Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Objective To evaluate the application of three deep learning algorithms in automatic segmentation of clinical target volumes (CTVs) in high-dose-rate brachytherapy after surgery for endometrial carcinoma. Methods A dataset comprising computed tomography scans from 306 post-surgery patients with endometrial carcinoma was divided into three subsets: 246 cases for training, 30 cases for validation, and 30 cases for testing. Three deep convolutional neural network models, 3D U-Net, 3D Res U-Net, and V-Net, were compared for CTV segmentation. Several commonly used quantitative metrics were employed, i.e., Dice similarity coefficient, Hausdorff distance, 95th percentile of Hausdorff distance, and Intersection over Union. Results During the testing phase, CTV segmentation with 3D U-Net, 3D Res U-Net, and V-Net showed a mean Dice similarity coefficient of 0.90 ± 0.07, 0.95 ± 0.06, and 0.95 ± 0.06, a mean Hausdorff distance of 2.51 ± 1.70, 0.96 ± 1.01, and 0.98 ± 0.95 mm, a mean 95th percentile of Hausdorff distance of 1.33 ± 1.02, 0.65 ± 0.91, and 0.40 ± 0.72 mm, and a mean Intersection over Union of 0.85 ± 0.11, 0.91 ± 0.09, and 0.92 ± 0.09, respectively. Segmentation based on V-Net was similarly to that performed by experienced radiation oncologists. The CTV segmentation time was < 3.2 s, which could save the work time of clinicians. Conclusion V-Net is better than other models in CTV segmentation as indicated by quantitative metrics and clinician assessment. Additionally, the method is highly consistent with the ground truth, reducing inter-doctor variability and treatment time.

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

Objective To observe the improvement effect and mechanism of salvianolic acid B on renal fibrosis mice.Methods Thirty-six BALB/c mice were randomly divided into sham operation group,model group,salvianolic acid B low-,medium-and high-dose groups and VX765(caspase-1 inhibitor)group,with 6 mice in each group.Salvianolic acid B low-,medium-and high-dose groups were intragastrically administered with corresponding doses of 50,100,200 mg-kg-1-d-1 salvianolic acid B normal saline suspension,respectively,VX765 group was intragastrically administered with 50 mg·kg-1·d-1 VX765 normal saline suspension,and the sham operation group and the model group were intragastrically administered with the same volume of normal saline,once a day.After seven days,except for the sham operation group,the mice in other groups were treated with unilateral renal ischemia-reperfusion injury combined with contralateral nephrectomy to establish an acute kidney injury-induced renal fibrosis model.After modeling,each group continued to be administered with the corresponding volume of drugs for 21 days.After the administration,the pathological changes of renal tissue were observed by hematoxylin-eosin(HE)staining and Masson staining.The serum creatinine(SCr)was detected by sarcosine oxidase method.The urea nitrogen(BUN)was detected by urease method.The level of serum neutrophil gelatinase-associated lipocalin(NGAL)was detected by enzyme-linked immunosorbent assay(ELISA).The expression of fibrosis-related proteins fibrosis-related proteins α-smooth muscle actin(α-SMA),vimentin and transforming growth factor-β(TGF-β)and pyroptosis-related proteins cleaved cysteine aspartate proteolytic enzyme 1(cl-caspase-1),pro-caspase-1(pro-caspase-1),NOD-like receptor hot protein domain-related protein 3(NLRP3),cleaved interleukin-1β(cl-IL-1β),interleukin-1β(IL-1β),GSDMD-N,GSDMD in renal tissue was detected by Western Blot.Results Compared with the sham operation group,the serum levels of SCr,BUN and NGAL in the model group were increased(P＜0.05 or P＜0.01).HE and Masson staining showed inflammatory cell infiltration and a large amount of collagen deposition in the renal interstitium,and the expression levels of fibrosis-related proteins α-SMA,vimentin and TGF-β were increased(P＜0.01).The expression levels of pyroptosis-related proteins cl-caspase-1/pro-caspase-1,NLRP3,cl-IL-1β/IL-1β,GSDMD-N/GSDMD were also increased(P＜0.05 or P＜0.01).Compared with the model group,the levels of serum SCr,BUN and NGAL in the high-dose salvianolic acid B group were significantly decreased(P＜0.05 or P＜0.01),the infiltration of renal interstitial inflammatory cells and collagen deposition were reduced,and the expression levels of fibrosis proteins α-SMA,vimentin,TGF-β and pyroptosis-related proteins cl-caspase-1/pro-caspase-1,NLRP3,cl-IL-1β/IL-1β,GSDMD-N/GSDMD were decreased(P＜0.05 or P＜0.01).There was no significant difference in the above indexes between the high-dose salvianolic acid B group and the VX765 group(P＞0.05).Conclusion Salvianolic acid B may alleviate renal fibrosis in mice by inhibiting pyroptosis mediated by NLRP3/caspase-1/GSDMD pathway.

Odontogenic maxillary sinusitis(OMS)is a subtype of maxillary sinusitis(MS).It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion.Due to the lack of unique clinical features,OMS is difficult to distinguish from other types of rhinosinusitis.Besides,the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis.Its current diagnosis and treatment are thus facing great difficulties.The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS.However,this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality.Based on systematically reviewed literature and practical experiences of expert members,our consensus focuses on characteristics,symptoms,classification and diagnosis of OMS,and further put forward multi-disciplinary treatment decisions for OMS,as well as the common treatment complications and relative managements.This consensus aims to increase attention to OMS,and optimize the clinical diagnosis and decision-making of OMS,which finally provides evidence-based options for OMS clinical management.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective:To evaluate the efficacy of hematoporphyrin monomethyl ether-mediated photodynamic therapy (HMME-PDT) in the treatment of adult patients with port-wine stains (PWS) in China, and to analyze factors influencing the efficacy.Methods:A retrospective study was conducted on the data from 265 adult patients with PWS who underwent HMME-PDT at the Department of Dermatology, West China Hospital, Sichuan University from February 2017 to October 2023. Patients were intravenously injected with hemoporfin at doses of 5 - 6.5 mg/kg, followed by irradiation with a 532-nm green light-emitting diode at the energy density of 100 - 130 J/cm 2 (power density, 85 - 100 mW/cm 2) for 19 - 25 minutes. Treatments were conducted every 2 - 6 months. The treatment response in the treated area was observed after each treatment, and the clinical efficacy was assessed at least two months after the last treatment. Chi-square test was used to analyze the differences in efficacy between groups. Results:Among the 265 adult patients with PWS, the male to female ratio was 90∶175, the patients' age ranged from 18 to 56 years (26.48 ± 6.88 years), and they underwent 1 to 8 treatment sessions (2.67 ± 1.33 sessions). After treatment, 102 (38.4%) patients achieved complete remission, 74 (27.9%) achieved marked improvement, 59 (22.2%) had moderate improvement, and 30 (11.3%) showed no response, resulting in an overall response rate of 88.7%. Among 146 patients without hypertrophic lesions, 69 (47.3%) achieved complete remission, with a response rate of 92.5%; among 102 with slightly thickened lesions, 32 (31.4%) achieved complete remission, with a response rate of 87.3%; among 17 with markedly thickened lesions, only 1 achieved complete remission, and 11 achieved marked improvement. Among 50 patients who received more than 3 treatment sessions, 28 (56%) had complete remission, with a response rate of 100%; among 45 who received only one session of treatment, 5 (11.1%) achieved complete remission, with a response rate of 68.9%. Among 232 patients without soft tissue hyperplasia, 95 (40.9%) achieved complete remission, with a response rate of 88.8%; among 33 with soft tissue hyperplasia, 7 (21.2%) achieved complete remission, with a response rate of 87.9%. The therapeutic effects significantly differed among patients with different lesion thicknesses, among those with different treatment sessions, as well as between patients with soft tissue hyperplasia and those without (all P < 0.05). There were no significant differences in the therapeutic effect among patients of different genders, different ages, with different lesion colors, as well as between patients with nodules and those without, and between patients with treatment history and those without (all P > 0.05). During and after the treatment, patients experienced varying degrees of swelling, burning sensation, pain, and itching, all of which could be relieved by common treatment; scars occurred in 10 (3.8%) patients, and were managed by symptomatic treatment; no systemic adverse reactions, such as drug allergies or impairment of liver and kidney function, were observed during the treatment. Conclusions:HMME-PDT is safe and effective in the treatment of adult patient with PWS. The therapeutic effect of HMME-PDT was associated with lesion thickening and soft tissue hyperplasia, and increased with the increase in treatment sessions.