Objective To investigate the effects and mechanism of β₂ adrenergic receptors (ADRB2) in ferroptosis and autophagy induced by erastin (Era) in prostate cancer. Methods PC-3 cells were infected with lentivirus or control and set to sh-NC group (normal culture), sh-NC+Era group (10 μmol/L Era treatment for 24 h), sh-ADRB2 group (normal culture), and sh-ADRB2+Era group (10 μmol/L Era treatment for 24 h). The viability of the cells treated with Era and ferrostatin-1 (Fer-1) was measured by CCK-8 assay. The cell morphology was analyzed by transmission electron microscopy. The malondialdehyde (MDA) content was measured by the Lipid Oxidation Detection Kit and the iron level by Iron Colorimetric Assay. Western blotting was used to detect the expressions of cystine-glutamate exchanger (XCT), ferritin heavy chain 1 (FTH1), glutathione peroxidase 4 (GPX4), p62, LC3, JNK, c-Jun, and p-c-Jun. PC-3 cells with ADRB2 knockdown were injected into nude mice to construct a xenograft model and then treated with Era. The animals were divided into sh-NC group, sh-NC+Era group, sh-ADRB2 group, and sh-ADRB2+Era group, with 4 mice in each group. The tumor volumes were recorded every other day and the final tumor weight was measured at study termination. The expressions of ADRB2, JNK, c-Jun, and p-c-Jun were detected by immunohistochemistry (IHC). Results The viability of PC-3 cells decreased after Era treatment (P<0.01) and recovered after Fer-1 treatment (P<0.01). Morphological changes of ferroptosis and autophagy were observed in Era-treated cells, and MDA and iron ion contents up-regulated (P<0.05 or P<0.01). Knockdown of ADRB2 and Era treatment further inhibited PC-3 cell viability (P<0.05), and MDA and iron ion contents up-regulated (P<0.01). The expressions of ferroptosis-related proteins FTH1, XCT, GPX4, and LC3 down-regulated (P<0.05 or P<0.05), p62 and JNK pathway-related proteins JNK, c-Jun, and p-c-Jun were up-regulated (P<0.01). After JNK inhibitor treatment, the expressions of FTH1, XCT, and LC3 increased, and p62 decreased (P<0.01). In the PC-3 xenograft model, tumor volume in sh-ADRB2+Era group was significantly smaller than those in sh-NC+Era group and sh-ADBR2 group (P<0.05 or P<0.01). IHC showed that compared with sh-NC group, ADRB2 protein expression level was down-regulated in sh-ADRB2 group (P<0.05), while JNK, c-Jun, and p-c-Jun protein expression levels were elevated (P<0.01). Compared with sh-NC+Era group, the ADRB2 protein expression level in sh-ADRB2+Era group was down-regulated, while JNK, c-Jun, and p-c-Jun protein expression levels were up-regulated (P<0.05). Conclusion ADRB2 regulated ferroptosis and autophagy induced by Era via JNK/c-Jun pathway in prostate cancer.

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.

Neuro-developmental disorders (NDDs) are chronic developmental brain dysfunctions that affect multifunctional areas of the brain,caused by various genetic or acquired factors. Vitamin D (Vit D), as a neurosteroid hormone, can exert its function through both genetic and non-genetic mechanisms. Over the past few decades, studies on the relationship between Vit D levels and NDDs have found that Vit D deficiency during development is a risk factor for some NDDs. Vit D deficiency in early life can affect brain development, disrupt the balance of neurotransmitters in the brain, and reduce the body's and brain's antioxidant capacity. This review examines the mechanism of Vit D in the brain, explores the relationship between Vit D and neurodevelopmental disabilities, highlights recent research progress and identifies unsolved problems, in order to deepen understanding of the role of Vit D in NDDs and provide novel insights for the diagnosis and treatment of NDDs.

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.

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.

Officers and soldiers exposed to high temperature and high-humidity environments are highly susceptible to exertional heat illness and even heatstroke. Reports indicated that after conventional treatment, the heat endurance damage in officers/soldiers with exertional heat illness can persist for months or even years. Therefore, the Expert Group of Heatstroke Prevention and Treatment of Heatstroke of Chinese PLA has specially formulated a technical proposal for the reconstruction of heat endurance in officers/soldiers suffering from exertional heatstroke, aiming to provide a safeguard for reconstruction of heat endurance in affected personnel. This article mainly elaborates on the basic concepts, technical requirements, initiation timing, implementation assessment, and follow-up of the heat endurance reconstruction for officers/soldiers with exertional heatstroke.

Objective To compare the outcomes of transplant kidneys and patient survival between simultaneous pancreas-kidney transplantation (SPKT) recipients and deceased donor kidney transplant (DDKT) recipients in patients with type 2 diabetes mellitus (T2DM) complicated with end-stage renal disease (ESRD), and to analyze the risk factors affecting patient survival post-SPKT. Methods Clinical and prognostic data of patients who underwent kidney transplantation from January 27, 2003, to January 1, 2021, were retrieved from the United Network for Organ Sharing (UNOS) database. A total of 50 230 cases were selected based on inclusion criteria, with 48 669 cases in DDKT group and 1561 cases in SPKT group. Kaplan-Meier analysis was employed to compare transplant kidney and patient survival between the two groups, and propensity score matching (PSM) was utilized to balance confounding factors between the groups. Cox regression model was used to analyze independent risk factors affecting patient survival post-SPKT. Results Compared with DDKT group, recipients in SPKT group had a younger median age (P<0.001), a higher proportion of males (P<0.001), lower BMI (P<0.001), shorter dialysis and transplant waiting times (P<0.001), a higher percentage of private medical insurance (P<0.001), a lower proportion of previous transplants (P<0.001), a younger age at diabetes diagnosis (P<0.001), and a lower incidence of peripheral vascular disease (P=0.033). Compared with DDKT group, the donors in SPKT group had a younger median age (P<0.001), a higher proportion of males (P<0.001), lower BMI (P<0.001), and a lower prevalence of hypertension and diabetes history (P<0.001). In terms of transplant-related factors, the SPKT group had a shorter donor kidney cold ischemia time (P<0.001), a higher degree of HLA mismatch (P<0.001), and a lower Kidney Donor Profile Index (KDPI) (P<0.001) when compared with DDKT group. The SPKT group had lower serum creatinine levels at discharge (P<0.001), lower rates of postoperative delayed graft function (DGF) and acute rejection (AR) (P<0.001), but longer hospital stays (P<0.001) when compared with DDKT group. Kaplan-Meier survival analysis curves, both original and after propensity score matching (PSM), consistently showed significantly higher transplant kidney and patient survival rates in SPKT group compared with DDKT group (P<0.001). Cox regression model analysis indicated that recipient age, recipient race, donor age, and donor kidney cold ischemia time were independent risk factors influencing patient survival post-SPKT. Conclusions For ESRD patients with T2DM, SPKT offers improved long-term graft and patient survival rates compared with DDKT. Recipient age, recipient ethnicity, donor age, and cold ischemia time for the donor's kidney are independent risk factors affecting post-SPKT patient survival.

Objective To explore the relationship between serum ferritin levels and body fat distribution in patients with type 2 diabetes mellitus (T2DM). Methods A retrospective analysis was conducted on 151 patients with T2DM who were hospitalized in the Department of Endocrinology of the First Hospital of Lanzhou University from June to November 2020, and all the patients were divided into high serum ferritin (n=50) and normal serum ferritin (n=101) groups according to their serum ferritin levels. The visceral fat area (VFA), subcutaneous fat area (SFA), liver fat, height, weight and waist circumference (WC) were measured, as well as blood glucose, lipid indexes, body mass index (BMI) and visceral adiposity index (VAI) were also calculated. t-test or nonparametric test was used to compare the differences between the two groups, and the relationship between serum ferritin levels and body fat distribution was analyzed by Pearson or Spearman correlation analysis, multiple linear regression and logistic regression. Results The VAI and WC were significantly higher in high serum ferritin group [3.13(2.16,4.58) and (96.66±7.78) cm] than in normal serum ferritin group [2.66(1.66,3.81) and (91.96±9.75) cm, P<0.05]. The prevalence of central obesity and dyslipidemia was higher in high serum ferritin group (88.0% and 90.0%) than in normal serum ferritin group (68.3% and 75.2%); and the composition ratios of poor glycemic control and insulin resistance (96.0% and 62.0%) were also higher than in normal serum ferritin group (78.2% and 40.6%) (P<0.05), there were no statistically significant differences in BMI, VFA, and SFA levels, as well as antidiabetic drug use and chronic complications of diabetes mellitus between the two groups (P>0.05). Serum ferritin levels in T2DM patients were positively correlated with VAI, WC, triglyceride (TG), fasting blood glucose (FPG), HbA1c, dyslipidemia and serum creatinine (r=0.171, 0.207, 0.187, 0.243, 0.270, 0.162, 0.162; P<0.05), and negatively correlated with age, sex and diabetes course (r=-0.191, -0.434, -0.352; P<0.05). Multivariate linear regression analysis showed that in male T2DM patients, duration of diabetes and FPG were risk factors for increased levels of serum ferritin. However, WC and VAI did not significantly affect serum ferritin levels. In female patients with T2DM, the course of diabetes, TG and VAI were the factors influencing serum ferritin (P<0.05). Conclusion Dyslipidemia and visceral fat accumulation are risk factors for elevated serum ferritin levels in female T2DM patients.

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.

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.