Ulcerative colitis（UC） is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulceration of the colonic mucosa and submucosa， and its complex pathogenesis involves immune abnormality， oxidative stress and other factors. The nuclear transcription factor E₂-related factor 2（Nrf2）， encoded by the Nfe212 gene， plays a central role in antioxidant responses. It not only activates various antioxidant response elements such as heme oxygenase-1（HO-1） and quinone oxidoreductase 1（NQO1）， but also enhances the activity of glutathione-S-transferase（GST） and superoxide dismutase 1（SOD1）， effectively eliminating reactive oxygen species（ROS） accumulated in the body， and mitigating oxidative stress-induced damage to intestinal mucosa. In addition， Nrf2 can reduce the release of inflammatory factors and infiltration of immune cells by regulating immune response， cell apoptosis and autophagy pathways， thereby alleviating intestinal inflammation and promoting the repair and regeneration of damaged mucosa. Based on this， this paper reviews the research progress of Chinese materia medica in the prevention and treatment of UC by modulating the Nrf2 signaling pathway. It deeply explores the physiological role of Nrf2， the molecular mechanism of activation， the protective effect in the pathological process of UC， and how active ingredients in Chinese materia medica regulate the Nrf2 signaling pathway through multiple pathways to exert their potential mechanisms. These studies have revealed in depth that Chinese materia medica can effectively combat oxidative stress by regulating the Nrf2 signaling pathway. It can also play a role in anti-inflammatory， promoting autophagy， inhibiting apoptosis， protecting the intestinal mucosal barrier， and promoting intestinal mucosal repair， providing new ideas and methods for the multi-faceted treatment of UC.

OBJECTIVES: To explore the value of serum cystatin C (CysC) levels in evaluating renal prognosis in IgA nephropathy (IgAN) patients. METHODS: We retrospectively collected the clinical data of IgAN patients diagnosed by renal biopsy at Guangdong Provincial People's Hospital from January, 2014 to December, 2018. Based on baseline serum CysC levels, the patients were divided into high serum CysC (>1.03 mg/L) group and normal serum CysC (≤1.03 mg/L) group. The composite endpoint for poor renal prognosis was defined as ≥50% decline in estimated glomerular filtration rate (eGFR) and/or progression to end-stage renal disease (ESRD). Lasso regression, multivariate Cox regression and Kaplan-Meier survival analysis were used to identify the risk factors and compare renal survival rates between the two groups. Smooth curves fitting and threshold effect analysis were used to explore the relationship between serum CysC levels and the outcomes. A nomogram model was constructed and its predictive performance was evaluated using concordance index, calibration curve, receiver operating characteristic (ROC) curve and the area under curve (AUC). RESULTS: A total of 356 IgAN patients were enrolled, who were followed up for 4.65±0.93 years. The composite endpoint occurred in 74 patients. High serum CysC was identified as an independent risk factor for poor renal prognosis in IgAN (HR=2.142, 95% CI 1.222 to 3.755), and the patients with high serum CysC levels had a lower renal survival rate (Log-rank χ²=47.970, P<0.001). In patients with serum CysC below 2.12 mg/L, a higher CysC level was associated with an increased risk of poor renal prognosis (β=3.487, 95% CI: 2.561-4.413, P<0.001), while above this level, the increase of the risk was not significant (β=0.676, 95% CI: -0.642-1.995, P=0.315). The nomogram model based on serum CysC and 3 other independent risk factors demonstrated good internal validity with a concordance index of 0.873 (95% CI: 0.839-0.907) and an AUC of 0.909 (95% CI: 0.873-0.945). CONCLUSIONS Serum CysC levels are associated with renal prognosis in IgAN patients, and high serum CysC an independent risk factor for poor renal prognosis.
Humans ; Glomerulonephritis, IGA/diagnosis* ; Cystatin C/blood* ; Prognosis ; Risk Factors ; Retrospective Studies ; Glomerular Filtration Rate ; Kidney Failure, Chronic ; Male ; Female ; Adult ; Nomograms ; Middle Aged

Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells, and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC)-derived skin organoids combined with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.
Animals ; Organoids/metabolism* ; Mice ; Humans ; Wound Healing ; Frostbite/metabolism* ; Skin/pathology* ; Induced Pluripotent Stem Cells/cytology* ; Cicatrix/pathology* ; Fibroblasts/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Extracellular Matrix/metabolism* ; Male

The environmental pollution and health hazards caused by the extensive use of organophosphorus flame retardants (OPFRs) have become a problem of wide concern around the world. As a typical OPFR, 2-ethylhexyl diphenyl phosphate (EHDPP) can be detected in water, atmosphere, soil and other environmental media. It widely exists in production and life and can accumulate in organisms, causing great risks the ecosystem and human health. This paper reviews the research of EHDPP domestically and abroad, and summarizes the physicochemical properties of EHDPP and the population situation of occupational exposure, environmental exposure, and population exposure in recent years. Besides, it summarizes the toxic effects and mechanisms of EHDPP, including acute toxicity, hepatotoxicity, neurotoxicity, reproductive and developmental toxicity, and carcinogenesis effects. This paper also proposes the future direction of toxicity and health risks of EHDPP, which provides a theoretical basis for further research on environmental hazards and safety evaluation of EHDPP.

The environmental pollution and health hazards caused by the extensive use of organophosphorus flame retardants (OPFRs) have become a problem of wide concern around the world. As a typical OPFR, 2-ethylhexyl diphenyl phosphate (EHDPP) can be detected in water, atmosphere, soil and other environmental media. It widely exists in production and life and can accumulate in organisms, causing great risks the ecosystem and human health. This paper reviews the research of EHDPP domestically and abroad, and summarizes the physicochemical properties of EHDPP and the population situation of occupational exposure, environmental exposure, and population exposure in recent years. Besides, it summarizes the toxic effects and mechanisms of EHDPP, including acute toxicity, hepatotoxicity, neurotoxicity, reproductive and developmental toxicity, and carcinogenesis effects. This paper also proposes the future direction of toxicity and health risks of EHDPP, which provides a theoretical basis for further research on environmental hazards and safety evaluation of EHDPP.

BACKGROUND:With a gradually aging population,improving the ability to screen for the risk of death after arthroplasty and implementing timely personalized intervention programs for the increasing number of elderly patients with femoral neck fractures is key to improving the postoperative status of patients and prolonging survival expectations. OBJECTIVE:To investigate the risk factors for postoperative mortality in elderly patients with femoral neck fractures and to construct a nomogram predictive model to predict their mortality risk. METHODS:The study was conducted on 155 elderly patients(≥65 years old)who underwent arthroplasty for femoral neck fracture from January 2016 to January 2021,and 147 patients who met the inclusion criteria were analyzed to collect clinical data that may affect the patients'postoperative mortality.Single-factor and multi-factor Cox regression analyses were successively used to screen independent risk factors associated with postoperative mortality.The column line graph model was constructed and validated using Rstudio software. RESULTS AND CONCLUSION:(1)Age,frailty(age-adjusted Charlson comorbidities score),preoperative activity status,osteoporosis,and postoperative serum albumin level were five independent risk factors for postoperative mortality in elderly patients with femoral neck fractures(P<0.05).(2)The nomogram predictive model was constructed based on the results of multifactorial analysis,with a consistency index of 0.819(95%CI:0.771-0.868).Receiver operating characteristic curve analysis showed that the area under curve for 1-year and 3-year survival prediction was 0.8543 and 0.7263,respectively,indicating that the nomogram predictive model has good discriminatory and predictive power;calibration curve and decision curve analysis also showed good model discriminative power and clinical utility value.(3)The constructed nomogram predictive model has good diagnostic efficacy and accuracy,and can effectively assess the risk of postoperative death of patients.

BACKGROUND:Arthroplasty is the primary treatment for displaced femoral neck fractures in the elderly,and the choice of total hip arthroplasty versus hemiarthroplasty is currently the subject of considerable debate. OBJECTIVE:To compare the mid-and long-term survival status of total hip arthroplasty versus hemiarthroplasty under a direct anterior approach for displaced femoral neck fractures in the elderly based on the propensity score matching method. METHODS:One hundred and forty-seven elderly patients(≥65 years of age)with displaced femoral neck fractures were admitted from January 2016 to January 2021,of whom 88 had total hip arthroplasty(total hip arthroplasty group)and 59 had artificial femoral head replacement(hemiarthroplasty group).For the patients'preoperative comorbidities,the age-corrected Charlson Comorbidity Scale was used to quantify the scores and calculate patient frailty.The propensity score matching method was used to match the two groups 1:1 and to compare the operation time,bleeding,postoperative hospitalization time,hospitalization cost,nutritional index,postoperative complications,and mortality between the two groups after matching.Postoperative survival time was determined by Kaplan-Meier Survival analysis. RESULTS AND CONCLUSION:(1)After propensity score matching,a total of 42 matched pairs were successful in both groups,and the preoperative data of patients in both groups were balanced and comparable after matching(P>0.05).(2)Compared with the hemiarthroplasty group,operation time(79.71 minutes vs.59.07 minutes,P<0.001),bleeding volume(839.64 mL vs.597.83 mL,P=0.001),and hospitalization cost(56 508.15 yuan vs.41 702.85 yuan,P<0.001)were significantly higher in the total hip arthroplasty group.However,the mortality rate was lower in the total hip arthroplasty group than in the hemiarthroplasty group(36%vs.57%,HR=0.44,95%CI:0.23-0.87,P=0.018),and the mean survival time was longer in the total hip arthroplasty group than in the hemiarthroplasty group(59.4 months vs.43.7 months,P=0.024).(3)There were no statistically significant differences in postoperative hospitalization time,preoperative and postoperative nutritional indicators,and overall postoperative complication rate between the two groups(P>0.05).However,in terms of postoperative pain,the incidence of pain was significantly higher in the hemiarthroplasty group than that in the total hip arthroplasty group(24%vs.7%,P=0.035).(4)Overall,total hip arthroplasty has a better prognosis for survival,while hemiarthroplasty is more appropriate for patients with poor physical fitness.At the same time,postoperative pain may largely affect the quality and survival time of patients after hip arthroplasty.

IgA nephropathy (IgAN) is the most common primary glomerular disease and main reason of progression to end-stage renal disease in patients with kidney diseases. Various clinical, pathological, demographic and new factors discovered by researchers in recent years play important roles in the prognosis assessment of IgAN. Furthermore, developing prognostic evaluation models based on several different factors to identify patients at high risk of progression in the early disease stage is clinically significant. This article reviews the researches progress of influencing factors and relevant evaluation models for prognosis of IgAN.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

The incidence of augmented renal clearance (ARC) in intensive care patients (ICU) is exceptionally high, and these patients are often co-morbid with infection. The occurrence of ARC will significantly increase the clearance rate of antibiotics, making it difficult for conventional doses to reach effective therapeutic concentrations and affect the patient's anti-infective treatment effect and prognosis. It can be seen that it is crucial to formulate a reasonable dosing regimen for ICU patients with ARC. Regrettably, few reports in China about the adjustment strategy of antibiotic dosing regimens for ARC patients. Therefore, this article reviews the domestic and foreign literature for reference to provide evidence for medical personnel to adjust the dose of antibacterial drugs for such patients.