[Objective] To explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4⁺ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.

Objective To investigate the effects of LBL-007, a novel fully human lymphocyte activation gene 3 (LAG-3) monoclonal antibody, in combination with programmed cell death protein 1 (PD-1) antibody, on the invasion, migration and proliferation of tumor cells, and to elucidate the underlying mechanisms. Methods Human lymphocyte cells Jurkat were co-cultured with A549 and MGC803 tumor cell lines and treated with the isotype control antibody human IgG, LBL-007, anti-PD-1 antibody BE0188, or tumor necrosis factor-alpha (TNF-α, the NF-κB signaling pathway agonist). Tumor cell proliferation was assessed using a colony formation assay; invasion was measured by Transwell^TM assay; migration was evaluated using a wound healing assay. Western blotting was employed to determine the expression levels of NF-κB pathway-related proteins: IκB inhibitor kinase alpha (Ikkα), phosphorylated Ikkα (p-IKKα), NF-κB subunit p65, phosphorylated p65 (p-p65), NF-κB Inhibitor Alpha (IκBα), phosphorylated IκBα (p-IκBα), matrix metalloproteinase 9 (MMP9), and MMP2. Results Compared with the control and IgG isotype groups, LBL-007 and BE0188 significantly reduced tumor cell proliferation, invasion, and migration. They also decreased the phosphorylation of p-IKKα, p-p65 and p-IκBα, and the expression of MMP9 and MMP2 of tumor cells in the co-culture system. The combined treatment of LBL-007 and BE0188 enhanced inhibitory effects. Treatment with the NF-κB signaling pathway agonist TNF-α reversed the suppressive effects of LBL-007 and BE0188 on tumor cell proliferation, invasion, migration, and NF-κB signaling. Conclusion LBL-007 and anti-PD-1 antibody synergistically inhibit the invasion, migration, and proliferation of A549 and MGC803 tumor cells by blocking the NF-κB signaling pathway.
Humans ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Neoplasm Invasiveness ; Antibodies, Monoclonal/pharmacology* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Cell Line, Tumor ; Antigens, CD/immunology* ; Lymphocyte Activation Gene 3 Protein ; A549 Cells ; I-kappa B Kinase/metabolism* ; Jurkat Cells ; Matrix Metalloproteinase 9/metabolism*

Objective To investigate the role of silencing regulatory protein 1(Sirt1)in the regulation of Vibrio vulnificus sepsis-induced macrophage apoptosis and the molecular mechanisms.Methods Mouse RAW264.7 macrophages which stably overexpressed Sirt1 were constructed and screened by genistein G418.CCK-8 analysis was used to detect the proliferation of cells in the control group and Sirt1-Flag group.The changes of expression levels of apoptosis-associated protein poly ADP-ribose polymerase(PARP),cleaved-PARP,caspase3,cleaved-caspase3 and acetylated p53 in different treatment groups were detected via Western blotting.A Vibrio vulnificus sepsis model in mice was established,and the expression levels of apoptosis-associated protein cleaved-caspase3 in the lung,spleen and liver of mice of different treatment groups were detected by immunohistochemistry.Results Overexpression of Sirt1 reduced VVC-induced RAW264.7 cell damage.Overexpression of Sirt1 as well as RSV pretreatment lowered the expression of apoptosis-associated protein cleaved-PARP,cleaved-caspase3 and acetylated p53 in VVC-stimulated RAW264.7 cells and mouse peritoneal macrophages.In the mouse model of Vibrio vulnificus sepsis,therapeutic administration of RSV reduced the expression of apoptosis-associated protein marker cleaved-caspase3 in lung,spleen and liver tissues.Conclusion Sirt1 can inhibit p53 acetylation and reduces apoptosis in mouse macrophages,which helps protect against Vibrio vulnificus sepsis.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Lymphocyte-activation gene 3(LAG-3)is an inhibitory immune checkpoint receptor that negatively regulates the function of T cells to prevent over-activation of the immune system from damaging human body.In the existence of tumors and chronic infections,persistent antigenic stimulation induces upregulation of LAG-3 expression in effector T cells,leading to T cell exhaustion and tumor immune escape.Targeting LAG-3 drugs can reactivate the anti-tumor function of T cells by specifically blocking the signaling pathway of LAG-3,and have shown promising efficacy in a variety of solid tumors,hematologic tumors and autoimmune diseases.In this paper,we summarize the current research progress on the structure,ligand and regulatory function of LAG-3,review the current status of clinical trials of LAG-3-targeted drugs,and further discuss the clinical application strategy and development direction of LAG-3-targeted drugs,with a view to providing reference for further in-depth research on LAG-3.

Objective To investigate the effect of thalidomide combined with infliximab (IFX) in treatment of refractory inflammatory bowel disease (IBD) and its effects on insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). Methods A total of 120 patients with refractory IBD were randomly divided into experimental group and control group, with 60 cases in each group. The two groups were given conventional treatment (mesalazine), the control group was given IFX, and the experimental group was given IFX combined with thalidomide, continuous treatment for two months. The efficacy, intestinal flora disturbance rate, adverse reactions, Crohn's disease activity index (CDAI), Lewis score, serum IGF-1, TGF-β1 levels and nutritional status indexes[albumin (ALB), transferrin (Tf)]before and after treatment for 1 month and 2 months of the two groups were compared. Results The total effective rate of the experimental group was significantly higher than that of the control group (P < 0.05). After one month and two months of treatment, CDAI and Lewis scores of the experimental group were significantly lower than those of the control group (P < 0.05); the serum levels of IGF-1, TGF-β1 as well as ALB and Tf in the experimental group were significantly higher than those in the control group (P < 0.05). The improvement of intestinal flora disturbance rate in the experimental group was significantly better than that in the control group (P < 0.05). There was no significant difference in the incidence of oral and nasal mucosa dryness, throat discomfort, nausea and vomiting between two groups (P>0.05). Conclusion In the treatment of refractory IBD patients, thalidomide combined with IFX can regulate serum IGF-1 and TGF-β1 levels, effectively relieve clinical manifestations, inhibit inflammatory activities, and improve nutritional status and intestinal flora disorders of patients, and it has high safety.

Objective To investigate the diagnostic value of photoplethysmography (PPG) in the detection of obstructive sleep apnea syndrome (OSAS) among critically ill patients with respiratory or cardiocerebrovascular diseases accompanied by snoring. Methods A total of 91 critically ill patients with respiratory or cardiocerebrovascular diseases accompanied by snoring, admitted to the internal medicine ward of Subei People's Hospital from January 2019 to October 2023 were enrolled. After informed consent, overnight polysomnography (PSG) and PPG were performed. The consistency of the sleep apnea parameters obtained of the two methods by sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic (ROC) curve. Results There were no statistically significant differences in apnea-hypopnea index (AHI), total sleep time, lowest oxygen saturation, and time with oxygen saturation below 90% between PPG and PSG (P>0.05). When AHI≥ 5 times/h and AHI≥15 times/h, the diagnostic sensitivity of the patients in this group was 94.37% and 93.10%, respectively, with specificities of 73.68% and 90.91%, positive predictive values of 91.78% and 94.74%, and negative predictive values of 77.78% and 88.23%, and areas under the ROC curves were 0.961 and 0.982, respectively. For critically ill patients with respiratory diseases, the diagnostic sensitivity was 89.29% and 87.10%, respectively, with specificities of 84.62% and 80.00%, positive predictive values of 92.59% and 93.10%, and negative predictive values of 78.57% and 72.72%, and the areas under the ROC curves were 0.978 and 0.987, respectively. For critically ill patients with cardiocerebrovascular diseases, the diagnostic sensitivity was 87.18% and 90.32%, respectively, with specificities of 83.33% and 89.47%, positive predictive values of 91.89% and 99.63%, and negative predictive values of 78.57% and 85.56%, and the areas under the ROC curves were 0.942 and 0.986, respectively. Conclusion PPG monitoring results show high consistency with PSG in critically ill patients with respiratory and cardiocerebrovascular diseases combined with OSAS.

This paper reviews the concepts, status, influencing factors and interventions of home self-management of diabetic foot ulcers patients, with a view to providing reference for establishing and improving the home self-management model of diabetic foot ulcers patients suitable for China.

Triangle chronic disease stratified management model, as an effective chronic disease management model, can divide patients into different levels according to the stratified disease assessment criteria, enhance intervention effectiveness, improve management efficiency, and reduce costs by implementing targeted and personalized nursing measures. This article summarizes the overview of the Triangle chronic disease stratified management model, research progress at home and abroad, and the current application status in transitional care for chronic disease patients in order to provide a reference for medical staff to carry out transitional care for chronic disease patients.