OBJECTIVE To evaluate the cost-effectiveness of iruplinalkib for ALK-positive non-small cell lung cancer （NSCLC） patients who had not previously received ALK-tyrosine kinase inhibitors （TKIs） from the perspective of the Chinese healthcare system. METHODS Based on the INSPIRE clinical trial， a three-health state partitioned survival model was developed to simulate the progression of disease， with model cycle of 3 weeks and a life-year time range of 15 years； the discount rate was 5%. For the treatment of ALK-positive advanced NSCLC， total cost， quality-adjusted life year （QALY）， and incremental cost- effectiveness ratio （ICER） were compared between iruplinalkib and crizotinib； using 1-3 times China’s per capita gross domestic product （GDP） （89 358-268 074 yuan） in 2023 as the willingness-to-pay （WTP） threshold， the cost-effectiveness of two regimens were compared. The sensitivity analysis and scenario analysis （altering the distribution of survival curves， utility values） were conducted to assess model robustness. RESULTS Compared with the crizotinib regimen， the ICER for the iruplinalkib regimen was 194 412.74 yuan/QALY， which was below the WTP threshold of three times China’s per capita GDP in 2023 yuan）. The results under the scenario of altering the survival curve distribution were consistent with the base case analysis. However， after increasing the utility value of the disease progression state， the ICER exceeded the WTP threshold， and iruplinalkib no longer had a cost-effective advantage. The results of the one-way sensitivity analysis indicated that the cost of iruplinalkib and the utility values of disease progression states had a significant impact on the ICER. The probabilistic sensitivity analysis confirmed the robustness of the base case analysis results. CONCLUSIONS From the perspective of China’s healthcare system， compared with crizotinib regimen， the therapy with iruplinalkib is cost-effective for ALK-positive NSCLC patients who have not previously received ALK-TKIs.

The advancement of medical technology has led to significant progress in the research of standardized surgical procedures for colorectal cancer, resulting in enhanced treatment regimens from preoperative to postoperative stages. Standardized surgical procedures are crucial for improving patient survival rates, reducing recurrence rates, minimizing complications, and improving quality of life. This article summarizes the latest research results on the classification, surgical methods, and adjuvant therapy of colorectal cancer surgery; analyzes and explores standardized surgical treatment strategies; and aims to provide reference and guidance for the clinical management of colorectal cancer.

Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

With the rapid advancement of vaccines, the research and application of vaccine adjuvants have garnered significant attention. Despite the development of numerous vaccine adjuvants, their applications in human vaccines remain limited due to either insufficient efficacy or severe side effects. Consequently, there is growing interest in developing bioactive compounds derived from traditional Chinese medicines (TCMs) as vaccine adjuvants, owing to their natural biocompatibility, diversity, and safety. Here, we systematically review the current application status and potential value of TCM-based bioactive compounds in vaccine adjuvants. Firstly, we elaborate on the types and characteristics of active ingredients, such as polysaccharides, saponins, flavonoids, acids, and alkaloids. The mechanisms by which these compounds function as vaccine adjuvants are then discussed, including their roles in enhancing humoral immunity, cellular immunity, and relieving the immune suppression in the microenvironment. Additionally, we summarize the current strategies for structural modification and platform optimization to adapt to different application scenarios. Finally, we offer insights into the future development directions for these potential adjuvants, highlighting research priorities, technical approaches, and application prospects. In conclusion, natural vaccine adjuvants derived from TCMs present broad application prospects and hold promise for future vaccine development.

Objective:To explore the effects of hinokiol on the cell cyle and apoptosis of CNE1 nasopharyngeal carcinoma cells and the relevant molecular mechanism.Methods:The CNE1 cells were cultured in vitro and incubated with different concentrations of honokiol, and the cells were divided into blank control group, 10 μmol/L, 20 μmol/L and 40 μmol/L hinokiol treatment groups, and 10 μg/ml cisplatin group. Cell viability was determined by methylthiazolyldiphenyl- tetrazolium bromide (MTT) method, the cell cycle distribution was detected by flow cytometry, mitochondrial membrane potential was detected by mitochondrial membrane potential test kit, apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method, and the proteins expression of proliferating cell nuclear antigen (PCNA) and G 1/S specific cyclin D1 (cyclin D1) were detected by immunoblotting. RNA-Seq was conducted in the hinokiol-treated cells. The mRNA expression of yes-associated protein delta (YAP) was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The proteins expression of phosphor-YAP (p-YAP) and nuclear YAP were detected by immunoblotting, the nuclear distribution of YAP protein was detected by immunofluorescence in the cells with or without treated with the mammalian STE20-like kinase 1/2 (MST1/2) inhibitor (XMU-MP-1), hinokiol, and XMU-MP-1+hinokiol. Statistical analysis of the data was conducted using GraphPad Prism 8.0 software. Resluts Compared with the control group, the cell viablity of CNE1 cells, the levels of mitochondrial membrane potential, the proteins expression of PCNA and cyclin D1 in hinokiol treatment groups were markedly decreased (all P values<0.05), while the proportion of G 0/G 1 phase cells and the ratio of TUNEL-positive cells were significantly increased (both P values<0.05). Transcriptome analysis showed that differential genes were mainly enriched in Wnt signaling pathway, tumor necrosis factor pathway, and Hippo signaling pathway. The mRNA level of YAP and the protein expression of YAP in the nucleus were decreased and the level of p-YAP protein was increased in cells treated with hinokiol, which were significantly different from control group (all P values<0.05). Compared with the hinokiol group, XMU-MP-1+hinokiol groups showed the decrease of p-YAP protein expression (1.157±0.076 vs 0.479±0.038, t=37.120, P<0.05), the increase of YAP protein expression in the nucleus (0.143±0.012 vs 0.425±0.031, t=29.181, P<0.05), the reduced proportion of cells in G 0/G 1 phase [(72.494±3.309)% vs (58.747±2.865)%, t=17.265, P<0.05], and the decrease of apoptosis ratio [(53.158±3.376)% vs (29.621±2.713)%, t=28.584, P<0.05]. Conclusion:Hinokiol can arrest the cell cycle and induce the cell apoptosis of CNE1 cells via Hippo/YAP signaling pathway.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To evaluate the effect of neoadjuvant chemotherapy combined with immunotherapy on the perioperative renal function in patients undergoing radical resection for esophageal cancer.Methods:This was a retrospective cohort study. Clinical data from patients undergoing neoadjuvant chemotherapy combined with immunotherapy for esophageal cancer in Tianjin Medical University Cancer Institute & Hospital and Tianjin University Chest Hospital from January 2020 to April 2022 were retrospectively collected. According to the preoperative treatment regimen, the patients were divided into neoadjuvant chemotherapy group (group nCT) and neoadjuvant chemotherapy combined with immunotherapy group (group nCT+ IT). nCT group underwent neoadjuvant chemotherapy, which included a platinum-based regimen combined with fluorouracil or taxanes. In nCIT+ IT group, programmed cell death protein 1 inhibitors were used for immunotherapy based on neoadjuvant chemotherapy. All the patients underwent 2-3 cycles of therapy, with each cycle lasting 21 days. Surgery was performed 4-6 weeks after the completion of the last therapy. The concentrations of serum creatinine, uric acid and blood urea nitrogen were detected before therapy, at 72 h before surgery and at 72 h after surgery. The acute kidney injury (AKI) diagnosed by the Kidney Disease: Improving Global Outcomes criteria at 72 h before surgery and 72 h after surgery were recorded. The pathological complete response rates, recurrence rate and disease-free survival time after surgery were collected.Results:Compared with group nCT, the serum urea concentration was significantly increased after treatment, the serum uric acid concentrations were increased at 72 h before surgery and 72 h after surgery, the pathological complete response rate was increased, the recurrence rate was decreased, the disease-free survival time was prolonged ( P<0.05), and no statistically significant changes were found in the incidence of AKI at 72 h before surgery and 72 h after surgery in group nCT+ IT ( P>0.05). Conclusions:Although neoadjuvant chemotherapy combined with immunotherapy can raise the pathological complete response rate and disease-free survival rate, it has a certain effect on renal function. Perioperative renal function testing should be strengthened to prevent the occurrence of AKI in the patients undergoing radical resection for esophageal cancer.

BACKGROUND:Confirming the reliability and validity of the My jump 2 application for measuring lower limb vertical stiffness may offer the possibility of it as an alternative to the Kistler three-dimensional force platform for measuring lower limb stiffness. OBJECTIVE:To verify the reliability and validity of the My Jump 2 application in measuring lower limb vertical stiffness of college students. METHODS:The drop jump data of the participants were collected through the Kistler three-dimensional force platform and the My Jump 2 application,and the vertical stiffness of the participants'lower limb vertical stiffness was calculated.The intraclass correlation coefficient was used to analyze the data measured by the My Jump 2 application and the Kistler three-dimensional force platform,attempting to verify the reliability of the My Jump 2 application.The bias and average between the two devices were drawn into a Bland-Altman diagram to verify the consistency between the two test methods.Finally,the test-retest reliability of the My Jump 2 applications at 30 cm and 40 cm was analyzed using the Cronbach's alpha(α)and coefficient of variation.Pearson product-moment correlation was used to analyze the correlation of My Jump 2 applications. RESULTS AND CONCLUSION:My Jump 2 application has high reliability and validity when measuring the vertical stiffness of the lower limb.At the same time,due to its advantages of low cost,convenient portability and field testing for large samples,it can be used as an alternative to the Kistler three-dimensional force platform to test the vertical stiffness of the lower limb in college students and similar populations.

OBJECTIVE: To explore the clinical application value of mineralized collagen (MC) bone scaffolds in repairing various types of skull defects, and to assess the suitability and repair effectiveness of porous MC (pMC) scaffolds, compact MC (cMC) scaffolds, and biphasic MC composite (bMC) scaffolds. METHODS: A retrospective analysis was conducted on the clinical data of 105 patients who underwent skull defect repair with pMC, cMC, or bMC between October 2014 and April 2022. The cohort included 63 males and 42 females, ranging in age from 3 months to 55 years, with a median age of 22.7 years. Causes of defects included craniectomy after traumatic surgery in 37 cases, craniotomy in 58 cases, tumor recurrence or intracranial hemorrhage surgery in 10 cases. Appropriate MC scaffolds were selected based on the patient's skull defect size and age: 58 patients with defects <3 cm² underwent skull repair with pMC (pMC group), 45 patients with defects ≥3 cm² and aged ≥5 years underwent skull repair with cMC (cMC group), and 2 patients with defects ≥3 cm² and aged <5 years underwent skull repair with bMC (bMC group). Postoperative clinical follow-up and imaging examinations were conducted to evaluate bone regeneration, the biocompatibility of the repair materials, and the occurrence of complications. RESULTS: All 105 patients were followed up 3-24 months, with an average of 13 months. No material-related complication occurred in any patient, including skin and subcutaneous tissue infection, excessive ossification, and rejection. CT scans at 6 months postoperatively showed bone growth in all patients, and CT scans at 12 months postoperatively showed complete or near-complete resolution of bone defects in all patients, with 58 cases repaired in the pMC group. The CT values of the defect site and the contralateral normal skull bone in the pMC group at 12 months postoperatively were (1 123.74±93.64) HU and (1 128.14±92.57) HU, respectively, with no significant difference ( t=0.261, P=0.795). CONCLUSION MC exhibits good biocompatibility and osteogenic induction ability in skull defect repair. pMC is suitable for repairing small defects, cMC is suitable for repairing large defects, and bMC is suitable for repairing pediatric skull defects.
Humans ; Tissue Scaffolds ; Male ; Female ; Collagen ; Retrospective Studies ; Adult ; Child ; Adolescent ; Middle Aged ; Child, Preschool ; Skull/surgery* ; Young Adult ; Infant ; Plastic Surgery Procedures/methods* ; Tissue Engineering/methods* ; Craniotomy/methods* ; Bone Regeneration ; Treatment Outcome ; Porosity ; Biocompatible Materials

Zhishi Xiebai Guizhitang is a classical prescription for the treatment of chest impediment with the method of warming Yang. It is included in the Catalogue of Ancient Classical Prescriptions issued by the National Administration of Traditional Chinese Medicine （First Batch）， with the effect of activating Yang， dissipating mass， moving Qi and resolving phlegm. Its main symptoms include chest fullness and pain， or even chest pain radiating to the back， wheezing， coughing， shortness of breath， and Qi reversal from the hypochondrium. In modern traditional Chinese medicine， Zhishi Xiebai Guizhitang is clinically used in the treatment of cardiovascular system， digestive system， respiratory system and other diseases， among which coronary heart disease， unstable angina pectoris， myocardial infarction， sinus bradycardia and other cardiovascular diseases have particularly significant effects. This paper reviewed the pharmacological studies of Zhishi Xiebai Guizhitang in the past 10 years. The results showed that each single medicine and the whole prescription alleviated the above cardiovascular diseases to a certain extent， with the pharmacological effects of improving intravascular environment， myocardial ischemia， myocardial ischemia-reperfusion injury， and myocardial hypoxia， anti-inflammation， plaque stabilisation， etc.， and the pharmacological mechanism involved the regulation of relevant active substances in vivo as well as related signaling pathways and ion channels， mainly including thromboxane B₂ （TXB₂）， prostacyclin I₂（PGI₂） and phosphatidylinositol 3-kinases/protein kinase B/endothelial nitric oxide synthase （PI3K/Akt/eNOS） signaling pathways， and ATP-sensitive potassium channels. In addition， the relationship between the pharmacological effects of some single medicines and transient receptor potential ankyrin 1 （TRPA1） has been reported that TRPA1 is a key to understanding the mechanism of Zhishi Xiebai Guizhitang in treating cardiovascular diseases， which is worth of further study.