Iguratimod attenuates general disease activity and improves lung function in rheumatoid arthritis-associated interstitial lung disease patients.

OBJECTIVE: Iguratimod is a new kind of synthetic small molecule disease modified anti-rheumatic drug with good efficacy for rheumatoid arthritis (RA) treatment; meanwhile, it exhibits potency to alleviate alveolar inflammation and pulmonary fibrosis. However, its application in RA interstitial lung disease (ILD) patients is seldomly reported. Thus, the current study aimed to investigate the efficacy and safety of iguratimod plus glucocorticoid/cyclophosphamide vs. glucocorticoid/cyclophosphamide in treating RA-ILD patients. PATIENTS AND METHODS: Totally 101 RA-ILD patients underwent glucocorticoid/cyclophosphamide (Control group: n=61) or iguratimod plus glucocorticoid/cyclophosphamide (Iguratimod group: n=40) treatment were analyzed. General inflammation, disease activity, serum disease marker levels, high resolution lung computed tomography (HRCT) score, lung function indexes were evaluated within 24-week (W) treatment. RESULTS: No difference of baseline demographic or disease-related features was observed between Iguratimod group and Control group. Iguratimod group showed lower levels of CRP and ESR at W4, W12 and W24; as well as decreased DAS28 score, rheumatoid factor and anti-cyclic citrullinate peptide antibody levels at W12 and W24 compared to Control group. HRCT score showed no difference between Iguratimod group and Control group at any time points. As to lung function indexes, forced vital capacity percent predicted [FVC (% predicted)], carbon monoxide diffusion capacity percent predicted [DLCO (%predicted)] and 6-minute-walk distance (6MWD) were all higher in Iguratimod group compared with Control group at W4, W12 and W24. Besides, no difference in adverse events was discovered between these two groups. CONCLUSIONS: Iguratimod attenuates general inflammation, disease activity, and improves lung function in RA-ILD patients.

Myriocin alleviates Oleic/Palmitate induced chondrocyte degeneration via the suppression of ceramide.

OBJECTIVE: Abnormal lipid metabolism plays a role that cannot be ignored in articular cartilage bone marrow lesions, synovial inflammation, and the destruction of chondrocytes (CHs). Ceramide is one of the key constructions of membrane lipid bilayers, which is an intracellular lipid mediator regulating varieties of cellular behaviors. The purpose of this study was to explore the role of ceramide and its inhibitor in the development of the CHs degeneration. PATIENTS AND METHODS: CHs were isolated from the cartilage collecting from the osteoarthritis (OA) patients, and oleic acid/palmitic (O/P) acid was used to induce CHs lipid disordered. Then, myriocin was used to inhibit the accumulation of ceramide. After that, the apoptosis, cell viability, glucose uptake, oxidative stress, and the chondrogenic gene expression were tested to evaluate the degenerated degree of CHs. RESULTS: Results revealed that O/P induced CH apoptosis, ceramide accumulation, a higher level of oxidative stress, IL-1ß and MMP-13, but it also decreased the collagen-Ⅱ and SOX-9 expressions and affected the glucose uptake of CHs. After the stimulation of myriocin, the side effects induced by O/P was partly reversed. CONCLUSIONS: O/P induces the accumulation of ceramide and the degeneration of CHs, and myriocin can reject the harmful effect caused by O/P via the suppression of ceramide.

Missense mutation in DNAJB13 gene correlated with male fertility in asthenozoospermia.

BACKGROUND: The most common type of male infertility is asthenospermia. We cloned DnaJ heat shock protein family member B13 (Dnajb13/DNAJB13), a type II HSP40 family member that is highly expressed in the testis. DNAJB13 plays a crucial role in sperm flagellar function. OBJECTIVES: The aim of this study was to investigate whether a correlation exists between DNAJB13 and low sperm motility in infertile men. MATERIALS AND METHODS: In the present study, we performed a mutation screening of the DNAJB13 gene in 92 idiopathic asthenozoospermia patients and 200 men with normal fertility. Additionally, we used immunoelectron microscopy, co-immunoprecipitation, mass spectrometric detection, indirect immunofluorescence assay, transmission electron microscopy studies, isobaric tags for relative and absolute quantitation, and multiple reaction monitoring studies to analyze changes in DNAJB13 protein. RESULTS: A novel c.106T>C mutation of DNAJB13 was present in nearly 10% (9/92) of idiopathic asthenozoospermia patients and was absent in 200 fertile men. A computer-assisted sperm analyzer and transmission electron microscopy analysis using samples from 9 patients with DNAJB13 mutations demonstrated that most spermatozoa were immotile due to sperm tail defects. Multiple reaction monitoring results indicated that DNAJB13 protein levels were reduced after gene mutation. We achieved a pregnancy rate of 100% in 8 patients with DNAJB13 mutations using ICSI. DISCUSSION AND CONCLUSION: The DNAJB13 heterozygous variant may affect fertility. ICSI can help these patients with low fertility to father children.

Continuous plasma filtration adsorption in treatment of severe infection-induced multiple organ dysfunction syndrome.

Multiple organ dysfunction syndrome (MODS), a high-risk disease, has a fatality rate of 70%. To improve treatment of this disease, in recent years many scholars have explored the pathological and physiological changes of MODS. To observe the curative effect of continuous plasma filtration adsorption (CPFA) in the treatment of MODS, we selected 96 patients who were diagnosed with severe infection-induced MODS and were treated in the First Affiliated Hospital of Zhengzhou University between February 2012 and October 2014 and divided them into an observation group and a control group. Besides conventional treatment, the observation group was also given CFPA in combination with high volume hemofiltration (HVHF), while the control group only received HVHF. Changes of blood routine index, balance of electrolyte and acid-base as well as vital signs were observed before and after treatment. Also, blood, kidney and blood gas were examined. For all patients, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were recorded at the start of treatment (0 h), and 5 h and 10 h after treatment. It was found that both therapies could lower blood urea nitrogen (BUN) and creatinine levels and maintain balance of electrolyte and acid-base, but had no obvious influence on leukocyte, blood platelet and hematocrit. In the observation group, PaO(2)/FiO(2) and mean arterial pressure (MAP) were significantly improved after surgery (P less than 0.05), while Acute Physiology and Chronic Health Evaluation (APACHE) II score had an obvious decrease (P less than 0.05). In contrast, the control group was observed with insignificantly changed PaO(2)/FiO(2), MAP and APACHE II score (P>0.05). TNF-α, IL-6 and CRP levels of the two groups had no statistically significant difference at the start of treatment (P>0.05), but TNF-α, IL-6 and CRP levels of the observation group became remarkably lower than those of the control group 5 h and 10 h after treatment (P less than 0.05). Therefore, CPFA is proved to be safe and effective in treating patients with severe infection-induced MODS as it can lower the level of proinflammatory cytokines and improve the level of anti-inflammatory cytokines; thus, it is worthy of clinical promotion.

Mitochondrial transfer RNA mutations and hypertension.

Mutations in mitochondrial DNA have been found to be associated with hypertension. Of these, mitochondrial transfer RNA (mt-tRNA) is a hot spot for these pathogenic mutations. It is generally believed that these mutations may result in the failure of mt-tRNA metabolism, thereby worsening mitochondrial dysfunction and resulting in hypertension. mt-tRNA is known for its high frequency of polymorphisms and mutations, and the number of reports regarding mt-tRNA mutations and hypertension is increasing significantly. To better understand the molecular basis of maternally inherited hypertension, we reassessed the link between four mt-tRNA mutations (G15927A in tRNA(Thr), C7492T in tRNA(Ser(UCN)), A4386G in tRNA(Gln), and C14686T in tRNA(Glu)) and hypertension. We first used the phylogenetic approach to investigate the deleterious roles of these mutations, then we used RNA Fold Web Server to predict the minimum free energy of these mt-tRNAs with and without mutations. Using the pathogenicity scoring system, we found that the G15927A and C7492T mutations are classified as pathogenic while all other studied mutations are neutral polymorphisms. Our study provides valuable information for the detection of pathogenic mt-tRNA mutations in hypertension.

Is low anticoagulation intensity more beneficial for patients with bileaflet mechanical mitral valves? a meta-analysis.

AIM: For the mitral valve replacement(MVR) patients using the lowest thrombogenic risk bileaflet valves (St. Jude Medical, Carbomedics and On-X Prosthetic Heart Valve), excellent results can be achieved by adopting the anticoagulation intensity(median INR<2.5)which is lower than the recommended intensity(INR:2.5~3.5). Our aim was to provide a pooled estimate of potential benefit from clinical studies using low anticoagulation intensity and high intensity in these patients. METHODS: Relevant studies published before Feb. 2014 were searched through a number of digital databases(MEDLINE, EMBASE, Cochrane Library, etc.). They were pooled by SPSS19.0 using the random effect method in three fields: occurrence rate of major thromboembolism, major hemorrhage and major total events. RESULTS: 14 studies with 3595 patients were included. The follow-up period was 12846.6 patient*year. Pooled estimates indicated reduction in major hemorrhage (RR: 0.420, 95%CI: 0.296~0.595, P<0.001) and major total events(RR: 0.738, 95%CI: 0.604~0.902, P=0.003) in the low intensity group. No difference was noted in major thromboembolism(RR: 1.045, 95%CI: 0.814~1.341, P=0.75). CONCLUSION: Compared with the recommended high intensity, low anticoagulation intensity (median INR<2.5) may be more beneficial for the MVR patients using the lowest thrombogenic risk bileaflet valves. We recommended an INR between 2.0 and 2.5, with a median INR of 2.3 for these MVR patients.

CD4+CD45RBHi T cell transfer induced colitis in mice is accompanied by osteopenia which is treatable with recombinant human osteoprotegerin.

BACKGROUND AND AIMS: Transfer of CD4+CD45RBHi T cells into semi syngeneic immunodeficient mice represents a model of inflammatory bowel disease (IBD). As patients with IBD often suffer from osteopenia, we studied if this T cell transfer in mice results in osteopenia in addition to colitis, and if treatment with osteoprotegerin (OPG) has effects on the bone mineral density of T cell transferred mice. We also investigated whether osteopenia was due to malabsorption as a result of a dysregulated digestive tract or as a consequence of the inflammatory process. METHODS: CD4+CD45RBHi or CD4+CD45RBLo T cells (4 x 10(5)) were sorted from CB6F1 and transferred into C.B.17 scid/scid mice. Recipient mice were treated with human IgG1 Fc (control) or Fc-OPG three times per week in a prophylactic regimen as well as a therapeutic regimen (after 10% body weight loss) and were evaluated for osteopenia and colitis. RESULTS: Mice that received CD4+CD45RBHi T cells developed osteopenia (as indicated by decreased bone density accompanied by decreased osteoblasts and increased osteoclasts) and colitis (as indicated by histological changes in the large intestine). Mice that received CD4+CD45RBLo T cells developed neither osteopenia nor colitis. All animals consumed, on average, the same amount of food and water over the course of the study. Prophylactic treatment with Fc-OPG increased bone density in mice that received either CD4+CD45RBHi or CD4+CD45RBLo T cells but had no effects on the gastrointestinal tract. Fc-OPG treatment of osteopenic mice with established IBD caused the normalisation of bone density. Osteopenia in CD4+CD45RBHi T cell recipients was accompanied by hypoparathyroidism that was partially normalised by treatment with Fc-OPG. CD4+CD45RBHi T cell recipients also had a bone marrow inflammatory cell infiltrate expressing tumour necrosis factor alpha which was unaffected by treatment with Fc-OPG. CONCLUSIONS: CD4+CD45RBHi T cell transfer results in osteopenia in addition to colitis. Evidence suggests that this osteopenia was induced by inflammatory cell infiltration and not by malabsorption of calcium. Recombinant human osteoprotegerin effectively treated the osteopenia. OPG may be a useful therapeutic option for treating osteopenia in patients with IBD.

[Comparison of immunoenzymatic staining technique (IEST), double gluing strip circumoval precipitin test (DGS-COPT) and conventional circumoval precipitin test (CV-COPT) for diagnosis of schistosomiasis japonica].

IEST, DGS-COPT and CV-COPT using lyophilized ova of schistosoma japonicum were performed on sera from 120 cases of schistosomiasis japonica, 120 cases of schistosomiasis japonica 3-8 years after being cured with praziquantel and 120 healthy individuals by single-blind method. The sensitivity and specificity of IEST was 91.7% and 95.8% respectively which were significantly higher than that of both DGS-COPT and CV-COPT. The negative conversion rate of cured patients was 70.8% with IEST, 80.8% with DGS-COPT and 81.7% with CV-COPT. The results showed that IEST has higher diagnostic value for schistosomiasis than both COPT. DGS-COPT has the same diagnostic value as CV-COPT, however, it was easy to perform and time-saving, thus it might be applied in the fields for practical purposes.