Highly Efficient Oral Iguratimod/Polyvinyl Alcohol Nanodrugs Fabricated by High-Gravity Nanoprecipitation Technique for Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA), a systemic autoimmune disease, poses a significant human health threat. Iguratimod (IGUR), a novel disease-modifying antirheumatic drug (DMARD), has attracted great attention for RA treatment. Due to IGUR's hydrophobic nature, there's a pressing need for effective pharmaceutical formulations to enhance bioavailability and therapeutic efficacy. The high-gravity nanoprecipitation technique (HGNPT) emerges as a promising approach for formulating poorly water-soluble drugs. In this study, IGUR nanodrugs (NanoIGUR) are synthesized using HGNPT, with a focus on optimizing various operational parameters. The outcomes revealed that HGNPT enabled the continuous production of NanoIGUR with smaller sizes (ranging from 300 to 1000 nm), more uniform shapes, and reduced crystallinity. In vitro drug release tests demonstrated improved dissolution rates with decreasing particle size and crystallinity. Notably, in vitro and in vivo investigations showcased NanoIGUR's efficacy in inhibiting synovial fibroblast proliferation, migration, and invasion, as well as reducing inflammation in collagen-induced arthritis. This study introduces a promising strategy to enhance and broaden the application of poorly water-soluble drugs.

ChatGPT4's proficiency in addressing patients' questions on systemic lupus erythematosus: a blinded comparative study with specialists.

OBJECTIVES: The efficacy of artificial intelligence (AI)-driven chatbots like ChatGPT4 in specialized medical consultations, particularly in rheumatology, remains underexplored. This study compares the proficiency of ChatGPT4' responses with practicing rheumatologists to inquiries from patients with SLE. METHODS: In this cross-sectional study, we curated 95 frequently asked questions (FAQs), including 55 in Chinese and 40 in English. Responses for FAQs from ChatGPT4 and five rheumatologists were scored separately by a panel of rheumatologists and a group of patients with SLE across six domains (scientific validity, logical consistency, comprehensibility, completeness, satisfaction level and empathy) on a 0-10 scale (a score of 0 indicates entirely incorrect responses, while 10 indicates accurate and comprehensive answers). RESULTS: Rheumatologists' scoring revealed that ChatGPT4-generated responses outperformed those from rheumatologists in satisfaction level and empathy, with mean differences of 0.537 (95% CI, 0.252-0.823; P < 0.01) and 0.460 (95% CI, 0.227-0.693; P < 0.01), respectively. From the SLE patients' perspective, ChatGPT4-generated responses were comparable to the rheumatologist-provided answers in all six domains. Subgroup analysis revealed ChatGPT4 responses were more logically consistent and complete regardless of language and exhibited greater comprehensibility, satisfaction and empathy in Chinese. However, ChatGPT4 responses were inferior in comprehensibility for English FAQs. CONCLUSION: ChatGPT4 demonstrated comparable, possibly better in certain domains, to address FAQs from patients with SLE, when compared with the answers provided by specialists. This study showed the potential of applying ChatGPT4 to improve consultation in SLE patients.

Individualized treatment with voriconazole in the Chinese population: Inflammation level as a novel marker for dose optimization.

AIMS: The aim of this study was to explore the influence and possible mechanisms of pharmacokinetics-related gene polymorphisms, especially CYP2C19 polymorphisms, and non-genetic factors combined with the inflammatory status on the voriconazole (VRC) metabolism of the Chinese population. METHODS: Clinical studies were performed by collecting more than one VRC trough concentration and C-reactive protein (CRP) level. A total of 265 blood samples were collected from 120 patients. RESULTS: Results of multiple regression analyses demonstrated that CYP2C19 genotypes and albumin (Alb) level remained predictors of Cmin ss/D in patients with no to mild inflammation (R2 = 0.12, P < .001). In addition, in patients with moderate to severe inflammation, it resulted in a significant model containing factors of CRP and total bilirubin (T-Bil) levels (R2 = 0.19, P < .001). In non-clinical studies, 32 rats were divided into control and inflammatory groups, and it was found that the mean residence time (MRT(0-t) ) of VRC in the inflammatory group was significantly longer than that in the control group (P < .001), which may be due to down-regulation of mRNA and protein expression of CYP2C19 (CYP2C6 in rats) through interleukin (IL)-6/signal transducer and activator of transcription (STAT) 3 pathway. CONCLUSIONS: Therefore, the effect of CYP2C19 polymorphisms on VRC metabolism may be masked by inflammatory status, which should be of more concern than CYP2C19 polymorphisms in patients with moderate to severe inflammation. Additionally, the impact of Alb and T-Bil on VRC metabolism should not be disregarded.

Urate-lowering agents do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout: a prospective open-label cohort study.

OBJECTIVE: The objective of this study was to analyze and compare the effects of different urate-lowering agents on testicular functions in men with gout in a clinical setting. METHODS: In this prospective cohort study (Clinical Trial Registration Number: NCT04213534), a total of 49 male patients aged 18-45 years with gout were enrolled. They were divided into three groups and received treatment with either allopurinol, febuxostat or benzbromarone for a duration of 3 months. Semen parameters, reproductive hormones and biochemical assessments were evaluated at baseline, month 1, and month 3. RESULTS: Overall, 40 individuals (81.6%) completed the follow-up visits. In allopurinol group, there were no significant differences in semen parameters from baseline to month 3. Most of sperm parameters in febuxostat group did not show notable changes, except for a decrease in sperm motility at month 3(33.6%, [22.9-54.3] vs 48.4%, [27.4-67.6], p = 0.033). However, the total motile sperm count did not differ significantly after febuxostat treatment. Surprisingly, administration of benzbromarone resulted in improved sperm concentration (37.19 M/mL, [29.6-69.92] vs 58.5 M/mL, [49.8-116.6], p = 0.001). There were no significant changes observed in sperm DNA integrity and reproductive hormones in the three groups from baseline to month 3. The incidence of adverse events did not differ significantly among the three groups as well. CONCLUSION: This study is the first to demonstrate that urate-lowering agents, allopurinol and febuxostat, do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout, and benzbromarone presents improving sperm concentration. Results provide important preliminary guidance for the development of reproductive health management guidelines for patients RCID with gout.

Population Pharmacokinetics and Pharmacogenetics Analyses of Dasatinib in Chinese Patients with Chronic Myeloid Leukemia.

AIMS: Dasatinib, a second-generation tyrosine kinase inhibitor of BCR-ABL 1, used for first-line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML), exhibits high pharmacokinetic (PK) variability. However, its PK data in Chinese patients with CML remains rarely reported to date. Thus, we developed a population pharmacokinetic (PPK) model of dasatinib in Chinese patients and identified the covariate that could explain the individual variability of PK for optimal individual administration. METHODS: PPK modeling for dasatinib was performed based on 754 plasma concentrations obtained from 140 CML patients and analysis of various genetic and physicochemical parameters. Modeling was performed with nonlinear mixed-effects (NLME) using Phoenix NLME. The finally developed model was evaluated using internal and external validation. Monte Carlo simulations were used to predict drug exposures at a steady state for various dosages. RESULTS: The PK of dasatinib were well described by a two-compartment with a log-additive residual error model. Patients in the current study had a relatively low estimate of CL/F (126 L/h). A significant association was found between the covariate of age and CL/F of dasatinib, which was incorporated into the final model. None of the genetic factors was confirmed as a significant covariate for dasatinib. The results of external validation with 140 samples from 36 patients were acceptable. Simulation results showed significantly higher exposures in elderly patients. CONCLUSIONS: This study's findings suggested that low-dose dasatinib would be better suited for Chinese patients, and the dosage can be appropriately reduced according to the increase of age, especially for the elderly.

Impact of cigarette smoking on rheumatoid arthritis-associated lung diseases: a retrospective case control study on clinical and radiological features and prognosis.

Our study aimed to investigate the clinical and radiological features and prognosis of male smoker patients with rheumatoid arthritis (RA). We consecutively enrolled male inpatients with RA who received chest HRCT during hospitalization in Peking University Third Hospital from Jan 1st, 2012 to August 1st, 2021. 154 male patients with RA were eligible for analysis, of whom 76.6% (n = 118) were current smokers or had a history of cigarette smoking. Compared to never-smokers, smoker patients had more respiratory symptoms, including cough (31.4% vs 5.6%, p = 0.002) and sputum production (26.3% vs 2.8%, p = 0.002), and a higher positive rate of rheumatoid factor (RF) (77.6% vs 58.8%, p = 0.030). A higher percentage of smoker patients showed emphysema (45.8% vs 16.7%, p = 0.002) and signs of lung fibrosis (51/54, 94.4% vs 7/13, 53.8%, p < 0.001) in those with interstitial lung disease (ILD, n = 67) on chest HRCT. The overall survival rate was different between smoker and never-smoker patients (p = 0.031), but instead of cigarette smoking, lung fibrosis on HRCT was the risk factor for survival of our patients. In conclusion, male patients with RA who were current smokers or had a history of cigarette smoking presented more respiratory symptoms and a higher positive rate of RF. They also showed more emphysema and signs of lung fibrosis on chest HRCT. Cigarette smoking impacted on the overall survival as a confounding factor in this cohort of male patients with RA.

A multi-predictor model to predict risk of scleroderma renal crisis in systemic sclerosis: a multicentre, retrospective, cohort study.

OBJECTIVES: Scleroderma renal crisis (SRC) is a life-threatening syndrome. The early identification of patients at risk is essential for timely treatment to improve the outcome. Therefore, it is of great interest to provide a personalised tool to predict risk of SRC in systemic sclerosis (SSc). METHODS: We tried to set up a SRC prediction model based on the PKUPH-SSc cohort of 302 SSc patients. The least absolute shrinkage and selection operator (Lasso) regression was used to optimise disease features. Multivariable logistic regression analysis was applied to build a SRC prediction model incorporating the features of SSc selected in the Lasso regression. Then, a multi-predictor nomogram combining clinical characteristics was constructed and evaluated by discrimination and calibration, with further assessment by external validation in a validation cohort composed of 400 consecutive SSc patients from other 4 tertiary hospitals. RESULTS: A multi-predictor nomogram for evaluating the risk of SRC was successfully developed. In the nomogram, four easily available predictors were contained, including disease duration <2 years, cardiac involvement, anaemia and corticosteroid >15mg/d exposure. The nomogram displayed good discrimination with an area under the curve (AUC) of 0.843 (95% CI: 0.797-0.882) and good calibration. High AUC value of 0.854 (95% CI: 0.690-1.000) could still be achieved in the external validation. The model is now available online for research use. CONCLUSIONS: The multi-predictor nomogram for SRC could be reliably and conveniently used to predict the individual risk of SRC in SSc patients, and be a step towards more personalised medicine.

The performance of the diagnostic scoring system or criteria for macrophage activation syndrome in systemic juvenile idiopathic arthritis for adult-onset Still's disease. A multicentre case-control study in China.

OBJECTIVES: To evaluate the performance of the diagnostic scoring system/criteria for macrophage activation syndrome (MAS) used in systemic juvenile idiopathic arthritis (sJIA) for adult-onset Still's disease (AOSD). METHODS: This retrospective case-control study included AOSD patients with and without MAS from six hospitals in China. The cut-off values that best discriminated MAS from active AOSD were determined by receiver operating characteristic (ROC) curve analysis. The performance of the present diagnostic scoring system/criteria for sJIA-MAS was evaluated in AOSD-associated MAS. The optimal critical value of the ROC curve replaces the relevant indicators of the existing scoring system and different models were tested for sensitivity/specificity. RESULTS: A total of 56 AOSD-associated MAS patients (AOSD-MAS) and 112 AOSD patients without MAS matched with age and sex treated at six centres between 2007 and 2017 were enrolled. The 2016 MAS in sJIA classification criteria had an overall sensitivity of 100.0% and specificity of 80.4% for classifying AOSD-MAS. Excluding hypertriglyceridemia and substituting some other criteria with newly obtained cut-off values could increase specificity. An MS score ≥-2.1 yielded a sensitivity of 95.2% and a specificity of 76.6% in classifying AOSD-MAS. ROC curve analysis revealed that a score of -1.74 could best discriminate AOSD-MAS from AOSD without MAS. An MS score ≥-1.74 yielded a sensitivity of 93.5% and a specificity of 92.6% in diagnosing AOSD-MAS (AUC=0.96, 95%CI: 0.93-0.99, p<0.0001). CONCLUSIONS: The diagnostic tool for MAS in sJIA with modification appears to apply to AOSD-MAS.

Establishment of a new protein C detection system based on chromogenic substrate assay and its clinical diagnostic value for deep vein thrombosis.

BACKGROUND: Deficiency of protein C (PC) affects the balance between blood coagulation and fibrinolysis in the human body. Chromogenic-based assay is recommended as the preferred screening method for detecting PC deficiency. We established a PC detection system based on the chromogenic substrate assay. METHODS: First, a kit for the determination of PC activity in plasma was elaborately developed and its reaction parameters on XL-3200c were explored. Then, we evaluated its performance and collected specimens to compare the test results obtained with those of the Siemens detection system. Finally, the clinical diagnostic efficacy of this detection system for deep vein thrombosis (DVT) was assessed. RESULTS: Optimum conditions for PC detection were 0.25-0.1 U/ml protein C activator Protac® and 2.5-1 mM Pefachrome® PCa5297. The composition and concentration ranges of buffer substances and stabilizers in the kit were also explored. Satisfactory results were observed in performance evaluation. The test results of the newly built detection system were highly correlated with those of the Siemens detection system (R2  = 0.9771 in the control group and R2  = 0.9776 in the DVT group), and Bland-Altman plots also showed high consistency between the two detection systems. In addition, the area under the curve (AUC) of the newly built PC detection system for DVT was 0.888, indicating this system could effectively improve the diagnostic sensitivity and specificity for DVT. CONCLUSION: In this study, a sensitive, wide linear range and reliable PC activity detection system were established.

Validation of new classification criteria of rheumatoid arthritis in an international multicentre study.

OBJECTIVES: Early identification of patients with rheumatoid arthritis (RA) is essential to allow prompt therapy. In this study, we aimed to evaluate the performance of the newly proposed ERA criteria, compared to the 1987 ACR and 2010 ACR/EULAR criteria in an international multicentre study. METHODS: A total of 606 patients with disease duration ≤2 years and age ≥16 years who were diagnosed as RA or non-RA were enrolled from China, Sweden and India. The clinical and laboratory parameters were recorded. We compared the sensitivity, specificity, predictive value, likelihood ratio (LR), and the area under the ROC curve (AUC) of three criteria in these cohorts. Concordance between the three criteria was calculated with the Kappa coefficient. RESULTS: Three hundred and twelve RA and 294 non-RA patients were included. The Early Rheumatoid Arthritis (ERA) criteria had significantly higher specificity compared to the 2010 ACR/ EULAR criteria (83.7% vs. 78.2%, p=0.02) and sensitivity were similar (79.2% vs. 78.5%, p=0.883). In comparison with the 1987 ACR criteria, the ERA criteria had higher sensitivity (79.2% vs. 54.5%, p<0.001) but lower specificity (83.7% vs. 89.1%, p<0.001), and the AUC of the ERA criteria (0.878) was comparable to the 2010 ACR/EULAR criteria (0.849) and higher than the 1987 ACR criteria (0.791, p<0.0001). Patients from the three countries, seronegative and very early arthritis cohorts yielded consistent results. CONCLUSIONS: The ERA criteria demonstrate a better performance across ethnics in early RA diagnosis, and is more feasible in daily practice.

Interleukin-21 enhances Toll-like receptor 2/4-mediated cytokine production via phosphorylation in the STAT3, Akt and p38 MAPK signalling pathways in human monocytic THP-1 cells.

Interleukin-21 (IL-21) is a type I cytokine produced by activated T cells that promotes cytokine production in monocytes. Monocytes are activated by Toll-like receptors (TLRs) to produce pro-inflammatory mediators. However, little is known about the regulatory effect of IL-21 on TLR-mediated inflammation in human monocytes. This study investigated the potential association between IL-21 and TLR2/4-mediated inflammation in human monocytic THP-1 cells. First, the expression of the IL-21 receptor (IL-21R) in human monocytic THP-1 cells was examined by flow cytometry. Then, THP-1 cells were treated with either the TLR2 ligand peptidoglycan (PGN) or the TLR4 ligand lipopolysaccharide (LPS) with or without IL-21. Then, the production of several cytokines (IL-6, IL-8, TNF-α, IFN-γ and IL-10), expression of TLR2/4, and activation of the downstream signaling pathways of mitogen-activated protein kinase (MAPK), Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and nuclear factor-kappa B (NF-κB) were determined. We found that IL-21R was highly expressed in human monocytic THP-1 cells and that IL-21 induced TLR2 and TLR4 expression and further enhanced PGN/LPS-mediated TLR2/4 expression. In addition, IL-21 also upregulated the expression of IL-6, IL-8, TNF-α, IFN-γ and IL-10 and enhanced TLR2/4-mediated cytokine production in THP-1 cells via phosphorylation of the STAT3, Akt and p38 MAPK signalling pathways. Our study suggests, for the first time that IL-21 enhances TLR2/4-mediated cytokine production in human monocytic THP-1 cells by activating the STAT3, PI3K/Akt and p38 MAPK signalling pathways.

Constant hypoxia inhibits osteoclast differentiation and bone resorption by regulating phosphorylation of JNK and IκBα.

BACKGROUND: Osteoclasts are responsible for the bone loss in rheumatoid arthritis (RA). Hypoxia has been suggested to play key roles in pathological bone loss. However, the current understanding of the effects of hypoxia on osteoclastogenesis is controversial. Effects of hypoxia on both the formation and function of osteoclasts requires examination. In the current study, we aimed to explore the effect of hypoxia on osteoclast differentiation and the underlying mechanisms. METHODS: RAW264.7 cells and murine bone-marrow-derived monocytes were used to induce osteoclastogenesis in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL). Hypoxic conditions were maintained in a hypoxic chamber at 5% CO2 and 1% O2, balanced with N2. Osteoclasts were detected by tartrate-resistant acid phosphatase (TRAP) staining. A bone resorption assay was carried out in vitro using bone slices. RT-PCR was conducted to detect osteoclast markers and transcription factors. The phosphorylation of nuclear factor-κBα (IκBα), c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK), and p38 was detected by western blotting. Mann-Whitney U test or Student's t test was used to compare differences between the two groups. RESULTS: TRAP staining and the bone resorption assay revealed that hypoxia-restrained osteoclast differentiation and bone resorption. Expression of osteoclast markers including cathepsin K, RANK, and TRAP decreased during osteoclast differentiation under hypoxic conditions (all P < 0.05). Hypoxia at 1% O2 did not affect cell viability, whereas it dramatically abated RANKL-dependent phosphorylation of the JNK-mitogen-activated protein kinases (MAPK) and IκBα pathways. Moreover, the expression of nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) was inhibited under hypoxic conditions (all P < 0.05). CONCLUSIONS: These results suggest that constant hypoxia at 1% O2 significantly restrains osteoclast formation and resorbing function without affecting cell viability. Constant hypoxia might inhibit RANKL-induced osteoclastogenesis by regulating NFATc1 expression via interfering the phosphorylation of JNK and IκBα.

Systemic vasculitis involving the breast: a case report and literature review.

Systemic vasculitis involving the breast is a rare clinical condition and may mimic breast cancer or mastitis clinically or radiographically. Here, we report a case of polyarteritis nodosa (PAN) with breast involvement and perform a literature review of published cases of systemic vasculitis affecting the breast to better understand this disorder. We report a case of PAN affecting the right breast in a young woman. A retrospective review was performed by searching Medline, Embase, Web of Science, the Cochrane Library, and Scopus for cases of systemic vasculitis involving the breast written in English up to June 1st, 2018. A 27-year-old woman presented with a painful mass in the right breast was diagnosed as PAN by the biopsy. She was treated with prednisone and methotrexate for 6 months, at which time her condition had stabilized and inflammatory markers had normalized. A total of 66 cases were identified, with granulomatosis with polyangiitis (GPA), giant cell arteritis (GCA), and PAN as the main types. The typical manifestation was mass (79.2%, 53/67) in the breast, and all diagnoses were made by the pathology of the breast biopsy. Glucocorticoid and immunosuppressant were the main therapies, and 74.6% (50/67) patients achieved remission during follow-up. Our case and a literature review of 66 cases of systemic vasculitis involving the breast reveal the importance of tissue biopsy to obtain a definitive diagnosis, because the vasculitis subtype strongly influences prognosis.

Correction to: Systemic vasculitis involving the breast: a case report and literature review.

The article "Systemic vasculitis involving the breast: a case report and literature review" written by Jinxia Zhao, was originally published electronically on the publisher's internet portal (currently SpringerLink) on March 14, 2019 with open access. With the author(s) decision to step back from Open Choice, the copyright of the article changed to ©Springer-Verlag GmbH Germany, part of Springer Nature 2019 and the article is forthwith distributed under the terms of copyright.The original article has been corrected.

CXCL16 upregulates RANKL expression in rheumatoid arthritis synovial fibroblasts through the JAK2/STAT3 and p38/MAPK signaling pathway.

OBJECTIVE: To explore the influence of chemokine, CXCL16, on the expression of the receptor activator nuclear factor κB ligand (RANKL) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS). METHODS: The expression of CXCL16/CXCR6 and RANKL in RA or osteoarthritis (OA) patient synovia was examined by Western blot and immunohistochemistry. The serum concentration of CXCL16 and RANKL was measured by enzyme-linked immunosorbent assay (ELISA). RA-FLS were treated with recombinant CXCL16, and RANKL mRNA and protein were measured using PCR, Western blot and ELISA. RESULTS: The synovial expression of CXCL16, CXCR6, and RANKL was higher in RA patients than in patients with OA. The serum CXCL16 and RANKL levels were higher in RA patients compared with OA patients and healthy controls. CXCL16 correlated with erythrocyte sedimentation rate, C reactive protein, disease activity, serum rheumatoid factor, and RANKL. RA-FLS treated with CXCL16 showed markedly increased expression of RANKL. When STAT3 or p38 activation was blocked by an inhibitor, CXCL16 failed to upregulate RANKL expression. In contrast, inhibiting the Akt or Erk pathway did not achieve the same effect. CONCLUSIONS: CXCL16 upregulates RANKL expression in RA-FLS and these effects are mainly mediated by the JAK2/STAT3 and p38/MAPK signaling pathways.

Anxiety disorder symptoms in Chinese preschool children.

The present study investigated anxiety disorder symptoms in Chinese preschool children. A total of 1,854 mothers of children aged 3-6 years completed the 28-item Chinese version of Spence Preschool Anxiety Scale (PAS). Results demonstrated that the structure of anxiety in Chinese preschool children included five factors, and this five-factor structure applied to different age and gender groups. Inconsistent with the study by Edwards et al. (J Clin Child Adolesc Psychol 39:400-409, 2010) suggesting that obsessive-compulsive disorder did not comprise an independent factor in Australian preschoolers, this symptom can be viewed as an independent factor in Chinese preschoolers. Younger children displayed higher anxiety levels than older children. Anxiety symptoms of Chinese preschoolers were found at a high level compared to other studies. Substantial differences were found with regard to the content of prevalent anxiety symptoms among Chinese and Australian preschool children. The applicability of the five-factor structure of PAS and research implications are discussed.

Combination of bladder cancer-specific oncolytic adenovirus gene therapy with cisplatin on bladder cancer in vitro.

Bladder cancer-specific oncolytic adenovirus Ad/PSCAE/UPII/E1A, carrying E1A gene regulated by human Uroplakin II (UPII) promoter and prostate stem cell antigen enhancer (PSCAE), could kill bladder tumor cells preferentially. The aim of this study was to examine the effects of Ad/PSCAE/UPII/E1A combined with cisplatin on human bladder cancer cells and to identify the underlying mechanisms. The combined effects of Ad/PSCAE/UPII/E1A and cisplatin on EJ, 5637, and BIU-87 bladder cancer cells were evaluated by MTT cell proliferation assay. Cell apoptosis was detected by flow cytometry with fluorescein isothiocyanate-conjugated annexin V (annexin V-FITC) and propidium iodide staining. The activation of the caspase pathway and the expression of Bcl-2 family proteins were determined by western blot assay. Ad/PSCAE/UPII/E1A adenovirus vector could infect bladder cancer cell lines selectively and induce growth inhibition effectively. Of note, the combination treatment of cisplatin and Ad/PSCAE/UPII/E1A could inhibit the proliferation of bladder cancer cells significantly compared with the "alone" treatment. Furthermore, Ad/PSCAE/UPII/E1A plus cisplatin combined treatment resulted in enhanced apoptosis in bladder cancer cells. The enhanced antitumor effects in vitro elicited by Ad/PSCAE/UPII/E1A plus cisplatin were closely related to the increased Fas expression and cleavage of caspase-8 and Bid and decrease in the ratio of anti- to pro-apoptotic proteins followed by activation of caspase-9 and caspase-3, which may contribute to the activation of extrinsic and intrinsic apoptotic pathways. Our results indicate that the combination of Ad/PSCAE/UPII/E1A with cisplatin exerts a synergistic antitumor effect on human bladder cancer cells and is a potential combined treatment strategy for bladder cancer.

Classification criteria of early rheumatoid arthritis and validation of its performance in a multi-centre cohort.

OBJECTIVES: To develop classification criteria for early rheumatoid arthritis (ERA) based on a large cohort of early inflammatory arthritis patients and to evaluate the performance of these criteria. METHODS: The study population comprised a cohort of early inflammatory arthritis patients with symptom duration less than one year. Classification criteria of ERA were developed by incorporating the most sensitive or specific variables. Performance of the ERA criteria, 1987 ACR and 2010 ACR/EULAR criteria were evaluated. RESULTS: A total of 803 patients were enrolled in this study. By the end of the one year follow-up, 514 patients were diagnosed with RA, 251 with other rheumatic diseases, and 38 patients with undifferentiated arthritis. The ERA criteria are as follows: 1) morning stiffness ≥30 minutes; 2) arthritis of 3 or more joint areas; 3) arthritis of hand joints; 4) positive RF; 5) positive anti-CCP antibody. Rheumatoid arthritis is defined by the presence of 3 or more of the criteria. The sensitivity (84.4%) of the ERA classification criteria was much higher than the 1987 ACR criteria (58.0%). In a validation cohort of early inflammatory arthritis patients, the area under the ROC curves (AUC) showed a better performance for the ERA criteria (0.906, 95%CI 0.866 to 0.945) than the 1987 ACR criteria (0.786, 95%CI 0.725 to 0.848) and the 2010 ACR/EULAR criteria (0.745, 95%CI 0.677 to 0.814). CONCLUSIONS: A set of ERA classification criteria has been developed with good performance for early RA. It is applicable in clinical practice and research.

Pathogenic roles of follicular helper T cells in IgG4-related disease and implications for potential therapy.

IgG4-related disease (IgG4-RD) is a recently described autoimmune disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4+ plasma cells in multiple organ systems. Recent advancements have significantly enhanced our understanding of the pathological mechanism underlying this immune-mediated disease. T cell immunity plays a crucial role in the pathogenesis of IgG4-RD, and follicular helper T cells (Tfh) are particularly important in germinal center (GC) formation, plasmablast differentiation, and IgG4 class-switching. Apart from serum IgG4 concentrations, the expansion of circulating Tfh2 cells and plasmablasts may also serve as novel biomarkers for disease diagnosis and activity monitoring in IgG4-RD. Further exploration into the pathogenic roles of Tfh in IgG4-RD could potentially lead to identifying new therapeutic targets that offer more effective alternatives for treating this condition. In this review, we will focus on the current knowledge regarding the pathogenic roles Tfh cells play in IgG4-RD and outline potential therapeutic targets for future clinical intervention.

Reliability and validity of the short version of the childhood abuse self report scale in Chinese college students.

BACKGROUND: The reliability and validity of the current scale for measuring childhood abuse in China are worrying. The development of the Short Version of the Childhood Abuse Self Report Scale (CASRS-12) helps to change this situation, but the effectiveness of the tool has not yet been tested in Chinese participants. This study aims to test the reliability and validity of the CASRS­12 in Chinese college students. METHODS: A total of 932 college students were investigated, of whom 418 were investigated for the first time, and only the CASRS­12 was filled out. In the second survey, 514 participants filled out the CASRS­12, Depression Scale, Self-esteem Scale and Subjective Well-being Scale in turn. After 4 weeks, 109 participants were selected for retest. RESULTS: Each item of the CASRS­12 had good discrimination. Exploratory factor analysis and confirmatory factor analysis (χ2/df = 4. 18, RMSEA = 0. 079, CFI = 0. 95, TLI = 0. 94, IFI = 0. 95, NFI = 0. 94) all supported the four-factor structure of the scale, and the cumulative contribution rate of variance was 76.05%. Cronbach's α coefficient and retest reliability were 0.86 and 0.65, respectively. Childhood abuse was positively correlated with depression (r = 0. 42, p < 0.01), and negatively correlated with self-esteem (r=-0. 33, p < 0.01) and subjective well-being (r=-0. 32, p < 0.01). CONCLUSION: The Chinese version of CASRS­12 meets the measurement standard and could be used to measure the level of childhood abuse of Chinese college students.