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Journal: Zhonghua nei ke za zhi

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To develop a new evidence-based diagnosis, treatment guideline for rheumatoid arthritis (RA) in China.A multidisciplinary guideline development group was established. The grading of recommendations assessment, development and evaluation (GRADE) system was used to rate the quality of evidence and the strength of recommendations. Recommendations were derived from evidence body, the balance of benefits and harmsand patient’s values and preferences.The guideline development group developed 10 recommendations for the diagnosis and treatment of RA. The guideline covered the classification criteria, disease activity monitoring and assessing, antirheumatic drugs (DMARDs) and glucocorticoids with treat-to-target approach of RA.This rheumatoid arthritis guideline was intended to serve as a tool for clinicians and patients for best decisions-making in China.

Concepts: Hospital, Rheumatoid arthritis, Rheumatology, China, Methotrexate, Disease-modifying antirheumatic drug, Hydroxychloroquine, Human Development Index

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Asthma exacerbations can do a lot of harm to the patients and consume large amounts of medical resources. This consensus is based on the domestic and foreign guidelines and literatures to standardize the evaluation and management of asthma exacerbations in China. Asthma exacerbations are characterized by a progressive increase in symptoms of shortness of breath, cough, wheezing or chest tightness and progressive decrease in lung function, and usually require modification of treatment. Recognizing risk factors and triggering factors of asthma exacerbations is helpful for the prevention and long-term management. Evaluation of asthma exacerbations is based on symptoms, lung function, and arterial blood gas. Management is stratified according to the severity of disease. Different regimens to treat asthma exacerbations are discussed in this consensus. Glucocorticoids should be used properly. Overuse of antibiotics should be avoided. Management of life-threatening asthma is discussed separately. Special attention should be paid in some special respects, such as asthma during peri-operation period, gestation period, and childhood. Diagnosis and management of complications are also of great significance and are discussed in details.

Concepts: Pulmonology, Asthma, Pneumonia, Heart, Chronic obstructive pulmonary disease, Arterial blood gas, Bronchitis, Respiratory therapy

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According to the national survey data over the past five years, there are about 50.16 million elderly diabetic patients (≥60 years old) in China. With the increase in the total number of the elderly, this number will be expected to increase. Among the elderly patients, most of them are newly diagnosed, and are associated with a number of risk factors for cardiovascular diseases at the time of initial diagnosis. Those who were with young-onset have a long-term clinical course, and often complicated with diabetic chronic complications and potential organ dysfunctions. Most of the elderly diabetic patients in China are with poor glycemic control. The diabetes-related complications have become one of the major reasons for the senile death. It is well accepted that early diagnosis and reasonable treatment could reduce the occurrence of diabetic complications, and the disability and fatal cardiovascular and cerebrovascular events. Thus, it is recommended, in the consensus, to conduct a comprehensive assessment of the glycemic control, metabolic cardiovascular risk factors, diabetes complications, multiple organ functions of the elderly patients, as well as their intelligence and physical fitness. Personalized control targets on blood glucose, pressure, lipids, uric acid and body weight would be established based on the assessment of each patient and consideration of the balance between benefits and risks in order to achieve the goal of early detection, early diagnosis, early treatment and early target reaching. Moreover, it is also recommended, in the consensus, to focus on the basic treatments (diets, exercises, self-monitoring and management), initiate suitable hypoglycemic drugs with complementary mechanisms when needed, and take into consideration of management of multiple cardiovascular risk factors and drug usage together with the caution of mutual interactions of multiple drugs.

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Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease. As a dengue non-endemic country, China has experienced several dengue outbreaks in recent years. However, dengue patients in China displayed distinct clinical characteristics compared to patients in endemic countries. To standardize the diagnosis and treatment of dengue fever, the experts of the Society of Infectious Diseases, Society of Tropical Medicine and Parasitology of Chinese Medical Association, and the Society of Emergency Medicine, China Association of Chinese Medicine have reached this guideline based on guidelines for diagnosis, treatment, prevention and control of dengue (World Health Organization, 2009); guidelines for diagnosis and treatment of dengue (National Health and Family Planning Commission of the People’s Republic of China, 2014, Edition 2), health industry standard of the People’s Republic of China “diagnosis for dengue fever (WS216-2018)” and systemic reports on dengue. The guideline includes 8 aspects: introduction, terminology, epidemiology and prevention, etiology and pathogenesis, clinical features, diagnosis, treatment and problems to be solved.

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Objective: To explore the incidence and severity of hepatic adverse events (AEs) and identify factors associated with hepatic AEs in patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with tyrosine kinase inhibitors (TKIs). Methods: Liver biochemistry parameters [including ALT(alanine aminotransferase), AST(aspartate aminotransferase), ALP(alkaline phosphatase), and TBil(total bilirubin)] during the first 6 months on imatinib (Gleevec(®)), dasatinib (Sprycel(®)) or nilotinib (Tasigna(®)) in CML-CP patients were collected and analyzed retrospectively. Results: A total of 436 patients were enrolled in this study, including 271 with imatinib, 58 with dasatinib, and 107 with nilotinib. The incidences of any abnormality of liver injury were 21.8%(59/271), 15.5%(9/58) and 32.7%(35/107) in the imatinib, dasatinib and nilotinib groups, respectively. Most of the hepatic AEs were CTCAE grade 1 or 2 and mild or moderate liver injury except 1.9% of TBil CTCAE grade 3 in the nilotinib group. Multivariate analyses showed nilotinib [OR=2.9(1.3-6.6), P=0.012; OR=4.4(1.2-15.6), P=0.023] and male gender [OR=2.3(1.4-3.9), P=0.002; OR=3.0(1.2-7.6), P=0.018] were significantly associated with moderate liver impairment. Conclusions: TKIs including imatinib, dasatinib and nilotinib were well tolerated with mild to moderate hepatic AEs in CML-CP patients. Nilotinib and male sex were associated with occurrence of liver biochemistry abnormalities and moderate hepatic injury.

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Objective: To investigate the significant of peripheral CD(4)(+) CD(69)(+) T lymphocytes in patients with autoimmune hemolytic anemia (AIHA)/Evans syndrome (ES). Methods: In this study peripheral blood samples from 32 patients with AIHA/ES (15 hemolytic episode patients, 17 remission patients) and 13 healthy controls were collected. Patients with AIHA/ES were recruited in Tianjin Medical University General Hospital from October 2015 to May 2016. The percentages of CD(69)(+) T lymphocytes were analyzed by flow cytometry. The expression of CD(69) mRNA in CD(4)(+) T lymphocytes which was sorted from peripheral blood by magnetic activated cell sorting (MACS) was detected using real-time PCR. Soluable CD(69) was measured by ELISA. Results: In hemolytic episode patients, the ratio of CD(3)(+)CD(69)(+)/CD(3)(+)T lymphocytes [(3.08±1.48)%] was significantly higher than that in healthy controls [(1.28±0.83)%, P<0.01] and in remission group[(1.96±1.33)%, P<0.05]. The absolute count of CD(3)(+)CD(69)(+)T lymphocytes in hemolytic episode group [(2.94±1.81)×10(7)/L] was higher than that in healthy controls [(1.48±1.42)×10(7)/L, P<0.05]. The ratio of CD(3)(+)CD(4)(+)CD(69)(+)/CD(3)(+)CD(4)(+)T cells in hemolytic episode group [(2.16±1.56)%] was significantly higher than that in remission group [(1.16±0.62)%, P<0.05] and healthy controls[(0.94±0.78)%, P<0.05]. The quantity of CD(3)(+)CD(4)(+)CD(69)(+)T lymphocytes in hemolytic episode group[(1.04±0.98)×10(7)/L] was higher than in healthy controls [(0.44±0.38)×10(7)/L, P<0.05]. The ratio of CD(3)(+)CD(8)(+)CD(69)(+)/CD(3)(+)CD(8)(+)T lymphocyte in hemolytic episode group [(4.87±2.56)%] was significantly higher than that in healthy controls[(1.83±1.27)%, P<0.01]. The quantity of CD(3)(+)CD(8)(+)CD(69)(+)T lymphocytes in three groups did not show significant difference. The ratio of CD(3)(+)CD(4)(+)CD(69)(+)/CD(3)(+)CD(4)(+) T lymphocytes in hemolytic episode group was negatively correlated with hemoglobin (Hb) (P<0.01) , positively correlated with the percentage of reticulocytes (Ret%) (P=0.01) total bilirubin(TBil), indirect bilirubin(IBil) (P<0.01) and not correlated with absolute reticulocytes count, lactic dehydrogenase (LDH), complement 3(C3), complement 4 (C4). The ratio of CD(3)(+)CD(4)(+)CD(69)(+)/CD(3)(+)CD(4)(+)T lymphocytes in remission group was negatively correlated with Hb (P<0.05). In hemolytic episode patients CD(69) mRNA (32.26±35.11) was significantly higher than that in remission group(6.05±5.87) (P<0.05) and healthy controls (1.76±1.85)(P<0.01). CD(69) mRNA in remission group was significantly higher than healthy controls (P<0.05). Serum CD(69) in hemolytic episode patients [(494.21±16.06) ng/L] was significantly higher than that in healthy controls [(441.39±104.6) ng/L, P<0.05]. Conclusion: Our findings suggest that the proportion of CD(4)(+)CD(69)(+) T lymphocytes increase in AIHA/ES patients, which is correlated with the severity of disease.

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Objective: To investigate the clinical significance of soluble Semaphorin 5A(Sema 5A) in patients of rheumatoid arthritis(RA) and the effect of Sema 5A on osteoclastogenesis in RAW264.7 cells. Methods: (1)Soluble Sema 5A was detected in the serum of 62 RA patients, 30 osteoarthritis(OA) patients and 48 healthy controls(HC) by enzyme-linked immunosorbent assay(ELISA).The relationships between serum Sema 5A and disease activity, radiographic severity and laboratory parameters were investigated in RA patients.(2)RAW264.7 cells were treated with different concentrations of Sema 5A(0,0.5,1,2.5,5 μg/ml).After 7 days, tartrate-resistant acid phosphate(TRAP) staining was performed. The mRNA levels of TRAP, cathepsin-K and matrix metallopeptidase 9(MMP-9) were tested using real-time polymerase chain reaction (RT-PCR).(3)Bone resorption area of dentine slides cultured with RAW264.7 cells was calculated after Sema 5A(5μg/ml) treatment. Results: (1)The serum Sema 5A in RA patients[(5.24±0.59)μg/L] was significantly higher than those in healthy controls[(2.93±0.34)μg/L,P<0.01] and OA patients[(2.68±0.47)μg/L,P<0.05]. The Sema 5A level in RA patients was positively correlated with disease activity score with 28 joint using C-reactive protein(DAS28-CRP), clinical disease activity index (CDAI),C-reactive protein(CRP) and sharp scores(P<0.05 or P<0.01).In addition,the serum Sema 5A in RA patients with positive anti-cyclic citrullinated peptide(CCP) antibody was significantly greater than that of anti-CCP antibody-negative patients(P<0.05).(2)After RAW264.7 cells were treated with Sema 5A, the number of TRAP positive osteoclasts increased according to the increase of Sema 5A concentration with maximal effect at 5 μg/ml. Meanwhile, Sema 5A promoted mRNA expression of TRAP,Cathepsin-K and MMP-9.(3)Bone resorption area increased when RAW264.7 cells were treated with Sema 5A(5 μg/ml). Conclusions: Serum Sema 5A is elevated in RA patients and correlated with disease activity and radiographic severity. Sema 5A promotes osteoclastogenesis of RAW264.7 cells.

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Objective: The aims of the study were to investigate the effects of human islet amyloid polypeptide (hIAPP) on autophagy in INS-1 cells and its underlying mechanism, and to explore the role of autophagy in hIAPP-induced cytotoxicity and oxidative stress. Methods: INS-1 cells were treated with hIAPP (10 μmol/L) for 24 h in the presence or absence of N-acetyl-L-cysteine (NAC), compound C, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and 3-methyladenine (3-MA), respectively. Transmission electron microscopy was used to observe the number of autophagosome in cells. Cell viability was determined by methyl thiazolyl tetrazolium (MTT) test. 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to measure the relative levels of reactive oxygen species (ROS). Western blot was used to detect expression of adenosine monophosphate-activated protein kinase (AMPK) and autophagic markers p62 and microtubule associated protein 1 light chain3 (LC3). Results: Treatment of INS-1 cells with hIAPP resulted in a significant increase in the number of autophagosomes and the expression of LC3-Ⅱ/LC3-Ⅰ (both P<0.05). Meanwhile, treatment of INS-1 cells with hIAPP enhanced the level of ROS to 1.76 times of control cells (P<0.01). Co-treatment with NAC, an antioxidant, inhibited hIAPP-induced ROS generation, and the expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK in the INS-1 cells (all P<0.05). Pretreatment of INS-1 cells with AMPK inhibitor compound C suppressed hIAPP and AICAR, an activator of AMPK, induced expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK (all P<0.05). Autophagic inhibitor 3-MA and compound C aggravated the hIAPP-induced cell death and ROS generation in INS-1 cells (All P<0.05). The cytotoxic effects of hIAPP were significantly attenuated by co-treatment with AICAR (P<0.05). Conclusion: Autophagy may act as an adaptive mechanism to alleviate hIAPP-induced oxidative damage and toxicity in INS-1 cells.

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Objective: To study the expression of dishevelled-2 (DVL2) in rheumatoid arthritis cartilage and its effect on cartilage destruction. Methods: Cartilage DVL2 expression in rat models of rheumatoid arthritis (RA), osteoarthritis(OA) and collagen-induced arthritis(CIA) were tested by Western blotting. DVL2 overexpressed lentivirus was transfected into the knee of CIA rats. Primary chondrocytes were extracted from RA patients by knee arthroplasty and transfected with DVL2 overexpressed lentivirus. Gene expression of related inflammation related cytokines was detected by real-time polymerase chain reaction (PCR) . Results: Compared with knee articular cartilage in OA patients and normal rats, DVL2 protein was highly expressed in knee cartilage of RA patients and CIA rats (P values 0.041 and 0.032, respectively). DVL2 did not significantly affect the destruction of knee cartilage in CIA rats (P=0.885). DVL2 overexpression in chondrocytes enhanced gene expression of cyclo-oxygenase-2 (COX-2), inducible nitric oxide synthase (NOS), matrix metalloproteinase (MMP) 2, MMP-3, and MMP-9, which could be more pronounced when tumor necrosis factor alpha was added. Conclusions: DVL2 is highly expressed in RA articular cartilage and promotes the expression of inflammatory cytokines and MMP gene in chondrocytes by activating Wnt/β-catenin pathway, which involves in the destruction of articular cartilage in RA.

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The safety of decitabine as bridging treatment before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with refractory hematological malignancies was evaluated. All 11 cases succeeded in hematopoietic reconstitution. The main adverse reaction was hematological toxicity. Neither did infections occur, nor drug-induced liver damage and renal impairment during decitabine administration. Most cases showed grade Ⅰ-Ⅱgastrointestinal adverse events. One case was diagnosed as severe acute graft versus host disease and died of intracranial hemorrhage on day 61 after allo-HSCT. The other 10 patients survived. Decitabine bridge is a safe regimen before allo-HSCT in children with refractory hematological malignancies.