BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

BACKGROUND:Plate fixation is the mainstream method for the surgical treatment of distal femoral fractures.The intramedullary nailing has the advantages of minimally invasive,such as less soft tissue injury and bone blood supply destruction.At the same time,it is a central fixation and has better biomechanical effect.Therefore,retrograde intramedullary nailing has become another option for the internal fixation of distal femoral fractures.OBJECTIVE:The biomechanical characteristics of new retrograde intramedullary nail on lateral femur condyle,common femoral retrograde intramedullary nail,and lateral femur condyle anatomical locking plate for the treatment of A2-type distal femoral fractures were compared using finite element analysis,and the advantages of new retrograde intramedullary nail on lateral femur condyle was studied.METHODS:A new retrograde intramedullary nail on lateral femur condyle was designed,which was inserted into the bone cortex in front of the insertion point of the lateral collateral ligament of the lateral femoral condyle.A CT scan was performed on the lower limb bone of a male volunteer,and a three-dimensional model of the femur was established.The model was then segmented to create a three-dimensional model of a femoral distal A2-type fracture,The three-dimensional models of small(small group),standard type retrograde intramedullary nail on the lateral femoral condyle(standard group),common retrograde intramedullary needle(common group),and lateral femur condyle anatomical locking plate(plate group)were established respectively.The axial stresses of 600,1 800 N and the torsional load of 4 000,8 000 N·mm were applied to the models,and the displacement and stress of femur and the displacement,stress and shear force of internal fixators were observed in each group.RESULTS AND CONCLUSION:(1)When subjected to axial load of 600 and 1 800 N,the femoral peak displacement,the femoral peak stress,and the peak stress of interal fixation in the standard group were the lowest among the four groups.(2)When subjected to torsional load of 4 000 and 8 000 N·mm,the femoral peak displacement and peak displacement of the internal fixation in the standard group were the lowest among the four groups.(3)Compared with femoral lateral condylar locking plate and common retrograde intramedullary needle,the new retrograde intramedullary needle on lateral femur condyle has mechanical advantages of reducing stress concentration and decreasing the risk of internal fixation failure.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective To explore the number of peripheral blood regulatory T cells (Treg) in patients with chronic kidney disease (CKD) and its correlation with vascular calcification. Methods This was a single-center, cross-sectional, and observational study. Non-dialysis patients with CKD treated at Zhongshan Hospital, Fudan University from March 2021 to March 2022 were enrolled. Abdominal aortic calcification (AAC) was assessed using lateral abdominal X-ray. Number of Treg and cytokine levels were measured by flow cytometry. Logistic regression analysis was performed to evaluate the related factors for AAC in CKD patients. Results A total of 83 patients were included, aged 17–86 years, with 57 males (68.7%). The distribution of CKD stages was as follows: stage G1 in 7 patients (8.4%), stage G2 in 17 patients (20.5%), stage G3 in 21 patients (25.3%), stage G4 in 19 patients (22.9%), and stage G5 in 19 patients (22.9%). No AAC was observed in patients with stages G1 and G2, while the prevalence of AAC in patients with stages G3, G4, and G5 was 23.8%, 21.1%, and 26.3%, respectively. Compared with stage G1 patients, those with stages G3–5 showed decreased number of peripheral blood Treg and elevated levels of interleukin (IL)-6 and IL-17F (P＜0.05). The area under the receiver operating characteristic curve for number of peripheral blood Treg in predicting AAC in CKD patients was 0.766 (95%CI 0.652–0.879, P＝0.002). Logistic regression analysis showed that decreased number of Treg was related factor for AAC in CKD patients (OR＝0.957, 95%CI 0.922–0.992, P＝0.018). Conclusion As CKD progresses, number of peripheral blood Treg significantly decreases, which is correlated with AAC in CKD patients.

Objective To explore the correlation between changes in spleen volume and stiffness before and after transjugular intrahepatic portosystemic shunt (TIPS) and the occurrence of hepatic encephalopathy. Methods A retrospective study was conducted on 104 patients who underwent TIPS in the Department of Interventional Therapy, Zhongshan Hospital, Fudan University, from January 1, 2023 to July 30, 2024. Spleen volume and stiffness were measured before and after surgery. Patients were divided into the overt hepatic encephalopathy (OHE) group and the non-OHE group. Univariate and multivariate logistic regression analyses were used to identify factors correlated with OHE after TIPS. The predictive values of the related factors of OHE were evaluated using receiver operating characteristic (ROC) curves. Results OHE occurred in 34 patients (32.69%). Compared with the non-OHE group, the OHE group had a smaller percentage reduction in spleen volume after TIPS (P＜0.001), but there was no statistically significant difference in the percentage reduction in spleen stiffness between the two groups. Multivariate logistic regression analysis revealed that the percentage reduction in spleen volume was correlated with postoperative OHE (OR＝0.90, P＜0.001). ROC analysis showed that the area under the curve (AUC) for spleen volume reduction percentage in predicting postoperative OHE was 0.773, superior to spontaneous portosystemic shunt (SPSS; Z＝2.088, P＝0.037). Conclusions Reduction in spleen volume after TIPS may be a protective factor against hepatic encephalopathy, while changes in spleen stiffness were not found to be correlated with its occurrence.

Chaihu Guizhi Ganjiangtang was first recorded in the Treatise on Cold Damage （Shang Han Lun）. This prescription is composed of Bupleuri Radix， Scutellariae Radix， Cinnamomi Ramulus， Zingiberis Rhizoma， Trichosanthis Radix， Ostreae Concha， and Glycyrrhizae Radix et Rhizoma. It has the effects of soothing Lesser Yang， warming the spleen， and stimulating the generation of body fluid. It is mainly used to treat digestive tract diseases such as chronic cholecystitis （CC）， irritable bowel syndrome， and non-alcoholic fatty liver disease. Dyspepsia caused by CC presents a variety of gastrointestinal symptoms such as abdominal pain， poor appetite， postprandial fullness， aversion to greasy food， soft stool， and bitter mouth， being a type of biliary dyspepsia. In modern medicine， dyspepsia caused by CC is mainly managed by medical treatment and surgical treatment. Internal medicine mainly focuses on reducing inflammation， promoting the function of gallbladder， resolving stones， alleviating spasms， and relieving the pain for CC， demonstrating definite short-term efficacy but suffering from single effects， high recurrence rate， and poor compliance. Although surgical treatment can cure cholecystitis， it is accompanied by the increased incidence of adverse events such as abdominal pain， diarrhea， and dyspepsia. Modern clinical studies have confirmed that Chaihu Guizhi Ganjiangtang can significantly alleviate the symptoms such as abdominal pain and dyspepsia of CC patients. Pharmacological studies have found that Chaihu Guizhi Ganjiangtang mainly contains active ingredients such as Bupleuri Radix saponins， baicalin， cinnamaldehyde， gingerol， Trichosanthis Radix polysaccharide， Ostreae Concha polysaccharide， and Glycyrrhizae Radix et Rhizoma total flavonoids. Chaihu Guizhi Ganjiangtang can ameliorate the symptoms of dyspepsia caused by CC by inhibiting inflammatory responses， improving gallbladder contraction and gastrointestinal motility， regulating the bile acid-intestinal flora axis and the brain-gut axis， and modulating blood lipids through multiple targets. By reviewing the previous literature， this article summarizes the research progress in the treatment of dyspepsia caused by CC with Chaihu Guizhi Ganjiangtang and its main active ingredients as well as the pathogenesis of this disease and puts forward the shortcomings and improvement strategies for the current research. The review aims to provide a reference for the further research on Chaihu Guizhi Ganjiangtang in the treatment of dyspepsia caused by CC.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

OBJECTIVE To upgrade the drug traceability code management system for a pediatric hospital under the “payment by code” background， aiming to comprehensively enhance traceability integrity， efficiency， and compliance. METHODS Taking Xiamen Children’s Hospital as the implementation setting， a before-and-after control design was adopted to construct an intelligent drug traceability code management system through systematic upgrades involving the technology platform， core mechanisms， and coordination with medical insurance. Key interventions included： upgrading a traceability code management platform and designing a dynamic code pool； innovating differentiated traceability mechanisms for routine， split-dose， and special drugs； establishing a tiered early-warning and emergency response system； and constructing a data coordination and quality control system. The drug traceability code upload rate served as the primary outcome. Process indicators such as the root causes distribution of failed uploads and the duration of medication returns， and a comprehensive outcome （the number of insurance-flagged abnormal prescriptions） were also analyzed. The data between the baseline period （April 2025） and the observation period （June-August 2025） were compared and evaluated. RESULTS After the upgrade， the overall upload rate of drug traceability codes increased from 9.21% （baseline） to 99.86% （August 2025）. The upload rate of traceability codes in previously unmanaged areas， such as the inpatient pharmacy and pharmacy intravenous admixture services， soared from 0 to nearly 100%. The proportion of non-uploads due to system issues fell from 66.44% （June 2025） to 2.62% （August Additionally， the number of insurance-flagged） abnormal prescriptions dropped sharply from 2 275.00 in the first “payment by code” policy month （July 2025） to 212.00 by the end of the observation period （August 2025）， a 90.70% decrease. CONCLUSIONS The developed management system effectively addresses complex scenario challenges such as high-frequency drug splitting. It significantly enhances traceability code upload performance and ensures a high degree of compliance with medical insurance data requirements. These outcomes contribute to proactive risk mitigation against insurance claim denials and demonstrate a concurrent optimization of pharmacy operations.

[摘 要] 目的：制备低亲和力的CD117 CAR-T细胞，探讨其对急性髓系白血病（AML）细胞Kasumi-1的体外杀伤效应。方法：调取CD117低亲和力抗体巴佐利单抗（barzolvolimab）和Fab-79D VH和VL序列，设计VH-(G4S)3-VL结构的单链抗体，分别构建带4-1BB共刺激分子的经典二代CAR分子，经基因合成后分别亚克隆至pMFG逆转录病毒载体，获得CD117-79D CAR和CD117-0159 CAR质粒。将两种CAR质粒分别包装制备逆转录病毒，检测其滴度合格后转导活化后的T细胞，构建CD117-79D CAR-T和CD117-0159 CAR-T细胞，采用流式细胞术检测两种CAR-T细胞的阳性率。将未转导T细胞与两种CAR-T细胞分别与CD117+ Kasumi-1细胞共培养，通过流式细胞术检测Kasumi-1细胞凋亡率，以评估两种CAR-T细胞的抗肿瘤活性。结果：成功构建CD117-79D CAR-T和CD117-0159 CAR-T细胞，其阳性率分别为（59.4 ± 2.6）%、（62.5 ± 1.2）%。未转导T细胞、CD117-79D CAR-T和CD117-0159 CAR-T细胞体外培养均能稳定增殖，且三者的增殖能力均无显著差异（均P > 0.05）。体外杀伤Kasumi-1细胞结果显示，不同效靶比条件下，CD117-79D CAR-T和 CD117-0159 CAR-T细胞较未转导T细胞展现出显著增强的杀伤能力（P < 0.05或P < 0.01），但两种CAR-T细胞的杀伤效率无显著差异（P > 0.05）。结论：成功构建低亲和力的CD117-79 CAR-T和CD117-0159 CAR-T细胞，体外实验证实其可有效杀伤CD117+ Kasumi-1细胞，为AML的靶向治疗提供了实验依据。

ObjectiveBased on the clinical characteristics of chronic gouty arthritis （CGA） in both traditional Chinese and western medicine， this study aims to systematically evaluate the clinical concordance of existing CGA animal models， providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure， Wanfang， VIP Chinese Science and Technology Periodical Database （VIP）， and PubMed， all relevant literature on CGA animal models was collected. Based on the guidelines， the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes， and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction， high-protein diet induction （poultry lack urate oxidase）， and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature， the traditional Chinese and western medicine scoring data of each model were extracted， and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%， respectively. Among them， the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection， achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA， they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore， in the future， it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria， providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.