA parameters between the two groups. The diagnostic efficacy of CWA parameters in distinguishing AHA and LA-positive patients was evaluated using the area under the receiver operating characteristic(ROC) curve AUC and the cut-off values were calculated. Results:The reference values for PT-Min1, APTT-Min1, APTT-Min2, APTT-Max2, TT-Min1, TT-Min2, TT-Max2 were 203.41-516.89, 144.63-324.03, 526.46-1 190.03, -404.96±157.22, 159.17±60.34, 272.29-686.99, and -289.47--113.76, respectively. Compared with the CWA parameters in AHA patients, APTT-Max2 was significantly lower in LA-positive patients [-422.74(-577.50, -239.22) vs. -68.87(-92.85,30.28), Z=-7.43, P<0.01], while PT-Min1, APTT-Min1, APTT-Min2, TT-Min1, TT-Min2 were significantly elevated [287.01(188.03, 382.50) vs. 107.45(90.20, 151.39), 972.88(601.20, 1 351.19) vs. 229.10(118.38, 371.67), Z=6.68, 6.69, all P<0.01]. ROC analysis demonstrated the APTT-CWA parameter exhibited high diagnostic efficacy in patients with AHA (AUC>0.900 for both).Additionally, APTT-Min1 and APTT-Max2 were found to be useful in distinguishing between AHA patients and those with LA-positive status accompanied by APTT prolongation (AUC=0.660, 0.700, respectively). Conclusions:Reference values for CWA parameters were successfully established. The APTT-CWA is useful for differentiating between AHA and LA-positive patients and APTT-Max2 demonstrated a good diagnostic value in differentiating AHA patients from those with LA-positive status accompanied by APTT prolongation.

Objective To investigate the value of gemstone spectral CT multiparameter for risk assessment in acute pulmonary embolism(APE).Methods A total of 83 patients diagnosed with APE were categorized into three groups based on the European Society of Cardiology(ESC)guidelines:high-risk group(n=23),medium-high-risk group(n=29),and medium-low-risk group(n=31).The spectral CT multiparameters for each group were subsequently analyzed and compared.The predictive value of the region of interest perfusion defect iodine group value(ROI vPD),whole lung mean perfusion iodine group value(vMeanIP),and lung perfusion defect volume ratio(rPDvol)in high-risk APE patients were assessed using receiver operating characteristic(ROC)curves.Pearson correlation was employed to analyze the correlation of gemstone spectral CT multiparameter with pulmonary artery obstruction index(PAOI)and right ventricle/left ventricle diameter ratio(rRVD/LVD).Results Whole lung minimum perfusion iodine group value(vMinIP),whole lung maximum perfusion iodine group value(vMaxIP),vMeanIP,rPDvol and right ventricle/left ventricle volume ratio(rRVV/LVV)exhibited significant differences across all groups.The area under the curve(AUC)for ROI vPD,vMeanIP,and rPDvol in high-risk APE patients were 0.792,0.831,and 0.884,respectively.The sensitivity and specificity for ROI vPD(≤0.3),vMeanIP(≤1.1),and rPDvol(≥23.7％)were recorded at 95.7％and 60.0％,78.3％and 75.0％,as well as 91.3％and 75.0％,respectively.Simultaneously,the gemstone spectral CT multiparameter exhibited correlations with PAOI and rRVD/LVD.Conclusion The gemstone spectral CT multiparameter can be utilized to evaluate the severity and progression of patients with APE.

Objective To construct an in vitro co-culture model of gastric cancer organoids and cancer-associated fibroblasts(CAFs),and investigate the role of cancer-associated fibroblasts in the proliferation and chemotherapy resistance of gastric cancer organoids.Methods Tumor tissues from 12 gastric cancer patients undergoing surgical treatment in Department of General Surgery of Second Affiliated Hospital of Army Medical University from February 2023 to March 2024 were collected to construct gastric cancer organoids using 3D culture.HE staining was used to observe the morphology,and immunohistochemical assay was employed to determine the expression of cytokeratin CK7,carcinoembryonic antigen(CEA),and proliferation marker Ki-67.After CAFs derived from the same patient were cultured,observed for their morphology under a light microscope,and detected for the phenotype by flow cytometry,the cells were co-cultured with gastric cancer organoids in a 1:1 ratio.Phase-contrast microscopy was applied to observe the growth of the organoids and analyze the number,average diameter,and total area.Then,organoids cultured alone served as the control group.After the control and co-culture groups were treated with chemotherapy drugs,5-fluorouracil and oxaliplatin,for 48 h,the viability and apoptosis of organoids were assessed with CellTiter-Glo??3D assay and CellEvent? Caspase 3/7 activity,respectively.Results Gastric cancer organoids and CAFs were successfully established from 10 gastric cancer patient-derived samples.The gastric cancer organoids exhibited morphological characteristics consistent with the corresponding primary tumors,and showed positive expression of CK7,CEA,and Ki-67.CAFs displayed typical spindle-shaped morphology and exhibited the phenotypic markers CD326-,CD45-,CD31-,α-SMA+,CD73+,CD90+,and CD105+.Compared to the organoids cultured alone,the organoids co-cultured with CAFs showed more formation of organoids,in larger average diameter,and taking larger total area(P<0.05).After the treatment of 5-fluorouracil and oxaliplatin,the half-maximal inhibitory concentration(IC50)was 10.66 and 3.26 μmol/L,respectively in the control group,while was 46.23 and 91.11 μmol/L in the co-culture group.Additionally,the number of CellEvent? Caspase 3/7 positive apoptotic cells was significantly less in the co-culture group than the control group.Conclusion Compared with individually cultured gastric cancer organoids,the co-culture model of gastric cancer organoids and CAFs better simulates the pro-tumor proliferation and drug resistance effects of in vivo tumor microenvironment.

Objective To explore the impact of electrostimulation biofeedback therapy combined with pelvic floor muscle training on postpartum pelvic floor function in first vaginal birth women.Methods A retrospective analysis was conducted on the clinical data of in first vaginal birth women.The control group(n=49)received pelvic floor muscle training,while the observation group(n=49)received electrostimulation biofeedback therapy in addition to pelvic floor muscle training.Com-parisons were made between the two groups before treatment and 10 weeks after treatment in terms of uterine artery blood flow indicators[peak systolic velocity(PSV),resistance index(RI),and pulsa-tility index(PI)of uterine artery],serological indicators[C-reactive protein(CRP),interleukin-6(IL-6)],pelvic floor ultrasound indicators(bladder neck mobility,anteroposterior diameter of levator hi-atal area,levator hiatal volume),pelvic floor function[Pelvic Floor Distress Inventory-20(PFDI-20)],pelvic floor muscle strength,and quality of life[Short Form-36 Health Survey(SF-36)].The costs of the two treatments were compared at the end of treatment.Results Ten weeks after treatment,PSV,muscle potential values of type Ⅰ and type Ⅱ muscles,and SF-36 scores were significantly increased in both groups compared with those before treatment,with the observation group showing higher values than the control group(P＜0.05).RI,PI,CRP,IL-6,bladder neck mobility,anteroposterior di-ameter of levator hiatal area,levator hiatal volume,and PFDI-20 scores were decreased in both groups compared with those before treatment,with the observation group showing lower values than the control group(P＜0.05).After treatment,the treatment cost in the observation group was significantly higher than that in the control group(P＜0.05).Conclusion Electrostimulation biofeedback ther-apy combined with pelvic floor muscle training can effectively improve postpartum uterine artery blood flow indicators,serological indicators,pelvic floor ultrasound indicators,pelvic floor muscle strength,and promote pelvic floor function recovery in first vaginal delivery women.