[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 correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.

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.

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.

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).

Objective:To establish a new classification system for distal clavicle fracture and evaluate its clinical effectiveness.Methods:A retrospective case series study was conducted to analyze the clinical data of 101 patients with distal clavicle fracture admitted to First Affiliated Hospital of Nanjing Medical University from January 2015 to March 2022, including 57 males and 44 females, aged 19-86 years [(53.8±14.0)years]. Before treatment, patients were routinely subjected to bilateral anteroposterior radiography of the shoulder joints to measure the length of the fractured fragments, coracoclavicular distance, and acromioclavicular distance. According to the correlation between the location of the fracture line and the insertion of the coracoclavicular ligament, distal clavicle fracture was divided into three types: type I, with the fracture line lateral to the coracoclavicular ligament region; type II, with the fracture line in the coracoclavicular ligament region; type III, with the fracture line medial to the coracoclavicular ligament region. According to the injury severity of the coracoclavicular ligament and acromioclavicular ligament, type I was further subdivided into type IA, IB, IC and ID, and type II fracture was further subdivided into type IIA, IIB, IIC, IID and IIE. All the 101 patients were classified and randomly reclassified at an interval of 3 months by 10 senior and 10 junior shoulder surgeons according to the new classification method. Kappa coefficients were used to evaluate the inter- and intra-observer consistency of the new classification. Fifty-two patients with stable fracture (types IA, IB, IIC, and IID) were treated non-surgically, while 49 patients with unstable fracture (types IC, ID, IIA, IIB, IIE, and III) were treated surgically, including 26 patients with anatomic coracoclavicular ligament reconstruction, 9 with locking plate fixation, 8 with clavicle hook plate fixation, 4 with anatomic coracoclavicular ligament reconstruction combined with locking plate fixation, and 2 with anatomic coracoclavicular ligament reconstruction combined with tension screw fixation. The patients were assessed using the visual analogue scale (VAS) and Constant-Murley shoulder score before treatment and at 3, 6, 12, and 18 months after treatment. The coracoclavicular distance and acromioclavicular distance on the anteroposterior radiographs of the healthy and affected shoulder joints were measured at 3, 6, 12, and 18 months after treatment, and fracture healing time and complications were observed.Results:The length of the fractured fragments was 12.9 (9.7, 17.6)mm in patients with type I fracture, 24.7 (21.8, 27.8)mm in patients with type II fracture, and 43.6 (41.2, 46.9)mm in patients with type III fracture ( P<0.01). There were no significant differences in the coracoclavicular distance and acromioclavicular distance of the affected and healthy shoulders among the patients with types IA, IB, IIC, IID, and III fracture ( P>0.05); For the patients with types IC, IIA, IIB and IIE fracture, the coracoclavicular distance of the affected shoulder was significantly increased compared with that of the healthy shoulder ( P<0.01), while there was no significant difference in the acromioclavicular distance of the affected and healthy shoulders ( P>0.05). Both of the inter- and intra-observer consistency of the new classification was good. The inter- and intra-observer Kappa values were 0.69 and 0.71 respectively among the senior shoulder surgeons, and 0.61 and 0.64 respectively among the junior shoulder surgeons. All the patients were followed up for 18-104 months [28(23, 32)months]. At 3, 6, 12 and 18 months after treatment, the VAS scores of non-surgical patients were 3(2, 3)points, 2(1, 2)points, 1(0, 1)points and 0(0, 1)points respectively, significantly decreased compared with 6(5, 6)points before treatment ( P<0.01); the VAS scores of surgical patients were 3(2, 3)points, 2(1, 2)points, 1(1, 1)points and 0(0, 1)points respectively, significantly decreased compared with 6(5, 7)points before treatment ( P<0.01); the Constant-Murley shoulder scores of non-surgical patients were (76.6±5.3)points, (84.3±5.0)points, (88.4±4.0)points and (91.9±3.8)points respectively, significantly higher than (42.7±5.2)points before treatment ( P<0.01); the Constant-Murley shoulder scores of surgical patients were (77.4±4.6)points, (84.4±4.7)points, (87.6±3.7)points and (91.7±4.0)points respectively, significantly higher than (42.8±5.3)points before treatment ( P<0.01). At 3, 6, 12 and 18 months after treatment, the coracoclavicular distance of the affected shoulder in non-surgical patients was not significantly different from that before treatment ( P>0.05), while the acromioclavicular distance of the affected shoulder in surgical patients was significantly reduced compared with that before treatment ( P<0.01). There were no significant differences in the coracoclavicular distance of the healthy shoulder or bilateral acromioclavicular distance in non-surgical and surgical patients at 3, 6, 12, and 18 months after treatment compared with those before treatment ( P>0.05). Fractures were healed within 12 months after treatment in all the patients, without dislocation or subluxation of the acromioclavicular joint, internal fixation failure or internal fixator breakage. Eight patients treated with clavicular hook plate fixation had shoulder pain associated with limited mobility after operation, and all underwent a second operation to remove the clavicular hook plate at 12 months after operation. Conclusions:The new classification system for distal clavicle fracture is established, which comprehensively considers the position of the fracture line, injury of the coracoclavicular and acromioclavicular ligaments, and fracture stability. The new classification system exhibits good inter- and intra- observer consistency, and the effectiveness of its preliminary clinical application is satisfactory.

Objective To analyze the values of serum tumor necrosis factor-α stimulated gene 6 protein (TSG-6) and type ⅩⅥ collagen (col-16) in predicting the prognosis of patients with ulcerative colitis (UC). Methods A total of 160 patients with UC were enrolled as UC group, another 160 volunteers were selected as control group, and the levels of serum TSG-6 and col-16 were compared between the two groups. According to the modified Mayo scoring criteria, patients in the UC group were divided into mild group (n=63), moderate group (n=52), and severe group (n=45), and the levels of serum TSG-6 and col-16 were compared among the three groups. Based on the colonoscopy follow-up results, patients in the UC group were divided into good prognosis group (n=121) and poor prognosis group (n=39), and the levels of serum TSG-6 and col-16 were compared between the two groups. Spearman correlation analysis was used to explore the correlations of serum TSG-6 and col-16 with the modified Mayo score. Logistic regression analysis was used to investigate the impact of serum TSG-6 and col-16 on the prognosis of patients in the UC group. Receiver operating characteristic (ROC) curve was used to assess the values of serum TSG-6 and col-16 in predicting the prognosis of patients in the UC group. Results The levels of serum TSG-6 and col-16 in the UC group were significantly higher than those in the control group (P < 0.01). The levels of serum TSG-6 and col-16 in the moderate and severe groups were significantly higher than those in the mild group, and the levels of serum TSG-6 and col-16 in the severe group were significantly higher than those in the moderate group (P < 0.01). The levels of serum TSG-6 and col-16 in the poor prognosis group were significantly higher than those in the good prognosis group (P < 0.01). Spearman correlation analysis showedthat serum TSG-6 and col-16 were positively correlated with the modified Mayo score (r=0.691, P < 0.05; r=0.635, P < 0.05). Logistic analysis results showed that serum TSG-6 and col-16 were risk factors for poor prognosis (P < 0.001). ROC curve analysis showed that the areas under the curve for predicting poor prognosis in patients with UC were 0.773 and 0.765 for serum TSG-6 and col-16, respectively. Conclusion The levels of serum TSG-6 and col-16 are abnormally elevated in patients with UC, and there is a certain correlation of the two indexes with the severity and prognosis of disease, and the two indexes can be used as predictors of poor prognosis.