[A multicenter study on the tolerance of intravenous low-dose cyclophosphamide in systemic lupus erythematosus].

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m2 of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION: Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.

[Association between platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio with disease activity in Takayasu arteritis patients].

Objective: To explore the relation between platelet-to-lymphocyte ratio (PLR) or neutrophil-to-lymphocyte ratio (NLR) with disease activity in Takayasu arteritis (TA) patients. Methods: Present retrospective study involved 289 patients with TA, who were hospitalized in our department between January 2010 and October 2017, and 280 age and gender matched healthy controls,who underwent thealth examination in our health examination center during the same period (control group). TA patients were further divided into active and inactive groups (180 and 109 cases respectively) according to Kerr scores. The clinical data were compared between groups. Pearson correlation analysis was used to evaluate the relationship between PLR or NLR and disease activity (Kerr score or C-reactive protein or erythrocyte sedimentation rate). Receiver operating characteristic (ROC) curve was employed to judge the cut-off value of disease activity for TA patients. Results: PLR and NLR were significantly higher in TA group than in control group(137.33 (97.38, 193.37) vs. 120.55 (96.86, 144.60) and 2.38 (1.76, 3.57) vs. 1.66 (1.35, 2.08) , respectively, all P<0.001). PLR and NLR were significantly higher in active TA group than in inactive TA group (163.43 (123.64, 224.15) vs. 110.53 (84.22, 147.24) and 2.59 (1.96, 3.94) vs. 1.95 (1.53, 2.86) respectively, all P<0.001). PLR and NLR of active group were significantly decreased after 6 months treatment (164.05 (123.29, 226.29) vs. 104.67 (77.22, 138.43) and 2.58 (1.96, 3.91) vs. 2.15 (1.67, 2.60) respectively, all P<0.001). PLR was positively correlated with Kerr score (r=0.439, P<0.001), C-reactive protein (r=0.328, P<0.001) and erythrocyte sedimentation rate (r=0.410, P<0.001). NLR also exhibited a positive relationship with Kerr score (r=0.235, P<0.001), C-reactive protein (r=0.169, P=0.005) and erythrocyte sedimentation rate (r=0.123, P=0.037). A PLR level of 176.709 was shown to be the best predictive cut-off value for TA disease activity (sensitivity 44.6%, specificity 93.0%, and area under the curve=0.766).A NLR level of 2.128 was shown to be the best predictive cut-off value for TA disease activity (sensitivity 70.9%, specificity 47.7%, and area under the curve=0.691). Conclusion: PLR and NLR are useful markers for predicting disease activity of TA patients.

[Follistatin-like 1-engineered mesenchymal stem cells prevent myocardial ischemic reperfusion injury].

OBJECTIVE: To investigate the role of follistatin-like protein 1 (FSTL1) on bone marrow mesenchymal stem cells (BM-MSCs)-mediated cardioprotection during myocardial ischemia/reperfusion injury. METHODS: Rat bone marrow mesenchymal stem cells were isolated by whole bone marrow adherence method in vitro. A total of 60 Wistar rats were randomly divided into 4 groups: control group, ischemic /reperfusion injury (IRI) group, ischemia/reperfusion injury group treated with natural BM-MSCs (IRI+ MSC group), ischemia/reperfusion injury group treated with BM-MSCs which did not contain FSTL1 (IRI+ MSC FSTL1 siRNA group). Survival analysis was used to analyze survival time of rats, besides, expression of FSTL1 was detected by Western blotting. Myocardial pathological changes were detected by Hematoxylin and Eosin (HE) staining. Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and enzyme-linked immunosorbent assay (ELISA) were used to determine the associated biomarkers and apoptosis 7 days after operation. RESULTS: Compared with IRI group, rats in IRI+ MSC group had a higher survival rate and lived longer. Meanwhile, IRI+ MSC group had higher FSTL1 expression in blood and myocardial tissues than IRI group. Control group showed significantly lower apoptosis rate of myocardial cells[(1.4±0.1)% vs (29.8±4.5)%, P<0.05], less histological changes and infarction areas (0 vs 24.48±4.27, P<0.05) than IRI group. Compared with IRI group, IRI+ MSC group had an improvement of apoptosis rate[(4.2±0.3)% vs (29.8±4.5)%, P<0.05], less histological injury and infarction areas (15.12±3.82 vs 24.48±4.27, P<0.01). IRI+ MSC group had lower expression of LDH, MDA, CK and higher expression of SOD than IRI group (P<0.05). However, IRI+ MSC FSTL1 siRNA group showed weaker protection of myocardial cells than IRI+ MSC group after knockdown of FSTL1 (P<0.05). CONCLUSION: FSTL1, which was secreted by BM-MSCs, plays a protective role in myocardial IRI.

Variants in mitochondrial tRNA gene may not be associated with thyroid carcinoma.

Thyroid cancer is a very common form of endocrine system malignancy. To date, the molecular mechanism underlying thyroid cancer remains poorly understood. Studies of oncocytic tumors have led to a hypothesis which proposes that defects in oxidative phosphorylation (OX- PHOS) may result in a compensatory increase in mitochondrial replication and gene expression. As a result, mitochondrial DNA (mtDNA) mutation analysis has become a useful tool to explore the molecular basis of this disease. Among these mutations, mitochondrial transfer RNAs (mttRNAs) are the hot spots for pathogenic mutations associated with thyroid cancer. However, due to its high mutation rate, the role of mt-tRNA variants in thyroid cancer is still controversial. To address this problem, in this study, we reassessed seven reported mt-tRNA variants: tRNAAsp G7521A, tRNAArg T10411C and T10463C, tRNALeu(CUN) A12308G, tRNAIle G4292C and C4312T, and tRNAAla T5655C, in clinical manifestations of thyroid cancer. We first performed the phylogenetic conservation analysis for these variants; moreover, we used a bioinformatic tool to compare the minimum free energy (G) of mt-tRNA with and without mutations. Most strikingly, none of these variants caused the significant change of the G between the wild-type and the mutant form, suggesting that they may not play an important roles in thyroid cancer. In addition, we screened the frequency of the "pathogenic" A12308G alternation in 300 patients with thyroid cancer and 200 healthy controls. We found that there were five patients and three control subjects carrying this variant. It seemed that the A12308G variant may be a common polymorphism in the human population. Taken together, our study indicated that variants in mt-tRNA genes may not play active roles in patients with thyroid cancer.

Mitochondrial ND3 G10398A mutation: a biomarker for breast cancer.

Mitochondrial DNA mutations have been found to play important roles in carcinogenesis. The most common G10398A mutation, a non-conservative amino acid substitution from Thr to Ala, seems to be involved in the tumorigenesis of breast cancer. Results from studies concerning this mutation remain inconclusive. In the current study, we first took clinical and molecular datasets from case-control studies to determine the association between the G10398A mutation and breast cancer. We further used the Phylotree to determine the haplogroups of this mutation. The frequencies of this mutation in 500 unrelated healthy controls were also screened. We found that this mutation is very common in the human population, and may be a polymorph.