Urticarial vasculitis is a skin disease with urticaria-like lesions and a histopathological pattern of leukocytoclastic vasculitis. It is considered a "hidden rash" in traditional Chinese medicine. Xuanfu is the portal that regulates qi, blood, fluid, and the ascending, descending, exiting, and entering of nutrition qi and defensive qi. Collaterals are the pathways for the circulation of qi and blood. The two accompany each other, connecting zang-fu organs, reaching the surfaces of the skin, hair, and external body, circulating qi and fluid, and moistening and protecting the skin. Based on the theory of Xuanfu-collateral, this study aimed to clarify the etiology, pathogenesis, and treatment method of urticarial vasculitis. External assault by wind and Xuanfu blockage are believed to be the initiating factors of this disease. The malnutrition of Xuanfu and collaterals and accumulated dampness-heat are important links in the occurrence and development of urticarial vasculitis. It spreads from Xuanfu to the collaterals, and blockage of the collaterals is the immanent trend of this disease. Clinically, by closely adhering to the core pathogenesis of blockage of Xuanfu-collateral, treatment method such as using wind medicinals to open Xuanfu with pungent and dispersing properties, using the method of supplement deficiency and removing the blockage, and using medicinals to promote blood circulation and remove blood stasis to unblock the blocked collaterals. The herbs are flexibly added or subtracted to unblock Xuanfu and collaterals, harmonize qi and blood, thus all symptoms can be relieved. We hope that this study will provide new ideas for the treatment of urticarial vasculitis with traditional Chinese medicine.

BACKGROUND: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between LE8 scores and the risk of chronic kidney disease (CKD) remains uncertain. We aimed to explore the association of LE8 scores with new-onset CKD and examine whether socioeconomic deprivation and genetic risk modify this association. METHODS: A total of 286,908 participants from UK Biobank and without prior CKD were included between 2006 and 2010. CVH was categorized using LE8 scores: low (LE8 scores <50), moderate (LE8 scores ≥50 but <80), and high (LE8 scores ≥80). The study outcome was new-onset CKD, ascertained by data linkage with primary care, hospital inpatient, and death data. Cox proportional hazard regression models were used to investigate the association between CVH categories and new-onset CKD. RESULTS: During a median follow-up of 12.5 years, 8857 (3.1%) participants developed new-onset CKD. Compared to the low CVH group, the moderate (adjusted hazards ratio [HR], 0.50; 95% confidence interval [CI]: 0.47-0.53) and high CVH (adjusted HR, 0.31; 95% CI: 0.27-0.34) groups had a significantly lower risk of developing new-onset CKD. The population-attributable risk associated with high vs. intermediate or low CVH scores was 40.3%. Participants who were least deprived ( vs.  most deprived; adjusted HR, 0.75; 95% CI: 0.71-0.79) and with low genetic risk of CKD ( vs.  high genetic risk; adjusted HR, 0.89; 95% CI: 0.85-0.94) had a significantly lower risk of developing new-onset CKD. However, socioeconomic deprivation and genetic risks of CKD did not significantly modify the relationship between LE8 scores and new-onset CKD (both P -interaction >0.05). CONCLUSION Achieving a higher LE8 score was associated with a lower risk of developing new-onset CKD, regardless of socioeconomic deprivation and genetic risks of CKD.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Male ; Female ; Middle Aged ; Genetic Predisposition to Disease/genetics* ; Aged ; Risk Factors ; Adult ; Proportional Hazards Models ; Socioeconomic Factors

The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

Objective To investigate the association of proton pump inhibitors(PPIs)use with short-term and long-term mortality risk in patients with severe ischemic stroke.Methods This retrospective study based on the U.S.Medical Information Mark for Intensive Care Ⅲ(MIMIC-Ⅲ)database,ICU patients aged ≥18 years with the first ICU admission and a diagnosis of ischemic stroke were finally included in the study.All enrolled subjects were divided into PPIs group and non-PPIs group according to whether they had used PPIs(pantoprazole,lansoprazole and omeprazole)during hospitalization.Kaplan-Meier survival analyses and Cox regression models were used to analyze the association between the use of PPIs and the risk of ICU death,30 d risk of death,90 d risk of death in patients with severe ischemic stroke.Results A total of 1 015 patients were included,402 cases in the PPIs group and 613 in the non-PPIs group.The ICU-mortality,30 d and 90 d mortality were 15.37％,13.60％and 20.10％,respectively.Kaplan-Meier survival analyses illustrated that the PPIs group survived better than non-PPIs group in ICU mortality analysis(P=0.002).In Cox regression analysis,after adjustment for potential confounders,the hazard ratio(HR)for ICU mortality in the PPIs group relative to the non-PPIs group was 0.671 9(95％CI 0.478 8 to 0.942 8,P=0.021),but there was no significant difference between 30 d and 90 d mortality(P＞0.05).Conclusion In patients with severe ischemic stroke,the use of PPIs may be effective in reducing the risk of ICU death,but does not improve 30 d and 90 d risk of death in patients.

Tumor microenvironment(TME)is a complex cellular environment where tumor cells reside,along with various types of cells and extracellular components surrounding the tumor cells.Immune cells are key components of TME,including tumor-associated macrophages(TAMs),myeloid-derived suppressor cells(MDSCs),lymphocytes,regulatory T cells(Tregs),natural killer cells(NK cells),dendritic cells(DCs),and many others.It is worth noting that drug resistance is currently a major factor limiting the efficacy of cancer treatment methods such as chemotherapy,radiotherapy,targeted therapy,and immunotherapy,and a leading cause of treatment failure.Research has found that the development of drug resistance in tumor cells is the result of interactions between tumor cells and TME.Consequently,overcoming drug resistance in tumors caused by TME is considered a significant challenge in cancer treatment.In recent years,with in-depth research into immune cells within TME,significant progress has been made in understanding the specific mechanisms by which immune cells regulate drug resistance in tumor cells.Furthermore,therapeutic strategies that target these immune cells,signaling pathways,or cytokines have been shown to effectively combat tumor drug resistance and enhance the therapeutic outcomes of cancer treatment.This article reviews the research advancements regarding the roles of TAMs,MDSCs,Tregs,and NK cells in tumor drug resistance within TME and discusses the development of targeting strategies to overcome this resistance.Additionally,we explore the relationship of tumor-associated neutrophils(TANs)and B regulatory cells(Bregs)with tumor drug resistance.It is hoped that this review will offer insights and serve as reference for reducing tumor drug resistance and improving the efficacy of anti-tumor therapies.

Diabetes mellitus(DM)is an endocrine metabolic disease mainly characterized by chronic hyperglycemia,which seriously threatens the health and quality of life of human beings,and with the improvement of living standard and unhealthy lifestyle in China,the incidence of DM continues to rise and tends to be younger,so it is urgent to carry out in-depth research on hypoglycemic treatment.DM is pathologically based on absolute or relative insulin deficiency,and there is no radical cure for it,and Western medicine mostly adopts insulin injection or oral hypoglycemic drugs for symptomatic treatment,which is effective but prone to toxic side effects in long-term use.Chinese medicine has the advantages of multi-path and multi-target in treating DM,and plays a role in lowering blood sugar by promoting insulin secretion,improving insulin resistance,regulating glucolipid metabolism and anti-oxidative stress,etc.Its efficacy is remarkable and the rate of toxic side effects is low.In recent years,there have been more studies on the mechanism of action of traditional Chinese medicine and compound prescriptions on animal models of DM.By reviewing the relevant literature in recent years,the author has systematically sorted out the mechanism of hypoglycemic action of single Chinese medicine,traditional Chinese medicine compound prescriptions,effective components of traditional Chinese medicine and their related experimental designs,from promoting insulin secretion,inhibiting gluconeogenesis,promoting glycogen synthesis,improving insulin resistance,inhibiting glycosidase activity,alleviating oxidative stress damage,inhibiting inflammatory response and regulating intestinal stress.The study and experimental design of the hypoglycemic mechanism of Chinese medicine were summarized in terms of promoting insulin secretion,inhibiting gluconeogenesis,promoting glycogen synthesis,improving insulin resistance,inhibiting glucosidase activity,alleviating oxidative stress damage,inhibiting inflammatory response and regulating intestinal flora,etc.,with a view to providing reference for the wider clinical application of Chinese medicine in hypoglycemia and its in-depth pharmacodynamic study.

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.

Objective To investigate the relationship between insomnia,gastrointestinal symptoms,and glycosylated hemoglobin(HbA1c)levels in individuals diagnosed with type 2 diabetes mellitus(T2DM),as well as the related influencing factors.Methods A total of 910 T2DM patients treated in our multicenter from January 2022 to December 2022 were enrolled in this study.General information(gender,age,smoking and drinking history,exercise,course of disease,treatment and complications),HbA1c,Athens Insomnia Scale(AIS)scores and Gastrointestinal Symptoms Rating Scale(GSRS)scores of patients were collected.The differences of sleep and gastrointestinal symptoms between groups were analyzed,and the correlation between the differences and HbA1c was analyzed.Furthermore,the risk factors for non-standard HbA1c were analyzed.Results The AIS score and GSRS score in the HbA1c control group were less than those in the non-standard group(P＜0.01).Insomnia was reported by 37.0％of T2DM patients,and the HbA1c level in the insomnia group was significantly higher than that in the non-insomnia group(10.00％±2.38％vs.8.26％±1.73％,P＜0.01).Gastrointestinal symptoms were present in 57.5％of T2DM patients,and the HbA1c levels in the group with gastrointestinal symptoms were significantly higher than those in the group without gastrointestinal symptoms(9.26％±2.23％vs.8.43％±1.98％,P＜0.01).Furthermore,26.3％of T2DM patients experienced both insomnia and gastrointestinal symptoms.Remarkably,the HbA1c levels in the group with both insomnia and gastrointestinal symptoms were significantly higher than those in the group without either condition(10.18％±2.44％vs.8.45％±1.86％,P＜0.01).Correlation analysis demonstrated a significant association between sleep quality,gastrointestinal function,and HbA1c levels(P＜0.01).The logistic regression analysis result revealed that age,GSRS score,AIS score,and the presence of insomnia combined with gastrointestinal symptoms were independent risk factors for predicting HbA1c≥6.5％(P＜0.01).Having both insomnia and gastrointestinal symptoms concurrently was the strongest risk factor for substandard HbA1c control,and the risk of blood sugar control may increase about 5 times when both appear together.Conclusion Insomnia and gastrointestinal symptoms are common comorbidities in T2DM patients,showing a cross-interfering relationship,and they appear together with poor blood sugar control,interact causally,and amplify each other.

Background::Whether functional gastrointestinal disorders (FGIDs) are associated with the long-term risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association.Methods::About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included. Participants with FGIDs (including irritable bowel syndrome [IBS], dyspepsia, and other functional intestinal disorders [FIDs; mainly composed of constipation]) were the exposure group, and non-FGID participants were the non-exposure group. The primary outcome was incident CKD, ascertained from hospital admission and death registry records. A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD, and the mediation analysis was performed to investigate the mediation proportions of mental health.Results::At baseline, 33,156 (8.0%) participants were diagnosed with FGIDs, including 21,060 (5.1%), 8262 (2.0%), and 6437 (1.6%) cases of IBS, dyspepsia, and other FIDs, respectively. During a mean follow-up period of 12.1 years, 11,001 (2.6%) participants developed CKD. FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.28–1.44). Similar results were observed for IBS (HR, 1.27; 95% CI, 1.17–1.38), dyspepsia (HR, 1.30; 95% CI, 1.17–1.44), and other FIDs (HR, 1.60; 95% CI, 1.43–1.79). Mediation analyses suggested that the mental health score significantly mediated 9.05% of the association of FGIDs with incident CKD and 5.63–13.97% of the associations of FGID subtypes with CKD. Specifically, the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD.Conclusion::Participants with FGIDs had a higher risk of incident CKD, which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

OBJECTIVE To observe the clinical efficacy of endoscopic type Ⅰ tympanoplasty in patients with chronic suppurative otitis media accompanied by fungal otitis media.METHODS Based on the symptom characteristics of the external auditory canal and tympanic mucosa,80 patients were divided into four groups:dry ear without fungi group,dry ear with fungi group,wet ear without fungi group,and wet ear with fungi group.Record its clinical characteristics.Patients with fungal otitis externa should receive medication treatment during the perioperative period.Failure to heal the tympanic membrane repaired 6 months after surgery,recurrent perforation of the graft,and/or persistent inability to dry the ear are considered repair failures.RESULTS A total of 80 patients were included in this study,and the overall healing rate of the tympanic membrane in the four groups of patients was 98.8％.There was no significant difference in the postoperative tympanic membrane healing rate among the four groups of patients.The postoperative air bone conduction difference in all four groups of patients decreased compared to preoperative levels,but the difference was not statistically significant.CONCLUSION Patients with chronic suppurative otitis media accompanied by fungal otitis media undergoing type Ⅰ tympanoplasty showed no decrease in tympanic membrane healing rate and no significant improvement in efficacy.