The efficacy and safety of tacrolimus in patients with dermatomyositis/polymyositis: A meta-analysis and systematic review.

OBJECTIVE: To evaluate the efficacy and safety of tacrolimus for dermatomyositis (DM) and polymyositis (PM) treatment. METHODS: We searched the Embase, PubMed, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure were used as searching tools from inception up to October 2022. Two authors independently selected studies. The available studies were comprehensively reviewed and investigated. RESULTS: A total of 9 studies, including 350 patients, were analysed. Pooled results showed a higher overall survival rate in tacrolimus therapy group. Creatine kinase (CK) levels and forced vital capacity (FVC) showed significant improvement after tacrolimus therapy. The incidence of adverse events including infection and renal dysfunction showed no significant differences between the tacrolimus therapy group and conventional therapy group. CONCLUSION: The results of this meta-analysis indicated that GC therapy in combination with tacrolimus therapy could help improving overall survival rate, pulmonary function and had similar safety outcomes compared to conventional therapy in DM and PM patients.

NK/T-cell lymphoma with rash and peripheral neuropathy as the first manifestation: a case report and literature review.

BACKGROUND: Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT), is a rare, aggressive subtype of non-Hodgkin lymphoma, and it usually presents as a destructive sinus mass that may attend epistaxis. However, ENKTCL-NT with the manifestation of peripheral neuropathy is pretty unusual. CASE PRESENTATION: A 17-year-old Chinese patient presented with peripheral neuropathy and positive auto-antibodies. However, she failed methylprednisolone pulse therapy and developed hemophagocytic syndrome. The diagnosis of CD30-positive primary cutaneous ENKTCL-NT was confirmed by pathological biopsy. Her disease was brought under control after five cycles of chemotherapy. CONCLUSIONS: The report findings are helpful in the differential diagnosis of peripheral neuropathy and autoimmune disease. We should be alert for the development of ENKTCL-NT when the rash and peripheral neuropathy are the first symptoms and are accompanied by Epstein-Barr virus (EBV) infection.

A cross-sectional study on the association of anxiety and depression with the disease activity of systemic lupus erythematosus.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects multiple systems and increases the risk of mental disorders such as depression and anxiety. We conducted an observational, single-center, cross-sectional study to investigate the relationship between depression, anxiety, and SLE disease activity. METHODS: The Patient Health Questionnaire 9 (PHQ-9) was used to assess depression, and the 7-item Generalized Anxiety Disorders Scale was used to assess anxiety (GAD-7). Using the chi-square/exact Fisher's tests, socio-demographic data, clinical and other characteristics of SLE patients were compared between depression or anxiety and non-depression/non-anxiety groups. To identify optimal levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) for predicting depression or anxiety, receiver-operator curves (ROC) were drawn. RESULTS: Among the 325 patients involved in this study, patients with depression or anxiety had significantly higher SLE activity (p < 0.001), and more frequent musculoskeletal (p < 0.05) and neuropsychiatric symptoms (p < 0.05). Depression and anxiety are more common in the moderate-severe active group than in the inactive-mild active group (depression: OR 3.350, 95%CI 2.015, 5.570, p < 0.001; anxiety: OR 4.085, 95%CI 2.493, 6.692, p < 0.001). The optimal SLEDAI cutoff value of 8.5 predicted depression with a sensitivity of 50.5% and a specificity of 78.4% (AUC 0.660, p < 0.001) and anxiety with a sensitivity of 54.2% and a specificity of 78.4% (AUC 0.684, p < 0.001). CONCLUSION: SLE disease activity is positively associated with the severity of depression and anxiety. Those patients whose SLEDAI scores are greater than 8.5 are more likely to suffer from mental disorders which require additional attention to them.

Acquired Hemophilia Associated with Rheumatic Diseases: A Case-Based Systematic Review.

To strengthen the understanding of rheumatic diseases (RDs) as the most common underlying conditions associated with acquired hemophilia (AH), a potentially fatal bleeding condition due to the development of autoantibodies or inhibitors to coagulation factor VIII, and rarely to factor IX, here we presented two cases of RDs associated AH to elucidate the disease progression, treatment, and prognosis. The presented 2 cases showed good responses to glucocorticoid (GC) and immunosuppressive agents. And then, a case-based systematic review was conducted to better understand the clinically practiced diagnosis and treatment of RDs associated AH. A total of 14 articles were included in the final literature review. All the identified 14 patients with underlying RDs and AH presented with bleeding symptoms, increased APTT, decreased FVIII activity, and positive FVIII inhibitors. Twelve of the 14 patients (85.7%) started an eradication of autoantibodies treatment with GC and immunosuppressive agents. Among which six patients achieved partial or complete remission, and four patients (28.6%) switched to Rituximab and responded well. Nine of the 14 patients received hemostasis therapy, including recombinant human FVIIa (rFVIIa). Two patients (14.3%) died due to mass bleeding and key organ failure. AH should be highly suspected in patients with RDs presenting spontaneous mucocutaneous or internal bleeding and an isolated prolonged APTT. Given the high morbidity of AH, it is important to facilitate efficient and proper management.

Influencing Factors of International Students' Anxiety Under Online Learning During the COVID-19 Pandemic: A Cross-Sectional Study of 1,090 Chinese International Students.

Objective: We conducted the following cross-sectional study to comprehensively assess the anxiety among Chinese international students who studied online during the COVID-19 pandemic and its influencing factors. Methods: Questionnaires were distributed through "Sojump," and a total of 1,090 valid questionnaires were collected. The questionnaire was divided into two parts: general situation and anxiety assessment of students. The former used a self-made questionnaire, and the international general GAD-7 scale was used to measure anxiety. Chi-square test was used to analyze the differences between groups, and logistic regression analysis was performed for the factors with differences. Results: Anxiety was found in 707 (64.9%) of 1,090 international students. Chi-square test and multivariate Logistic regression analysis showed that the incidence of anxiety was higher in the group under 22 years of age than in the group over 22 years of age (68% vs. 61%, p = 0.015; OR = 1.186, 95% CI 1.045-1.347, p = 0.008); International students living in big cities had a higher incidence of anxiety than those living in rural areas (67% vs. 60%, p = 0.022; OR = 1.419, 95%CI 1.038-1.859, p = 0.011); international students who socialized 3 times or less monthly had a higher incidence of anxiety than those who socialized more than 3 times per month (68% vs. 58%, p = 0.003; OR = 1.52, 95%CI 1.160-1.992, p = 0.002); international students who expected purely online teaching had a higher incidence of anxiety than those who expected purely offline teaching or dual-track teaching (72% vs. 64%, p = 0.037; OR = 1.525, 95%CI 1.069-2.177, p = 0.02); international students with a subjective score of online learning experience of 6 or less had a higher incidence of anxiety than those with subjective scores of more than 6 (70% vs. 60%, p = 0.001, OR = 1.25, 95%CI 1.099-1.422, p = 0.001). However, gender, emotional status, BMI, major of study, vaccination status, and degree type had no significant difference in the incidence of anxiety among international students who studied online during the COVID-19 pandemic. Conclusion: During COVID-19, international students who were younger, came from big cities, had low social frequency, expected purely online teaching, and had poor experience of online classes were risk factors for anxiety during online classes.

iTRAQ and PRM-Based Proteomic Analysis Provides New Insights into Mechanisms of Response to Triple Therapy in Patients with Rheumatoid Arthritis.

BACKGROUND: Approximately 30% of patients with rheumatoid arthritis (RA) respond poorly to combination therapy of multiple drugs. The molecular mechanisms of different responses to methotrexate + leflunomide + infliximab therapy in patients with RA were explored in this study. METHODS: Infliximab was administered to patients with RA whose disease activity score was higher than 5.1 after 1 month of combination therapy with methotrexate and leflunomide. After 14 weeks of undergoing triple therapy, patients with RA were classified as responders and non-responders. Protein profiles at baseline and 14th week were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and proteins with significant differences ≥1.2 folds change or ≤0.8 folds change were defined as differentially expressed proteins (DEPs). Overlapping DEPs between responders and non-responders were confirmed by parallel reaction monitoring (PRM). Bioinformatic analyses were performed for DEPs. RESULTS: The results revealed 5 non-responders (NRs) and 15 responders (Rs). iTRAQ analysis indicated 13 overlapping DEPs and included 6 opposite change DEPs such as testicular tissue protein Li 70, cofilin 1, fibrinogen beta chain, galectin-10, serotransferrin (TF) and albumin. The difference in serotransferrin between responders and non-responders confirmed by PRM was significant. Verification by PRM indicated that TF was elevated in the Rs group and was reduced in the NRs group. Bioinformatic analysis indicated that serotransferrin was involved in the hypoxia-inducible factor-1 pathway and ferroptosis. CONCLUSION: Serotransferrin-related molecular mechanism may be a new direction to study refractory RA.

Persistence of Salmonella Typhimurium in apple-pear (Pyrus bretschneideri Rehd.) orchard soils influenced by bacterial communities and soil properties.

2In this study, we investigated the persistence of Salmonella Typhimurium in 26 soil samples from apple-pear orchards in Yanji, Longjing and Helong in northeastern China. The time to reach detection limit (ttds) of Salmonella Typhimurium in soils varied from 20 to 120 days. Redundancy analysis and variation partition analysis elucidated that bacterial communities, clay content, pH, electrical conductivity (EC) salinity, and NO3--N could explain more than 85% of overall variation of the persistence behaviors. Results of structural equation models and Mantel tests revealed that clay content and EC displayed both direct and indirect effect on ttds, while NO3--N and pH exhibited direct and indirect effect on the survival patterns, respectively. Furthermore, Actinobacteria, Acidobacteria and Deltaproteobacteria at class level showed highly close correlations with ttds. Our results revealed that certain biotic and abiotic factors could greatly contribute to the overall persistence of Salmonella in apple-pear orchard soils.

Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis.

OBJECTIVE: To explore the main components and unravel the potential mechanism of simiao pill (SM) on rheumatoid arthritis (RA) based on network pharmacological analysis and molecular docking. METHODS: Related compounds were obtained from TCMSP and BATMAN-TCM database. Oral bioavailability and drug-likeness were then screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Additionally, target genes related to RA were acquired from GeneCards and OMIM database. Correlations about SM-RA, compounds-targets, and pathways-targets-compounds were visualized through Cytoscape 3.7.1. The protein-protein interaction (PPI) network was constructed by STRING. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed via R packages. Molecular docking analysis was constructed by the Molecular Operating Environment (MOE). RESULTS: A total of 72 potential compounds and 77 associated targets of SM were identified. The compounds-targets network analysis indicated that the 6 compounds, including quercetin, kaempferol, baicalein, wogonin, beta-sitosterol, and eugenol, were linked to ≥10 target genes, and the 10 target genes (PTGS1, ESR1, AR, PGR, CHRM3, PPARG, CHRM2, BCL2, CASP3, and RELA) were core target genes in the network. Enrichment analysis indicated that PI3K-Akt, TNF, and IL-17 signaling pathway may be a critical signaling pathway in the network pharmacology. Molecular docking showed that quercetin, kaempferol, baicalein, and wogonin have good binding activity with IL6, VEGFA, EGFR, and NFKBIA targets. CONCLUSION: The integrative investigation based on bioinformatics/network topology strategy may elaborate on the multicomponent synergy mechanisms of SM against RA and provide the way out to develop new combination medicines for RA.

Disentangling survival of Escherichia coli O157:H7 in soils: From a subpopulation perspective.

Soil physicochemical properties and microbial community have been proved to be correlated to survival behaviors of Shiga toxin-producing Escherichia coli O157:H7, but the roles of biotic and abiotic factors in the different stages of inactivation process remain unclear. Here, fruit producing soils were collected, and soils physicochemical properties, bacterial and fungal community structure were characterized. Survival experiments were performed by inoculating E. coli O157:H7 in soils. Double Weibull survival model was found to better fit the experimental data, and two subpopulations with different capability on resistance to stress were identified. The sensitive subpopulation with smaller δ (time needed for first decimal reduction) (i.e., δ1) died off faster compared to the more resistant subpopulation with greater δ (i.e., δ2). Partial Mantel test revealed that ttd (time needed to reach detection limit) was jointly influenced by physical factors, chemical factors, and bacterial composition (P < 0.05); δ1 was shaped by physical factors (P < 0.01) and additional bacterial composition (P < 0.05); and δ2 was strongly steered by bacterial community (P < 0.001). Bacterial co-occurrence network analysis revealed that samples with lower δ2 were coupled with higher network complexity and closer taxa relationship (e.g. higher average (weighted) degree, higher network diameter, higher graph density, and lower modularity), and vice versa. Taken together, the sensitive subpopulation had difficulty in adapting to coarse particles conditions, while resistant subpopulation might eventually succumb to the robust biodiversity. This study provides novel insights into the E. coli O157:H7 survival mechanism through subpopulation perspective and sheds light on the reduction of edaphic colonization by pathogens via agricultural management strategy.

Interaction between Fungal Communities, Soil Properties, and the Survival of Invading E. coli O157:H7 in Soils.

Pathogens that invade into the soil cancontaminate food and water, andinfect animals and human beings. It is well documented that individual bacterial phyla are well correlated with the survival of E. coliO157 (EcO157), while the interaction betweenthe fungal communities and EcO157 survival remains largely unknown. In this study, soil samples from Tongliao, Siping, and Yanji in northeast China were collected and characterized. Total DNA was extracted for fungal and bacterial community characterization. EcO157 cells were spiked into the soils, and their survival behavior was investigated. Results showed that both fungal and bacterial communities were significantly correlated (p < 0.01) with the survival of EcO157 in soils, and the relative abundances of fungal groups (Dothideomycetes and Sordariomycetes) and some bacterial phyla (Acidobacteria, Firmicutes, gamma- and delta-Proteobacteria)weresignificantly correlated with ttds (p < 0.01). Soil pH, EC (electric conductance) salinity, and water-soluble nitrate nitrogen were significantly correlated with survival time (time to reach the detection limit, ttd) (p < 0.05). The structural equation model indicated that fungal communities could directly influence ttds, and soil properties could indirectly influence the ttds through fungal communities. The first log reduction time (δ) was mainly correlated with soil properties, while the shape parameter (p) was largely correlated with fungal communities. Our data indicated that both fungal and bacterial communities were closely correlated (p < 0.05)with the survival of EcO157 in soils, and different fungal and bacterial groups might play different roles. Fungal communities and bacterial communities explained 5.87% and 17.32% of the overall variation of survival parameters, respectively. Soil properties explained about one-third of the overall variation of survival parameters. These findings expand our current understanding of the environmental behavior of human pathogens in soils.

Predictors of late atrial fibrillation recurrence after cryoballoon-based pulmonary vein isolation: a meta-analysis.

BACKGROUND: The recurrence rate of atrial fibrillation (AF) after cryoballoon ablation in drug refractory AF patients is high. Late-recurrence of AF has various predictors. AIM: The aim of the study was to explore the related risk factors that can effectively predict late AF recurrence after cryoballoon-based pulmonary vein isolation. METHODS: The PubMed and Web of Science databases were searched from 1 January 2013 to 1 August 2016, and studies were chosen that met the pre-stated inclusion criteria. The reference lists of the retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies. The strength of the relationship between different risk factors and late recurrence was assessed by the adjusted hazard ratio. RESULTS: A total of 16 papers met the inclusion criteria and were included in the meta-analysis. The hazard ratio of late atrial arrhythmia recurrence in patients with early recurrence was 4.19 compared with the reference group (95% CI 2.73-6.44, p < 0.00001); that of increased left atrial diameter was 1.25 (95% CI 1.12-1.3, p < 0.0001); that of a long duration of AF before ablation was 1.10 (95% CI 1.04-1.17, p < 0.0009); and that of persistent AF was 2.44 (95% CI 1.30-4.58, p < 0.006). However, there exists significant heterogeneity for each indicator, and a slight publication bias was observed. CONCLUSIONS: Our study suggests that early recurrence in the blanking period, increased left atrial size, a longduration of AF before ablation and persistent AF are independent predictors of late recurrence after cryoballoon ablation.

Comparison of efficacy of different treatments for pulmonary embolism.

An optimal therapy for pulmonary embolism (PE) was explored by comparing three different methods in order to alleviate the sufferings of PE patients and reduce the mortality. Eighty patients with PE diagnosed by computed tomography angiography (CTA) were treated with thrombolysis, anticoagulation only, or surgery/intervention. The clinical efficacy of different treatments were compared and analyzed. Twenty-four out of the 26 patients (92%) in anticoagulation only group showed improvement in CTA and clinical presentations, which was significantly higher than that in the thrombolysis group (87%, n=39, P<0.05). However, there was no significant difference in the rate of mortality between thrombolysis group and anticoagulation only group. In the surgery/interventional group (n=15), the success rate was 47%, and the mortality rate was 14%. Both of them were significantly different from those in thrombolysis and anticoagulation only groups (both P<0.05). Log-rank analysis of the data of 5-year follow-up revealed that the survival time in surgery/intervention group was significantly shorter than in the other two groups (P<0.05). It was suggested that it is of importance to choose the appropriate therapeutic regimen for PE patients. Mortality may be reduced and prognosis may be improved with anticoagulation only and thrombolysis therapy.

Regulator of G-protein signaling 5 protects cardiomyocytes against apoptosis during in vitro cardiac ischemia-reperfusion in mice by inhibiting both JNK1/2 and P38 signaling pathways.

Ischemic heart disease is one of the most common diseases in modern society. Ischemic myocardium can be salvaged by vascular recanalization therapy, but its benefit is attenuated by injury that can occur during reperfusion. And apoptotic cell death plays an important part in myocardial ischemia-reperfusion (IR) injury. Regulator of G-protein signaling 5 (RGS5), highly expressed in different cell types of the human adult heart, is a guanosine triphosphatase-activating protein to inhibit many signaling pathways such as c-Jun NH2-terminal kinase 1/2 (JNK1/2) and p38 which promote cardiac IR-induced apoptosis. However the role of RGS5 in cardiac IR-induced apoptosis remains unclear. An in vitro IR model was applied to the isolated hearts of wild type mice (WT), RGS5-transgenic mice (TG), and RGS5-knockout mice (KO). Our results revealed that compared with either WT or KO mice, TG mice showed inhibition of cardiomyocyte apoptosis as indicated by a greater increase of B cell lymphoma/lewkmia-2 (Bcl-2), and an obvious reduction in the positive expression of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), Bcl-2 Associated X protein (Bax), and active caspase-3. Moreover, the inhibition of both JNK1/2 and p38 signaling markedly reversed IR-induced cardiomyocyte apoptosis in RGS5-KO mice. These studies show that RGS5 protects cardiomyocytes against apoptosis during IR through inhibiting both JNK1/2 and p38 signaling pathways.

Effects of low-level carotid baroreflex stimulation on atrial electrophysiology.

PURPOSE: This study aimed to investigate the effects of low-level carotid baroreflex stimulation (LL-CBS) on atrial electrophysiology. METHODS: In protocol 1 (LL-CBS on physiological state), anesthetized rabbits were subjected to LL-CBS (n = 10) or surgical exposure (n = 6) for 1 h. In protocol 2 (LL-CBS on acute rapid atrial pacing), anesthetized rabbits underwent 3 h of rapid atrial pacing (RAP) with concomitant LL-CBS in the third hour (n = 7) or 3h-RAP without LL-CBS (n = 6). Carotid baroreceptor surrounded by electrodes allowed LL-CBS at 20 % below the voltage required to reduce systolic blood pressure or heart rate. Effective refractory period (ERP) and monophasic action potential duration (MAPD) were determined, and power spectral of heart rate variability (HRV) was analyzed at baseline as well as after interventions in all groups, respectively. RESULTS: In protocol 1, LL-CBS significantly prolonged the ERPs, MAPD90, and MAPD50 and increased high-frequency (HF) HRV component but it decreased low-frequency (LF) HRV component and LF/HF ratio. In protocol 2, 3h-RAP significantly shortened ERPs, MAPD90, and MAPD50 and decreased HF but it increased LF and LF/HF ratio. However, LL-CBS reversed the variations caused by RAP. CONCLUSIONS: LL-CBS prolongs ERPs and MAPD of the left atrium and attenuates RAP-induced atrial electrical remodeling including the shortening of ERPs and MAPD, probably by modulating the autonomic nervous system.

Left atrial appendage morphology in patients with atrial fibrillation in China: implications for stroke risk assessment from a single center study.

BACKGROUND: The left atrial appendage (LAA) is thought to be the main source of thrombi in patients with atrial fibrillation (AF). The purpose of this study was to describe the LAA orifice diameter, LAA length, and morphologic type of the LAA in Chinese patients with AF as well as to evaluate whether these LAA parameters are associated with a history of stroke in patients with AF from a single center in China. METHODS: The study population consisted of 219 consecutive patients with drug-refractory, symptomatic paroxysmal, or persistent AF scheduled to undergo radiofrequency catheter ablation in our single center. All patients underwent extensive clinical assessment and multidetector computed tomography to fully explore the anatomy of the LAA. RESULTS: Of the 219 patients who underwent catheter ablation procedures, chicken wing LAA morphology was found in 114 patients (52.2%), windsock in 52 (23.9%), cauliflower in 29 (13.0%), and cactus in 24 (10.9%). Compared with the windsock LAA morphology, cactus had a larger left atrial diameter ((42.40 ± 3.68) and (37.91 ± 4.32) mm, P = 0.005) and LAA orifice diameter ((27.38 ± 3.70) and (24.14 ± 3.58) mm, P = 0.048). The LAA length was significantly larger in the chicken wing morphology than in the windsock ((37.50 ± 6.74) and (31.33 ± 3.92) mm, P = 0.015) and cauliflower morphologies ((37.50 ± 6.74) and (31.33 ± 3.92) mm, P = 0.015). According to their medical records, 26 patients (11.9%) had suffered a prior stroke. Compared with patients who had no history of stroke, the prior-stroke patients were older (62.04 ± 8.07 and 58.24 ± 9.24, P = 0.047) and there were fewer patients with chicken wing (23.1% and 59.1%, P = 0.001) and more patients with cauliflower (26.9% and 9.8%, P = 0.046). Multivariate Logistic regression analysis demonstrated that age (odds ratio (OR) 1.26; 95% confidence interval (CI) 1.08-1.47; P = 0.003), non-chicken wing morphology (OR 5.82; 95% CI 1.61-21.03; P = 0.007), and LAA orifice diameter (OR 1.25; 95% CI 1.05-1.49; P = 0.014) were independent predictors of stroke after adjusting for all parameters that emerged as potential confounders with univariate analysis. CONCLUSION: LAA analysis can potentially be used to inform guidance on the implication for stroke risk assessment.