ObjectiveTo explore the effects and possible mechanisms of VCR combined with low dose cyclophosphamide(CTX) intermittently to treat severe systemic lupus erythematosus(SLE).It is assumed that this might be a new combination therapy for SLE and expected to improve the overall prognosis and outcome of SLE.MethodsMurine chronic graft-versus-host disease(cGVHD) model were developed for study.They were randomly divided into the control group,vincristine (VCR) pulse therapy group,CTX pulse therapy group,CTX every other day(EOD) group,VCR+CTX combination group.One way ANOVA and repeated measure variance analysis were used for statistical analysis.Results① Six weeks after cGVHD models were set up,the average 24-hour urine protein quantification was(5.02±0.88) mg,anti-dsDNA antibody was positive,and Ⅳ LN pathology could be observed histologically in the model murine.So cGVHD models were successfully developed.② Significantly difference in decreasing of 24-hour urine protein quantification was found in the CTX EOD group,VCR+CTX combination group and other groups (P＜0.01).Significant decrease in Cr,ALT,anti-dsDNA,was found in the CTX EOD group,VCR+CTX combination group,CTX pulse therapy group and other groups(P＜0.05).Decrease in urine MCP-1 and TGF-β1 could be detected,and statistical significant difference in these parameters could be found in the CTX EOD group,CTX pulse therapy group,VCR+CTX combination group and other groups (P＜0.01).MCP-1 and TGF-β1'expression in model kidney were reduced in the CTX EOD group,VCR+CTX combination group and had statistical significant difference in the CTX EOD group,VCR+CTX combination group,VCR pulse therapy group,and CTX pulse therapy group.③ VCRand CTX combination treatment was effectivein 24-hour urine protein quantification,blood Cr,ALT,anti-dsDNA and urine MCP-1,as well as urine TGF-β1 (P＜0.05).Conclusion ① The combination of VCR and CTX is synergistic in decreasing 24-hour urine protein quantification,Cr,and the expression of MCP-1,TGF-β1.② The adverse effect of VCR+CTX combination group is similar to VCR pulse therapy group and CTX pulse therapy group.

ObjectiveTo examine whether Shenfu injection (SFI) reduces post-resuscitation myocardial dysfunction in a pig model by modulating expression imbalance of transcription factors of regulatory T cell, namely GATA-3 and T-bet.Methods Thirty pigs were randomly divided into sham group (n = 6) and cardiopulmonary resuscitation (CPR) group (n = 24) according to the random number table method, and the pigs in the CPR group were randomly subdivided into normal saline (NS) group, epinephrine (EP) group, and SFI group (n = 8 per group). After 8minutes of untreated ventricular fibrillation (VF) followed by 2 minutes of CPR, animals in three groups respectively received central venous injection of either 20 mL SFI (1.0 mL/kg, SFI group), EP (0.02 mg/kg, EP group) or NS (NS group). Blood samples were obtained before VF and 0.5, 2, 6 hours after restoration of spontaneous circulation (ROSC), and the parameters of hemodynamics and oxygen metabolism were determined. Surviving pigs were sacrificed at 24 hours after ROSC, the pathological changes in myocardium were observed, the levels of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α) andγ-interferon (IFN-γ) were measured by enzyme linked immunosorbent assay (ELISA), and expressions of protein and mRNA of GATA-3 and T-bet were determined by Western Blot and quantitative real-time polymerase chain reaction (RT-qPCR), respectively.Results Six pigs of three resuscitation groups were successfully resuscitated. The CPR time, number of defibrillation, defibrillation energy, and ROSC time were significantly decreased in the EP and SFI groups compared with those in the NS group. Compared with the sham group, the parameters of left ventricular systolic function and oxygen metabolism were significantly decreased, myofibril organelles were extensively damaged, and progressive and severe deterioration of the myocardium was found, and mitochondrial structure was not recognizable in the NS group; the level of IL-4 in myocardium were markedly decreased, while that of TNF-α, IFN-γand IFN-γ/ IL-4 [reflecting helper T cell 1/2 (Th1/Th2)] were significantly increased. Protein and mRNA expressions of GATA-3 were markedly reduced in the myocardium of pigs in the NS group compared with that of the sham group at 24 hours after ROSC, while T-bet was significantly increased. Compared with the NS group, animals treated with SFI had minimal myocardial intracellular damage, with decreased heart rate (HR, bpm: 90.33±3.79 vs. 106.83±5.36) and increased mean arterial pressure (MAP), cardiac output (CO), oxygen delivery (DO2), and oxygen consumption (VO2) at 6 hours after ROSC [MAP (mmHg, 1 mmHg = 0.133 kPa): 107.67±1.96 vs. 86.83±1.85, CO (L/min): 2.47±0.08 vs. 2.09±0.04, DO2 (mL/min): 364.31±4.21 vs. 272.33±3.29, VO2 (mL/min): 95.00±2.22 vs. 82.50±2.28, allP<0.05]. Compared with the NS groups at 24 hours after ROSC, level of IL-4 was markedly increased in myocardial cells (ng/L: 33.80±3.06 vs. 16.15±1.34,P< 0.05), while the levels of TNF-α, IFN-γ and IFN-γ/IL-4 were lowered significantly [TNF-α (ng/L): 18.16±0.71 vs. 29.64±1.89, IFN-γ (ng/L): 373.75±18.36 vs. 512.86±27.86, IFN-γ/IL-4: 16.15±1.34 vs. 33.80±3.06, allP< 0.05], and myocardial T-bet protein and mRNA expressions were reduced [T-bet protein (gray value): 0.41±0.07 vs. 0.59±0.11, T-bet mRNA (2-ΔΔCt): 4.37±0.21 vs. 7.57±0.55, bothP< 0.05], furthermore, myocardial GATA-3 protein and mRNA expressions were significantly up-regulated in SFI group [GATA-3 protein (gray value): 0.25±0.07 vs. 0.16±0.07, GATA-3 mRNA (2-ΔΔCt): 0.63±0.07 vs. 0.34±0.05, bothP< 0.05]. The parameters in SFI group were significantly improved compared with those of the EP group.ConclusionsMyocardial immune dysfunction is induced by Th1/Th2 imbalance following myocardial injury subsequent to CPR in pigs. SFI can attenuate myocardial injury and regulate myocardial immune disorders, protect post-resuscitation myocardial injury by modulating expression imbalance of transcription factors GATA-3 and T-bet.

Objective To confirm whether in post-resuscitation myocardial dysfunction involved in myocyte apoptosis mechanism in porcine model of cardiac arrest and apoptosis index varied from different modalities of cardiopulmonary resuscitation or not.Methods A total of 22 WZSP inbred small swine were randomly (random number) divided into sham operation group (SHAM) (n =6),defibrillation first group (DF,n =8) and chest compression first group (CF,n =8).Eight minutes after ventricular fibrillation was set up,standard CPR was carried out subsequently after defibrillation in porcine models of cardiac arrest in DF group and defibrillation after standard CPR in CF group,and hemodynamics were monitored.Twentyfour hours after restoration of spontaneous circulation (ROSC),animals were sacrificed,and myocardial specimens were examined with electron microscopy,Western blot,quantitative RT-PCR,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.The experimental data were analyzed by SPSS 17.0.Student's t test was employed for comparisons between two groups.Differences within groups at different time intervals were compared with repeated measures ANOVA.A two-tailed value of P ＜ 0.05 was considered statistically significant.Results Myocardial function was significantly impaired after ROSC.Levels of Bcl-2,Bax and caspase-3 protein was markedly increased in the CF and DF groups than those in the SHAM group (P ＜ 0.05) at 24 h after ROSC,while Bcl-2/Bax was significantly reduced in the CF and DF group compared with the SHAM group (P ＜ 0.05),and much more apoptotic cells were observed in cardiac arrest animals in comparison with sham-operation animals (P ＜ 0.05).Six hours after ROSC,hemodynamic indicators improved significantly in group DF than those in group CF,but Bcl-2,Bax and caspase-3 protein levels and apoptotic index were not significantly different bewteen the DF group and CF group (P ＞ 0.05).Conclusions Caspase-3-mediated apoptosis might be one of the main pathological mechanisms of postresuscitation myocardial injury in a porcine model of cardiac arrest,but there was no statistically significant difference in apoptosis index between two resuscitation modalities,showing no one modality was superior over another.

Objective To study the role of imbalance between transcription factors GATA-3 and T-bet expressions in causing acute lung injury after resuscitation in cardiac arrest model of swine.Methods Mter swine model of electrically induced cardiac arrest was established for 8 minutes,animals were resuscitated to get restoration of spontaneous circulation (ROSC).The swine with ROSC were randomly assigned to be sacrificed at 12 and 24 h after ROSC (n =8 in each group).CD3 +,CD4+ and CD8 + lymphocyte subsets were determined by flow cytometry,and the levels of serum IL-4,TNF-α,and IFN-γ were measured by using ELLSA.The protein levels and expressions of GATA-3/T-bet mRNA were detected in lung tissue by western blotting and quantitative real-time PCR device,respectively.Results Pulmonary function was significantly impaired after ROSC.CD4 + lymphocyte subsets (28.4 ± 2.3) ％,(24.1 ± 1.6) ％ and CD4 +/CD8 + (1.7 ±0.9),(1.5 ± 1.0) were significantly lower in the post-ROSC group compared with the sham-operated group (48.4±2.9)％,(51.1±5.4)％ (2.5±1.3),(2.7±1.1) (P＜0.05) at 12 h and 24 h after ROSC.The levels of serum IL-4 and TNF-α were markedly increased,while IFN-γ and IFN-γ/IL-4 were significantly decreased in the post-ROSC group compared with the sham-operated group (P ＜0.05) at 2-12 h after ROSC.Protein level and expression of GATA-3 mRNA in lung tissue were markedly increased,while those of T-bet were significantly reduced in the post-ROSC group compared with the sham-operated group (P ＜0.05) at 12 and 24 h after ROSC.Conclusions The lung immune dysfunction induced by imbalance between transcription factors GATA-3 mRNA and T-bet mRNA expressions may complicate in the process of post-resuscitation lung injury in a porcine model of cardiac arrest.

Objective To evaluate the value of IgA and IgG antibodies against α-fodrin in both serum antibodies in SS is also assessed.Methods Samples from 39 patients with SS(25 primary and 14 secondary),8 patients with systemic lupus erythematosus(SLE),and 15 patients with rheumatoid arthritis (RA)as well as 10 healthy blood donors were collected.Anti-α-fodrin antibodies were measured using ELISA.Results The titer of serum anti-α-fodrin was higher in SS than in other connective tissue diseases group and healthy group(P<0.01).IgA type anti-α-fodrin antibodies was detected in 60%.44% of serum and saliva in patients with pSS respectively.IgG antibodies were detected in 43% of sera,and 29% of saliva of patients with pSS.The sensitivity and specificity of serum anti-α-fodrin IgA in SS was 54%and 85%.The level of anti-α-fodrin was positively associated with xerostomia and parotid swelling (P<0.05),and was negatively associated with xeroma,renal tubule acidosis,lung interstitial disease and hepatic damages(P>0.05).Conclusion Saliva and serLlm anti-α-fodrin level may be diagnostic for SS.It may be a useful screening marker.

Objective To explore the relationship between high-sensitivity C-reactive protein (hsCRP)and obesity/metabolic syndrome(MetS)related factors in children. Methods 403 children aged 10-14 and born in Beijing were involved in this study. Height,weight,waist circumference,fat mass percentage(Fat%),blood pressure(BP),hsCRP,triglyceride(TG),total cholesterol(TC), fasting plasma glucose(FPG),high and low density lipoprotein cholesterol(HDL-C,LDL-C)were observed among these children. hsCRP was transformed with base 10 logarithm(lgCRP). MetS was defined according to the International Diabetes Federation 2007 definition. Associations between MetS related components and hsCRP were tested using partial correlation analysis,analysis of covariance and linear regression models. Results 1) lgCRP was positively correlated with BMI,waist circumference,Fat%,BP,FPG,LDL-C and TC while negatively correlated with HDL-C. With BMI under control,the relationships disappeared,but LDL-C(r=0.102). 2)The distributions of lgCRP showed obvious differences in all the metabolic indices,in most groups,respectively. With BMI under control,close relationships between lgCRP and high blood pressure/high TG disappeared and the relationship with MetS weakened. 3) Through linear regression models, factors as waist circumference,BMI,Fat% were the strongest factors related to hsCRP,followed by systolic BP, HDL-C,diastolic BP,TG and LDL-C. With BMI under control,the relationships disappeared,but LDL-C (β=0.045). Conclusion hsCRP was correlated with child obesity,lipid metabolism and MetS. Waist circumference was the strongest factors related with hsCRP. Obesity was the strongest and the independent influencing factor of hsCRP.

Objective:To perform adenovirus detection and genetic evolutionary analysis on specimens from a fever outbreak in Kunming city.Methods:Pharyngeal swabs from typical febrile patients were collected and tested for nucleic acids of 30 common respiratory pathogens using TaqMan Array Card technology. The full-length sequences of three important genes of adenovirus, Penton base, Hexon and Fiber, were amplified, sequenced and typed using Nanopore high-throughput sequencing. A phylogenetic tree was constructed. Molecular variations and genetic evolution of the three genes were analyzed.Results:Five specimens were collected and all of them tested positive for adenovirus and Haemophilus influenzae. The sequences of the full-length coding regions of the Penton base, Hexon and Fiber genes were obtained by Nanopore sequencing. The homology of the three gene sequences in the five specimens was 100.0%, 99.9%-100.0% and 100.0% in nucleotide sequences, and 100.0% in amino acid sequences. The three genes in the specimens had the highest homology with those of the reference strain of human adenovirus type 3 (HAdV3, accession number: AY599834) in nucleotide sequences, which was 98.6%, 98.7% and 98.9%, respectively. Results of the phylogenetic analysis of the three genes were basically consistent. These Kunming strains were clustered into an independent clade with the reference HAdV3 strain and had a distant relationship with the strains isolated in foreign countries and Taiwan, China in the early years. They were closely related to the domestic and foreign strains in recent years and highly homologous to the 2019 Japanese strain (accession: LC703523) and the Guangzhou strain (accession: MZ540961). Compared with the reference strain, these Kunming strains had five amino acid variations in Penton base, 10 in Hexon and 11 in Fiber. Conclusions:All of the adenovirus strains isolated in this outbreak belong to P3H3F3 type based on the full-length sequences of Penton base, Hexon and Fiber genes. They share high homology with the domestic and foreign HAdV3 strains, including the reference strain. Compared with the reference strain, several amino acid mutations are identified in these Kunming strains, and most of them are in the high variability region or functional regions. M7L in the Hexon protein is an unique amino acid mutation site of Kunming strains.

Studying the ability of the brain to recognize different odors is of great significance in the assessment and diagnosis of olfactory dysfunction. The wavelet energy moment (WEM) was proposed as a feature of olfactory electroencephalogram (EEG) signal and used for odor classification. Firstly, the olfactory evoked EEG data of 13 odors were collected by an experiment. Secondly, the WEM was extracted from olfactory evoked EEG data as the signal feature, and the power spectrum density (PSD), approximate entropy, sample entropy and wavelet entropy were used as the contrast features. Finally, -nearest neighbor ( -NN), support vector machine (SVM), random forest (RF) and decision tree classifier were used to identify different odors. The results showed that using the above four classifiers, the classification accuracy of WEM feature was higher than other features, and the -NN classifier combined with WEM feature had the highest classification accuracy (91.07%). This paper further explored the characteristics of different EEG frequency bands, and found that most of the classification accuracy based on the features of γ band was better than that of the full band and other bands, among which the WEM feature of the γ band combined with the -NN classifier had the highest classification accuracy (93.89 %). The research results of this paper could provide a new objective basis for the evaluation of olfactory function. On the other hand, it could also provide new ideas for the study of olfactory-induced emotions.

Objective: To analyze the clinical characteristics of oral candidiasis (OC) in in-patients with rheumatism, in order to provide theoretical basis for the prevention and treatment of OC in rheumatism patients. Methods: One thousand eight hundred and eight in-patients were recruited in the Department of Rheumatology, the Second Hospital of Shanxi Medical University from January 2017 to December 2017. The patients included 607 males and 1 201 females. Their average age was (49.5±15.5) years old with a ranging from 14 to 81 years. According to occurrence of OC or not, the patients were divided into OC group and non-OC group. The differences of general data, primary diseases, laboratory examinations, usage of glucocorticoid and immunosuppressant therapy were compared between the two groups, and the risk factors of OC occurrence were analyzed. Results: Two hundred and sixty-nine patients had OC and 1 539 patients had no OC. Age [(54.9±14.7) years], duration of illness [(9.4±4.4) years] and hospital stay [(15.3±5.7) d] in OC group were significantly longer than those in non-OC group. OC incidence in patients with connective tissue disease (CTD) [17.40% (193/1 109)] was higher than that in non-CTD patients [10.87% (75/699)] (P<0.001). OC most likely occurred in patients with such CTD as Sjögren syndrome (SS) and Behcet syndrome. OC incidence in non-CTD patients with osteoarthritis (OA) was highest. The salivary flow rate in OC group [(0.65±0.45) ml/min] was significantly lower than that in non-OC group [(0.78± 0.39) ml/min] (t=2.394, P=0.017). There was no statistical differences in other laboratory examinations between the two groups, including white blood cells (WBC), lymphocyte, platelet count, liver function, renal function, erythrocyte sedimentation rate, C-reactive protein, procalcitonin, immunoglobulin G, immunoglobulin M, immunoglobulin A, C₃, C₄ and so on. OC incidence in patients using prednisone≥15 mg/d [17.16% (133/775)] was higher than that in patients using prednisone<15 mg/d [12.53% (94/750)] and patients not using prednisone [14.84% (42/283)] (P<0.05). The incidence of OC in patients with immunosuppressant therapy [16.11% (226/1 403)] was statistically higher than that in non-immunosuppressant patients [10.62% (43/405)] (P<0.01). Logistic regression analysis showed that the risk factors of OC occurrence included primary diseases (P<0.001), age (P<0.001), duration of illness (P=0.001) and duration of hospitalization (P=0.002). Conclusions OC occurred commonly in rheumatism in-patients, especially in elder patients, patients with long duration of illness and hospital stay. OC incidence in CTD patients is significantly higher than that in non-CTD patients. Glucocorticoid and immunosuppressant therapy might significantly reduce the anti-fungal immunity of the patients.

Objective:To explore the impact of cognitive function and childhood trauma in individuals with clinical high risk of psychosis (CHR).Methods:From June 2017 to September 2022, a total of 62 individuals with CHR(CHR group) were screened by structured interviews with psychiatric risk syndrome (SIPS) at Beijing Anding Hospital, and 61 healthy controls(healthy control group) matched in gender, age, and educational years were recruited. All participants were evaluated by the childhood trauma questionnaire (CTQ) and the Chinese version of the MATRICS consensus cognitive test battery (MCCB). Differences in cognitive function and childhood trauma between the two groups were compared by R4.1.1 software, and the correlation between cognitive function and childhood trauma in the CHR group was analyzed.Results:The scores of MCCB composite score (41.46±6.97), information processing speed (40.20±8.40), attention vigilance (40.92±11.00), working memory (41.09±9.97), verbal learning, and visual learning of CHR group were significantly lower than those of healthy controls(MCCB composite score(46.26±7.64), information processing speed(45.83±8.36), attention vigilance(46.30±9.57), working memory(46.18±8.49)), and with statistically significant differences ( t=-3.73--2.03, P<0.05). The total CTQ score, emotional abuse, physical abuse, and physical neglect factor scores of the CHR group (40.0 (36.0, 50.8), 7.5 (6.0, 10.0), 5.0 (5.0, 7.0), 9.0 (7.0, 11.0)) were significantly higher than those of the healthy control group (34.0 (31.0, 40.0), 6.0 (5.0, 8.0), 5.0 (5.0, 6.0), 9.0 (6.0, 10.0) ) ( Z=-4.07--2.06, P<0.05). In the CHR group, the total score of childhood trauma and the score of physical abuse factors were negatively correlated with working memory ( r=-0.29, -0.28, P<0.05), and the total score of cognitive function, attention vigilance, and word learning were negatively correlated with physical neglect ( r=-0.28, -0.26, -0.31, P<0.05). After partial correlation analysis using gender, age, years of education, and total SIPS score as covariates, the aforementioned correlation remained significant. Conclusion:CHR individuals have multiple cognitive deficits, and childhood trauma is more serious. Childhood trauma, especially physical trauma, may affect the cognitive function of CHR individuals.