OBJECTIVE: A multicenter survey is conducted to study the application,the long-term effect and safety of hydroxychloroquine(HCQ)in the treatment of rheumatic diseases in Suzhou. METHODS: Retrospectively collect the data of outpatients and inpatients from Rheumatology Department of four general hospitals in Suzhou(the First Affiliated Hospital of Suzhou University, and Suzhou Hospital of Traditional Chinese Medicine, the First People's Hospital of Kunshan, the First People's Hospital of Changshu)from June 2017 to July 2018. A special questionnaire was used to collect data on general information, diagnosis, methods and courses in the use of hydroxychloro-quine, duration, efficacy and compliance, combined medication, adverse reactions of ophthalmology and other systems, and the use of hydroxychloroquine(HCQ)during pregnancy.Result Totally there were 856 cases, including 68 males(7.9%)and 788 females(92.1%).Classification of diseases: 147 cases of RA(including secondary SS of RA), 425 cases of SLE,12 cases of APS, 167 cases of PSS,104 cases of others, and 1 case of overlap syndrome(RA with SLE)The treatment course of HCQ: minimum 0.5 years, maximum 22.75 years, with an average of 3.59(SD=3.08)years.Dosage: 0.2 g/day in 604 cases, 0.4 g/day in 424 cases, 193 cases of using 0.4 and 0.2 successively, and 21 in other cases;721 cases used continuously. There were adverse reactions in 183 cases(7 males and 176 females), which were distributed in 30 cases of RA, 105 cases of SLE, 2 cases of APS, 31 cases of SS and 15 other cases. Ophthalmological adverse reactions occurred in 70 cases, with positive correlation in 4 cases. Ophthalmological examination: 121 cases(14.1%)every year;68 cases(7.9%)every two years. There were 92 cases of adverse skin reactions, with 8 cases of positive correlation. Other systems had few adverse reactions and there was no positive correlation. Continuous medication, combination of anti-rheumatic drugs and adverse reactions were associated, and continuous medication or combination of anti-rheumatic drugs were significantly associated with adverse reactions in ophthalmology and skin, respectively. The adverse reactions of ophthalmology were related to the course of treatment, and the adverse reactions of fundus increased after taking medicine for more than 7 years.There were 37 pregnancies and HCQ was used in 17 cases throughout pregnancy, and only 1 case had non-drug-related neonatal defects. CONCLUSION: HCQ is mainly used in the treatment of SLE, SS, RA and APS in Rheumatology Department in Suzhou. HCQ medication is standardized, but ophthalmic follow-up monitoring is not. Adverse reactions are mainly in skin and ophthalmology. Continuous medication and combination of antirheumatic drugs are associated factors of adverse reactions.Long-term treatment with HCQ is safe and well-toleratrd.

Objective This study aimed to verify the association between osteoprotegerin gene () and its variants with osteoporosis (OP) by performing integrative analysis.Methods We used the KGG software to perform gene-based association analysis, which integrated all publicly available single-nucleotide polymorphism (SNP)-based values and obtained an overall value for the . The significant SNPs were screened for expression quantitative trait loci (eQTLs). Meta-analysis was used to combine the associations between the variants of and bone mineral density (BMD) reported in the literatures. Then we performed dual-luciferase reporter gene systems for the functional verification of the variants of .Results In the gene-based association analysis, the over all value of was 6.24×10 for BMD at femoral neck (FN) and 7.37×10 for BMD at lumbar spine (LS), indicating the importance of for OP. The publicly available eQTL database identified 5 eQTLs which exert cis-regulation effects on at FN and LS. Literature searching found that rs2073617 (known as T950C) was the hot spot SNP. There were 13 relevant studies on rs2073617 besides the GEFOS-2 study identified from the PubMed. Significant differences among TT, TC and CC genotypes at FN (= 0.047) and LS (= 0.025) were shown by meta-analysis, demonstrating the associations between T950C polymorphism and BMD. Luciferase gene expression was significantly higher at the presence of allele C than allele T in the 293T cells (=-9.47, <0.01). Conclusion The integrative analysis further confirmed the importance of in OP and the correlation of T950C polymorphism with BMD of OP. The strategy can be used as a reference for functional interpretation of other disease-related genes.

The expert consensus on clinical practice of Chinese patent medicines shall be regarded as the same with clinical practice guidelines,which shall be concise,readable and applicable. Therefore,a formal expert consensus is unable to contain the whole compilation process and the content of its important process documents. It is necessary to write instructions for continuation,expansion and publicity. In 2018 Standardization Department of China Association of Chinese Medicine invited methodologists with the background of evidence-based medicine drafted a series of standards for expert consensus on clinical practice of Chinese patent medicines,including the guidance for compilation the instructions. It will be useful for readers of expert consensus to understand the work behind the compilation,so as to make the compilation process more transparent and standardized. We proposed nine requirements for compilation the instructions,namely content and requirements,work overview,main technical content,compilation process,process and basis for handling major disagreements,expert consensus implementation requirements and measure suggestions,other issues need to be explained,appendix and format for instructions.
China ; Consensus ; Evidence-Based Medicine ; Medicine, Chinese Traditional ; standards ; Nonprescription Drugs ; standards

In 2018,Standardization Department of China Association of Chinese Medicine invited methodologists with the background of evidence-based medicine to discuss and draft a series of standards for expert consensus on clinical practice of Chinese patent medicines. These standards have been made by reference to the published standards for developing expert consensus and clinical practice guidelines. These standards were made based on full consideration of the current evidence status and the history of clinical practice of Chinese patent medicines. These standards were composed of four parts,namely information summary items,normative general items,normative technical items and information supplementary items,including cover,content,preface,introduction,title,scope,basic Information of Chinese patent medicine,suggestions for clinical application,safety,conflict of interest,appendix,and references,so as to provides reference for improving the quality of expert consensus-based compilation and enhancing the applicability of expert consensus.
China ; Consensus ; Evidence-Based Medicine ; Humans ; Medicine, Chinese Traditional ; standards ; Nonprescription Drugs ; standards

Chinese patent medicine is widely used in clinical practice, but improper use will not only weaken the efficacy of drugs, but even cause adverse consequences. Evidence-based medicine provides guidance for clinical practice based on the best available evidence, experience of experts and needs of patients. However, considering the situation of "insufficient evidence" or "very low quality" in Chinese medicine research, experts consensus is the main basis for clinical decision-making, but expert opinions on which the consensus depends are susceptible to various subjective biases. Therefore, a reliable and scientific consensus-making process is needed to maximally avoid bias on consensus. Unlike the clinical practice guidelines, there is no unified formulating process for consensus in the world today. This article learns from a set of formulating processes from some international consensus formulating institutions/associations, combined with the characteristics and current situation of traditional Chinese medicine, and draws up a set of standard process that is suitable for the clinical experts consensus on Chinese patent medicine, with the expect of providing evidence and reference for consensus makers, and then bringing evidence-based assistance for the clinical standardized application of Chinese patent medicines.
Consensus ; Evidence-Based Medicine ; Expert Testimony ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs

In this review, we focused on a few obstacles that hinder three-dimensional (3D) bioprinting process in tissue engineering. One of the obstacles is the bioinks used to deliver cells. Hydrogels are the most widely used bioink materials; however, they aremechanically weak in nature and cannot meet the requirements for supporting structures, especially when the tissues, such as cartilage, require extracellular matrix to be mechanically strong. Secondly and more importantly, tissue regeneration is not only about building all the components in a way that mimics the structures of living tissues, but also about how to make the constructs function normally in the long term. One of the key issues is sufficient nutrient and oxygen supply to the engineered living constructs. The other is to coordinate the interplays between cells, bioactive agents and extracellular matrix in a natural way. This article reviews the approaches to improve the mechanical strength of hydrogels and their suitability for 3D bioprinting; moreover, the key issues of multiple cell lines coprinting with multiple growth factors, vascularization within engineered living constructs etc. were also reviewed.
Animals ; Bioprinting ; Cell Line ; Humans ; Hydrogels ; Nanoparticles ; Tissue Engineering

OBJECTIVETo investigate the diagnostic value of clinical manifestation, laboratory examination and imaging changes for pyogenic spondylitis and to summarize the clinical characteristics of patients with pyogenic spondylitis.

METHODSThe clinical data, of 20 patients with pyogenic spondylitis were diagnosed by histopathological examination from March 2012 to March 2015, were retrospectively analyzed. There were 9 males and 11 females, aged from 43 to 72 years old with an average of 58.9 years. Included 3 cases of cervical vertebrae, 7 cases of thoracic vertebrae, 10 cases of lumbar vertebrae. Patients of blood analysis, erythrocyte sedimentation rate(ESR), C reactive protein(CRP), X rays, CT and MRI were performed before treatment. Visual analogue scale (VAS) was used to evaluate the pain of patients suffering from vertebral pain.

RESULTSAll the patients had suffered from vertebral pain before treatment. VAS was 9 points in 4 cases, 8 points in 6 cases, 7 points in 1 case, 3 points in 6 cases, and 2 points in 3 cases. Among them, 7 patients complicated with neurological symptoms, 11 with aggravating night pain, 10 with fever. WBC and Neutrophil count (NEU) of 5 cases were increased and other 15 cases were normal;CRP of 19 cases were increased and 1 case was normal;ESR of all 20 cases were increased. X rays showed the intervertebral space narrowing in all 20 cases, 13 cases complicated with destruction of vertebral body; CT showed the lesions of vertebral body in the 20 cases and complicated with destruction, sclerosis of sclerotin; MRI showed that the lesions of the vertebral body in the T1 image had uneven medium low signal, in the T2 image of the 16 cases had uneven high signal and 2 cases had uniform and high signal, 2 cases had main high signal compliated with mixed signal. Thirteen patients underwent surgical treatment and 7 patients received conservative treatment, and the patients left hospital while VAS had significantly improved after treatment.

CONCLUSIONSPyogenic spondylitis is easy to be misdiagnosed or missed in clinic. It can be combined with the clinical manifestations, laboratory examination and imaging characteristics in order to make a definite diagnosis for purulent spondylitis in early.

BACKGROUNDIncreased blood pressure and elevated total cholesterol (TC) level are the two most important modifiable risk factors of cardiovascular disease (CVD) in the world. Hypertension and hypercholesterolemia co-exist more often than would be expected and whether there is a synergistic impact on fatal CVD between elevated TC and hypertension need to be further examined in Chinese population.

METHODSWe conducted a cohort study which recruited 5092 Chinese male steelworkers aged 18 - 74 years in 1974 - 1980 and followed up for an average of 20.84 years. Totally 302 fatal CVD events were documented by the year of 2001. Cox proportional hazards regression models were undertaken to adjust for baseline variables with fatal CVD events as the outcome variable. Additive interaction model was used to evaluate the interaction between elevated TC and hypertension.

RESULTSHypercholesterolemia and hypertension were significantly associated with an increased hazard ratio (HR) of fatal CVD (1.67 (95%CI 1.18 - 2.38) and 2.91 (95%CI 2.23 - 3.80) respectively. Compared to participants with normotension and TC < 240 mg/dl, the HRs were 1.11 (95%CI 0.56 - 2.21), 2.74 (95%CI 2.07 - 3.64) for hypercholesterolemia and hypertension respectively, and 5.51 (95%CI 3.58 - 8.46) for participants with both risk factors. There was an additive interaction with a 2.65 (95%CI 0.45 - 4.85) relative excess risk (RERI) between hypercholesterolemia and hypertension on CVD.

CONCLUSIONWe found that the risk of fatal CVD was significantly associated with an additive interaction due to hypercholesterolemia and hypertension besides a conventional main effect derived from either of them, which highlights that the prevention and treatment of both risk factors might improve the individual risk profile thus reduce the CVD mortality.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Cardiovascular Diseases ; blood ; etiology ; mortality ; Cholesterol ; blood ; Humans ; Hypercholesterolemia ; blood ; complications ; Hypertension ; blood ; complications ; Male ; Middle Aged ; Steel ; Young Adult

Genome-Wide Association Study ; Genotype ; Humans ; Molecular Epidemiology ; methods

OBJECTIVE: To determine the effect of different concentrations of glucose on the differentiation of 3T3-L(1) and the expression of insig-1 and insig-2 mRNA, and to explore the effect of insulin-induced gene in the differentiation and formation of adipocytes and lipogenesis. METHODS: The 3T3-L(1) cells were induced to differentiate in high glucose concentration (25 mol/L G.S), low glucose concentration (5.5 mol/L G.S), and mannitol (19.5 mol/L Mannitol +5.5 mol/L G.S), respectively. The differentiation of 3T3-L(1) cells was examined by oil red "O" straining, and the expression of insig-1,insig-2 mRNA and AP2 mRNA was examined by RT-PCR and in situ hybridization. RESULTS: With the differentiation of 3T3-L(1) cells, the expression of insig-1 and insig-2 mRNA was gradually up-regulated. The expression of insig-1 and insig-2 mRNA significantly increased while AP(2) mRNA decreased in the low glucose concentration inducing group and mannitol inducing group. In the high glucose concentration inducing group, the cell differentiation was poor (P<0.05). There was no difference between the low glucose concentration and the mannitol group in the differentiation of 3T3-L(1) cells, and in the expression of insig-1 and insig-2 and AP(2) mRNA. CONCLUSION Different concentrations of glucose may influence the cell differentiation and the low glucose concentration promotes insig-1 and insig-2 gene expression, which may lead to the inhibition of the differentiation and lipogenesis of preadipocytes.
3T3-L1 Cells ; Animals ; Cell Differentiation ; drug effects ; Dose-Response Relationship, Drug ; Glucose ; pharmacology ; Membrane Proteins ; biosynthesis ; genetics ; Mice ; RNA, Messenger ; biosynthesis ; genetics