Alzheimer's disease （AD） is a common type of dementia， primarily characterized by cognitive and behavioral impairments as well as deficits in learning and memory. The progression of AD has imposed a significant economic burden on society and families. However， its exact pathogenesis has not yet been fully elucidated. Currently， available therapeutic drugs are limited and are often accompanied by serious adverse effects. Traditional Chinese medicines （TCMs） and their extracts are mostly natural products and possess advantages such as multi-pathway regulation and relatively few adverse reactions. Experimental studies have shown that TCMs exhibit great potential in the prevention and treatment of AD. For example， Huanglian Jieduang， Danggui Shaoyaosan， Kaixin San， Liuwei Dihuangwan， Buyang Huanwutang， as well as Ginseng Radix et Rhizoma， Astragali Radix， Uncariae Ramulus cum Uncis， Coptidis Rhizoma， Gardeniae Fructus， Ginkgo Folium， Salviae Miltiorrhizae Radix et Rhizoma， and Curcumae Longae Rhizoma， can reduce β-amyloid deposition， inhibit excessive Tau protein phosphorylation， restore mitochondrial function， alleviate oxidative stress， suppress neuroinflammation and apoptosis， repair synaptic function， and improve gut microbiota. This article mainly summarizes the effects of several TCMs and compound prescriptions on AD， aiming to provide a reference for subsequent TCM-based treatment of AD.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective To construct an in vitro co-culture model of gastric cancer organoids and cancer-associated fibroblasts(CAFs),and investigate the role of cancer-associated fibroblasts in the proliferation and chemotherapy resistance of gastric cancer organoids.Methods Tumor tissues from 12 gastric cancer patients undergoing surgical treatment in Department of General Surgery of Second Affiliated Hospital of Army Medical University from February 2023 to March 2024 were collected to construct gastric cancer organoids using 3D culture.HE staining was used to observe the morphology,and immunohistochemical assay was employed to determine the expression of cytokeratin CK7,carcinoembryonic antigen(CEA),and proliferation marker Ki-67.After CAFs derived from the same patient were cultured,observed for their morphology under a light microscope,and detected for the phenotype by flow cytometry,the cells were co-cultured with gastric cancer organoids in a 1:1 ratio.Phase-contrast microscopy was applied to observe the growth of the organoids and analyze the number,average diameter,and total area.Then,organoids cultured alone served as the control group.After the control and co-culture groups were treated with chemotherapy drugs,5-fluorouracil and oxaliplatin,for 48 h,the viability and apoptosis of organoids were assessed with CellTiter-Glo??3D assay and CellEvent? Caspase 3/7 activity,respectively.Results Gastric cancer organoids and CAFs were successfully established from 10 gastric cancer patient-derived samples.The gastric cancer organoids exhibited morphological characteristics consistent with the corresponding primary tumors,and showed positive expression of CK7,CEA,and Ki-67.CAFs displayed typical spindle-shaped morphology and exhibited the phenotypic markers CD326-,CD45-,CD31-,α-SMA+,CD73+,CD90+,and CD105+.Compared to the organoids cultured alone,the organoids co-cultured with CAFs showed more formation of organoids,in larger average diameter,and taking larger total area(P<0.05).After the treatment of 5-fluorouracil and oxaliplatin,the half-maximal inhibitory concentration(IC50)was 10.66 and 3.26 μmol/L,respectively in the control group,while was 46.23 and 91.11 μmol/L in the co-culture group.Additionally,the number of CellEvent? Caspase 3/7 positive apoptotic cells was significantly less in the co-culture group than the control group.Conclusion Compared with individually cultured gastric cancer organoids,the co-culture model of gastric cancer organoids and CAFs better simulates the pro-tumor proliferation and drug resistance effects of in vivo tumor microenvironment.

Objective:To investigate the effects of propionic acid produced by Akkermansia muciniphila on the radiosensitivity of colorectal cancer and the underlying mechanism. Methods:Normal human colon mucosal epithelial cells (NCM460) were used to determine the appropriate concentration of propionic acid. Human colorectal cancer cells (HCT-8) were treated with A. muciniphila-conditioned medium or propionic acid, followed by exposure to 6 Gy γ-ray irradiation, and cell survival and proliferation were measured by clone formation assay and Cell Counting Kit-8 (CCK-8) assay, respectively. A mouse model of colorectal cancer was established using azoxymethane/dextran sodium sulfate. The mice were divided into control model group, irradiation group, and irradiation+ propionic acid group. Their body weight, colorectal length, tumor count, and tumor area were recorded. The radiosensitizing effect of propionic acid was assessed with HE staining, immunohistochemical staining, and enzyme-linked immunosorbent assay. The mechanism was explored by using RT-PCR and flow cytometry. Results:CCK-8 assay showed that 1-mmol/L propionic acid had no significant effect on the proliferation of NCM460 cells ( P>0.05), which was used for subsequent experiments. Pretreated with A. muciniphila-conditioned medium or propionic acid, the survival and proliferation abilities of irradiated HCT cells were significantly decreased ( t=3.14-34.98, P<0.05). Compared with the irradiation group, the colorectal cancer mice in the irradiation+ propionic acid group showed a significantly longer colorectal length ( t=3.50, P<0.05) and a significantly smaller number of tumors ( t=3.48, P<0.05); the two groups had significantly smaller tumor areas than the control model group ( t=5.97, 7.30, P<0.05). HE staining and immunohistochemical staining showed that propionic acid restored colorectal structure, and decreased Ki67 expression in colorectal tissue ( t=14.50, 3.40, P<0.05). Propionic acid treatment significantly reduced the levels of the inflammatory factors interleukin-6 and tumor necrosis factor-α, as compared with the mice receiving irradiation alone ( t=4.86, 5.06, P<0.05). Irradiation plus propionic acid treatment significantly increased p53 expression and significantly aggravated G 2/M phase block and cell apoptosis ( t=20.35, 13.05, P<0.05). Conclusions:The A. muciniphila metabolite propionic acid plays a sensitizing role in radiation therapy for colorectal cancer by promoting G 2/M phase block and apoptosis in colorectal cancer cells.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective To explore the effect of rituximab on cellular immunity and cytokines in children with new-onset steroid-sensitive nephrotic syndrome(SSNS).Methods Clinical data of 60 children with new-onset SSNS treated at Xuzhou Children's Hospital from December 2021 to March 2023 were retrospectively analyzed.Children were allocated according to rituximab use into a control group(no rituximab)and an observation group(rituximab).The relapse rate,T-lymphocyte subsets and cytokines before and after treatment,and the incidence of adverse reactions were compared between groups.Results The relapse rate was lower in the observation group than in the control group(27%vs 73%,P<0.05).After treatment,CD3+and CD4+T-lymphocyte counts,the CD4+/CD8+ratio,and serum interleukin-2 increased in the observation group and were higher than in the control group(P<0.05).Interleukin-6 and tumor necrosis factor-α levels decreased after treatment in the observation group and were lower than in the control group(P<0.05).After treatment,CD8+T-lymphocyte counts decreased,interferon-γ increased,and interleukin-10 decreased in both groups,with no significant differences between the two groups(P>0.05).The incidence of adverse reactions did not differ significantly between the two groups(P>0.05).Conclusions Rituximab can reduce the relapse rate in children with new-onset nephrotic syndrome and shows good safety.Its therapeutic effect is achieved by regulating the number and function of T cells and by modulating the anti-inflammatory effects of cytokines.

Needle-free injection(NFI)has emerged as a novel vaccine delivery technology,utilizing high-pressure jet streams to deliver vaccines into intradermal or subcutaneous tissues.In recent years,the application of this technology in the fields of medicine and veterinary medicine has a-chieved significant progress.Compared with traditional needle injection,the core advantages of NFI have been highlighted in several aspects:it has significantly improved vaccination efficiency,mak-ing it particularly suitable for mass vaccination campaigns;it has reduced animal stress;it has en-hanced the comfort of vaccination;it has more effectively induced immune responses;and it has a-voided the risk of needle contamination,thereby lowering the infection rate.However,NFI has also faced challenges such as high equipment costs,complex operation,and the need to improve market acceptance.Future research directions have focused on the development of new vaccines and adju-vants as well as the design and optimization of needle-free injectors to enhance their universality and safety among different populations.In summary,NFI has provided an important solution for the innovation of vaccine delivery systems by improving vaccination comfort and immune efficacy and has offered theoretical basis and technical references for its industrial development.

Objective To understand the epidemiological characteristics and trends of postoperative pneumonia(POP)in tertiary general hospitals in Jiangsu Province,and provide theoretical basis for carrying out targeted pre-vention and control measures.Methods Surgery patients from 22 tertiary general hospitals in 12 cities in north,central,and south of Jiangsu Province from January 1,2022 to December 31,2023 were chosen as studied subjects,occurrence of POP was analyzed and compared.Results A total of 848 274 surgical procedures were performed in 22 hospitals,and 3 606 cases of POP occurred,with an incidence of 0.43％.The incidence in 2023 was 0.37％,which was lower than that in 2022(0.49％),with statistically significant difference(P＜0.001).The top three de-partments with high incidence of POP were neurosurgery(6.71％),cardiothoracic surgery(2.91％),and general surgery(0.77％).Among hospitals of different grades,the incidence of POP in tertiary first-class hospitals was 0.44％,which was higher than that in other tertiary hospitals(0.37％).There was no statistically significant difference in the incidence of POP between municipal and district/county hospitals(P＞0.05).The incidence of POP in hospitals with a bed:infection control full-time staff ratio＜200∶1 was lower than that in hospitals with the ratio ≥200∶1(0.39％vs 0.47％,P＜0.001),while the incidence of POP in hospitals with a proportion ≥30％of full-time staff being doctors was higher than that in hospitals with a proportion＜30％(0.45％vs 0.36％,P＜0.001).The incidence of POP in male patients was higher than that in female patients(0.62％vs 0.26％,P＜0.001).The incidence of POP in elderly patients aged≥65 was higher than that in patients aged＜65(0.73％vs 0.26％,P＜0.001).A total of 2 667 strains of infectious pathogens were detected,with the top three being Acine-tobacter baumannii,Klebsiella pneumoniae,and Pseudomonas aeruginosa,accounting for 28.95％,22.72％,and 15.45％,respectively.The detection rates of carbapenem-resistant Acinetobacter baumannii(CRAB),carba-penem-resistant Klebsiella pneumoniae(CRKP),and carbapenem-resistant Pseudomonas aeruginosa(CRPA)were 60.75％,21.45％,and 32.28％,respectively.The detection rate of CRKP decreased in 2023 compared with 2022,with statistically significant difference(P＜0.05).Conclusion The overall incidence of POP in tertiary general hos-pitals in Jiangsu Province is relatively low,but there are significant differences among different hospitals.There-fore,perioperative prevention and control measures should be carried out based on the epidemiological characteristics of patients.

Quality control of pediatric musculoskeletal ultrasound(MSKUS)must be integrated throughout the entire diagnostic process.Its core lies in a thorough understanding of the growth,development,and pathophysiological characteristics of the pediatric musculoskeletal system,mastery of MSKUS examination techniques,and the establishment of a systematic and comprehensive diagnostic framework.This review focuses on the core aspects of pre-examination,during examination,and post-examination to describe the quality control points and strategies for pediatric MSKUS.

Objective:To investigate the effects of propionic acid produced by Akkermansia muciniphila on the radiosensitivity of colorectal cancer and the underlying mechanism. Methods:Normal human colon mucosal epithelial cells (NCM460) were used to determine the appropriate concentration of propionic acid. Human colorectal cancer cells (HCT-8) were treated with A. muciniphila-conditioned medium or propionic acid, followed by exposure to 6 Gy γ-ray irradiation, and cell survival and proliferation were measured by clone formation assay and Cell Counting Kit-8 (CCK-8) assay, respectively. A mouse model of colorectal cancer was established using azoxymethane/dextran sodium sulfate. The mice were divided into control model group, irradiation group, and irradiation+ propionic acid group. Their body weight, colorectal length, tumor count, and tumor area were recorded. The radiosensitizing effect of propionic acid was assessed with HE staining, immunohistochemical staining, and enzyme-linked immunosorbent assay. The mechanism was explored by using RT-PCR and flow cytometry. Results:CCK-8 assay showed that 1-mmol/L propionic acid had no significant effect on the proliferation of NCM460 cells ( P>0.05), which was used for subsequent experiments. Pretreated with A. muciniphila-conditioned medium or propionic acid, the survival and proliferation abilities of irradiated HCT cells were significantly decreased ( t=3.14-34.98, P<0.05). Compared with the irradiation group, the colorectal cancer mice in the irradiation+ propionic acid group showed a significantly longer colorectal length ( t=3.50, P<0.05) and a significantly smaller number of tumors ( t=3.48, P<0.05); the two groups had significantly smaller tumor areas than the control model group ( t=5.97, 7.30, P<0.05). HE staining and immunohistochemical staining showed that propionic acid restored colorectal structure, and decreased Ki67 expression in colorectal tissue ( t=14.50, 3.40, P<0.05). Propionic acid treatment significantly reduced the levels of the inflammatory factors interleukin-6 and tumor necrosis factor-α, as compared with the mice receiving irradiation alone ( t=4.86, 5.06, P<0.05). Irradiation plus propionic acid treatment significantly increased p53 expression and significantly aggravated G 2/M phase block and cell apoptosis ( t=20.35, 13.05, P<0.05). Conclusions:The A. muciniphila metabolite propionic acid plays a sensitizing role in radiation therapy for colorectal cancer by promoting G 2/M phase block and apoptosis in colorectal cancer cells.