OBJECTIVE To optimize the extraction process of standard decoction of Longan seed. METHODS The amount of water added， extraction time and extraction times as the influencing factors， using the extract yield， gallic acid content， corilagin content， ellagic acid content， half clearance concentration （IC50） of 1，1-diphenyl-2-picryl-hydrazyl （DPPH） free radical and IC50 of 2，2′-azino-bis （3-ethylbenzothiazoline-6-sulfonic acid） ammonium salt （ABTS） free radical as the evaluation indexes， the analytic hierarchy process （AHP）， criteria importarue though inter-criteria correlation （CRITIC） and AHP-CRITIC method were used to calculate the weight values of each index； the extraction process of Longan seed standard decoction was optimized by single factor test combined with orthogonal experiment； validation test was also performed. RESULTS According to the AHP-CRITIC method， the weights of the above indicators were determined to be 9.224%， 11.784%， 19.320%， 11.206%， 20.597%， 27.869%， respectively. The best process of standard decoction of longan seed was to add 14 times water for the first extraction and extract for 30 minutes； and 12 times water for the second and third extractions， and extract for 20 minutes. Average comprehensive score of the 3 times validation experiments was 97.96 and the RSD was 0.97% （n＝3）. CONCLUSIONS The process is simple to operate， stable and feasible， which can provide a experimental basis for the further development and utilization of standard decoction of longan seed.

OBJECTIVE To evaluate the long-term cost-effectiveness of insulin degludec and insulin aspart （IDegAsp） in patients with type 2 diabetes mellitus （T2DM） in China. METHODS A cost-effectiveness analysis was conducted from the perspective of the Chinese healthcare system， using the CORE diabetes model to simulate long-term （20-year） health and economic outcomes. Baseline cohort characteristics and treatment effect data were derived from the CREATE study. The prices of glucose- lowering drugs were obtained from medical insurance payment standards and the average winning bid prices in the follow-up round of the specialized centralized procurement for insulin， while the daily dosages were derived from the CREATE study. The costs of complications and utility values were obtained from published literature， with a discount rate of 5%. One-way sensitivity analysis， scenario analysis， and probabilistic sensitivity analysis were performed to verify the robustness of the results. RESULTS Patients switching from previous once-daily basal insulin regimens to IDegAsp therapy gained an incremental 0.190 quality-adjusted life year （QALY） with direct medical cost savings of 42 163.58 yuan. For those switching from premixed insulin therapies， IDegAsp treatment provided 0.130 incremental QALY and reduced direct healthcare costs by 41 129.11 yuan. The outcome was significantly influenced by the discount rate and the cost of complications. Probabilistic sensitivity analysis and scenario analysis confirmed the robustness of these findings. CONCLUSIONS Switching from previous daily basal insulin or premixed insulin regimens to IDegAsp in Chinese patients with T2DM can improve patients’ long-term health outcomes and achieve cost savings， making it a more cost-effective treatment option.

ObjectiveTo investigate the safety and efficacy of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in the treatment of cirrhotic patients with gastric varices and gastric-renal shunt （GRS）. MethodsThe patients who attended Beijing Ditan Hospital， Capital Medical University， due to liver cirrhosis and gastric varices from February to June 2023 were enrolled， and all patients were confirmed to have GRS and received endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips. The primary evaluation index was alleviation or disappearance of varicose veins after surgery， and the secondary evaluation indices were surgical completion and complications. ResultsA total of 11 patients were enrolled in this study， among whom there were 7 male patients and 4 female patients， with a median age of 55 years. Of all patients， 1 had Child class A liver function， 7 had Child class B liver function， and 3 had Child class C liver function. The maximum （median） diameter of the shunt was 8 mm， and the minimum （median） diameter of the shunt was 4 mm. The median blood flow velocity of the target vessel was 11 cm/s before treatment and 5 cm/s after occlusion with metal clips. The median amount of tissue adhesive injected was 2 mL， and the amount of lauromacrogol used was 1 mL. Disappearance of blood flow signals was observed in all patients after surgery （100%）， and the success rate of surgery was 100%. No patient experienced rebleeding after follow-up for 6 weeks. Gastroscopy at 1 month after surgery showed that gastric varices were eradicated or almost disappeared in 9 patients and were alleviated in 2 patients. ConclusionEndoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips is a feasible， safe， and effective treatment method for cirrhotic patients with gastric varices and GRS.

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

Objective:To screen the key genes related to the prognosis,diagnosis,and immune infiltration of the hepatocellular carcinoma(HCC)patients by bioinformatics analysis methods,and to analyze their potential therapeutic drugs.Methods:The HCC gene expression profile data and corresponding clinical informations of the HCC patients were downloaded from the Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA)database.The R software package limma was used to screen the differentially expressed genes(DEGs)in HCC.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the DEGs.The STRING database was used to construct the protein-protein interaction(PPI)network;the Cytoscape software was used to visualize the PPI network and screen the key genes;Kaplan-Meier survival curve and LASSO regression algorithm were used to identify the key genes related to the HCC prognosis;external data sets were used to validate their expressions and analyze the diagnostic efficacy;CIBERSORT algorithm was used to detect the relationship between the expression of prognosis-related key genes and HCC immune cell infiltration.The MiRNet and Network Analyst databases were used to construct the microRNA(miRNA)-key gene mRNA and transcription factors(TFs)-key gene mRNA molecular regulatory networks;CMap database was used to screen the potential small molecule drugs for HCC treatment.Results:A total of 146 DEGs were screened,including 30 upregulated genes and 116 downregulated genes.The GO functional enrichment analysis and KEGG pathway enrichment analysis results showed that the DEGs were significantly enriched in biological processes(BP)such as steroid,alkene compound,and hormone metabolism,as well as signaling pathways such as retinol metabolism,drug metabolism-cytochrome P450(CYP450),complement and coagulation cascades.The PPI network analysis identified 14 key genes,among which formimidoyltransferase cyclodeaminase(FTCD),secreted phosphoprotein 2(SPP2),thrombin-antithrombin complex(TAT),complement C6(C6),and cytochrome CYP450 family member 2C9(CYP2C9)were significantly associated with the prognosis,clinical pathological stage,and histological grade of the HCC patients and also had high diagnostic efficacy for HCC and were closely related to immune cell infiltration in HCC.Hsa-mir-182-5p,CUT-like homeobox 1(CUX1),early growth response 1(EGR1),SMAD family member 4(SMAD4),and tumor protein P53(TP53)were identified as the important regulators targeting the above-mentioned prognosis-related key genes.DL-thiorphan,promethazine,and apigenin may have the therapeutic effects on HCC.Conclusion:FTCD,SPP2,TAT,C6,and CYP2C9 may be the potential targets for the diagnosis,prognosis,and treatment of HCC.Three predicted small molecule drugs,DL-thiorphan,promethazine,and apigenin,may provide the references for the development of therapeutic drugs for HCC.

Digital therapy shows promise in providing precise assessments and enhancing the efficacy of treatments for mental illness,offering advantages such as convenience,flexibility,and the potential to reduce costs by shifting towards preventive care.This article reviews the development and benefits of digital therapy in mental health care and discusses the challenges it faces,including concerns over privacy,ethics,security,acces-sibility issues,digital divides,and the lack of sufficient clinical validation and standardization.It also highlights specific risks to mental health patients and explores potential future developments such as integration with brain-computer interfaces and neurofeedback,the use of robot therapists based on large language models,applications of virtual reality or the metaverse,and combinations with traditional physical treatments and medications.The author calls for urgent policy recommendations to refine regulations,establish unified evidence standards,enhance train-ing and education for healthcare providers and patients,and to build multidisciplinary collaborative mechanisms to advance personalized and effective digital therapy in mental health.

Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in young patients with high-risk multiple myeloma (HRMM) and analyzed the factors affecting patient prognosis.Methods:In this retrospective study, we analyzed the clinical data of 14 patients with HRMM with cytogenetic abnormalities or high-risk biological factors who underwent allo-HSCT at the Hematopoietic Stem Cell Transplantation Center of the Institute of Hematology & Blood Diseases Hospital between November 2016 and November 2022.Results:There were seven males and seven females included in the study, with a median age of 39.5 (31-50) years at the time of allo-HSCT. The median number of treatment lines before transplantation was 2 (1-6) . Before allo-HSCT, 42.9% (6/14) of the patients did not achieve complete remission, while 35.7% (5/14) of the patients achieved measurable residual disease positivity. After transplantation, all patients were evaluated for their treatment response, and the overall response rate was 100% (14/14) . All 14 patients successfully underwent allo-HSCT, with median engraftment times for neutrophils and platelets of 11 (10-14) days and 13 (9-103) days, respectively. Acute grade Ⅱ-Ⅳ graft-versus-host disease (GVHD) occurred in five patients (35.7%) , and two patients (14.3%) developed moderate-to-severe chronic GVHD. The median follow-up time after allo-HSCT was 18.93 (4.10-72.53) months, with an expected 2-year transplant-related mortality rate of 7.1% (95% CI 0%-21.1%) and an expected 2-year overall survival rate of 92.9% (95% CI 80.3%–100.0%) . Moreover, the expected 1-year and 2-year progression-free survival rates were 92.9% (95% CI 80.3%-100.0%) and 66.0% (95% CI 39.4%-100.0%) , respectively, and the 2-year cumulative incidence of relapse was 28.9% (95% CI 0%-56.7%) . Upfront allo-HSCT following complete remission after induced therapy and the presence of chronic GVHD might be favorable prognostic factors. Conclusion:allo-HSCT is an effective treatment for improving the prognosis of young patients with HRMM.

"Toxicity Testing in the 21st Century—A Vision and Strategy"proposed by the National Research Council of US has brought innovative directives and objectives for toxicity evaluation and risk assessment,pushing forward the next generation of toxicity testing and risk assessment.In this initiative,the concept of adverse outcome pathways(AOPs)has emerged as a prominent methodology,capturing the attention of toxicologists and researchers due to its promising applications in recent years.The quantitative AOP(qAOP)is an extension of the adverse outcome pathway,which is built upon the foundational qualitative adverse outcome pathway model and leverages mathematical frame-works to depict dose-response and/or response-response relationships.This article reviews the princi-ples and advancement surrounding qAOP,introduceds two prevalent methodologies for constructing qAOP,Bayesian network models and regression models,and demonstrates diverse applications of qAOP.Actual cases are used to underscore the transformative role of qAOP in contemporary toxicology and risk assessment practices.

Objective To form the expert consensus on the limb management of patients with transvenous temporary cardiac pacing,standardize the limb management of patients with transvenous temporary cardiac pacing,and reduce complications related to the limb.Methods Using evidence-based methods,the evidence in this field was searched,evaluated and summarized,and relevant recommendations and research conclusions were extracted and classified by the level of evidence quality,and then the first draft of the consensus was formed.From December 2023 to January 2024,through 2 rounds of expert consultation and 4 rounds of expert meetings,the content was adjusted and the consensus was reached.Results Totally 16 experts participated in the consultation.The positive coefficient is 100%;the authoritative coefficient is 0.847 and 0.836;the average value of each index is more than＞3.8;the coefficient of variation is less than 0.21.The Kendall's harmony coefficient of the 2 rounds of expert consultation is 0.372 and 0.314,respectively,which were statistically significant.The consensus covers the preoperative,intraoperative and postoperative on limb management of patients with transvenous temporary cardiac pacing.Totally 11 themes were involved,including the preoperative preparation,position and catheter fixation in operation,position and catheter fixation in postoperative,activity,turn and transfer,duty shift on limb,nursing care after withdrawal of the catheter,prevention of deep vein thrombosis of the operative limb and prevent infection.Conclusion The consensus is highly scientific,and it is helpful to standardize the limb management of patients with transvenous temporary cardiac pacing.

The study explored the effect of acteoside on renal fibrosis in rats with unilateral ureteral obstruction. Twenty-four healthy adult male SD rats were randomly divided into sham (CON) group, unilateral ureteral obstruction (UUO) group, UUO+acteoside (ACT) group, UUO+benazepril (BZ) group by random number table method. The animal model of renal fibrosis was established by unilateral ureteral ligation. The pathological changes of renal tissues in each group of rats were observed by HE staining and Masson staining. Immunohistochemical method was used to detect the protein expression levels of collagenⅢ, heat shock protein (HSP)-47, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), β-catenin, Bcl-2, and caspase-3. Western blotting was used to detect the protein expression of glucose-regulated protein 78 (GRP78) in renal tissue. Compared with CON group, UUO group had renal tubular dilation and significantly increased interstitial collagen fiber deposition; The degree of renal tubular dilation and interstitial collagen fibers in UUO+ACT group and UUO+BZ group were significantly reduced compared to UUO group, but still significantly heavier than CON group. Compared with CON group, the protein expression levels of collagenⅢ, HSP-47, CTGF, α-SMA, β-catenin and GRP78 in renal tissues of UUO group were significantly higher, while the protein expression level of Bcl-2 was significantly lower (all P<0.05). In comparison with UUO group, the expression levels of Bcl-2 in UUO+ACT group and UUO+BZ group were significantly higher, while the expression levels of other proteins were all significantly lower (all P<0.05). The study shows that acteoside may improve renal fibrosis by decreasing the expression levels of collagenⅢ, HSP-47, CTGF, α-SMA, β-catenin and GRP78, and upregulating the expression level of Bcl-2 in renal tissues.