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.

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.

Objective:To investigate the effect of long noncoding RNA (lncRNA) 5033413D16Rik (lncRNA 5033413D16Rik) on the activity of interphotoreceptor retinoid-binding protein 1-20 (IRBP) 1-20-specific T helper 17 (Th17) cells in experimental autoimmune uveitis (EAU). Methods:Twelve SPF grade C57BL/6 female mice aged 8 to 10 weeks were selected and divided into EAU group and normal control group using the random number table method, with 6 mice in each group.Mice in the normal control group received no treatment.Mice in the EAU group were immunized with IRBP 1-20 emulsified in complete Freund's adjuvant to induce EAU.On day 13 after immunization, fundus examination and inflammation scoring were performed, and retinal histopathological changes were observed with hematoxylin and eosin staining.T cells were isolated from the spleen and lymph nodes of EAU mice, and the relative expression of lncRNA 5033413D16Rik was detected by real-time fluorescence quantitative PCR (qRT-PCR).In addition, the isolated T cells were divided into short hairpin RNA (shRNA)-5033413D16Rik transfected group and shRNA-negative control (NC) transfected group, and transfected with corresponding shRNAs, respectively.The knockdown efficiency of shRNA-5033413D16Rik was verified by qRT-PCR.T cells in the two groups were co-cultured with bone marrow-derived dendritic cells (BMDCs) under Th17 polarizing conditions.The relative expression of retinoic acid-related orphan receptor (RORγt), interleukin 17 (IL-17), IL-23 receptor (IL-23R), and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA in co-cultured cells were analyzed by qRT-PCR.The IL-17 concentration in co-culture supernatants was assayed by ELISA and percentages of Th17 cells were determined by flow cytometry.The use and care of experimental animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals promulgated by the State Science and Technology Commission.The study protocol was reviewed and approved by the Experimental Animal Ethics Committee of Tianjin Medical University (No.TJYY2019110117). Results:EAU model was established successfully.qRT-PCR analysis showed that the expression of lncRNA 5033413D16Rik was significantly decreased in T cells from EAU mice compared with normal control mice ( t=-13.332, P<0.001).Compared with the shRNA-NC transfected group, the relative expression of lncRNA 5033413D16Rik in T cells of the shRNA-5033413D16Rik transfected group was significantly reduced ( t=-6.338, P<0.01).In co-cultured T cells, the expression levels of RORγt, IL-17, IL-23R, and GM-CSF mRNA in shRNA-5033413D16Rik transfected group were 1.61±0.13, 1.51±0.13, 1.85±0.33 and 1.45±0.11, which were significantly higher than 1.00±0.01, 1.00±0.01, 1.00±0.01 and 1.00±0.01 in shRNA-NC-transfected group ( t=-6.839, -8.221, -4.538, -4.189; all at P<0.05).ELISA analysis revealed that IL-17 concentraion in shRNA-5033413D16Rik transfected group was (2 350.39±367.02)pg/ml, which was significantly higher than (1 513.31±310.37)pg/ml ( t=-3.016, P=0.039).Flow cytometry showed that the percentage of Th17 cells in shRNA-5033413D16Rik transfected group was (17.20±0.44)%, which was higher than (14.10±0.84)% in normal control group ( t=-3.264, P=0.031). Conclusions:LncRNA 5033413D16Rik can inhibit the expression of pathogenicity related genes in antigen-specific Th17 cells and negatively regulates IRBP 1-20-specific Th17 cell responses.

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.

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 In order to clarify the identification path and the followed principles in this kind of pathological-related medical damage identification,explore the prevention and resolution ideas of pathological medical disputes in the medical and health departments,and build a path for the people's court to hear the cases of pathological medical injury liability disputes.Methods Taking the judgement of medical damage liability disputes that took effect in 2019-2023 and published on the judgement document network as a sample,conduct a retrospective analysis in terms of the site of lesion,medical fault,the consequences of the damage,the causal relationship and the degree of cause(degree of participation),the degree of accident classification and responsibility,the selection of appraisal method,and the acceptancde of appraisal opinions.Results From the analysis of the lesion site,there is a high proportion of misdiagnosis in breast,lung,thyroid,skin and uterus;from the analysis of medical fault,58.4%of delayed treatment and 41.6%of overtreatment due to improper selection of treatment plan;from the analysis of the consequences of damage,the consequences of death only account for about 20%.Most of them are in the category of living appraisal;from the analysis of responsibility division,medical institutions bear secondary reasons,accounting for 30.3%;from the analysis of appraisal and acceptance,medical damage identification methods are mostly used,and the court's acceptance of appraisal opinions reaches 92.1%.Conclusion(1)There are more pathological disputes involving women's bodies,and misdiagnosis is the most in the type of fault;(2)Forensic clinical professional appraisers can also participate in the identification of medical damage involving pathological diagnosis;(3)For cases of medical damage liability disputes involving pathological diagnosis and the consequences of death,the cause of death should be identified;(4)Medical damage identification should be in accordance with the principle of peer review.

Objective To investigate the diagnostic value of three-dimensional power Doppler ultrasound(3D-PDUS)in fetal growth restriction(FGR).Methods A total of 120 pregnant women in the third trimester who were given birth in Wenzhou People's Hospital from September 2021 to December 2023 were selected as study objects,50 pregnant women with FGR confirmed by clinical and ultrasound were included in case group,and 70 pregnant women with normal fetal development were included in control group.The renal volume and renal blood flow parameters of the fetuses in two groups were compared.The pregnancy outcomes and perinatal conditions of two groups were compared.Receiver operating characteristic(ROC)curve was plotted to calculate the area under the curve(AUC),and the diagnostic efficacy of various blood flow parameters for FGR was evaluated.Results The renal volume/gestational week,renal vascularization index,vascularization flow index and renal artery peak systolic velocity of the fetuses in case group were significantly lower than those in control group,while renal artery peak systolic velocity/end diastolic velocity,pulsation index and resistance index were significantly higher than those in control group(P＜0.05).There was no significant difference in renal flow index between two groups(P＞0.05).ROC curve results showed that the diagnostic efficacy of renal volume/gestational week and renal artery peak systolic velocity were higher,while the diagnostic efficacy of combined application was the highest,with an AUC of 0.89.The rate of low birth weight infants in case group was significantly higher than that in control group,and neonatal Apgar score was significantly lower than that in control group(P＜0.01).Conclusion 3D-PDUS quantitative analysis parameters evaluated renal volume and blood perfusion could predict FGR,which is conducive to early diagnosis of FGR and guide clinical intervention,and effectively reduce adverse pregnancy outcomes.

Objective To investigate the effects of dimethyl itaconate(DMI)on the secretion of pro-inflammatory factors in dendritic cells(DCs)and on the interphotoreceptor retinoid-binding protein(IRBP)1-20-specific T helper 17(Th17)cells in mice with experimental autoimmune uveitis(EAU).Methods Bilateral femur and tibia of C57BL/6J mice were isolated to obtain bone marrow cells,and these bone marrow cells were directionally induced with granulocyte macrophage-colony-stimulating factor(GM-CSF)and interleukin(IL)-4 to differentiate DCs.After 6 days,DCs were ran-domly divided into the DMI group and the phosphate-buffered saline(PBS)group.Cells in the DMI group were pretreated with 250 μmol·L-1 DMI,and cells in the PBS group were pretreated with the same volume of PBS for 3 hours.After-wards,100 μg·L-1 lipopolysaccharide was added in the every group to stimulate cells for 24 hours.The relative mRNA ex-pression levels of IL-6,IL-1 β,and IL-23 in DCs were measured by quantitative real-time polymerase chain reaction(qRT-PCR).The EAU model was constructed by actively immunizing mice with IRBP1-20,Freund's incomplete adjuvant,and my-cobacterium tuberculosis H37RA.Thirteen days after immunization,T cells in the spleen and lymph node isolated from EAU mice were cocultured with DMI-treatedor PBS-treated DCs in the medium containing IRBP1-20.They polarized toward Th17 cells.The percentage of Th17 cells in the cocultured cells was detected by flow cytometry.The IL-17 level in the coculture supernatant was detected by enzyme-linked immunosorbent assay(ELISA).qRT-PCR was performed to detect the relative mRNA expression levels of retinoid-related orphan receptor gamma t(RORγt),IL-17,IL-23R,and GM-CSF in the cocultured cells.Results qRT-PCR analysis revealed that the relative mRNA expression levels of IL-6,IL-1β,and IL-23 in the DMI group were significantly lower thanthose in the PBS group(all P＜0.05).Flow cytometry analysis showed that the proportion of Th17 cells in the cocultured cells in the DMI group was significantly lower than that in the PBS group(P＜0.05).ELISA analysis exhibited that the IL-17 level in the coculture supernatant in the DMI group was significantly lower than that in the PBS group(P＜0.05).The relative mRNA expression levels of IL-17,ROR-γt,IL-23R and GM-CSF in cocultured cells in the DMI group significantly decreased compared with the PBS group(all P＜0.05).Conclusion DMI can reduce the expression of IL-6,IL-1β and IL-23 in DCs,thus negatively modulating the responses of IRBP1-20-specific Th17 cells.