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

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.
Humans ; Venous Thromboembolism/etiology* ; Multiple Myeloma/diagnosis* ; Risk Assessment ; Risk Factors ; ROC Curve ; Retrospective Studies

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective:To investigate the clinical efficacy and safety of ixazomib-based therapy in patients with relapsed or refractory multiple myeloma (RRMM) .Methods:A retrospective analysis was performed on the efficacy and adverse reactions of 53 RRMM patients treated with a combined regimen containing ixazomib in the Hematology Department of Beijing Jishuitan Hospital from July 8, 2018 to November 30, 2020. Among them, 6 patients received ID regimen (ixazomib + dexamethasone) , 30 patients received ID regimen + immunomodulator, and 17 patients received ID regimen + other chemotherapy drugs.Results:Fifty-three patients with RRMM received ixazomib-based therapy. The median previous treatment line was 3, the median treatment course was 6 (2-30) , and the median follow-up time was 21 months (2-32 months) . The overall response rate (ORR) was 54.7% (29/53) after 2 courses of treatment. Among them, 26.4% (14/53) had very good partial response (VGPR) and 28.3% (15/53) had partial response (PR) . The ORR of the ID regimen group, ID regimen + immunomodulator group and ID regimen + other chemotherapy group were 83.3% (5/6) , 56.7% (17/30) and 41.2% (7/17) respectively, with no statistically significant difference among the three groups ( P=0.208) . The median time to progression (TTP) of 53 patients was 8 months (1-24 months) . The most frequent adverse events of ixazomib treatment were gastrointestinal reactions such as nausea, vomit and diarrhea, with an incidence of 37.7% (20/53) , and the incidence of grade 3-4 was 5.7% (3/53) . The most common hematological adverse events were thrombocytopenia (15.1%, 8/53) , neutropenia (11.3%, 6/53) and anemia (9.4%, 5/53) . Grade 1-2 peripheral neurotoxicity occurred in only 7.5% (4/53) of patients. Conclusion:Ixazomib has good efficacy and safety for the patients with RRMM in the real world.

Objective:To analyze the clinical efficacy of debridement, antibiotics irrigation and implant retention (DAIR) in the treatment of acute periprosthetic infection (PJI) and to explore the risk factors leading to the failure of DAIR.Methods:From January 2010 to January 2021, 122 patients underwent DAIR for acute PJI at Department of Orthopedics, General Hospital of Eastern Theater of PLA. They were 55 males and 67 females, aged from 50 to 86 years (mean, 68.0 years). Their C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), body temperature, white blood cell count and visual analogue scale (VAS) were compared at admission and discharge to analyze the clinical efficacy of DAIR. The 122 patients were assigned into a cured group (81 cases) and an uncured group (41 cases). Risk factors were screened by univariate analysis out of their gender, age, body mass index, site of infection, type of infection (early postoperative infection or acute hematogenous infection), type of surgery (primary or revision), comorbidities, CRP, ESR, albumin and hemoglobin at admission, duration of symptoms, Staphylococcus aureus infection, multiple bacterial mixed infection, and preoperative sinus tract. For the factors of P<0.05, multivariate binary logistic regression analysis was used to determine the risk factors for failure of DAIR. Survival curves were plotted for the patients using DAIR failure as the endpoint event. Results:The CRP, ESR, VAS score, body temperature and white blood cell count at discharge in the 122 patients were significantly lower than the corresponding values at admission ( P<0.05). The success rate of DAIR was 66.39%(81/122). The multivariate binary logistic regression analysis suggested that duration of symptoms over 3 weeks( OR=1.230, 95% CI: 1.092~1.576, P=0.020), Staphylococcus aureus infection( OR=4.607, 95% CI: 2.057~10.318, P<0.001), preoperative sinus tract( OR=6.115, 95% CI: 2.630~14.220, P<0.001) and multiple bacterial mixed infection( OR=2.600, 95% CI: 1.131~5.977, P=0.020) were risk factors for DAIR failure; Kaplan-Meier survival curve also confirmed that the patients with Staphylococcus infection, multiple bacterial mixed infection, duration of symptoms over 3 weeks, or preoperative sinus tract had a significantly lower rate of survival than their controls ( P<0.05). Conclusions:For acute PJI, DAIR can be used to retain the prosthesis and control infection. However, DAIR is not recommended for the patients with Staphylococcus aureus infection, multiple bacterial mixed infection, symptoms lasting more than 3 weeks, or preoperative sinus formation.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Objective: To screen and analyze the key differentially expressed genes characteristics in nonalcoholic fatty liver disease (NAFLD) with bioinformatics method. Methods: NAFLD-related expression matrix GSE89632 was downloaded from the GEO database. Limma package was used to screen differentially expressed genes (DEGs) in healthy, steatosis (SS), and nonalcoholic steatohepatitis (NASH) samples. WGCNA was used to analyze the output gene module. The intersection of module genes and differential genes was used to determine the differential genes characteristic, and then GO function and KEGG signaling pathway enrichment analysis were performed. The protein-protein interaction network (PPI) was constructed using the online website STRING and Cytoscape software, and the key (Hub) genes were screened. Finally, R software was used to analyze the receiver operating characteristic curve (ROC) of the Hub gene. Results: 92 differentially expressed genes characteristic were obtained through screening, which were mainly enriched in inflammatory response-related functions of "lipopolysaccharide response and molecular response of bacterial origin", as well as cancer signaling pathways of "proteoglycan in cancer" and "T-cell leukemia virus infection-related". 10 hub genes (FOS, CXCL8, SERPINE1, CYR61, THBS1, FOSL1, CCL2, MYC, SOCS3 and ATF3) had good diagnostic value. Conclusion: The differentially expressed hub genes among the 10 NAFLD disease-related characteristics obtained with bioinformatics analysis may become a diagnostic and prognostic marker and potential therapeutic target for NAFLD. However, further basic and clinical studies are needed to validate.
Computational Biology/methods* ; Gene Expression Profiling/methods* ; Gene Regulatory Networks ; Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Protein Interaction Maps/genetics*

Objective:To investigate the risk factors for postoperative delirium in the elderly patients with hip fracture and to construct an online nomogram of the risk factors.Methods:Retrospectively analyzed were the data of 483 elderly patients with hip fracture who had been treated with artificial joint replacement from May 2020 to August 2021 at Department of Orthopaedics (Department of Joint Surgery), Jinling Hospital Affiliated to Medical College of Nanjing University. There were 166 males and 317 females, aged from 61 to 99 years (average, 82.1 years). Fracture types: 333 femoral neck fractures and 150 intertrochanteric fractures. The patients were divided into a delirium group ( n=149) and a delirium-free group ( n=334) according to whether postoperative delirium occurred after surgery. The 2 groups were compared in terms of general data like age, gender, body mass index, and concomitant diseases, as well as in terms of indexes like pre-operative albumin, preoperative hemoglobin, and postoperative C-reactive protein (CRP). Factors with P < 0.05 were included in the multi-factor logistic regression analysis to screen out the risk factors for postoperative delirium. The "rms" package of R software was used to draw the nomogram; the Bootstrap method was used to repeat the sampling 1,000 times for evaluation, calculation of the consistency index ( CI), and drawing of the ROC curve and correction curve; the decision curve was plotted using the "rmda" package. Results:There were significant differences between the delirium group and the delirium-free group in age, preoperative anxiety, Alzheimer＇s disease, history of cerebrovascular disease, preoperative albumin, intraoperative hypotension and postoperative CRP ( P < 0.05). The multifactorial logistic regression analysis showed that high age, preoperative anxiety, Alzheimer＇s disease, preoperative albumin < 35 g/L, and postoperative CRP ≥90 mg/L were the risk factors for postoperative delirium in the elderly patients with hip fracture after artificial joint replacement ( P < 0.05). The area under the ROC curve of the nomogram constructed by incorporating the risk factors for postoperative delirium was 0.894 (95% CI: 0.865 to 0.923) with a CI of 0.889; the calibration curve showed that the calibration curve of this nomogram model tended to be close to the ideal curve. The decision curve analysis showed that the threshold value was 0.01 to 1.00, showing the net benefit rate of this nomogram model > 0 when used to predict the postoperative delirium in the elderly patients with hip fracture. Conclusions:High age, preoperative anxiety, Alzheimer's disease, preoperative albumin < 35 g/L, and postoperative CRP ≥90 mg/L may be the risk factors for postoperative delirium in the elderly patients with hip fracture after artificial joint replacement. The online nomogram based on these factors demonstrates a good value in prediction of postoperative delirium.

A determination method for bilirubin in cultured cow-bezoar was developed in this study, with which the bilirubin in 15 batches of samples was quantified. The samples were first processed with 10% oxalic acid solution for the conversion of bilirubin from conjugated to unconjugated, followed by the extraction with dichloromethane. Then the obtained sample solutions were analyzed at 450 nm by HPLC[chromatographic column: Agilent TC-C_(18)(4.6 mm × 250 mm, 5 μm); mobile phase: acetonitrile and 1% glacial acetic acid aqueous solution(95∶5); flow rate: 1.0 mL·min~(-1)]. The bilirubin content in the 15 batches of cultured cow-bezoar was ranged from 21.9% to 41.7% with the average of 32.4%. The proposed method is accurate and reliable, thus making it suitable for the quantitation of bilirubin in cultured cow-bezoar and its quality assessment and control.
Animals ; Bezoars ; Bilirubin ; Cattle ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Female

Multi-template molecularly imprinted solid phase extraction not only has the advantages of high selectivity, large adsorption capacity, easy preparation, reuse and low environmental pollution, but also can realize the enrichment and separation of many kinds of compounds. It has attracted wide attention in the extraction and separation of traditional Chinese medicine components. This study summarizes the latest development of multi-template molecularly imprinted solid phase extraction. At the same time, based on the classification of active components of traditional Chinese medicine (flavonoids, alkaloids, phenylpropanol, terpenes, etc.), the latest application of multi-template molecular imprinting solid phase extraction in multi-component separation of traditional Chinese medicine was reviewed, with a view to better application of multi-template molecularly imprinted polymer in active multi-component extraction and separation of traditional Chinese medicine and provide reference for the material basic research of the efficacy of traditional Chinese medicine.