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*

Chinese medicine (CM) has thousands of years of experience in prevention of diseases. As for CM, people's constitution is closely related to their health status, thus recognition of CM constitution is the fundamental and core content of research on constitution types. With development of technologies such as sensors, artificial intelligence and big data, objectification of the four diagnostic methods of CM has gradually matured, bringing changes in the mindset and innovations in technical means for recognition of CM constitution. This paper presents a systematic review of the latest research trends in constitution recognition based on objectification of diagnostic methods in CM.
Humans ; Medicine, Chinese Traditional ; Artificial Intelligence ; Health Status ; Body Constitution

The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in commemoration of the International Day of Radiology in 2020, as well as the 200th anniversary of the Singapore General Hospital in 2021. This pictorial essay comprises gastroenterology, musculoskeletal and obstetrics and gynaecology cases from the archives.

The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in 2020 in commemoration of the 20th anniversary of the formation of SingHealth, the 55th National Day of Singapore, and the 125th anniversary of the International Day of Radiology. This pictorial essay comprises cardiovascular, respiratory and neurological cases from the archives.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objectives: To evaluate study designs and citation counts of original research published in the Medical Journal of Malaysia (MJM). Methods: The bibliographic data of the MJM for the period 1980-2016 were retrieved from PubMed and analysed using Endnote bibliographic software. Study designs of original journal articles were analysed according to whether the articles were diagnostic study, prognostic study or clinical trial (collectively known as “evidence papers”). The citation counts of the original articles and case reports for the period 2012-2016 were compared in a sub-study using a case-control design. Results: A total of 3952 MJM journal items were retrieved from PubMed for the period 1980-2016; of these, 58.9% were original articles and 29.5% were case reports. Among the original articles, 14.6% were “evidence papers”; 2.3% were diagnostic studies, 7.7% were prognostic studies, 4.6% were clinical trials. In the study period 2012-2016, “other types of original articles” had statistically significantly more citations than case reports. However, there is no difference between “evidence papers” and case reports. Conclusion Our analysis shows the distribution of the types of articles appearing in the MJM for the period of study and serves as a reference for improving citations counts in the local context.
Bibliometrics

Objective:To explore the effects of suppress or enhancer of lin-12-like(Sel1L) on differentiation and function of bone marrow-derived dendritic cells.Methods:To generate conditional knockout mice by the Cre-Loxp recombination system.ELISA and Real-time fluorescence quantitative PCR(RT-PCR) was used for analyzing the protein levels and mRNA levels of IL-6/IL-12 in BMDCs.The protein levels of Sel1L in BMDCs were detected by Western bolt.The expression of CFSE,CD80,CD86,MHC-Ⅰ,MHC-Ⅱon BMDCs and the capability in priming OVA specific CD4+T cells proliferation were analyzed by the flow cytometry.Results:The deficiency of Sel1L decreases the proliferation of DCs during its differentiation,up-regulates the secretion of IL-6,IL-12 and the expression of MHC-Ⅰ.Notably,Sel1L-null DCs was failed to up-regulate MHC-Ⅱexpression and dramatically impaired their ability to prime OVA323-339specific CD4+T cell.Conclusion:The deletion of Sel1L can reduce the proliferation of BMDCs and down-regulate its ability in priming the proliferation of OVA specific CD4+T cells.

OBJECTIVETo investigate the association of maternal body composition and dietary intake with the risk of gestational diabetes mellitus (GDM).

METHODSA total 154 GDM subjects and 981 controls were enrolled in a prospective cohort study in 11 hospitals from May 20, 2012 to December 31, 2013. Bioelectrical impedance analysis and dietary surveys were used to determine body composition and to evaluate the intake of nutrients in subjects at 21-24 weeks' gestation (WG). Logistic regression analysis was applied to explore the relationships of maternal body composition and dietary intake with the risk of GDM morbidity.

RESULTSAge, pre-pregnant body weight (BW), and body mass index (BMI) were associated with increased risk of GDM. Fat mass (FM), fat mass percentage (FMP), extracellular water (ECW), BMI, BW, energy, protein, fat, and carbohydrates at 21-24 WG were associated with an increased risk of GDM. In contrast, fat free mass (FFM), muscular mass (MM), and intracellular water (ICW) were associated with a decreased risk of GDM.

CONCLUSIONMaternal body composition and dietary intake during the second trimester of pregnancy were associated with the risk of GDM morbidity.

Adult ; Asian Continental Ancestry Group ; Body Composition ; Body Mass Index ; Cohort Studies ; Diabetes, Gestational ; epidemiology ; Diet ; Diet Surveys ; Feeding Behavior ; Female ; Humans ; Pregnancy ; Pregnancy Trimester, Second ; Risk Factors

BACKGROUNDAtherosclerosis is the primary cause of cardiovascular disease, carotid artery disease, and peripheral vascular disease. However, it is hard to obtain human arterial tissue at different stages of atherosclerosis for a systematic study. The ApoE-deficient (ApoE(-/-)) mice predictably develop spontaneous atherosclerotic plaques with numerous features similar to the human lesions and contain nearly the entire spectrum of lesions observed during atherogenesis in humans. MicroRNA expression profiles at different stages of atherosclerosis in ApoE-deficient mice were screened to find out the differentially expressed microRNAs.

METHODSApoE-deficient mice were euthanized at 4, 8, and 20 weeks of age and divided into three groups according to the three time points, including groups A4 (fed a Western-type diet for 0 week), A8 (fed a Western-type diet for 4 weeks), and A20 (fed a Western-type diet for 16 weeks). Atherosclerotic lesions were analyzed. Fifteen aortas were collected and combined into three pools (five aortas in one pool) in each group. MicroRNA microarray analysis was replicated thrice in each group. The threshold of fold change ≥ 2.0 was used to screen up or down-regulated microRNAs. Differentially expressed microRNAs were subsequently verified with quantitative real-time polymerase chain reaction. Those increasingly up or down-regulated microRNAs during the progression of atherosclerosis were selected.

RESULTSAtherosclerotic lesions first appeared in the aortic arch in group A8. Severe atherosclerotic lesions were observed in group A20. In group A8, seven MicroRNAs were up-regulated while two were down-regulated. In group A20, 15 microRNAs were up-regulated while two were down-regulated. miR-34a-5p and miR-497-5p were increasingly up-regulated, while miR-434-3p was progressively down-regulated when atherosclerosis progressed.

CONCLUSIONSIn this study, we described that microRNAs are differentially expressed at different stages of atherosclerosis in ApoE-deficient mice. Those increasingly up or down-regulated microRNAs during the progression of atherosclerosis may play an important role in the pathogenesis of atherosclerosis and provide us opportunities for investigating atherosclerosis from early to advanced stages.

Animals ; Apolipoproteins E ; deficiency ; genetics ; Atherosclerosis ; genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs ; genetics ; Real-Time Polymerase Chain Reaction

Objective To investigate the toxic effect of hemin on primary cultured neurons,astrocytes,and brain capillary endothelial cells (BCECs),and the damage effect of hemin with different concentrations on the above cells. Methods (1) Primary cultured neurons,astrocytes and BCECs from the cortex of rats were exposed to different doses of hemin for 2 h,and continue culture of these cells for 24 to 96 h after withdrawing hemin was performed; the cellular morphology was examined under phase-contrast microscope; cellular survival rate was measured with Alama blue staining; and the releasing rate of lactate dehydrogenasing (LDH) was detected with regular biochemical method. (2) Primary cultured cells were exposed to different doses of hemin for 2 h,and continue culture of the cells for 4 h was performed after washing out the hemin; and then,concentrated formic acid was employed to dissociate the cells, and heme content in dissociated cells was measured with spectrophotometer. (3) Primary cultured cells was exposed to different doses ofhemin for 30,60 and 120 min,respectively,and continue culture of the cells for 4 h was performed after washing out hemin; and then,intracellular Fe3+was examined with Prussian blue staining. Results (1) Cultured neurons were injured by a low dose ofhemin (5 mmol/L) with a decreased survival rate by 40.2％ and an increased LDH releasing rate by 22.2％; and the pathological changes of cellular morphology were severe after 24 h of exposure to hemin.Following the increased doses ofhemin and time of post-exposure,the cellular death and LDH releasing were increased,and the morphological changes of cells were much severe. (2) The low and medium doses of hemin (5 mmol/L and 25 mmol/L) did not induce cellular death, LDH releasing and morphological changes in astrocytes; and a high dose ofhemin (50 mmol/L) could induce a death rate of astrocytes decreasing by 52.4％, a LDH releasing rate increasing by 31％ and obvious morphological changes of astrocytes; however, the injured astrocytes could regenerate fluent cellular monolayer 96 h after exposing to high dose of hemin treatment.(3) Hemin with either low or high dose did not induce any changes in cellular survival,LDH releasing and cellular morphology of BCECs.(4) The heme content in cultured neurons was significantly higher than that in astrocytes and BCECs after hemin treatment for 2 h.(5) The blue Fe3+ stained granules appeared in neurons as early as 30 min after neurons being exposed to hemin, and Fe3+ stained positive cells in neurons were significantly higher than those in astrocytes and BCECs at any dose ofhemin and any time point ofhemin treatment. Conclusion Hemin is highly toxic to neurons, but it can only injure astrocytes at a high dose and it can not induce direct damage in BCECs; free hemin could rapidly enter and accumulate in neurons,but less accumulate in astrocytes and not accumulate in BCECs.