A high level of serum neopterin is associated with rapidly progressive interstitial lung disease and reduced survival in dermatomyositis.

Neopterin is primarily synthesized and released by activated macrophages/monocytes upon stimulation with interferon-γ and is considered as a marker for macrophage activation. This study aimed to analyze the serum levels of neopterin in patients with dermatomyositis (DM) in association with clinical manifestations, laboratory data and patient prognosis. One hundred and eighty-two consecutive DM patients and 30 healthy controls were retrospectively enrolled into the study. Serum levels of neopterin were significantly increased in DM patients compared to healthy controls (P < 0·001). High serum neopterin levels were associated with anti-melanoma differentiation-associated gene (MDA5) antibody, rapidly progressive interstitial lung disease (RP-ILD) and characteristic DM cutaneous involvement. Longitudinal assessment of serum samples revealed that the serum neopterin levels were closely correlated with disease severity (ß = 30·24, P < 0·001). In addition, a significant increase in serum neopterin concentration of non-survivors was observed when compared to that of survivors (P < 0·001). Receiver operator characteristic curves showed that serum neopterin could distinguish non-survivors and survivors at an optimal cut-off level of 22·1 nmol/l with a sensitivity and specificity of 0·804 and 0·625, respectively (P < 0·001). Kaplan-Meier survival curves revealed that DM patients with serum neopterin > 22·1 nmol/l had a significantly higher mortality compared to the patient group with serum neopterin < 22·1 nmol/l (log-rank P < 0·001). Multivariate regression analysis identified high serum neopterin concentration to be an independent risk factor for poor prognosis in DM (adjusted hazard ratio = 4·619, 95% confidence interval = 2·092-10·195, P < 0·001). In conclusion, increased serum levels of neopterin were significantly associated with RP-ILD and reduced survival in DM patients, suggesting it as a promising biomarker in disease evaluation of DM.

[Effect of cyclophosphamide on ovarian function in patients with systemic lupus erythematosus in childbearing age].

Objective: Serum anti Müllerian hormone (AMH) was used to evaluate the effect of cyclophosphamide (CTX) on ovarian function in female patients with systemic lupus erythematosus (SLE). Methods: A total of 121 female patients who were 18-50 years old with normal menstruation were selected. Among them, 54 patients were treated with CTX as the study group and the remaining 67 cases as the control group. Before and after treatment for 6 months, the clinical characteristics, menstruation and AMH level of all patients were recorded and detected. At the same time, the method of using CTX and the cumulative measurement are recorded. Results: (1) Before treatment, there was no significant difference in AMH and mean age, duration of disease and SLEDAI score between the CTX treatment group and the control group. The renal injury in the CTX treatment group (44.4%) was higher than that of the control group (34.3%), and the difference was statistically significant (P<0.05). (2) After 6 months of treatment, the AMH of group CTX decreased from (2.39±1.58) µg/L to (1.56±1.42) µg/L, and the difference was statistically significant (P<0.01). But there was no significant change in the control group. In 54 cases of CTX treatment group, 23 cases (42.6%) had different degree of menstrual abnormalities, while 67 cases had only 8 cases (11.9%) in the control group. Moreover, the AMH level of 31 cases with abnormal menstruation was (0.95±0.59) µg/L, which was significantly lower than that of the other 90 normal cases (2.36±1.58) µg/L. (3) In 54 cases of CTX treatment group, the cumulative dose of CTX was less than 3 g in 14 cases, 33 cases of 3-6 g, 7 cases greater than 6 g. AMH was all were lower than those before treatment. But there was a statistical difference between the 3 g group and 3-6 g group before treatment, and there were statistical differences between the groups. Conclusion: CTX can damage ovarian function in women of childbearing age SLE. Low dose intravenous CTX may have less damage. Serum AMH can be used to monitor ovarian function in patients with SLE and to guide individualized treatment.

TRIP13 promotes proliferation and invasion of epithelial ovarian cancer cells through Notch signaling pathway.

OBJECTIVE: Growing evidence supports the involvement of Thyroid hormone Receptor Interactor 13 (TRIP13) in the progression and metastasis of multiple cancers. However, the roles of TRIP13 in epithelial ovarian cancer (EOC) remains unknown. The present study aimed to investigate the expression pattern and biological function as well as the underlying molecular mechanism. PATIENTS AND METHODS: The expression patterns of genes in EOC tissues and normal ovarian tissues via microarray from GEO and TCGA datasets. The expression levels of TRIP13 in EOC cell lines were detected by Real Time-Polymerase Chain Reaction (RT-PCR). Next, we investigated the effect of TRIP13 on the proliferation, apoptosis, migration and invasion in the EOC cells. Western blot assay was used to explore the role of TRIP13 on the Notch signaling pathway proteins (Notch1, P21, Hes1). RESULTS: Bioinformatics analysis showed that TRIP13 was one of the most significantly upregulated in EOC. The results of RT-PCR also indicated that TRIP13 expression was markedly upregulated in EOC cell lines (SKOV-3, HEY and OVCAR-3) compared to normal ovarian cell lines. Functionally, our data revealed that silencing TRIP13 in EOC cells inhibits cell proliferation, decreases cell invasion and migration, and stimulates EOC cell apoptosis in vitro. Mechanistically, the knockdown of TRIP13 suppressed the Notch signaling pathway activation and subsequently inhibited EMT progression. CONCLUSIONS: The present study provided the first evidence that TRIP13 acted as an onco-promotive regulator in EOC development by modulating the Notch signaling pathway. Our findings enlarged our knowledge in the molecular pathology of TRIP13 tumorigenesis.

Cigarette smoking and chromosome 9 alterations in bladder cancer.

Epidemiological studies suggest that bladder cancer may be caused by carcinogens in tobacco and certain occupational exposures. Molecular studies have shown that chromosome 9 alterations and TP53 mutations are the most frequent events in bladder cancer. To date, the relationships between epidemiological risk factors and genetic alterations have not been fully explored in bladder cancer. The purpose of this study was to explore the association between smoking and chromosome 9 aberrations in bladder cancer cases. Seventy-three patients with bladder cancer at Memorial Sloan-Kettering Cancer Center were evaluated for smoking history, occupational history, and chromosome 9 alterations. The epidemiological data were abstracted from medical charts. Patients' tumor tissues were analyzed using RFLP and microsatellite polymorphism assays for detection of chromosome 9 alterations. Elevated odds ratios (ORs) were found for chromosome 9 alterations in smokers compared to those in nonsmokers (OR = 4.2; 95% confidence interval, 1.02-17.0) after controlling for age, sex, race, occupational history, and stage of disease. The ORs were 3.6 for those smoking < or = 20 cigarettes per day and 5.8 for those smoking > 20 cigarettes per day. No association was found between occupational history and chromosome 9 alterations. This study supplies evidence suggestive of the link between smoking and chromosome 9 alterations in the etiology of bladder cancer and indicates that potential tumor suppressor genes on chromosome 9 may be involved in smoking-related bladder carcinogenesis.

Axonal degeneration induced by intraneural injection of Campylobacter jejuni antiserum containing high titer anti-GM1 antibody.

Ganglioside-like structures in CAMPYLOBACTER JEJUNI ( C. JEJUNI) lipooligosaccharide (LOS) can induce antiganglioside antibodies, which might cause nerve damage. In this study, we injected the following three antisera directly into the sciatic nerve of guinea pigs, to investigate the role of anti-glycolipids antibody in inducing neural injury: (i) the wild strain antiserum, a mixture of the sera obtained from the guinea pigs immunized with C. JEJUNI wild-type strain (HS:19) that had a high titer anti-GM1 IgG antibody (range: 800-6,400; median: 2,400) and a high titer anti-LOS IgG antibody; (ii) the GALE mutant antiserum, a mixture of the sera obtained from the guinea pigs immunized with the GALE mutant strain that had only a high titer anti-LOS IgG antibody but no anti-GM1 antibody; and (iii) the control antiserum, a mixture of the sera obtained from the guinea pigs immunized with Freund's complete adjuvant alone which had no anti-GM1 or anti-LOS IgG antibody. Pathological examinations showed that the wild strain C. JEJUNI antiserum produced axonal degeneration in sciatic nerves. Demyelination was rare, and no inflammatory cells were present. The pathological features are consistent with those seen in human patients with axonal GBS. No such changes were observed in nerves injected with the GALE mutant antiserum. The experiment showed that passive transfer of serum containing high titer GM1 antibody caused axonal degeneration of peripheral nerves. The result, which reproduced our previous findings in an active immunization study, therefore further confirmed the critical role of the anti-glycolipid antibody in the induction of neuropathy.