Colorectal cancer is a common and malignant tumor in the digestive tract. Invasion and metastasis of cancer cells are key factors leading to the high mortality rate and postoperative recurrence of colorectal cancer. Chemotherapy is the main treatment method for preventing recurrence of this disease. However， there are many toxic side effects in clinical application， which seriously hinder the treatment process. Therefore， it is imperative to search for efficient and low-toxicity drugs. Traditional Chinese medicine （TCM） has a long history of treating colorectal cancer and offers advantages such as safety， effectiveness， multiple targets， multiple pathways and minimal toxic side effects， which have made it increasingly popular worldwide. According to TCM， the pathogenesis of colorectal cancer is rooted in both deficiency and excess. TCM formulas mainly focus on tonifying the body to address the invasion and metastasis of colorectal cancer， such as Jianpi compound， Jianpi Xiaoai decoction， and Bushen Jiedu Sanjie decoction. TCM monomers， such as emodin， berberine， and tanshinone， mainly focus on clearing heat and removing toxin， circulating blood and transforming stasis， and resolving swelling and dispersing nodules. Signaling pathways play a crucial role for analyzing invasion and metastasis， and research has shown that pathways such as Wnt/β-catenin， phosphatidylinositol-3 kinase/protein kinase （PI3K/Akt）， Janus kinase 2/signal transduction and transcription activating factor 3 （JAK2/STAT3）， nuclear factors-κB （NF-κB）， vascular endothelial growth factor （VEGF） play important roles in the invasion and metastasis of colorectal cancer. The invasion and metastasis of colorectal cancer can be inhibited via regulating the key proteins and related factors in these pathways. In this review， we searched various literature databases， such as PubMed， China National Knowledge Infrastructure （CNKI）， and VIP， using keywords such as "colorectal cancer"， "signaling pathway"， "invasion and metastasis"， and "traditional Chinese medicine"， to summarize and analyze the relevant pathways of TCM compounds and monomers against invasion and metastasis of colorectal cancer published in the past five years. The review aims to provide new insights and references for in-depth research on the therapy for invasion and metastasis of colorectal cancer and new drug development.

Since its establishment in 2016, the National Rare Diseases Registry System of China (NRDRS) has accumulated valuable case data and bio-specimen for basic and clinical research on rare diseases in China. However, the emerging challenges in clinical diagnosis and treatment of rare diseases make it unable for data and resource platform to fully meet the diversified needs. Under this backdrop, we have developed a protocol to optimize and upgrade the system based on the core functions of the NRDRS platform. The goal is to leverage intelligent digital technologies to transform NRDRS into a new platform integrating multimodal data and auxiliary diagnostic and treatment functions. It is specified as the development and construction of "one platform and four intelligent tools." Currently, we have upgraded and developed NRDRS platform, intelligent tool for genotype-phenotype analysis of rare diseases, AI-assisted diagnostic tool for rare diseases, remote multidisciplinary diagnosis and teaching tool for rare diseases, drug screening and validation tool for rare diseases. The next step will focus on the promotion of the application of these tools in clinical settings in order to address the issue of severe imbalance in the allocation of resources for the diagnosis and treatment of rare diseases. This article provides an overview of the digital and intelligent upgrades of the NRDRS, the trials in applications in clinical settings, and direction in the future.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Objective: To investigate the occupational health literacy (OHL) level and its influencing factors of key populations in Jinhua City, Zhejiang Province, so as to provide a basis for promoting occupational health. Methods: The front-line workers of 7 secondary industry enterprises (institutions) and 15 tertiary industry enterprises (institutions) in Jinhua City were selected from April to October 2023 using a stratified random cluster sampling method. Date of gender, age, length of service, and OHL were collected using the National Occupational Health Literacy Monitoring Survey for Key Population Personal Questionnaire. Factors affecting OHL level among key populations were identified using multivariable logistic regression model. Results: A total of 3 305 people were investigated, including 1 750 males (52.95%) and 1 555 females (47.05%). The median age and the length of service were 37 (interquartile range, 17) and (interquartile range, 9) years, respectively. The level of OHL was 45.63%. Multivariable logistic regression analysis identified gender (female, OR=1.675, 95%CI: 1.428-1.964), educational level (junior high school, OR=1.499, 95%CI: 1.089-2.063; high school, OR=1.905, 95%CI: 1.361-2.667; junior college, OR=4.065, 95%CI: 2.858-5.782; bachelor degree and above, OR=5.087, 95%CI: 3.597-7.194), personal monthly income (3 000-< 5 000 yuan, OR=1.373, 95%CI: 1.035-1.821; 5 000-<7 000 yuan, OR=1.653, 95%CI: 1.230-2.220; ≥7 000 yuan, OR=1.798, 95%CI: 1.322-2.447) and length of service (2-<6 years, OR=1.265, 95%CI: 1.032-1.551; 6-<11 years, OR=1.517, 95%CI: 1.184-1.943; ≥11 years, OR=1.337, 95%CI: 1.040-1.719) as factors affecting OHL level among key populations. Conclusions The OHL level of the key populations in Jinhua City is related to gender, age, education level, personal monthly income, and length of service. It is necessary to strengthen the occupational health education and health promotion of the key populations.

This study aims to explore the intervention effects of isorhamnetin(Isor) on acute lung injury(ALI) and its regulatory effects on pyroptosis mediated by the NOD-like receptor family pyrin domain containing 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/cysteine aspartate-specific protease-1(caspase-1) axis. In the in vivo experiments, 60 BALB/c mice were divided into five groups. Except for the control group, the other groups were administered Isor by gavage 1 hour before intratracheal instillation of LPS to induce ALI, and tissues were collected after 12 hours. In the in vitro experiments, RAW264.7 cells were divided into five groups. Except for the control group, the other groups were pretreated with Isor for 2 hours before LPS stimulation and subsequent assessments. Hematoxylin-eosin(HE) staining was used to observe pathological changes in lung tissue, while lung swelling, protein levels in bronchoalveolar lavage fluid(BALF), and myeloperoxidase(MPO) levels in lung tissue were measured. Cell proliferation toxicity and viability were assessed using the cell counting kit-8(CCK-8) method. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin-1β(IL-1β), IL-6, IL-18, and tumor necrosis factor-α(TNF-α). Protein levels of NLRP3, ASC, cleaved caspase-1, and the N-terminal fragment of gasdermin D(GSDMD-N) were evaluated using immunohistochemistry, immunofluorescence, and Western blot. The results showed that in the in vivo experiments, Isor significantly improved pathological damage in lung tissue, reduced lung swelling, protein levels in BALF, MPO levels in lung tissue, and levels of inflammatory cytokines such as IL-1β, IL-6, IL-18, and TNF-α, and inhibited the high expression of the NLRP3/ASC/caspase-1 axis and the pyroptosis core gene GSDMD-N. In the in vitro experiments, the safe dose of Isor was determined through cell proliferation toxicity assays. Isor reduced cell death and inhibited the expression levels of the NLRP3/ASC/caspase-1 axis, GSDMD-N, and inflammatory cytokines. In conclusion, Isor may alleviate ALI by modulating pyroptosis mediated by the NLRP3/ASC/caspase-1 axis.
Animals ; Pyroptosis/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Acute Lung Injury/physiopathology* ; Mice ; Mice, Inbred BALB C ; Quercetin/pharmacology* ; Caspase 1/genetics* ; CARD Signaling Adaptor Proteins/genetics* ; Male ; RAW 264.7 Cells ; Humans ; Lung/metabolism*