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

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Objective:To investigate the main occupational hazards,occupational protection facilities and workers'health examination in 17 plywood manufacturing enterprises in Guangxi,so as to provide valuable basis for ensuring workers'physical and mental health.Methods:A total of 17 plywood enterprises in Guangxi were selected as the observation objects.Through the occupational hazard assessment survey,the occupational hazards in the working environment and the collection of workers'occupational health examination data,the main occupational health problems were comprehensively analyzed and evaluated.Results:The over-standard rates of wood dust,formaldehyde,noise,and high temperature in 17 plywood manufacturing enterprises were 5.6%,28.1%,24.9%,and 29.1%,respectively.The noise in 17 enterprises exceeded standards,the mood dust and formaldehyde in 5 enterprises exceeded standards,and high temperature in 2 enterprises exceeded standards.The coincidence rate of dustproof and poisonproof facilities in production protection was 98.3%,the coincidence rate of heat-proof facilities was 88.2%and the coincidence rate of noise protection facilities was 76.5%.The coincidence rate of wearing and using personal protective equipment was 52.9%,and the coincidence rate of installing eyewash spray devices was 58.8%.The total physical examination rate in 17 enterprises was 42.6%(705/1 654),and the abnormal detection rate of physical examination was 14.6%,among which the abnormal detection rates of hearing,chest X-ray,and lung function were 7.4%,2.1%,and 1.7%,respectively.Conclusions:The main occupational health problems in 17 plywood manufacturing enterprises in Guangxi are wood dust,formaldehyde,noise,and high temperature,especially noise.The prevention and control effects of wood dust and formaldehyde are good,but the prevention and control measures for high temperature and noise need to be further strengthened.

Objective To investigate the expression of TXNIP and NLRP3 in atherosclerotic plaque of coronary artery and their relationship with secondary lesion of plaque and sudden death of coronary heart dis-ease.Methods A total of 105 cases of cardiac coronary samples extracted from autopsy anatomy and related data in the Forensic Judicial Appraisal Center of Guizhou Medical University from January 2019 to March 2022 were analyzed retrospectively.They were divided into the non-lesion group (n=20) and plaque group (n=85) according to whether or not having harden plaque in coronary artery.Then the plaque group was divided into the non-coronary heart disease sudden death group (n=25),coronary heart disease sudden death without sec-ondary lesion group (n=30) and coronary heart disease sudden death complicating secondary lesion group (n=30).The hematoxylin-eosin (HE) dyed section was prepared.The IPP6.0 image analysis software was used to measure the thickness of coronary intima and lesion,the thickness of fibrous cap,the thickness of nec-rotic lesion and the degree of lumen stenosis.Immunohistochemical method,Western blot and real-time fluo-rescent quantitative reverse transcription-PCR (qRT-PCR) were used to detect the distribution characteristics and expression levels of TXNIP and NLRP3 in coronary arteries.Results Compared with the non-lesion group,the thickness of the intima,lesion,fibrous cap and necrosis lesion in the other three groups was thicker,the stenosis degree of lumen was higher,and the differences were statistically significant (P<0.05).Com-pared with the coronary heart sudden death without secondary lesion group,the thickness of the intima,lesion and necrose lesion in the coronary heart disease sudden death complicating secondary lesion group was thic-ker,the necrosis degree of lumen was higher,and the differences were statistically significant (P<0.05).The TXNIP and NLRP3 proteins expressions were not seen in the coronary arterial wall of the no-lesion group.The strong positive expression rates of TXNIP and NLRP3 in the non-coronary sudden death group were 40.0% and 36.0%,the weak positive expression rates were 32.0% and 36.0%,and the weaker positive ex-pression rates were 28.0% and 28.0%.The strong positive expression rates in the coronary heart disease sud-den death without secondary lesion group were 50.0% and 43.3%,the stronger positive expression rates were 33.3% and 36.7%,and the weak positive expression rates were 16.7% and 20.0%;the strong positive ex-pression rates in the coronary heart disease sudden death complicating secondary lesion group were 73.3% and 76.7%,the stronger positive expression rates were 26.7% and 23.3%.The coronary artery TXNIP and NLRP protein and mRNA levels in the coronary heart disease sudden death complicating secondary lesion group were higher than those in the other three groups with statistical difference (P<0.05).TXNIP in coro-nary arterial plaque was positively correlated with the absorbance value of NLRP3 expression absorbance val-ue,protein and mRNA expression level (P<0.05).The TXNIP and NLRP3 expression levels were positively correlated with the intima and lesion thickness,and negatively correlated with the fibrous cap thickness (P<0.05).The necrosis lesion area of coronary artery was positively correlated with the TXNIP and NLRP3 (P<0.05).Conclu-sion TXNIP and NLRP3 could serve as the diagnostic indicators of coronary heart disease sudden death.

Objective To compare the application effects of different anesthesia methods under preoper-ative optimization measures in elderly patients with hip fracture surgery.Methods A total of 120 elderly pa-tients (≥75 years old) with hip fracture surgery in this hospital from May 2022 to December 2023 were se-lected as the study subjects and divided into group A and group B,60 cases in each group.The two groups a-dopted the preoperative optimization measures.The group A performed "two single three low" (unilateral,once,low position,low concentration and low dose) lumbar anesthesia,while group B conducted the laryngeal mask artificial airway anesthesia.The hemodynamic changes at skin incision in operation beginning (T1),at 30 min after operation (T2),suture at operation end (T3),at the end of operation (T4) and at 30 min after opera-tion end (T5),postoperative recovery time and occurrence situation of complications such as nausea and vomi-ting,agitation,postoperative delirium (POD) were compared between the two groups.Results The systolic blood pressure and the heart rate at T1 in group B were lower than those in group A,and the differences were statistically significant (P<0.05).The systolic blood pressure and heart rate at T4 in group B were higher than those in group A,and the difference was statistically significant (P<0.05).The recovery time,agitation,nausea and vomiting and incidence rate of adverse reactions such as POD had no statistical difference between the two groups (P<0.05).Conclusion On the basis of preoperative optimization measures,selecting the "two single three low" lumbar anesthesia method in elderly patients with hip fracture surgery anesthesia has more stable hemodynamics,less complications and faster postoperative recovery.

Objective:To develop a limb function exercise program for patients on extracorporeal membrane oxygenation (ECMO) and provide theoretical guidance for clinical nursing staff.Methods:A research team was formed to systematically review domestic and international literature on functional exercise for ECMO patients, extracting relevant evidence to form the initial version of the limb function exercise program. From June to July 2023, the Delphi method was used to conduct two rounds of expert consultations with 18 experts from three provinces and municipalities directly under the central government, including Shanghai, Jiangsu, and Shanxi. Based on the experts' feedback, the program items were revised to form the final version of the exercise program.Results:In the first round, 18 experts were consulted, with a valid response rate of 94.44% (17/18); in the second round, 17 experts participated, with a 100.00% (17/17) response rate. The expert authority coefficient was 0.859 in both rounds. The coefficient of variation for each level of indicator in the second round ranged from 0 to 0.160, and Kendall's coefficient of concordance was 0.092 to 0.130 ( P<0.01). The final ECMO patient limb function exercise program consisted of four primary indicators (preparation, assessment, exercise methods, and safety monitoring), 13 secondary indicators, and 44 tertiary indicators. Conclusions:The ECMO patient limb function exercise program developed in this study is scientifically sound and reliable, offering a reference and guidance for the implementation of limb function exercises for ECMO patients.

Objective:To evaluate the clinical value of combined detection of placenta associated 8 (PLAC8) and platelet activating factor acetylhydrolase (PLA2G7) for early identification of sepsis and non-infectious systemic inflammatory response syndrome (SIRS).Methods:A cross-sectional study was conducted. A total of 189 febrile patients suspected infection who were admitted to Huashan Hospital, Fudan University from October 2022 to April 2023 were included. Based on etiological, laboratory test results and clinical data, patients were classified as infection or non-infection, and further classified as sepsis or non-infectious SIRS according to diagnostic criteria. Real-time fluorescence polymerase chain reaction was used to detect the mRNA levels of PLAC8 and PLA2G7 in peripheral venous blood of patients. Hematology, inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin, sepsis-related organ failure assessment (SOFA) score, and the difference of cycle threshold (Ct) values between PLA2G7 and PLAC8 ((PLA2G7-PLAC8)ΔCt value))were compared between the sepsis and non-infectious SIRS groups. Statistical comparison was analyzed using Mann-Whitney U test, and the diagnostic performance of (PLA2G7-PLAC8)ΔCt value in discriminating sepsis from non-infectious SIRS was evaluated using receiver operating characteristic curve. Results:Among the 189 febrile patients suspected infection, there were 80 non-infectious patients, including 51 non-infectious SIRS patients, and 109 infection patients, including 53 sepsis patients. The neutrophil ratio, CRP, IL-6, procalcitonin, and SOFA score of non-infectious SIRS patients were lower than those of the sepsis group, and the differences were all statistically significant ( Z=-2.70, -3.11, -2.16, -3.76 and -2.33, respectively, all P<0.05). The (PLA2G7-PLAC8)ΔCt value in the non-infectious SIRS group was 4.38(1.41), which was lower than 8.18 (6.19) in the sepsis group, with a statistically significant difference ( U=193.50, P<0.001). The area under the receiver operating characteristic curve (AUROC) for (PLA2G7-PLAC8)ΔCt value in the differential diagnosis of sepsis and non-infectious SIRS was 0.859, with the optimal cut-off value of 5.86. The sensitivity and specificity were 82.2% and 71.9%, respectively. When combined with procalcitonin, the AUROC was 0.917, with a sensitivity of 95.6% and specificity of 70.6%. Conclusions:The (PLA2G7-PLAC8)ΔCt value in peripheral blood has good clinical value for early identification of sepsis and non-infectious SIRS, especially when combined with procalcitonin, which could further improve the accuracy of differential diagnosis.

Objective To explore the mechanism of Nuanxinkang Powder(aka.NXK,composed of Ginseng Radix et Rhizoma Rubra and Ilex Pubescens Radix)on improving ventricular remodeling in post-infarction mice based on the"metabolic-inflammatory"network regulating macrophage polarization.Methods ①Thirty C57BL/6J male mice were randomly divided into three groups:sham-operation group,model group,and NXK group(1.65 g·kg-1),with 10 mice in each group;the mouse model of myocardial infarction was replicated using left anterior descending coronary artery ligation;and the drug was administered by gavage once a day for 4 consecutive weeks.Masson staining was used to detect collagen deposition in myocardial tissue;ultrasound was used to detect cardiac function in mice:left ventricular ejection fraction(LVEF),left ventricular anterior wall thickness at end-systole(LVAWS)and left ventricular anterior wall thickness at end-diastole(LVAWD);flow cytometry was used to detect distribution of cardiac macrophages in mice;qPCR was used to detect mRNA expressions of lactate dehydrogenase A(LDHA),carnitine palmitoyltransferase 1(CPT-1),glucose transport protein 4(GLUT4),isocitrate dehydrogenase(IDH),and succinate dehydrogenase(SDHa)in heart tissue.②NXK was given 1.15 g·kg-1 NXK suspension to rats by gavage twice a day for 5 consecutive days to prepare NXK-containing serum.Lipopolysaccharide(LPS)-induced RAW 264.7 cells were used to construct a pro-inflammatory macrophage model.The cells were grouped into the following groups:blank serum control group(medium containing 5%blank serum+5%fetal bovine serum),NXK drug-containing serum group(medium containing 5%NXK drug-containing serum+5%fetal bovine serum),lipopolysaccharide group(medium containing 5%blank serum+5%fetal bovine serum+200 μg·mL-1 lipopolysaccharide),NXK drug-containing serum+ lipopolysaccharide group(medium containing 5%NXK drug-containing serum+5%fetal bovine serum+200 μ g·mL-1 lipopolysaccharide),all the groups were intervened for 16 hours.Glycolysis stress test was used to detect the level of glycolysis in RAW 264.7 cells;qPCR was used to detect the mRNA expression of mitochondrial pyruvate carrier(MPC1)in RAW 264.7 cells;and MitoSox Red fluorescent staining was used to detect the level of oxidative stress damage in mitochondria of RAW 264.7 cells.Results ①Compared with the sham-operation group,the blue-stained area of cardiac collagen fibres in mice of the model group was significantly increased,accompanied by thinning of the ventricular wall and enlargement of the left ventricular cavity;cardiac function indexes,such as LVEF,LVAWS,LVAWD,etc.,were all significantly reduced(P＜0.01,P＜0.001);the mRNA expressions of LDHA and CPT-1 were significantly up-regulated in the cardiac tissues of mice(P＜0.05),and the mRNA expressions of GLUT4,IDH and SDHa were significantly down-regulated(P＜0.05,P＜0.01),and CD86 staining positive cell was significantly increased(P＜0.001).Compared with the model group,mice in the NXK group showed a significant decrease in cardiac collagen fiber deposition and an increase in the thickness of the ventricular wall;cardiac function indexes such as LVEF,LVAWS and LVAWD were significantly increased(P＜0.05,P＜0.01,P＜0.001);and the mRNA expressions of LDHA and CPT-1 in the cardiac tissues of the mice were significantly down-regulated(P＜0.01,P＜0.001),mRNA expressions of GLUT4,SDHa and IDH were significantly up-regulated(P＜0.01),and the number of CD86 positive cells was significantly reduced(P＜0.001).②Compared with the blank serum control group,the cytosolic glycolysis level and ROS level of macrophages in the NXK serum-containing group did not change significantly(P＞0.05),whereas the glycolysis level and ROS level of macrophages in the lipopolysaccharide group were significantly increased(P＜0.01),and the mRNA expression of MPC1 was significantly down-regulated(P＜0.001).Compared with the lipopolysaccharide group,the macrophage glycolysis level and ROS level were significantly reduced in the NXK serum-containing + lipopolysaccharide group(P＜0.05,P＜0.01),and mRNA expression of MPC1 was significantly up-regulated(P＜0.001).Conclusion NXK can reduce myocardial fibrosis and ventricular remodeling after myocardial infarction and improve cardiac function in mice,and its mechanism may be related to the down-regulation of mRNA expression of LDHA in cardiac tissues,the up-regulation of mRNA expression of GLUT4,the improvement of cardiac glucose uptake after myocardial infarction,the inhibition of pro-inflammatory macrophage glycolysis,the increase in the expressions of SDHa and IDH to alleviate the accumulation of succinate and citrate,and the reduction of reactive oxygen species(ROS)generation,thereby reducing pro-inflammatory macrophage hyperpolarisation.

Objective:To investigate COVID-19 vaccination status and relevant adverse reactions in patients with psoriasis treated with biological agents, and to explore the effect of COVID-19 vaccination on psoriatic lesions.Methods:Clinical data were collected from 572 psoriasis patients aged 18 - 60 years, who were registered in the management system of psoriasis patients treated with biological agents in the University of Hong Kong-Shenzhen Hospital from May 2019 to June 2021. The COVID-19 vaccination status was investigated by telephone interviews, and the vaccination-related information was obtained by fixed healthcare workers during a fixed time period according to a predesigned questionnaire. Measurement data were compared between two groups by using t test, and enumeration data were compared by using chi-square test or Fisher′s exact test. Results:The COVID-19 vaccination coverage rate was 43.13% (226 cases) among the 524 patients who completed the telephone interview, and was significantly lower in the biological agent treatment group (30.79%, 105/341) than in the traditional drug treatment group (66.12%, 121/183; χ2 = 60.60, P < 0.001) . The main reason for not being vaccinated was patients′ fear of vaccine safety (49.66%, 148/298) , followed by doctors′ not recommending (26.51%, 79/298) . In the biological agent treatment group after vaccination, the exacerbation of psoriatic lesions was more common in patients receiving prolonged-interval treatment (42.86%, 6/14) compared with those receiving regular treatment (4.40%, 4/91; Fisher′s exact test, P < 0.001) . Skin lesions were severely aggravated in two patients after COVID-19 vaccination, who ever experienced allergic reactions and whose skin lesions did not completely subside after the treatment with biological agents. Conclusions:The COVID-19 vaccination coverage rate was relatively low in the psoriasis patients treated with biological agents, and no serious adverse reaction was observed after vaccination. Prolonged-interval treatment due to COVID-19 vaccination ran the risk of exacerbation of skin lesions.

Objective:To observe any effect of ultrashortwave (USW) therapy on inflammatory cytokines and the MAPK pathway of rats with a spinal cord injury.Methods:Seventy-nine Sprague-Dawley rats were randomly divided into a control group ( n=35), an intervention group ( n=35) and a sham group ( n=9). Allen′s method was used to establish a contusion model of SCI in the rats of the control and intervention groups, while the sham group′s spinal tissues were exposed but not stricken. Beginning twenty-four hours after SCI modeling, the intervention group was given 7min of USW therapy daily, five days a week till the day of sacrifice for sampling the target area of spinal cord for tests. Then, motion function was evaluated using Basso, Beattie and Bresnahan (BBB) scoring. One, three and seven days after the SCI modeling, immunofluorescence and western blotting were employed to observe any changes in inflammatory factors and the MAPK pathway in the lesioned area. Results:Fourteen days after the modeling the average BBB score of the intervention group was significantly higher than the control group′s average. Moreover, 7 days after the modeling the average content of the domains containing protein 3 (NLRP3), interleukin-6 (IL-6), IL-6 receptor and tumor necrosis factor-α (TNF-α) in the target area of the spinal cord of sham group showed significantly lower levels than in the other 2 groups. And the levels in the intervention group were significantly lower than in the control group. Seven days after the modeling the number of cells positive for zinc finger protein 36 (TTP) in the lesioned area of the intervention group was significantly greater than among the control group. At the same time the levels of MAPK-activated protein kinase 2 (MK2), phosphorylated-mitogen-activated protein kinase-activated version (p-MK2) and TTP in the control and intervention groups were significantly higher than in the sham group. And there were significant differences between the intervention group and control group in the levels of MK2, p-MK2 and TTP.Conclusion:Ultrashortwave therapy can inhibit inflammation by regulating the MAPK inflammatory pathway, promoting the recovery of motion functions, at least in rats.