BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction. Iguratimod (IGU) is a novel conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with good efficacy and safety for the treatment of active RA in China and Japan. However, the long-term effects of IGU on the progression of bone destruction or radiographic progression in patients with active RA remain unknown. We aimed to investigate the efficacy and safety of iguratimod (IGU), a combination of methotrexate (MTX) and IGU, and IGU in patients with active rheumatoid arthritis (RA) who were naïve to MTX. METHODS: This multicenter, double-blind, randomized, non-inferiority clinical trial was conducted at 28 centers for over 52 weeks in China. In total, 911 patients were randomized (1:1:1) to receive MTX monotherapy (10-15 mg weekly, n = 293), IGU monotherapy (25 mg twice daily, n = 297), or IGU + MTX (10-15 mg weekly for MTX and 25 mg twice daily for IGU, n = 305) for 52 weeks. The patients' clinical characteristics, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints-C-reactive protein (DAS28-CRP) level, and disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) were assessed at baseline. The primary endpoints were the proportion of patients with ≥20% improvement according to the American College of Rheumatology (ACR20) response and changes in the van der Heijde-modified total Sharp score (vdH-mTSS) at week 52. RESULTS: The proportions of patients achieving an ACR20 response at week 52 were 77.44%, 77.05 %, and 65.87% for IGU monotherapy, IGU + MTX, and MTX monotherapy, respectively. The non-inferiority of IGU monotherapy to MTX monotherapy was established with the ACR20 (11.57%; 95% confidence interval [CI], 4.35-18.79%; P <0.001) and vdH-mTSS (-0.37; 95% CI, -1.22-0.47; P = 0.022). IGU monotherapy was also superior to MTX monotherapy in terms of ACR20 ( P = 0.002) but not the vdH-mTSS. The superiority of IGU + MTX over MTX monotherapy was confirmed in terms of the ACR20 (11.18%; 95% CI, 3.99-18.37%; P = 0.003), but not in the vdH-mTSS (-0.68; 95% CI, -1.46-0.11; P = 0.091). However, the difference in the incidence rates of adverse events was not statistically significant. CONCLUSIONS: IGU monotherapy/IGU + MTX showed a more favorable clinical response than did MTX monotherapy. IGU may have some clinical benefits over MTX in terms of radiographic progression, implying that IGU may be considered as an initial therapeutic option for patients with active RA. TRIAL REGISTRATION https://classic.clinicaltrials.gov/ , NCT01548001.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Chromones/adverse effects* ; Double-Blind Method ; Drug Therapy, Combination ; Methotrexate/adverse effects* ; Treatment Outcome ; Sulfonamides

Diverse types of GABAergic interneurons tend to specialize in their inhibitory control of various aspects of cortical circuit operations. Among the most distinctive interneuron types, chandelier cells (i.e., axo-axonic cells) are a bona fide cell type that specifically innervates pyramidal cells at the axon initial segment, the site of action potential initiation. Chandelier cells have been speculated to exert ultimate inhibitory control over pyramidal cell spiking. Thus, chandelier cells appear to share multiple similarities with basket cells, not only in firing pattern (fast spiking) and molecular components, but also in potentially perisomatic inhibitory control. Unlike basket cells, however, synaptic recruitment of chandelier cells is little known yet. Here, we examined the mediodorsal thalamocortical input to both chandelier cells and basket cells in medial prefrontal cortex, through combining mouse genetic, optogenetic and electrophysiological approaches. We demonstrated that this thalamocortical input produced initially weak, but facilitated synaptic responses at chandelier cells, which enabled chandelier cells to spike persistently. In contrast, this thalamocortical input evoked initially strong, but rapidly depressed synaptic responses at basket cells, and basket cells only fired at the initiation of input. Overall, the distinct synaptic recruitment dynamics further underscores the differences between chandelier cells and basket cells, suggesting that these two types of fast spiking interneurons play different roles in cortical circuit processing and physiological operation.
Mice ; Animals ; Neurons/physiology* ; Pyramidal Cells/physiology* ; Interneurons ; Action Potentials/physiology* ; Synaptic Transmission

OBJECTIVE: To investigate the molecular mechanisms underlying the effects of arsenic trioxide (As METHODS: Transplantation of LVG hamster hearts to Lewis rats was performed by anastomosis of vessels in the neck using end-to-end anastomosis with a non-suture cuff technique. Four groups of recipient rats (n=6 in each) were treated with normal saline (control), As RESULTS: Expression of Nrf2-ARE-HO-1 signaling pathway was upregulated in heart xenografts in rats treated with As CONCLUSION Combination treatment with As
Animals ; Arsenic Trioxide ; Cricetinae ; Heart Transplantation ; Heme Oxygenase-1/metabolism* ; Heterografts ; Leflunomide ; NF-E2-Related Factor 2/metabolism* ; Rats ; Rats, Inbred Lew ; Signal Transduction

Objective: To summarize the preliminary experience in the treatment of esthesioneuroblastoma (ENB) and to explore the effect of age, chemotherapy, modified Kadish stage and pathological grade on the prognosis of ENB. Methods: The clinical data of 87 ENB patients from the First Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University Cancer Center between June 2002 and November 2017 were retrospectively analyzed. The modified Kadish stage was used to evaluate the extent of the lesions, and the Hyams grading system was used for pathological grading. The patients were followed up regularly to evaluate the recurrence and metastasis of the tumor. Cox proportional hazard model was used for univariate and multivariate analyses. Prognostic factors with P<0.05 in univariate analysis were included in multivariate analysis. After controlling the confounding factors, the model coefficients were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: The median follow-up time of ENB patients was 29 months, and the 5-year overall survival rate was 39.3%. In univariate analysis, age, chemotherapy, modified Kadish stage and pathology grade were independent predictors of overall survival, while gender, radiotherapy and surgery were not prognostic factors. Multivariate analysis showed that modified Kadish stage and pathology grade were independent predictors of overall survival rate after excluding confounding factors. Conclusions: Age, chemotherapy, modified Kadish stage and pathological grade are taking important role in the overall survival rate of patients with ENB. Modified Kadish stage and pathological grade are independent predictors of overall survival rate.
Esthesioneuroblastoma, Olfactory/therapy* ; Humans ; Nasal Cavity/pathology* ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Nose Neoplasms/therapy* ; Prognosis ; Retrospective Studies

Objective:To report our experience in the admission and perioperative management of 88 patients with lower extremity fracture in a mildly affected area in the epidemic of COVID-19.Methods:A retrospective analysis was conducted of the 88 patients with 97 lower extremity fractures who had been admitted to Department of Orthopedic Trauma, Honghui Hospital Affiliated to Xi'an Jiaotong University College of Medicine from 23rd January, 2020 to 22nd February, 2020. They were 43 males and 45 females, aged from 15 to 95 years (average, 65.5 years). The patients underwent screening for COVID-19 infection before admission. Their fractures were located at the femoral neck in 33 cases and at the femoral trochanter in 26. Open reduction and internal fixation was performed for 29 cases, internal fixation with proximal femoral nail anti-rotation (PFNA) for 25 and hip replacement for 28. The time from injury to admission, time from admission to surgery, operation time, fracture reduction, hospital stay, and perioperative deep venous thrombosis (DVT) of lower limbs were recorded. COVID-19 infection was observed in the medical staff and patients as well.Results:All the 88 patients were COVID-19 negative in the screening before admission. The time from injury to admission averaged 4.5 days, the time from admission to surgery 3.7 days and hospital stay 6.6 days. The prostheses were all well located in the 28 patients undergoing hip replacement. The rate of functional and anatomic reduction was 94.2%(65/69) in the 69 patients undergoing internal fixation. Peri-operatively, DVT occurred in 25 cases (28.4%). High temperature was observed in 7 patients within 3 days after operation, which was diagnosed as absorption fever. No medical staff or patients were infected by COVID-19.Conclusion:In the epidemic of COVID-19, orthopedic surgeons in a medical institute in a mildly affected area can still provide effective and safe medical services for fracture patients and reduce nosocomial infection, as long as they comprehend the diagnosis and treatment guidelines for the epidemic, strictly screen the patients accordingly, stick to operative indications, protect against possible infection cautiously, and carry out the procedures in a standard manner.

Objective To predict the monthly reported echinococcosis cases in China with the autoregressive integrated mov-ing average(ARIMA)model,so as to provide a reference for prevention and control of echinococcosis. Methods SPSS 24.0 software was used to construct the ARIMA models based on the monthly reported echinococcosis cases of time series from 2007 to 2015 and 2007 to 2014,respectively,and the accuracies of the two ARIMA models were compared. Results The model based on the data of the monthly reported cases of echinococcosis in China from 2007 to 2015 was ARIMA(1,0,0)(1,1, 0)12,the relative error among reported cases and predicted cases was-13.97%,AR(1)=0.367(t=3.816,P<0.001),SAR (1)=-0.328(t=-3.361,P=0.001),and Ljung-Box Q=14.119(df=16,P=0.590).The model based on the data of the monthly reported cases of echinococcosis in China from 2007 to 2014 was ARIMA(1,0,0)(1,0,1)12,the relative error among reported cases and predicted cases was 0.56%,AR(1)=0.413(t=4.244,P<0.001),SAR(1)=0.809(t=9.584, P<0.001),SMA(1)=0.356(t=2.278,P=0.025),and Ljung-Box Q=18.924(df=15,P=0.217).Conclusions The different time series may have different ARIMA models as for the same infectious diseases.It is needed to be further verified that the more data are accumulated,the shorter time of predication is,and the smaller the average of the relative error is.The estab-lishment and prediction of an ARIMA model is a dynamic process that needs to be adjusted and optimized continuously accord-ing to the accumulated data,meantime,we should give full consideration to the intensity of the work related to infectious diseas-es reported(such as disease census and special investigation).

Postmenopausal women, who have reduced circulating estrogen levels, are more prone to develop obesity and related metabolic diseases than premenopausal women. The absence of safe and effective treatments for postmenopausal obesity has changed the focus to natural products as alternative remedies. Total salvianolic acids (TSA) are the major water-soluble ingredients of Danshen. Salvianolic acid (SA) is the major constituent of the TSA. Salvianolic acids, including TSA and SA, are widely used in traditional Chinese medicine. In the present study, ovariectomized rats and LO2 cells were used to study the effects of salvianolic acids on body weight gain and hepatic steatosis. Salvianolic acids reduced ovariectomy (OVX)-induced body weight gain, attenuated the expressions of hepatic lipogenic genes, such as sterol regulatory element binding protein (SREBP)1, fatty acid synthase (FAS), and stearoyl-CoA desaturase (SCD)1, and decreased the liver triglyceride (TG) and total cholesterol (TC). For the molecular mechanisms, OVX and high glucose-induced phosphorylation of signal transducer and activator of transcription (STAT)-3 was inhibited by salvianolic acids treatment. In LO2 cells, inhibition of STAT-3 by siRNA attenuated the increased expression of SREBP1 and TG induced by high glucose. Salvianolic acids reduced the upregulation of SREBP1 and TG induced by high glucose in LO2 cells. In conclusion, these findings illustrated that salvianolic acids markedly alleviated the lipid metabolism disorders and protected against the postmenopausal obesity. The underlying mechanism was probably associated with the regulation of STAT-3 signaling.
Alkenes ; administration & dosage ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Lipid Metabolism ; drug effects ; Liver ; drug effects ; metabolism ; Obesity ; drug therapy ; genetics ; metabolism ; Ovariectomy ; Polyphenols ; administration & dosage ; Postmenopause ; drug effects ; genetics ; metabolism ; Rats ; STAT3 Transcription Factor ; genetics ; metabolism ; Salvia miltiorrhiza ; chemistry ; Signal Transduction ; drug effects ; Sterol Regulatory Element Binding Protein 1 ; genetics ; metabolism ; Triglycerides ; metabolism

Objective To investigate the relationship between the initial change of Tg and clinical outcome in DTC patients with pulmonary metastases after 131I treatment.Methods A total of 47 DTC patients (13 males,34 females;average age (41.6±16.3) years) with pulmonary metastases from January 2008 to June 2014 were retrospectively analyzed.Patients were divided into 3 groups according to the variation of Tg: G1 with a declined (more than 50％) Tg;G2 with a declined (less than 50％) Tg or an increased (less than 10％) Tg;G3 with an increased (more than 10％) Tg.The median follow-up time was 1 501 d.Clinical outcomes were divided into remission,stable disease and progressive disease according to the serum test and imaging results.Data analysis was performed by χ2 test and Fisher exact test.Results The percentage of G1,G2,G3 patients was 44.7％(21/47),40.4％(19/47),and 14.9％(7/47) respectively.Results of follow-up showed 19.0％(4/21) patients achieved remission and 81.0％(17/21) with stable disease in G1.There were 2/19 with remission,12/19 with stable disease and 5/19 with progression disease in G2.All patients (7/7) had progressive disease in G3.The clinical outcome was related to the variation of Tg after 131I treatment (Fisher exact test,P<0.01).Conclusions Initial Tg after 131I treatment could be a predictor to the outcome of patients.The increased Tg level indicates a high possibility of 131I refractory disease.

Objective To evaluate the impact of BRAF(V600E) gene status on clinical outcome of radioiodine((131)I) therapy in low-intermediate risk recurrent papillary thyroid carcinoma (PTC). Methods Totally 135 PTC patients were enrolled and divided into two groups according to BRAF(V600E) gene status:BRAF(V600E) mutation group(n=105) and BRAF(V600E) wild group(n=30). The median follow-up time was 2.16 years(1.03-4.06 years),and clinical outcome after initial (131)I ablation therapy was divided into excellent response(ER),acceptable response(AR),and incomplete response(IR) according to the serological and imageological follow-up results. The cinical outcomes were then compared between these two groups. Results There was no significant difference in clinicopathological features and initial radioactive iodine dose between BRAF(V600E) mutation and wild groups (P>0.05). ER,AR,and IR after (131)I ablation therapy accounted for 74.3%,20.0%,and 5.7% in BRAF(V600E) mutation group and 73.3%,20.0%,and 6.7% in BRAF(V600E) wild group,and no statistical difference was found (P=0.891). Conclusion For low-intermediate risk recurrent PTC,BRAF(V600E) gene status may have no impact on the response to (131)I ablation therapy,and thus this molecular feature should not be used as an independent weighting factor for risk assessment in this population.
Carcinoma ; genetics ; radiotherapy ; Carcinoma, Papillary ; Humans ; Iodine Radioisotopes ; therapeutic use ; Mutation ; Prognosis ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Neoplasms ; genetics ; radiotherapy

OBJECTIVETo investigate the clinical outcome of (131)I therapy in differentiated thyroid cancer (DTC) with preablative stimulated thyroglobulin (ps-Tg) below 10 ng/ml and the value of ps-Tg for predicting clinical outcome.

METHODSTotally 167 DTC patients with ps-Tg below 10 ng/ml were included and divided into three groups [excellent response (ER, n=131), acceptable response (AR, n=34), and incomplete response (IR, n=2)] according to the response to initial (131)I therapy. One-way analysis of variance, χ(2) test, and Kruskal-Wallis test were used to evaluate the statistical differences of clinicopathological features, recurrence risk, and ps-Tg value among the three groups. The ps-Tg value between ER group and non-ER group were compared by Mann-Whitney rank-sum test. The ROC curve and optimal cut-off point were analyzed to evaluate the clinical value of ps-Tg for predicting disease-free status.

RESULTSThere was significant difference in ps-Tg level (H=14.305, P=0.001) among three groups but not in age (F=0.831, P=0.755), sex (χ(2)=0.178, P=0.915), cervical lymph node metastases (χ(2)=1.475, P=0.478), TNM stage (H=1.063, P=0.588), and recurrence risk (H=2.947, P=0.229). The median level of ps-Tg in ER group was 2.20 ng/ml (1.10, 4.40), which was significantly lower than 4.40 ng/ml (2.70, 5.90) of non-ER groups (U=1424.50, P=0.000). Area under the ROC curve was 0.717. The cut-off value of ps-Tg was 2.35 ng/ml,with a sensitivity of 83.33%, specificity of 53.43%, and negative predictive value of 92.11%.

CONCLUSIONThe serum ps-Tg value is a sensitive marker for predicting the disease-free status in DTC patients with ps-Tg below 10 ng/ml.

Adenocarcinoma ; Humans ; Iodine Radioisotopes ; Lymph Nodes ; Lymphatic Metastasis ; Neck ; Prognosis ; ROC Curve ; Thyroglobulin ; Thyroid Neoplasms ; Treatment Outcome