Inflammatory bowel disease (IBD) is a kind of immune disease. Although immune cells and related immunological reactions play a crucial role in the pathogenesis, non-immune cells of IBD, including intestinal epithelial cells, stromal cells, and endothelial cells are also involved in this process. Recent studies have shown that gut non-immune cells play an important role in the maintenance of intestinal epithelial homeostasis, matrix remodeling, immune response and inflammation. The composition, gene expression characteristics and cell functions of gut non-immune cells, as well as their role in the occurrence and progression of IBD, have been paid much attention in the field of gut research. In particular, recently, single-cell RNA sequencing (scRNA-seq) technology has initially clarified the gene expression characteristics and cell functions of different subgroups of intestinal cells, and the correlation between these changes and the occurrence and progression of IBD. Therefore, this review summarizes the progress of intestinal non-immune cells in IBD.

Objective To analyze and verify the role of senescent genes in the treatment, prognosis, and tumor microenvironment (TME) characteristics of osteoblastic osteosarcoma, bioinformatic methods were employed. Methods Senescent genes were obtained from the China National Genome Science database (https://ngdc.cncb.ac.cn/aging/index). The gene expression profile and clinical information of osteosarcoma patients were sourced from the TARGET database (https://ocg.cancer.gov/programs/target), while single-cell RNA-sequencing (scRNA-seq) data was collected from GSE162454 on the Gene Expression Omnibus (GEO) for downstream analysis. Osteosarcoma cells were classified based on scRNA-seq, and differential expression analysis between osteoblasts/chondroblasts and other cell types was conducted to identify differently expressed genes (DEGs). After matching with the senescent genes, prognostic senescent DEGs were identified through univariable and multivariable Cox regression analysis. Subsequently, the osteosarcoma senescent-related model (OSRM) was constructed, and the risk score was calculated. The role of OSRM in treatment, prognosis, and TME of osteosarcoma was further investigated. Results The analysis revealed that GSE162454 contained 6 osteosarcoma samples, with 19 933 cells identified after filtering, quality control, and normalization. Seventeen cellular subtypes were identified using uniform manifold approximation and projection (UMAP) methods. A total of 4821 DEGs were found between osteoblasts/chondroblasts and other subtypes, with 132 senescent DEGs obtained after matching with the senescent gene set. In the TARGET database, 4 prognostic senescent DEGs [ADH5 (alcohol dehydrogenase 5), ARHGAP1 (Rho GTPase activating protein 1), APOE (apolipoprotein E), and ATF4 (activating transcription factor 4)] were identified through univariable and multivariable Cox analyses to construct OSRM. Based on risk score, patients were stratified into high- and low-risk groups, with the latter showing better prognosis (HR=0.13, 95%CI 0.06-0.28, P<0.001) and higher sensitivity to immune checkpoint inhibitors. qRT-PCR and Western blotting confirmed the high expression of senescent genes ADH5 (P<0.01), APOE (P<0.01), and ATF4 (P<0.05) in the K7M2 osteosarcoma cell line, suggesting the potential for predicting the response to anti-PD-1 immunotherapy for osteosarcoma. Conclusions scRNA-seq facilitated the division of osteosarcoma into 17 cell subtypes. ADH5, ARHGAP1, APOE, and ATF4 emerged as potential cancer-promoting or suppressing senescent genes in osteosarcoma. OSRM was found to be associated with treatment response, prognosis, and TME characteristics, thereby promoting the molecular pathological diagnosis of osteoblastic osteosarcoma and prediction for anti-PD-1 immunotherapy.

Osteoporosis (OP) is a systemic bone disease characterized by low bone mass and damage to the microstructure of bone tissue, leading to increased bone fragility and susceptibility to fracture. Owing to its high prevalence, disability and mortality rates, as well as more sequelae, it brings heavy burden to patients and society. In recent years, as the research on the chemical and pharmacological effects of Psoralea corylifolia has made great progress, scholars have isolated compounds such as coumarins, flavonoids and monoterpene phenols, which have anti-OP, anti-oxidation, and anti-inflammatory properties, Psoralea corylifolia has been widely used in the treatment of OP. This article reviews the regulatory mechanism of active ingredients of Psoralea corylifolia in OP lipid metabolism, bone metabolism and oxidative stress, as well as related therapeutic strategies targeting Wnt/β-catenin, PI3K/Akt, PPAR-γ/Wnt, RANKL/RANK/MAPK and NF-κB signaling pathways, in order to provide further reference for the prevention and treatment of OP.

Organoids are cell mini-clusters and three-dimensional (3D) micro-organs cultured and spontaneously developed under suspension culture condition in vitro, possessing the abilities of self-organize and differentiate into functional cells. They are powerful, and can partially mimic the cellular heterogeneity, structure and function of the original tissues or organs. Lung organoids (LOs) can be cultured and constructed from human pluripotent stem cells or adult stem/progenitor cells. Co-culture of LOs with immune cells can better reflect the overall picture of the immune response of lung tissue and the full spectrum of infection in vivo. This review compares characteristics of LOs with those common models for respiratory infectious diseases, including animal models, two-dimensional cell culture, lung-on-chip and precision-cut lung slices. We provide an overview of the construction method of LOs and their application progress on respiratory system infectious diseases caused by viruses, bacteria, mycobacteria, cryptosporidium, and other pathogens.

Objective To investigate the epidemiological and clinical characteristics of 954 cases of central nervous system (CNS) infections in Chongqing. Methods A retrospective analysis was conducted on 954 patients with CNS infectious disease diagnosed and treated in the Second Affiliated Hospital of Army Medical University from 2008 to 2021. The analysis encompassed pathogens, patient gender, age of onset, time of onset, urban-rural distribution, education level, occupational distribution, and other epidemiological characteristics. The clinical manifestations, the positive rate of metagenomic next-generation sequencing (mNGS), and prognosis were also analyzed. ResultsAmong the 945 cases of CNS infectious diseases, the pathogens were viruses in 393(41.2%), Mycobacterium tuberculosis in 361(37.8%), other bacteria in 108(11.3%), Cryptococcus in 75(7.9%), Treponema pallidum in 16(1.7%) and parasites in 1(0.1%). The number of CNS infection cases from 2015 to 2021 increased by 85.6% compared with that from 2008 to 2014 (620 vs. 334, P<0.001). There was no significant difference in seasonal distribution of pathogens (P>0.05). CNS infectious diseases were more prevalent in rural areas (58.0%, P<0.001), with a male-to-female ratio of 1.7:1.0, and a higher incidence in individuals aged between 35 and 60 years. The majority of patients were educated at Junior high school level or below (68.7%) and were farmers or workers (68.1%). Clinical symptoms of CNS infectious disease mainly included fever, headache, signs of meningeal irritation, nausea and vomiting, which could be accompanied by consciousness disorder and focal neurological deficits. mNGS significantly improves the accuracy of clinical diagnosis. The rate of good prognosis of CNS infectious diseases was 97.5%, while the mortality rate was 0.3%. Conclusions In Chongqing area, the categories and species of CNS infectious pathogens are diverse, widely prevalent, and the clinical manifestations are complex. Moreover, the number of cases has been increasing in recent years. Understanding the epidemiological and clinical characteristics of CNS infectious diseases can help to recognize the regional differences, promote early accurate diagnosis and treatment, and improve prognosis.

Objective To investigate the genotypic and phenotypic characteristics of AB type GM2 gangliosidosis (GM2-GLS) with onset during childhood. Methods The report analyzed the clinical data and gene detection results of a 4-year-old child with AB type GM2-GLS diagnosed by Trio whole exome detection in March 2022 admitted to the Department of Pediatrics of Guangxi Zhuang Autonomous Region People's Hospital. The clinical data and genetic testing results are analyzed. A literature review was also conducted on relevant studies published between 1991 and 2022 in the PubMed database. Results The results of Trio whole exome sequencing and Sanger verification showed that the GM2A gene carried two compound heterozygous mutations: c.158_159delTG and c.496G>A, which caused p.L53Rfs*3 frameshift mutation and p.G166R missense mutation, respectively. A total of 20 cases were reported in 22 articles. A total of 11 mutation types of GM2A gene were included in the ClinVar Database. Conclusions AB type GM2-GLS is a rare autosomal recessive lysosomal storage disease, and its gene test is helpful for definite diagnosis.

Objective To analyze the prognostic significance and biological effects of cytochrome P450 family 27 subfamily A member 1 (CYP27A1) in hepatocellular carcinoma (HCC), and to preliminarily explore its molecular mechanism of regulating the malignant growth of HCC. Methods The Cance Genome Atlas (TCGA) database was used to analyze the expression level of CYP27A1 and its prognostic effect on HCC patients. The samples were divided into CYP27A1 high-expression group (n=170) and low-expression group (n=170) based on the median expression of CYP27A1 in HCC, gene set enrichment analysis (GSEA) was performed to investigate gene sets associated with CYP27A1 expression. The subcellular localization of CYP27A1 was detected by immunofluorescence staining and search database. The over-expression plasmid of CYP27A1 was constructed and then transfected into the HCC cells MHCC-97H and HCCLM3 cell lines, including two groups, namely control group (transfecting empty vector) and CYP27A1 over-expression group (transfecting CYP27A1 over-expressed vector). CCK-8, flow cytometer, and reactive oxygen species (ROS) fluorescence probe were applied to detect the effects of CYP27A1 over-expression on cell viability, apoptosis and ROS levels in HCC cells. Combining bioinformatics to analyze the correlation between CYP27A1 and the expression of ROS generation-related genes and HCC proliferation-related genes. Results Compared with the normal liver tissue, the expression level of CYP27A1 mRNA in HCC tissue was significantly reduced (P<0.01). The expression of CYP27A1 was significantly correlated with sex, T stage, tumor grade and tumor stage of HCC patients (P<0.05). Compared to the CYP27A1 high-expression group, patients in CYP27A1 low-expression group had lower survival rate (P<0.01). GSEA enrichment analysis revealed that the levels of HCC stem cell-related gene clusters and HCC proliferation gene clusters were remarkably increased in CYP27A1 low-expression group. The immunofluorescence showed that CYP27A1 was mainly located in nucleus in MHCC-97H and HCCLM3, whereas CYP27A1 was mainly located in mitochondria in HepG2. CYP27A1 over-expression attenuated cell viability (P<0.01), and reduced the ROS levels (P<0.05), whereas it had no effects on the apoptosis in HCC cells (P>0.05). The expression of CYP27A1 and the expression of inhibiting ROS generation-related genes were positively correlated (P<0.05), while the expression of inhibiting ROS generation-related genes and the expression of HCC proliferation-related genes were negatively correlated (P<0.05). Conclusions The expression of CYP27A1 was decreased in HCC, and down-regulated CYP27A1 promoted cell growth by enhancing ROS generation, although the precise mechanism requires future educidation.

Epilepsy is a chronic disease characterized by recurrent, sudden, and excessive synchronous discharge of neurons in the brain, leading to transient brain dysfunction, and inflammatory responses in specific regions within the central nervous system are common features of epilepsy. In recent years, there has been increasing evidence that endoplasmic reticulum stress is involved in the pathology of epilepsy, which activates the unfolded protein response, then regulate and control nuclear factor kappa-B (NF-κB), efficiently induces glial cell activation through the release of pro-inflammatory signals, in turn affects epileptogenesis and seizures by triggering neuroinflammation. This review focuses on the close link between endoplasmic reticulum stress and glial cell activation-mediated neuroinflammation in epilepsy pathology, aiming to provide insights for a deeper understanding of epilepsy.

Objective To observe the clinical efficacy of compound Wufengcao liquid combined with negative pressure wound therapy with instillation (NPWTi) for the treatment of stage Ⅲ-Ⅳ pressure injury (PI), and to preliminarily explore its action mechanism. Methods (1) Clinical research: from January 2019 to October 2022, 60 PI patients who were admitted to the Scrofula Department and Wound Care Clinic at Nanjing Municipal Hospital of Traditional Chinese and Western Medicine were randomly divided into normal saline NPWTi group and compound Wufengcao liquid NPWTi group, with 30 cases in each group. Both groups underwent NPWTi under the premise of systemic basic treatment, before treatment, after removing the negative pressure device in the 1st, 2nd and 3rd weeks of treatment, the pressure ulcer scale for healing (PUSH) score, the wound bacterial culture detection rate and the wound healing time were counted, and the vascular endothelial growth factor (VEGF) content of wound tissue was detected by ELISA method. (2) Animal experiments: 24 SD rats were randomly divided into blank group, model group, normal saline NPWTi group and compound Wufengcao liquid NPWTi group, 6 rats in each group. PI rat model was established by local tissue ischemia/reperfusion injury method, and the negative pressure device was removed at the end of each day of treatment. Before treatment and 3, 7 and 10 days after treatment, the wound morphology of each group of rats was observed, the wound histopathology was observed by HE staining, the CD34 positive cells rate of wound tissue was detected by immunohistochemistry, and the expressions of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor-κB p65 (NF-κB p65), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), arginase-1 (Arg-1) and transforming growth factor-β (TGF-β) in rat blood and wound tissue were detected by ELISA and RT-qPCR. Results (1) Clinical research: Both groups could effectively reduce the PUSH score and the wound bacterial culture detection rate, shorten the wound healing time, and promote the expression of VEGF in wound tissue, the compound Wufengcao liquid NPWTi group was better than the normal saline NPWTi group (P<0.05). (2) Animal experiments: Compared with blank group, the rats in the model group showed obvious wound inflammatory response and tissue damage, and the CD34 positive cells rate, blood and wound tissue p38 MAPK, NF-κB p65, iNOS and TNF-α levels were significantly increased, Arg-1 and TGF-β level was significantly reduced (P<0.05); Compared with model group, after 7 days of treatment, the normal saline NPWTi group and the compound Wufengcao liquid NPWTi group significantly decreased the wound morphology score, the histopathological morphology was significantly improved, the CD34 positive cells rate was significantly increased (P<0.05), the levels of blood and wound tissue p38 MAPK, NF-κB p65, iNOS, and TNF-α were significantly reduced, and the levels of Arg-1 and TGF-β were significantly increased (P<0.05), and the compound Wufengcao liquid NPWTi group was better than that of the normal saline NPWTi group (P<0.05). Conclusion Compound Wufengcao liquid combined with NPWTi can effectively promote the healing of PI wounds, and its mechanism of action may be by inhibiting the activation and expression of p38 MAPK/NF-κB signaling pathway, thereby regulating the polarization balance of M1/M2 macrophages.

Objective To investigate the independent risk factors of comprehensive complication index (CCI) ≥26.2 after radical resection of colon cancer, and use these factors to establish and verify a dynamic web-based nomogram model. Methods The clinical data of colon cancer patients who underwent radical resection in the Affiliated Hospital of Jiangnan University from November 2020 to April 2022 were retrospectively collected, and divided into main cohort (November 2020 to October 2021, n=438) and validation cohort (November 2021 to April 2022, n=196). CCI scores of all patients were obtained based on CCI calculator (http://www.assessurgery.com). Univariate and multivariate logistic regression analysis were performed to identify the risk factors for CCI ≥26.2, and a nomogram model was constructed. Receiver operator characteristic curve (ROC), C index and calibration curve were used to evaluate the differentiation and consistency of predictive nomogram model, and the decision curve analysis was conducted to assess the clinical benefits of the model. Internal validation of the model is performed in the validation cohort. Results A total of 438 patients were identified in present study, of which 63 cases (14.4%) had CCI ≥26.2. Multivariate logistic regression analysis revealed that age ≥60 years (OR=2.662, 95%CI 1.341-5.285, P=0.005), low third lumbar spine skeletal muscle mass index (L₃MI; OR=4.572, 95%CI 2.435-8.583, P<0.001), NRS2002 ≥3 (OR=4.281, 95%CI 2.304-7.952, P<0.001), and preoperative bowel obstruction (OR=3.785, 95%CI 1.971-7.268, P<0.001) were significant independent risk factors for postoperative CCI ≥26.2. Based on these results, a static and web-based dynamic nomogram was established (https://jndxfsyywcwksyf.shinyapps.io/DynNomCCI/). The C-index and area under the curve (AUC) of the nomogram were 0.742 and 0.787, respectively. The calibration curve indicated a good consistency between the predicted probability and the actual probability. In the validation cohort, the nomogram also presented good discrimination (C-index=0.722, AUC=0.795) and predictive consistency. The decision curve analysis indicated the clinical benefit and application value of the nomogram prediction model. Conclusion This easy-to-use dynamic nomogram based on 4 independent risk factors can conveniently and reliably predict the probability of CCI ≥26.2 after radical resection of colon cancer, which helps optimize the preoperative evaluation system, formulate precise individualized treatment strategies, and enhance recovery after surgery.