BACKGROUND: This study aims to compare the efficacy between neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy vs . chemotherapy, and neoadjuvant triplet vs . doublet chemotherapeutic regimens in locally advanced gastric/esophagogastric junction cancer (LAGC). METHODS: We included LAGC patients from 47 hospitals in China's National Cancer Information Database (NCID) from January 2019 to December 2022. Using propensity score matching (PSM), we retrospectively analyzed the efficacy between neoadjuvant ICIs plus chemotherapy vs . chemotherapy alone, and neoadjuvant triplet vs . doublet chemotherapeutic regimens. The primary study result was the pathologic complete response (pCR) rate. The secondary study results were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 1205 LAGC patients were included. After PSM, the ICIs plus chemotherapy and the chemotherapy cohorts had 184 patients each, while the doublet and triplet chemotherapy cohorts had 246 patients each. The pCR rate (14.13% vs . 7.61%, χ2 = 4.039, P = 0.044), and the 2-year (77.60% vs . 61.02%, HR = 0.67, 95% con-fidence interval [CI] 0.43-0.98, P = 0.048) and 3-year (70.55% vs . 61.02%, HR = 0.58, 95% CI 0.32-0.93, P = 0.048) DFS rates in the ICIs plus chemotherapy cohort were improved compared to those in the chemotherapy cohort. No significant increase was observed in the OS rates at both 1 year and 2 years. The pCR rates, DFS rates at 1-3 years, and OS rates at 1-2 years did not differ significantly between the doublet and triplet cohorts, respectively. No differences were observed in postoperative complications between any of the group comparisons. CONCLUSIONS Neoadjuvant ICIs plus chemotherapy improved the pCR rate and 2-3 years DFS rates of LAGC compared to chemotherapy alone, but whether short-term benefit could translate into long-term efficacy is unclear. The triplet regimen was not superior to the doublet regimen in terms of efficacy. The safety after surgery was similar between either ICIs plus chemotherapy and chemotherapy or the triplet and the doublet regimen.
Humans ; Stomach Neoplasms/metabolism* ; Female ; Neoadjuvant Therapy/methods* ; Immune Checkpoint Inhibitors/therapeutic use* ; Male ; Middle Aged ; Propensity Score ; Retrospective Studies ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Disease-Free Survival ; Cohort Studies

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

The production of healthy agricultural products has increased the demand for innovative and sustainable plant protection technologies, and the rapid advancement of nanotechnology has brought revolutionary breakthroughs to traditional agriculture. Nanocarrier-based drug delivery systems can not only significantly improve the utilization efficiency of pesticides, achieving enhanced efficacy and reduced application, but also decrease the pesticide residues and environmental pollution. Additionally, they have made breakthrough progress in the stability and persistence of RNA pesticides. This review summarized the research progress on nanopesticides and RNA pesticides, focusing on the mechanisms of nanocarriers in improving pesticide bioactivity and RNA interference (RNAi) efficiency. It also systematically summarized the types of nanomaterials and their applications in pest and disease management and provided an in-depth outlook for the future development of nanopesticides and RNA pesticides, which provided technical support for the high-quality development of agriculture in the future.
Pesticides/chemistry* ; Nanotechnology ; Nanostructures ; RNA ; Agriculture/methods* ; RNA Interference ; Drug Delivery Systems

The esophagus is referred to as the conduit for food and drink.It can be categorized into three distinct phases:an era characterized by written descriptions,a phase marked by anatomical illustrations,and a period of integration between Chinese and Western medical practices.In the initial phase of written descriptions,seminal texts such as The Yellow Emperor's Inner Classic and The Classic of Difficult Issues documented aspects regarding both length and function of the esophagus;however,these accounts were relatively succinct.The subsequent phase saw advancements in anatomical illustrations that refined our comprehension of esophageal structure and functionality.During the period of the integration of Chinese and Western medicine,insights from Western anatomy prompted a reevaluation within Chinese medicine concerning both anatomy and physiology related to the esophagus;concurrently,clini-cal cases involving esophageal disorders emerged prominently.Consequently,Chinese medicine's grasp on esophageal physiology,pa-thology,anatomy,and function became increasingly comprehensive over time.Choosing the esophagus as the starting point for observ-ing the theory of viscera in Chinese medicine is intended to illustrate that Chinese medicine's understanding of life,health and disease is based on the observation and continuous improvement of the anatomical functions of the viscera,integrating the physiological func-tions to form a highly integrated system with functional states,so as to facilitate the use of natural medicines for regulation and treatment.This is a distinctive feature different from Western medicine,and it can keep pace with the times and absorb modern re-search results,and continuously improve the theory and treatment system,so as to obtain strong vitality and benefit mankind.

Objective: To investigate the current situation and influencing factors of knowledge, attitude and practice (KAP) of fall prevention among the elderly in Huzhou City, Zhejiang Province, so as to provide the evidence for the development of fall intervention for the elderly. Methods: The permanent residents aged 60 years and over in Huzhou City were selected using multi-stratified cluster sampling method from March to April 2023. Demographic information, activity of daily living (ADL), fall risk, and KAP of fall prevention was collected using questionnaire surveys. Factors affecting KAP of fall prevention were identified using a multivariable logistic regression model. Results: Totally 2 160 questionnaires were allocated, and 2 104 valid questionnaires were recovered, with an effective recovery rate of 97.41%. There were 1 063 males (50.52%) and 1 041 females (49.48%), and 861 residents aged 60 to <70 years (40.92%). The awareness of fall prevention knowledge was 84.13%, the percentage of attitude towards fall prevention was 85.88%, and the percentage of practice of fall prevention was 14.59%. Multivariable logistic regression analysis showed that age, educational level, exercise duration and fall risk were associated with the awareness of fall prevention knowledge; age, educational level, marital status, exercise duration, ADL and fall risk were associated with the attitude towards fall prevention; gender, age, educational level, marital status, exercise duration, chronic diseases, ADL and fall risk were associated with the practice of fall prevention (all P<0.05). The desired access to fall prevention knowledge was mainly dominated by medical personnel, accounting for 75.51% (589/780). Conclusions The practice towards fall prevention among the elderly is relatively low in Huzhou City. The KAP of fall prevention is related to age, educational level, exercise duration and fall risk.

Objective:To evaluate alteration of autograft function by pathological types after total parathyroidectomy (tPTX) plus autotransplantation (AT) in patients of hyperthyroidism.Methods:A total of 51 patients with end-stage chronic renal failure who underwent total parathyroidectomy with autologous forearm transplantation from Mar 2017 to Feb 2021 were divided into chief cell type (CC) and oxyphil cell type (OC) according to dominating graft cell type. iPTH, calcium, phosphorus and ALP levels were compared between the two groups from the perioperative period to 6 months and the 3D ultrasonography was performed at 6 months to cocalculate the size of the autograft.Results:Between the two groups, there were no statistically significant differences in iPTH, blood calcium, blood phosphorus, or ALP levels pre-,and 30 minutes, one month post surgery (all P>0.05). On three months, there was no significant difference in ALP levels [CC group: (99±23) U/L, OC group: (89±35) U/L, t=0.776, P=0.442]. At 6 months the PTH level [CC group: (290±77) pg/ml, OC group: (246±59) pg/ml, t=2.034, P=0.047], and blood calcium [CC group: (2.62±0.65) mmol/L, OC group: (2.21±0.20) mmol/L, t=2.531, P=0.015] blood phosphorus [CC group: (1.38±0.28) mmol/L, OC group: (1.68±0.34) mmol/L; t=-3.269, P=0.002], were all in favor of CC group. By 3D ultrasnography at 6 months the size of autograft was larger in CC group than in OC group [V cc=(2.17±0.37) cm 3,V oc=(1.85±0.29) cm 3, t=3.172, P<0.05]. Recurrences at 1 year after surgery were not significantly different between the two groups ( ncc=3, noc=1, t=0.277, P>0.05). Conclusion:The biological activity of CC-type grafts is higher than that of OC suggesting a longer functioning period as a parathyroid autograft.

Over the past decade, research has increasingly identified unique dysregulations in lipid metabolism within the tumor microenvironment (TME). Lipids, diverse biomolecules, not only constitute biological membranes but also function as signaling molecules and energy sources. Enhanced synthesis or uptake of lipids in the TME significantly promotes tumorigenesis and proliferation. Moreover, lipids secreted into the TME influence tumor-resident immune cells (TRICs), thereby aiding tumor survival against chemotherapy and immunotherapy. This review aims to highlight recent advancements in understanding lipid metabolism in both tumor cells and TRICs, with a particular emphasis on exogenous lipid uptake and endogenous lipid de novo synthesis. Targeting lipid metabolism for intervention in anticancer therapies offers a promising therapeutic avenue for cancer treatment. Nano-drug delivery systems (NDDSs) have emerged as a means to maximize anti-tumor effects by rewiring tumor metabolism. This review provides a comprehensive overview of recent literature on the development of NDDSs targeting tumor lipid metabolism, particularly in the context of tumor immunotherapy. It covers four key aspects: reprogramming lipid uptake, reprogramming lipolysis, reshaping fatty acid oxidation (FAO), and reshuffling lipid composition on the cell membrane. The review concludes with a discussion of future prospects and challenges in this burgeoning field of research.

Embryo implantation involves a complex interaction between the embryo and the endometrium of the mother, the study of which faces a variety of problems. The modeling of endometrial epithelial organoids and endometrial assembloids provides a new way to study the process of embryo implantation in vitro. This paper summarized the latest research progress in embryo implantation, the regulation mechanism of endometrial receptivity by estrogen- progesterone coordination and embryo-derived signals, the establishment of endometrial organoids, and the development and application of endometrial assembloids in the research on mother-embryo interaction, providing new strategies for studying the communication between embryo and maternal uterus during implantation.
Endometrium/physiology* ; Organoids/cytology* ; Embryo Implantation/physiology* ; Female ; Animals ; Progesterone/pharmacology* ; Pregnancy ; Estrogens/metabolism* ; Humans

Objective:To explore the development, application and practical experience of investigator-initiated integrated clinical research information platform.Methods:The process of developing and constructing an integrated clinical research platform in a tertiary hospital in Beijing was introduced, the functions and advantages of the platform were described and displayed, and the main problems and risk points in the development and construction process were analyzed.Results:The integrated clinical research platform meets the management requirements of clinical research initiated by investigators, and the standardized management of the whole life cycle of the project can be realized through the platform, and the key issues of data security, information capture, sharing and interoperability need to be further explored in terms of platform docking.Conclusions:The integrated clinical research platform effectively improves the standardization, management quality and efficiency of investigator-initiated clinical research.