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

Treatment based on meridian differentiation is a characteristic method in clinical acupuncture diagnosis and treatment. Accurately defining and explaining its main content and core concepts is essential for effective clinical guidance. This paper reviews the historical and contemporary understanding, concepts, and primary content of treatment based on meridian differentiation. It proposes a four-step process for clinical application: meridian examination, treatment based on meridian differentiation, acupoint selection, and appropriate treatment methods, with TCM syndrome differentiation applied throughout. Constructing a diagnostic and treatment system which is based on meridian differentiation and suited to clinical acupuncture is significant for enhancing therapeutic efficacy and maximizing the benefits of acupuncture in disease treatment.
Humans ; Meridians ; Acupuncture Therapy/methods* ; Acupuncture Points ; Medicine, Chinese Traditional

BACKGROUND:Adjustable piezoelectric effect can promote tissue regeneration and repair.Piezoelectric materials are widely used in weight-bearing tissue engineering. OBJECTIVE:To prepare a piezoelectric film material that can promote bone regeneration,and to explore its structural characterization,electrical output performance,biocompatibility,and effect of electrical output on osteogenic differentiation of rabbit bone marrow mesenchymal stem cells. METHODS:Using poly-3-hydroxybutyrateco/4-hydroxybutyrate(P34HB)as raw material,barium calcium stannate titanate powder(Ba0.94Ca0.06Sn0.08Ti0.92O3,BCST)was added according to mass ratios of 0%,5%,10%,15%,and 20%.Dichloromethane was added to solve P34HB,and the thickness of 150-200 μm BCST/P34HB piezoelectric film was prepared by vacuum drying method.After polarization in the oil bath,the surface morphology,crystal phase composition,piezoelectric coefficient and open circuit voltage were tested.The effect of BCST/P34HB electrical output at 110 Hz and 0.25 N force on the proliferation and osteogenic differentiation of rabbit bone marrow mesenchymal stem cells was tested. RESULTS AND CONCLUSION:(1)Scanning electron microscopy,X-ray diffraction,water contact angle,piezoelectric coefficient and electrical output performance tests showed that when the mass ratio of BCST increased to 20%,the BCST/P34HB piezoelectric film had good piezoelectric properties(d33=5.9 pC/N)and electrical output performance(180 mV),which was closer to the suitable range of 500 mV for electrical stimulation.(2)Live and dead staining showed that on the first day of co-culture,15%group and 20%group showed less red fluorescence.On the 5th day of culture,the number of green fluorescence in each group was significantly higher than that on the first day,and the red fluorescence was not observed in the 10%,15%and 20%groups,and only a small amount of red fluorescence was observed in the 0%and 5%groups.(3)On the 1st,3rd and 5th days of co-culture with rabbit bone marrow mesenchymal stem cells,Almar blue staining exhibited that the number of cells in each group showed an increasing trend with the increase of time.On the 5th day of culture,the number of cells in the 20%group was significantly more than that in the 0%group(P<0.05).(4)On day 10 of osteogenic induction,alkaline phosphatase staining results showed that the positive rate of the 20%group was significantly higher than that of the 0%group(P=0.000 1).On day 21,alizarin red staining and quantitative analysis of calcium nodules showed a similar trend to alkaline phosphatase staining.Compared with the 0%group,the 15%group and 20%group showed significant differences(P<0.01,P<0.000 1).(5)The results showed that 20%BCST/P34HB films had good piezoelectric properties,electrical output properties,biocompatibility and the ability of promoting osteogenic differentiation of bone marrow mesenchymal stem cells.

ObjectiveTo mine the medication patterns of Chinese medicines for neurodermatitis based on contemporary medical cases in published articles. MethodThe medical cases of treating neurodermatitis with Chinese medicines were retrieved from the medical case articles published by contemporary famous and old Chinese medicine doctors in the library of Shandong University of Traditional Chinese Medicine， CNKI， VIP， and Wanfang Data. A case library was established， and SPSS Statistics 26.0 and SPSS Modeler 18.0 were employed to analyze the symptoms and syndromes of neurodermatitis and mine the medication patterns. ResultAccording to the inclusion and exclusion criteria， 130 medical case articles were included in this study. Neurodermatitis was prevalent in young adults between 20 and 39 years old （female patients of 30-49 years old and male patients of 20-39 years old）， and male patients were more than female patients. The patients mainly presented the clinical manifestations of itchy rashes， thickened skin， and lichenification. Symptoms included skin injury， emotional abnormalities， and Yin damage caused by prolonged illness. Red tongue， thin white or yellow tongue coating， and wiry pulse were common in the patients. The patients with the syndrome of blood deficiency and wind dryness were often treated with Angelicae Sinensis Radix， Rehmanniae Radix， Glycyrrhizae Radix et Rhizoma， Tribuli Fructus， and Chuanxiong Rhizoma. The commonly used herb pairs included Chuanxiong Rhizoma-Paeoniae Radix Alba， Chuanxiong Rhizoma-Glycyrrhizae Radix et Rhizoma， and Rehmanniae Radix Praeparata-Saposhnikoviae Radix， and the commonly used prescriptions were Siwutang and Dangguiyinzi. The patients with the syndrome of muscle and skin dystrophy were mainly treated with Rehmanniae Radix， Sophorae Flavescentis Radix， Paeoniae Radix Alba， Tribuli Fructus， and Dictamni Cortex. The commonly used herb pairs included Polygoni Multiflori Caulis-Sophorae Flavescentis Radix， Polygoni Multiflori Caulis-Dictamni Cortex， and Salviae Miltiorrhizae Radix et Rhizoma-Paeoniae Radix Alba， and the commonly used prescriptions were Jingjie Siwutang and Baixianpiyin. The patients with the syndrome of liver depression transforming into fire were often treated with Rehmanniae Radix， Gentianae Radix et Rhizoma， Gardeniae Fructus， Bupleuri Radix， and Scutellariae Radix. The commonly used herb pairs included Gentianae Radix et Rhizoma-Polygoni Multiflori Caulis， Polygoni Multiflori Caulis-Gardeniae Fructus， and Gentianae Radix et Rhizoma-Saposhnikoviae Radix， and the commonly used prescriptions were Longdan Xiegantang and Danzhi Xiaoyaosan. ConclusionThis study enriches the knowledge about neurodermatitis， clarifies the treatment principles and methods as well as the medication patterns， and provides a theoretical basis for clinical treatment and medication based on syndrome differentiation.

ObjectiveTo evaluate the effect of Astragali Radix （AR）-Angelicae Sinensis Radix （ASR） drug pair on supplementing Qi and activating blood circulation in rats with Qi deficiency and blood stasis and provide a theoretical basis for clinical rational medication and identification and quality control of compound pharmacodynamic substances from the three aspects of characteristic map， identification of pharmacodynamic substances， and comparison of blood components. MethodHigh-performance liquid chromatography （HPLC） was employed to establish the fingerprint of AR∶ASR （3∶1）， and ultra-high performance liquid chromatography-Q-Exactive Orbitrap-mass spectrometry （UPLC-Q-Exactive Orbitrap-MS） was employed to analyze the ingredients of the decoction. Adult male Wistar rats with SPF grades were selected and randomly divided into a blank group， a model group， a 3∶1 group， and a 5∶1 group. The rat model of Qi deficiency and blood stasis syndrome was prepared by controlling food intake and swimming in cold water every day. In parallel， each group was given medicine （or water） once a day. The dose of drug groups was 10.2 g∙kg^-1， and the model group and blank group were given the same amount of distilled water for 15 d. Animal behavior， body weight， whole blood and plasma viscosity， thymus index， spleen index， the levels of adenosine triphosphate （ATP）， adenosine diphosphate（ADP）， von willebrand factor （vWF）， and ATP/ADP value in serum of rats were recorded. The morphology of vascular endothelium was observed by hematoxylin-eosin （HE） staining and scanning electron microscopy. UPLC-Q-Exactive Orbitrap-MS was used to analyze prototype and metabolic components in serum. ResultThe fingerprint of AR-ASR drug pair （AR-ASR 3∶1） was established. UPLC-Q-Exactive Orbitrap MS identified 49 chemical components in vitro and preliminarily identified 11 prototype components absorbed into blood in vivo. As compared with the blank group， the body mass decreased significantly （P<0.01）， the whole blood （high shear， middle shear， and low shear） viscosity and plasma viscosity were significantly increased （P<0.05， P<0.01）， the thymus index and spleen index decreased significantly （P<0.05， P<0.01）， serum ATP content decreased significantly （P<0.01）， ADP content increased significantly （P<0.01）， ATP/ADP value decreased significantly （P<0.01）， and vWF content increased significantly （P<0.01）. The results of HE staining and scanning electron microscopy showed that the vessels were partially damaged， showing the structural disorder of the intima， the bulge， defect， and roughness of the endothelium， and the obvious cell adhesion and migration in the model group. As compared with the model group， the body mass also increased significantly （P<0.01）. The results of whole blood and plasma viscosity showed that the whole blood low shear viscosity was significantly decreased in the 3∶1 group （P<0.05）. The results of thymus index and spleen index showed that 5∶1 group significantly increased the thymus index of rats （P<0.05）. The results of serum ATP and ADP levels showed that the 5∶1 group had more significant effects on ATP and ADP levels （P<0.05）， and both groups significantly reduced ATP/ADP values （P<0.01）. The results of serum vWF level showed that the vWF content in the 3∶1 group decreased significantly （P<0.05）. The results of HE staining and scanning electronic microscopy showed that the damage of vascular endothelium was improved in the treatment group and the structure of intima was neat. ConclusionAR-ASR drug pair can improve the macro and micro indexes of rats with qi deficiency and blood stasis in the 3∶1 and 5∶1 groups. Overall， the 5∶1 ratio has a better effect on supplementing Qi but 3∶1 ratio has a better effect on promoting blood circulation.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

Objective:To explore the relationship between clinical nurses' psychological capital, compassion fatigue with work engagement, and analyze the mediating effect of psychological capital between compassion fatigue and work engagement, so as to provide scientific evidence for reducing compassion fatigue and improving work engagement of clinical nurses.Methods:From December 2021 to February 2022, 494 clinical nurses from 7 general hospitals in Sichuan Province were selected for the study using convenience sampling. The General Information Questionnaire, the Compassion Fatigue Short Scale, the Work Engagement Short Scale and the Psychological Capital Questionnaire for Nurses were used to conduct the survey. Pearson correlation was used to analyze the correlation between compassion fatigue, work engagement and psychological capital. And stepwise regression analysis and Bootstrap method were used to analyze the effects of compassion fatigue and psychological capital on work engagement as well as the mediating effect of psychological capital between compassion fatigue and work engagement.Results:Of the 494 clinical nurses, 33 (6.7%) were male and 461 (93.3%) were female, with an average age of (31.47±6.89) years old and an average working years (9.87±7.61) years. The average scores of psychological capital, compassion fatigue and work engagement of clinical nurses were (5.01±0.76), (3.19±2.08) and (4.60±1.37) points, respectively. Compassion fatigue was negatively correlated with psychological capital and work engagement ( r=-0.608, -0.580, P<0.001), and work engagement was positively correlated with psychological capital ( r=0.771, P<0.001). Compassion fatigue and psychological capital together accounted for 61.3% of the variation in work engagement, with the direct effects on work engagement were -0.206 (95% CI: -0.283--0.138, P<0.001) and 0.677 (95% CI: 0.599-0.744, P=0.001), respectively. Psychological capital partially mediated the relationship between compassion fatigue and work engagement, with a mediating effect of -0.397 (95% CI: -0.456--0.340, P<0.001), accounting for 65.8% of the total effect. Conclusion:The work engagement of clinical nurses is at a high level. Managers should take targeted measures to alleviate the symptoms of clinical nurses' compassion fatigue, improve their psychological capital, and then stabilize and improve their level of work engagement.

Objective:To explore the relationship between clinical nurses' psychological capital, compassion fatigue with work engagement, and analyze the mediating effect of psychological capital between compassion fatigue and work engagement, so as to provide scientific evidence for reducing compassion fatigue and improving work engagement of clinical nurses.Methods:From December 2021 to February 2022, 494 clinical nurses from 7 general hospitals in Sichuan Province were selected for the study using convenience sampling. The General Information Questionnaire, the Compassion Fatigue Short Scale, the Work Engagement Short Scale and the Psychological Capital Questionnaire for Nurses were used to conduct the survey. Pearson correlation was used to analyze the correlation between compassion fatigue, work engagement and psychological capital. And stepwise regression analysis and Bootstrap method were used to analyze the effects of compassion fatigue and psychological capital on work engagement as well as the mediating effect of psychological capital between compassion fatigue and work engagement.Results:Of the 494 clinical nurses, 33 (6.7%) were male and 461 (93.3%) were female, with an average age of (31.47±6.89) years old and an average working years (9.87±7.61) years. The average scores of psychological capital, compassion fatigue and work engagement of clinical nurses were (5.01±0.76), (3.19±2.08) and (4.60±1.37) points, respectively. Compassion fatigue was negatively correlated with psychological capital and work engagement ( r=-0.608, -0.580, P<0.001), and work engagement was positively correlated with psychological capital ( r=0.771, P<0.001). Compassion fatigue and psychological capital together accounted for 61.3% of the variation in work engagement, with the direct effects on work engagement were -0.206 (95% CI: -0.283--0.138, P<0.001) and 0.677 (95% CI: 0.599-0.744, P=0.001), respectively. Psychological capital partially mediated the relationship between compassion fatigue and work engagement, with a mediating effect of -0.397 (95% CI: -0.456--0.340, P<0.001), accounting for 65.8% of the total effect. Conclusion:The work engagement of clinical nurses is at a high level. Managers should take targeted measures to alleviate the symptoms of clinical nurses' compassion fatigue, improve their psychological capital, and then stabilize and improve their level of work engagement.

Objective:To observe the clinical efficacy and adverse reactions of rituximab in the treatment of systemic sclerosis (SSc).Methods:Eight SSc patients who received rituximab treatment in the Department of Rheumatology of Shanghai Ruijin Hospital from November 2016 to May 2020 were treated with rituximab at week 0, week 2, week 4, week 24 and week 48. The clinical symptoms and laboratory parameters were evaluated at baseline, week 4, week 24 and week 48 respectively. All data were analyzed by Wilcoxon test.Results:All the patients were diagnosed as diffuse SSc, including seven females and one male, with a median disease course of 2.5 years. At week 0, week 24 and week 48, the modified Rodnon skin scores (MRss) were 16.5 (11.8, 29.5) , 14.5 (9.5, 27) ( Z=0.841) and 10.5 (7, 24.3) ( Z=0.420) respectively, which were significantly improved as compared with the baseline ( P<0.05). The patients' self-scores were 60(50, 77.5), 52.5(41.3, 67.5)( Z=0.113) and 47.5(36.3, 57.5)( Z=0.474) respectively, which were significantly improved at week 24 and week 48, and the High Resolution CT (HRCT) scores at baseline and week 48 were 2.7(1.02, 3.7) and 1.6(0.65, 2.95)( Z=0.964) respectively, significantly improved after treatment ( P<0.05). The pulmonary aterial hypertension (PAH) values were 48(41, 58.5) mmHg and 47(38.5, 57) mmHg ( Z=0.315) respectively. There was no significant difference between the two groups. Clinical observation showed that the condition was improved and no adverse reaction occurred at the same time period. Conclusion:The improvement of skin sclerosis, pulmonary interstitial lesion and pulmonary artery pressure can be observed during the treatment with rituximab, which may be a new choice for the treatment of SSc. There is no serious adverse reaction during the treatment, and the patients are well tolerated and safe.

Objective:To investigate the clinical manifestations, laboratory and imaging features, treatment and prognosis of systemic lupus erythematosus (SLE) with primary sclerosing cholangitis (PSC).Methods:This is a retrospective case series study describing the clinical, laboratory and imaging manife-stations, treatment and prognosis of 3 SLE patients with PSC. The related literatures were reviewed.Results:In total, 10 patients were included. SLE with PSC, with an average age of (43±17) years old, was more common with hematological and renal involvement, jaundice and arthralgia, positive anti-double-stranded DNA (anti-dsDNA) antibody, hypocomplementemia, elevated erythrocyte sedimentation rate (ESR) and abnormal liver function with predominately elevated alkaline phosphatase (ALP). The classic magnetic resonance cholangio-pancreatography (MRCP) features of PSC include multifocal strictures, beading and areas of dilatation involving the intra- and/or extrahepatic bile ducts. The treatment included glucocorticosteroids, immunosup-pressants and ursodeoxycholic acid (UDCA), and some patients required biliary drainage. Most patients had a good prognosis.Conclusion:Although PSC is rare, attention should be paid to SLE patients with abnormal liver function, especially with elevated ALP, in order to differentiate from PSC.