Discussion on the status quo and norms of epidemiology research of osteoarthritis in China / 中国实用内科杂志

Osteoarthritis(OA) is the most common joint disease. With the aging of the world population and the increase of obesity, the prevalence of OA is increasing year by year. Although China's OA epidemiological research has carried out many regional investigations and studies, the data differs a lot, which may be related to the inconsistency of the diagnostic criteria used in the survey and the non-standard test methods. Analyze the root causes of these problems, start with the epidemiological diagnostic criteria of OA, standardize the imaging examination methods of OA, and not only carry out cross-sectional research but also conduct cohort research, as well as multi-joint, multi-regional and multiethnic investigations. Improving the epidemiological data of China's OA is conducive to clarifying the prevalence and risk factors of OA in China,providing a strong basis for early diagnosis and early prevention and treatment and reducing the occurrence and development of OA.

A multi-center cross-sectional survey of medicine application in patients with osteoarthritis in China / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical characteristics, the medicine application and to evaluate the disease activity in patients with osteoarthritis (OA) in China.@*METHODS@#This was a cross-sectional study. Totally 1 066 cases of OA from 40 hospitals in China from April to October 2017 were retrospectively enrolled. Demographic characteristics, clinical data, medicine application, and joint function were evaluated. All the data were analyzed by SPSS software 19.0. t test, Mann-Whitney U test and chi-square test were used for statistical analysis.@*RESULTS@#In the 1 066 cases, the male-to-female ratio was 1:3.6 and the average age was (61.9±11.0) years, with an age range from 36 to 94 years. The incidence of knee OA, hip OA, and hand OA were respectively 81.9% (873/1 066), 14.1% (150/1 066), and 36.3% (387/1 066). In the study, 242 (22.7%) cases had two kinds of joint areas involved and three joint areas were involved in 51 cases (4.8%), and 56.6% (603/1 066) of the patients used more than one kind of non-steroid anti-inflammatory drugs (NSAIDs) while 61.2% (652/1 066) used disease modifying osteoarthritis drugs (DMOADs), including glucosamine (37.5%, 400/1 066), chondroitin sulfate (2.0%, 21/1 066), diacetate (5.9%, 63/1 066), and the combination of these drugs (15.8%, 168/1 066). 8.6% (92/1 066) patients only took analgesics to relieve the pain, not using any kind of NSAIDs or DMOADs. And 232 patients (21.7%) had intra-articular injections, including 9.2% (98/1 066) sodium hyaluronate, 4.5%(48/1 066) glucocorticoid, and 8.1% (86/1 066) combination of the two drugs. The proportion of the patients taking topical drugs accounted for 26.5% (283/1 066) and physical therapy accounted for 15.8% (168/1 066). Compared with those who suffered from knee OA, the patients who suffered from hip OA had more severe disease assessment. Moreover, there were significant differences in pain (Z=-7.625, P<0.001), morning stiffness (Z=-6.229, P<0.001), and joint function (Z=-6.777, P<0.001) between the two groups of the patients who suffered from knee or hip OA with The Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. Furthermore, patients with hip OA took more analgesics (χ2=24.838, P<0.001).@*CONCLUSION@#Oral NSAIDs and DMOADs are wildly used in patients with OA in China. However, the treatment of some patients still need to be improved. Patients with hip OA are more seriously ill and require aggressive treatment.

Role of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in rheumatic diseases / 中华医学杂志(英文版)

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily of structurally related cytokines and is known to induce proliferation, migration, differentiation, apoptotic cell death, inflammation, and angiogenesis. These physiological processes are induced by the binding of TWEAK to fibroblast growth factor-inducible 14 (Fn14), a highly inducible cell-surface receptor that is linked to several intracellular signaling pathways, including the nuclear factor-κB (NF-κB) pathway. This review discusses the role of the TWEAK-Fn14 axis in several rheumatic diseases and the potential therapeutic benefits of modulation of the TWEAK-Fn14 pathway.

Impaired brachial artery flow-mediated dilation and increased carotid intima-media thickness in rheumatoid arthritis patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilation percentage (FMD%) are common parameters used for detecting subclinical atherosclerosis. This study compared subclinical atherosclerosis of the carotid and brachial arteries in rheumatoid arthritis (RA) patients and healthy controls using high resolution ultrasonography. We also investigated their correlation with clinical factors and the association between FMD% and CIMT.</p><p><b>METHODS</b>One hundred and two RA patients and 46 age-gender matched healthy controls were included in the study. FMD of the brachial artery and CIMT were measured ultrasonographically. Patients with diabetes mellitus, hypertension, renal failure, history of cardiovascular or cerebrovascular disease were excluded. Subjects who were receiving or used high dose steroids were also excluded.</p><p><b>RESULTS</b>The CIMT was significantly higher in patients than that in the control group ((0.697±0.053) vs. (0.554±0.051) mm, P<0.001), whereas brachial artery FMD% was lower in patients than that in the controls ((5.454±2.653)% vs. (8.477±2.851)%, P<0.001). CIMT was related to age, disease duration, tender and swollen joint score, C-reactive protein, systolic blood pressure and high-density lipoprotein. However, FMD% was only association with systolic blood pressure. There was no significant correlation between CIMT and FMD%.</p><p><b>CONCLUSIONS</b>Compared with the healthy control subjects, RA patients without clinically evident cardiovascular disease had subclinical atherosclerosis in terms of impaired FMD% and increased CIMT. FMD% and CIMT may measure a different stage of subclinical atherosclerosis in RA patients.</p>

Testosterone alleviates tumor necrosis factor-alpha-mediated tissue factor pathway inhibitor downregulation via suppression of nuclear factor-kappa B in endothelial cells / 亚洲男科学杂志(英文版)

We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor (TFPI) gene expression through the androgen receptor in endothelial cells. This study further investigated the impact of testosterone on TFPI levels in response to inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Cultured human umbilical vein endothelial cells were incubated in the presence or absence of testosterone or TNF-alpha. TFPI protein and mRNA levels were assessed by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction. To study the cellular mechanism of testosterone's action, nuclear factor-kappa B (NF-kappaB) translocation was confirmed by electrophoretic mobility shift assays. We found that after NF-kappaB was activated by TNF-alpha, TFPI protein levels declined significantly by 37.3% compared with controls (P < 0.001), and the mRNA levels of TFPI also decreased greatly (P < 0.001). A concentration of 30 nmol L(-1) testosterone increased the secretion of TFPI compared with the TNF-alpha-treated group. NF-kappaB DNA-binding activity was significantly suppressed by testosterone (P < 0.05). This suggests that physiological testosterone concentrations may exert their antithrombotic effects on TFPI expression during inflammation by downregulating NF-kappaB activity.

The effect of homocysteine on fibrinolytic system in human umbilical vein endothelial cells / 中华心血管病杂志

<p><b>OBJECTIVES</b>To investigate the relationship between homocysteine (Hcy) and the fibrinolytic system in acute myocardial infarction (AMI) and human umbilical vein endothelial cells (HUVEC).</p><p><b>METHODS</b>Cultured HUVEC was divided into 10 groups (0, 10, 50, 200, 500 micromol/L Hcy with or without 15 micromol/L of folic acid). There were 53 patients of acute myocardial infarction (AMI) and 48 healthy controls. The plasminogen activator inhibitor-1 (PAI-1) and activator of plasminogen (tPA) antigen levels in HUVEC's supernatant and plasma were measured with Elisa kit. Concentration of plasma Hcy was measured by reverse-phase high-performance liquid chromatography with precolumn derivatization and fluorometric detection in the patients and healthy controls. Total RNA was extracted using the guanidinium isothiocyanate method. The semi-quantification of PAI-1 and tPA mRNA in HUVEC was carried out by reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>(1) PAI-1 mRNA and secreted protein levels were both significantly enhanced by Hcy at the concentration of 500 micromol/L, compared with the control group (P < 0.05). (2) The tPA mRNA and antigen levels were decreased significantly at concentration of 500 micromol/L of Hcy, compared with that of 10 micromol/L Hcy (P < 0.05), but compared with the control group (0 micromol/L), the tPA mRNA and antigen levels of 10 micromol/L of Hcy were much higher (P < 0.05). (3) The addition of folic acid reduced PAI-1 but increased tPA at both mRNA and protein levels, which were both obvious at concentrations of 500 micromol/L Hcy, compared with only Hcy group (P < 0.05). (4) Hcy, tPA, and PAI-1 antigen levels were increased in AMI group. Hcy is a independent risk factor of AMI (P < 0.05). There weren't significant correlation between Hcy and tPA or Hcy and PAI-1 in both groups (P > 0.05), although the coefficient correlation was higher in patients than in controls.</p><p><b>CONCLUSIONS</b>These results suggested that hyperhomo-cysteinemia increased the incidence of thrombotic disease, which may be caused by decreasing the activity of fibrinolytic system, whereas, folic acid may be protective against the toxic action of Hcy.</p>

Testosterone has beneficial effects on human umbilical vein endothelial cells / 中国应用生理学杂志

<p><b>AIM</b>To investigate the influences of testosterone with varied concentrations on the functions of HUVEC.</p><p><b>METHODS</b>Human umbilical vein endothelial cells within 2-3 passages were cultured with testosterone (3 x 10(-10) to 3 x 10(-8), 3 x 10(-6), 3 x 10(-5) mol/ L), and the control confluent cells were cultured in the same medium without steroid. MTT experiment was repeated for 7 days to investigate each groups' cell proliferation. The values of NO were tested as recommended. The tPA and PAI-1 antigen levels were assayed with ELISA Kits.</p><p><b>RESULTS</b>Testosterone at physiologic or lower concentrations (3 x 10(-10) to 3 x 10(-8) mol/L ) had no adverse effect on A490 and NO level, meanwhile, stimulated the secretion of tPA (P < 0.01). However, tPA levels markedly reduced at larger dose (3 x 10(-6) to 3 x 10(-5) mol/L). On the other hand, PAI-1 antigen levels decreased significantly at the testosterone concentrations ranging from 3 x 10(-10) to 3 x 10(-5) mol/L (P < 0.05).</p><p><b>CONCLUSION</b>Testosterone at physiologically relevant concentrations affectively decreased PAI-1, while increased tPA levels, which suggested that testosterone might have beneficial effects on the Human umbilical vein endothelial cells and cardiovascular system to prevent atherosclerosis.</p>

Homocysteine' s effect on tPA and PAI-1 gene expression in HUVEC / 中国应用生理学杂志

<p><b>AIM</b>In order to elucidate the relationship between homocysteine (Hcy) and the fibrinolytic system, we examined the effect of Hcy on tissue- type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) gene expression in human umbilical vein endothelial cells (HUVEC) in vitro.</p><p><b>METHODS</b>Total RNA was extracted from HUVEC exposed to physical and pathological concentrations of Hcy (0, 10, 50, 200, 500 micromol/L ) for 24 hours, using the guanidinium isothiocyanate method. The semi-quantification of tPA and PAI-1 mRNA in HUVEC was carried out by reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>PAI-1 mRNA levels was enhanced by Hcy at concentrations of 500 micromol/L of Hcy, compared with that of 0 micromol/L Hcy (P < 0.05). The mRNA expression of tPA, however, was significantly decreased at concentrations of 500 micromol/L Hcy, compared with that of 10 micromol/L Hcy (P < 0.05), but compared with the control group, the tPA level of 10 micromol/L Hcy was much higher (P < 0.05).</p><p><b>CONCLUSION</b>Hyperhomocysteinemia increases the incidence of cardio cerebral vascular disease, which may be caused by decreasing the activity of fibrinolytic system, whereas, the physiological concentration of Hcy may be decreased the incidence by enhancing the activity of fibrinolytic system.</p>

The mechanism of arsenic trioxide on apoptosis of human flbroblast-like synoviocytes of rheumatoid arthritis / 中华风湿病学杂志

Objective To observe the effects of arsenic trioxide (ATO) on apoptosis of human fibrob- last-like synoviocytes of rheumatoid arthritis (HFLS-RA) and to study the mechanism.Methods HFLS-RA were cultured with standard medium as control group or with mediums supplemented with 0.5,2,8?mol/L ATO respectively.The apoptosis of HFLS-RA cultured for 72 h with different concentrations of ATO were in- vestigated under electron microscope.Apoptosis exponent was measured by terminal deoxynucleotidyl transf erase-mediated dUTP nick-end labeling (TUNEL).To detect the proliferation of HFLS-RA euhured with ATO,MTr assay were carded out in 5 consecutive days.Moreover,the NF-kB mRNA level of HFLS-RA was measured by RT-PCR after treated with ATO for 24 h.Results ATO induced the apoptosis of HFLS-RA. Apoptosis exponent was increased in a dose dependent manner in TUNEL experiment,especially in the cells treated with 2 and 8?mol/L ATO (P＜0.05).HFLS-RA proliferation was inhibited in both dose and time de- pendent manner when cultured with ATO.Meanwhile,the NF-kB mRNA level was decreased in ATO treated groups,which was especially significant in mediums cultured in higher than 2?mol/L ATO (P＜0.05).Con- clusion ATO depresses the proliferation of HFLS-RA and may increase the apoptosis by decreasing the ex- pression of NF-kB mRNA.These findings suggest that ATO have the potential to be a novel therapeutic agents for rheumatoid arthritis.