ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Objective:To investigate the predictive value of a nomogram based on multimodal CT parameters for the outcome of endovascular therapy (EVT) in patients with acute vertebrobasilar artery occlusion (AVBAO).Methods:Patients with AVBAO underwent EVT at Xuzhou Central Hospital from January 2021 to March 2024 were included retrospectively. At 90 days after EVT, the modified Rankin Scale was used to evaluate clinical outcome. 0-3 points were defined as good outcome and 4-6 points were defined as poor outcome. Multivariate stepwise logistic regression model was used to screen for predictive variables. Then a nomogram was drawn and the prediction model was evaluated. Results:A total of 91 patients with AVBAO were included. There were 60 males (65.9%), aged 69.09±10.57 years. Thirty-eight patients (41.8%) had good outcome, 53 (58.2%) had poor outcome, and 35 (38.5%) died. Univariate analysis showed that there were significant differences in white blood cell count, neutrophil count, National Institutes of Health Stroke Scale (NIHSS) score, Glasgow Coma Scale (GCS) score, posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS), Basilar Artery on Computed Tomography Angiography (BATMAN) score, core infarct volume, mismatched volume ratio, onset to door time between the poor outcome group and the good outcome group (all P<0.05). The above indicators were included in a binary multivariate stepwise logistic regression model. The results showed that higher NIHSS scores (odds ratio [ OR] 1.154, 95% confidence interval [ CI] 1.070-1.244; P<0.001), lower BATMAN scores ( OR 0.626, 95% CI 0.416-0.943; P=0.025), and larger core infarct volumes ( OR 1.147, 95% CI 1.046-1.258; P=0.004) on admission were the independent risk factors for poor outcome. A nomogram was plotted using the above three independent risk factors as predictor variables. Its area under the receiver operating characteristic curve for predicting poor outcome was 0.942 (95% CI 0.894-0.990). The sensitivity and specificity were 81.1% and 97.4%, respectively. The calibration curve fluctuates within a small range around the ideal curve. A mean absolute error was 0.027 and a mean square error was 0.001. The clinical decision curve suggested that the model had good clinical applicability. The dynamic nomogram is shown in: https://yuepeng.shinyapps.io/VBAO_model/. Conclusion:The nomogram prediction model based on multimodal CT parameters has good predictive performance for poor outcome in patients with AVBAO after EVT.

Modern Chinese medicine studies have confirmed that the interaction between traditional Chinese medicine(TCM)and intestinal flora is the key to the treatment of diseases with tradi-tional Chinese medicine.This interplay includes such activities as:traditional Chinese medicine can be metabolized by intestinal flora into effective components with different biological activities from its precursors;TCM chemicals improve the composition of gut microbiota,consequently ameliorating its dysfunction as well as associated pathological conditions;and gut microbiota mediate the interactions between the multiple chemicals in TCM.There-fore,it becomes an important way to understand the modern sci-entific connotation of traditional Chinese medicine theory to study the pharmacological mechanism of the efficacy of traditional Chi-nese medicine by targeting Gut microbiota.

Objective To evaluate and compare the success rate and short-term clinical prognosis of transfemoral transcatheter aortic valve replacement(TF-TAVR)for patients with pure aortic regurgitation(PAR)of different annulus sizes.Methods This study is a single center retrospective study,selecting symptomatic PAR patients who received TF-TAVR treatment at Zhongshan Hospital Fudan University from September 2019 to September 2023.Based on preoperative CT results,all patients were divided into three groups:Group A(aortic annulus circumference＜80 mm),Group B(80 mm≤aortic annulus circumference＜85 mm),and Group C(aortic annulus circumference≥ 85 mm).The primary endpoint was success rate and 30d all-cause mortality,while the secondary endpoint was TAVR related complications.Results A total of 61 PAR patients were included in this study,including 27 in Group A,21 in Group B,and 13 in Group C.The overall success rate is 82.0％,and the 30 d all-cause mortality rate is 3.3％.The success rate of Group C patients was significantly lower(P=0.012),with higher rates of conversion to surgery and valve-in-valve implantation(P=0.022 and P=0.040).In terms of secondary endpoint events,there were no significant differences among the three groups in major bleeding events,major vascular complications,stroke,myocardial infarction,newly developed atrial fibrillation,implantation of new pacemakers,coronary artery occlusion,and postoperative moderate to severe perivalvular leakage(all P＞0.05).Conclusions The circumference of the aortic valve annulus is a key factor affecting the success rate of TF-TAVR in PAR,and PAR patients with an aortic valve annulus circumference less than 85mm may be more suitable for TF-TAVR.

Rheumatoid arthritis(RA)is a type of chronic autoimmune disease with unknown etiology and inflammatory syno-vitis.The occurrence and development of RA are closely related to intestinal mucosal immunity.Imbalance of intestinal flora,impaired intestinal barrier integrity,production of local autoantibodies and changes of immune cells in the lamina propria are all potential risks of RA.We explored the relationship between intestinal mucosal immunity and RA(gut-joint axis)in detail,with respect to provide novel thought and theoretical basis for the treatment of RA.

Objective To investigate the inhibition of gigantol on corneal neovascularization(CNV)in rats after corneal alkali burn.Methods Animal models of corneal alkali burn were made with SD rats,which were divided into normal control group,model control group,low-concentration gigantol group,high-concentration gigantol group and aflibercept group,with 10 rats in each group.The rats in low-concentration gigantol group,high-concentration gigantol group and aflibercept group were treated with 2.5 mg/0.05 mL gigantol,5 mg/0.05 mL gigantol,and 2 mg/0.05 mL aflibercept by subconjunctival injection after modeling.The CNV,corneal opacity score,and thickness of the cornea were observed and compared on the 3rd,7th,and 14th days after alkali burn.The ratio of CNV area to corneal area was calculated.On the 14th day,all rats were sacrificed.Hematoxylin and eosin staining and immunohistochemistry were used to detect the expression of CD34 and VEGF.The protein expression of VEGF,IL-1β,and TNF-α was detected by ELISA.Results On the 7th and 14th days after alkali burn,the percentages of CNV to total corneal area in low-concentration gigantol group,high-concentration gigantol group and aflibercept group were significantly smaller than those in model control group(all P＜0.05).On the 14th day,the corneal opacity score was lower in high-concentration gigantol group than model control group(P＜0.05).The corneal thickness in model control group and low-concentration gigantol group were significantly greater than that in normal control group(all P＜0.001).However,the corneal thickness in high-concentration gigantol group and aflibercept group were not significantly different from that in normal control group(all P＞0.05).In addition,the protein expression of VEGF,IL-1β,and TNF-α in corneal tissues in low-concentration gigantol group,high-concentration gigantol group and aflibercept group were significantly lower than that in model control group(all P＜0.01).Conclusions Gigantol administration by subconjunctival injection can inhibit the formation of CNV in rats after alkali burn and promote absorption of the corneal edema.

Colorectal cancer is the most common malignant tumor of digestive tract, and BRAF V600E mutations occur in approximately 10% of patients with metastatic colorectal cancer (mCRC). Cancer patients harboring this mutation have a unique molecular profile and clinical phenotype; they show poor response to systemic chemotherapy, insensitivity to single BRAF inhibitor, and short survival rate. It is important to develop new therapeutic agents and clinical strategies to improve the prognosis of these patients. This review mainly introduces treatment methods for BRAF V600E-mutated mCRC and rationally derived combinations of targeted agents and immunotherapy.

Objective:To explore the effects of posterior malleolar fracture fixation on the rotational stability of the ankle joint.Methods:A total of 20 fresh cadaveric specimens of lower limbs were anatomized to measure the area of attachment of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia. One healthy volunteer was selected to construct a finite element model for the intact tibiofibular and ankle joints and finite element models for posterior malleolar fracture with different posterior projection areas. A load of 600 N was vertically applied to the inferior calcaneus along the tibial mechanical axis. The contact area and maximum Von Mises stress of the distal tibial articular surface were analyzed to verify the validity of the model for the intact tibiofibular and ankle joints. In the finite element models for the posterior malleolar fracture (S, 1/2S, 1/4S, 1/8S and 1/16S model groups, with S standing for the complete projection area of the ligament complex on the posterior surface of the tibia), the width increase in the tibiofibular clear space was measured when a vertical load of 600 N and external rotation load of 5 N·m were applied to the ankle joint after the reduction and fixation of posterior malleolar fracture. The cutoff value of the posterior projection area of posterior malleolar fracture that could maintain the rotational stability of the ankle joint was assessed.Results:The measurement results of the cadaveric specimens showed that the area of attachment of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia was relatively large. It was attached to the posterolateral area of the distal tibia with the highest point located at (45.2±5.6)mm from the articular surface. With the increase in the distance from the joint line, the width of the posterior attachment area of the ligament complex was decreased. Results of the finite element analysis showed that in the finite element model for the intact tibiofibular and ankle joints, the tibiotalar joint contact area was 324.02 mm 2 and the maximum Von Mises stress was 4.495 1 MPa with a vertical load of 600 N. In the finite element models for the posterior malleolar fracture, the distal tibiofibular clear spaces of the S, 1/2S, 1/4S and 1/8S model groups increased by less than 2 mm following loading, while it was increased by 3.445 8 mm in the 1/16S model group. The cutoff value of the posterior tibial projection area that could maintain the rotational stability of the ankle joint was 1/8S. Conclusions:The attachment area of the posterior inferior tibiofibular ligament and transverse ligament complex to the posterior surface of the tibia is large. Both the axial stability and rotational stability of the ankle joint should be considered in the treatment selection for posterior malleolar fracture. Simple posterior malleolar fixation is recommended to restore the rotational stability and axial stability of the ankle joint when tibiofibular syndesmosis is unstable and the cutoff value is larger than or equal to 1/8, while tibiofibular syndesmosis screws must be implanted when tibiofibular syndesmosis is unstable and the cutoff value is less than 1/8.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.