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

Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

【Objective】 To explore the promote and deter factors of blood donation among street blood donors in Nanjing, in order to improve the accuracy of street blood donors recruitment. 【Methods】 A questionnaire with high confidence was designed based on the theory of planned behavior(TPB). The multi-stage hierarchical sampling method was adopted according to the geographical location and economic development level of 11 districts(regions) in Nanjing, and the street blood donors were divided into three groups according to the history of blood donation: one donation(n=361), donation numbers ≥ 2(n=417)and non-donation (n=241). The blood donation behavior was investigated from four aspects as external promote factors (such as seeking a free blood examination, self-interest factors, etc.), internal promote factors(such as altruistic, self-interest factors, blood donation can help others, etc.), external deter factors (too busy to donate blood, opposition from my family, etc.) and internal deter actors ( worry about dizziness after blood donation, fear of needles, ect.). The database was established using Epidata software, and chi-square test was applied for statistical analysis between groups. 【Results】 The groups mainly affected by the promote factors (altruistic and self-interest factors) of Nanjing street population in blood donation were unmarried, 18~24 years old, childless, below bachelor degree, and have barely no income. The main groups less affected by the deter factors were students, male, unmarried, 18~24 years old, childless and have barely no income.Promote factors increases with the number of blood donations, while deter factors decreases with the number of blood donation. 【Conclusion】 TBP can better analyze and explain the promote and deter factors affecting blood donation behavior among street blood donors in Nanjing, which is helpful for blood stations to formulate targeted measures to improve the availability of street blood donors.

Retrospective analysis of 18 cases of occupational acute 1, 2-dichloroethane (1, 2-DCE) poisoning. The results showed that all patients have the main manifestations such as dizziness, headache, unresponsiveness and other symptoms of nervous system damage; Brain CT showed varying degrees of diffuse white matter lesions. Brain MRI showed extensive involvement of white matter in both cerebral hemispheres. Affected white matter area presented low intensity on T1WI, hyperintensity on T2WI and T2-Flair; Lumbar puncture examination of cerebrospinal fluid (CSF) pressure (262.5±48.39) mm H₂O; After treatment, the required time for CSF pressure to restore was (161.56±75.27) days (50-280) days. Summary, Occupational acute 1, 2-DCE poisoning caused by toxic encephalopathy can be manifested as persistent abnormalities in CSF pressure, and the CSF pressure drops slowly during treatment; Early head CT and lumbar puncture examination will be helpful for early detection of intracranial pressure in toxic encephalopathy caused by acute 1, 2-DCE poisoning. Dynamic monitoring of CSF provides guidance for acute 1, 2-DCE poisoning with a long time of treatment and various types of dehydrating agents.

This study aimed at unfolding the therapeutic effects of freeze-dried powder separated from Shuang Xia decoction (SXD) on female senile drosophila melanogaster with fragmented sleep.Taking drosophilas as the model organisms,the locomotor activity was monitored using the autonomic monitoring software to explore the regulation of fragmented sleep in senile drosophilas by the treatment of SXD.As a result,it was found that the optimum concentration of SXD was 2.50％,while the desirable therapeutic duration was 4 days.In comparison with the control group,35-day-old virgin drosophilas'sleep was prolonged in the SXD group and the positive control group.The positive drug mainly affected their sleep in the daytime,while SXD impacted their sleep at night featuring the prolonged fragmented sleep.In conclusion,it was demonstrated that the freeze-dried powder of SXD effectively alleviated intermittent insomnia in the female senile drosophilas.Compared with positive drug,SXD also mitigated intermittent insomnia at night without significant changes in the sleep of the drosophilas in the daytime.Above all,SXD was beneficial in the regulation of sleep-wake rhythm in the drosophilas.

Objective To explore in vitro the best time window for using sinusoidal electromagnetic fields to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).Methods BMSCs were isolated and cultured from 4-week-old Sprague-Dawley rats (male and female,80-120g).The BMSCs (from passage 3) were exposed 0,1,4 or 8h/d for 7d,14,or 28d,respectively,to 15Hz sinusoidal electromagnetic fields with a maximum amplitude of lmT.Those exposed 0h/d served as the control.The relative expressions of runt related gene-2 (RUNX2),bone sialoprotein (BSP) and osteopontin (OPN) were determined using real-time,quantitative reverse transcription-polymerase chain reactions (RT-PCRs).The level of RUNX2 protein was determined by Western blotting after 14d.Alizarin red staining was used to compare calcium distribution in each group.Results Obvious promotion of differentiation to osteoblasts was observed after 7 days of exposure to the15 Hz sinusoidal electromagnetic fields,most obviously manifested by an outstanding increase of the early osteogenic index RUNX2 in those exposed 4h/d.After 14 days of intervention,the 1h/d exposure showed to be most effective,especially in inducing the changes of the late osteogenic index OPN.The trends of changes in RUNX2 protein were similar in all groups.After stimulating 1h/d for 14 and 28days,calcium deposition increased to the greatest extent.Conclusions Exposure to sinusoidal electromagnetic fields induces osteogenic differentiation to osteoblasts in rat BMSCs in vitro.There is an apparent window effect.The best results are observed with more days of exposure and shorter exposure time (1h) every day.

Objective To compare the short-term effects and toxicity of one cycle of TPF regimen induction chemotherapy with that of two cycles of PF regimen induction chemotherapy in the N advanced local nasopharyngeal carcinoma (NPC). Methods A total of 47 patients initially treated with N advanced local NPC without distant metastasis from Jan 2007 to Dec 2008 were enrolled in this study. The TPF chemotherapy regimen was administered as follows: TAX 60 mg/m2, i.v. infusion on day 1st, cisplatin 80 mg/m2, i.v. infusion on day 1st and 5-Fu 800 mg/m2, bolus infusion in 96 hours on day lst-4th. The PF chemotherapy regimen was as follows: cisplatin 100 mg/m2, i.v. infusion on day 1 and 5-Fu 1000 mg/m2, bolus infusion in 96 hours on day lst-4th. Twenty-six patients received one cycle of TPF regimen and 21 patients received two cycles of PF regimen, with 21 days each cycle and a total of 3 courses in each group, then chemoradiotherapy with cisplatin 30 mg/m2 (weekly) was followed. Results The short-term efficacy was no significant difference between two groups, after one cycle TPF chemotherapy, the CR+PR rates of primary site and lymph nodes were 57.7 % and 69.2 %, respectively, while after two cycles PF chemotherapy in control group, those were 66.7 % and 71.4 %, respectively (P>0.05). In 3 months after treatment, the CR rates of primary site and lymph nodes in TPF group were 92.3 % and 88.7 %, respectively, while those in control group were 100.0 % and 90.5 %, respectively (P>0.05). The main adverse reactions were Grade Ⅲ-Ⅳ neutropenia and alopecia in TPF group. Conclusion Short-term effects of induction chemotherapy with one cycle of TPF regimen in the N advanced local NPC is satisfied, and the main toxicity is neutropenia.

: Objective To develop a rehabilitation device and software game, and provide the system for evaluation and training of anterior cruciate ligament (ACL) reconstruction.MethodsThe development and clinical application of a biofeedback knee joint movement rehabilitation system for ACL reconstruction were very important.ResultsBIOKS readings reproduce Zebris 3D motion analysis system measurements reliably between 0° and 150° ( P>0.05). Significant knee joint movement training effect ( P<0.05 ) in JPS assessment. However, there were no differences ( P≥0.05) between SST and KAS assessments.ConclusionThe improvement of joint position sense and body centroid sway under single leg support conditions.

To evaluate the inhibitory effect of recombinant adenoviruses p16 (Ad p16) combined with Ad p53 on human cholangiocarcinoma cell line QBC939 in vitro. Expression of p16 was low and p53 was negative in QBC939 cells. High level of p16 and p53 expressions were observed in QBC939 cell line transfected with Ad p16 and Ad p53. The growth rates of the Ad p16 infected combined with Ad p53 infected QBC939 cells were inhibited, which was higher than those of the Ad p53 or close to Ad p16 transfection. Colony formation in Ad p16 with Ad p53 transfected cells greatly decreased versus Ad p16 transfected or Ad p53 transfected cells. The Ad p16, Ad p53 and Ad p16 with Ad p53 transfected cells manifested apoptosis and G 1 arrest, which were confirmed by the flow cytometry. The suppression effects mediated by expression of the exogenous p16 with p53 in tumor cell resulted mainly from apoptosis and G 1 arrest, which is higher than exogenous p16 or p53.