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.

[Comparison of efficacy and safety between two different methods of nephroureterectomy in two centers].

OBJECTIVE: To compare the efficacy and safety of complete transperitoneal laparoscopic nephroureterectomy (CTNU) and traditional retroperitoneoscopic nehroureterectomy (TRNU) for the management of upper urinary tract urothelial carcinoma(UTUC). METHODS: We retrospectively collected the clinical data of UTUC patients who underwent CTNU or TRNU surgery from January 2011 to December 2018 in Peking University First Hospital and Fujian Provincial Hospital, and compared the clinical characteristics, perioperative parameters, and follow-up results between the CTNU and TRNU surgeries. RESULTS: Finally, a total of 266 cases were included, with 94 cases in the CTNU group and 172 cases in the TRNU group. The proportion of left side lesions was bigger in TRNU group when compared with CTNU group (P<0.05). No significant differences were observed in clinical characteristics, such as age, gender, body mass index (BMI), American society of anesthesiologists score (ASA score) and tumor laterality. All surgery procedures were completed. The vascular resparing was performed by reason that left arteria renalis was injured accidently during surgical operation in one case of TRNU group. No serious complications were observed in both CTNU and TRNU groups. In CTNU group, operating time was (202.9±76.7) min, estimated blood loss was (68.4±73.3) mL, drainage duration was (3.9±1.5) d, drainage volume was (181.7±251.5) mL, and postoperative hospital stay was (7.8±4.1) d. In TRNU group, operating time was (203.5±68.7) min, estimated blood loss was (130.2±252.1) mL, drainage duration was (4.3 ±1.6) d, drainage volume was (179.1±167.5) mL, and postoperative hospital stay was (8.2±3.7) d. The estimated blood loss in CTNU group was significantly less than that in TRNU group (P=0.005).The median follow-up time was 39 months (range: 1-88 months). The 5-year overall survival rate (OS), cancer specific survival rate (CSS), intra-vesical recurrence free survival rate (IvRFS), disease free survival rate (DFS) of CTNU group was 75.6%, 86.9%, 73.8%, 57.5%, respectively. The OS, CSS, IvRFS and DFS of TRNU group was 66.3%, 83.5%, 75.9%, 58.6%, respectively.No significant differences were observed in the OS, CSS, IvRFS and DFS between the CTNU and TRNU groups. CONCLUSION: CTNU technique is a safe and effective surgical option, and further prospective randomized controlled trial is needed for further evaluation.

MiR-198 affects the proliferation and apoptosis of colorectal cancer through regulation of ADAM28/JAK-STAT signaling pathway.

OBJECTIVE: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. microRNA-198 (miR-198) was reported to be a tumor suppressive miRNA but its role in CRC is largely unknown. Thus, we aimed to investigate the role of miR-198 and its downstream signaling pathway in CRC. PATIENTS AND METHODS: Quantitative Real-time PCR was conducted to measure miR-198 expression in human CRC cell lines (SW620, SW480 and HT29) and normal colon cell line (FHC). Using MTT, colony formation and flow cytometry assay, we investigated the effects of miR-198 on cell proliferation, colony formation and apoptosis. Luciferase activity reporter assay and Western blot assay were performed to validate the target of miR-198. Using Western blot assay, we detected the protein levels of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. RESULTS: The results showed that miR-198 expression was significantly reduced in CRC cell lines compared with FHC. Overexpression of miR-198 inhibits CRC cell proliferation and colony formation but promotes apoptosis. Further study revealed ADAM metallopeptidase domain 28 (ADAM28) was a direct target of miR-198, and the overexpression of ADAM28 reversed the effects of miR-198 on cell behaviors. Besides that, miR-198 blocks the JAK/STAT pathway through regulating ADAM28. CONCLUSIONS: These results collectively revealed miR-198 inhibited cell proliferation but promoted apoptosis through targeting ADAM28 and blocking JAK/STAT pathway in CRC cells.

[Extracorporeal membrane oxygenation for rescuing 12 children with acute fulminant myocarditis].

Objective: To summarize clinical experience of using extracorporeal membrane oxygenation (ECMO) in rescuing children with acute fulminant myocarditis (AFM). Method: Data of 12 children with acute fulminate myocarditis (6 boys and 6 girls, median age 8.3 (0.6, 13.0) years, median weight 33.1 (6, 61) kg) who were rescued with ECMO in Children's Hospital, Zhejiang University from September 2009 to August 2015 were analyzed retrospectively. The analysis focused on the intervene timing of ECMO for the cardiogenic shock and hypoperfusion caused by heart failure and(or) lethal arrhythmia and the essentials of ECMO cardiopulmonary resuscitation(ECPR) for cardiac arrest in pediatric AFM were summarized. Result: The median ECMO duration was 110(22, 240) h. Ten cases survived and 2 were dead of the total of 12 patients. Six ECPR patients survived and 2 were dead in the total of 8 ECPR patients. The complication of 10 survivors were cannula site bleeding (3 cases), hypernatremia and intracranial hemorrhage (1 case), limping (1 case), hoarse voice (1 case), and cerebral injury (1 case). Conclusion: The key points of improving ECMO rescuing outcome for the AFM children are grasping the ECMO intervene timing and training skilled ECMO team. For ECPR patients, keeping effective chest compressions resuscitation is the key to achieve survival and improve the quality of life.

Intracellular expression profile and clinical significance of the CCR9-CCL25 chemokine receptor complex in nasopharyngeal carcinoma.

OBJECTIVES: This study aimed to investigate the association of C-C chemokine receptor type 9 (CCR9) and C-C motif chemokine 25 (CCL25) expression levels with clinical and tumour-node-metastasis stage in nasopharyngeal carcinoma. METHODS: A total of 42 nasopharyngeal carcinoma patients (nasopharyngeal carcinoma group) and 18 patients with a normal nasopharynx (control group) were included in this study. Tissues were collected during surgery and medical examinations. The CCR9 and CCL25 messenger RNA and protein levels were measured using quantitative reverse transcription polymerase chain reaction, Western blotting and immunohistochemical analysis. RESULTS: CCR9 and CCL25 messenger RNA and protein levels were significantly increased in the nasopharyngeal carcinoma group compared with the control group (p < 0.05). Both CCR9 and CCL25 messenger RNA and protein levels were significantly higher in advanced-stage nasopharyngeal carcinoma (stages III and IV) patients compared with early-stage nasopharyngeal carcinoma (stages I and II) patients (p < 0.05). CONCLUSION: The extent of CCR9 and CCL25 upregulation in nasopharyngeal carcinoma correlates with the tumour-node-metastasis stage.

Protective effect of melatonin against gentamicin ototoxicity.

OBJECTIVE: To research the protective effect of melatonin against gentamicin ototoxicity. METHODS: Guinea pigs were randomly divided into four groups. The first group received intramuscular gentamicin (120 mg/kg body weight/day) for 17 days. Over the same time period, a second group simultaneously received intramuscular gentamicin (120 mg/kg body weight/day) plus (on the other side) intramuscular melatonin (0.3 ml kg body weight/day). Two groups of controls were treated for 17 days with either intramuscular melatonin or intramuscular saline. After the 17 days, each animal underwent distortion product otoacoustic emission testing (both ears). The guinea pigs were sacrificed by decapitation just after the final injection. Their cochleae were used to produce a tissue section, surface preparation and scanning electron microscope preparation. RESULTS: Distortion product otoacoustic emission testing indicated gentamicin-induced hearing loss at 3, 4, 6 and 8 kHz in gentamicin-treated animals. Animals receiving melatonin co-therapy had significantly attenuated hearing loss and their cochleae showed lower rates of outer hair cell loss (comparing the same cochlear turns), compared with gentamicin-treated animals (p < 0.01). CONCLUSION: These findings confirm the occurrence of outer hair cell loss after gentamicin treatment, and the attenuation of such loss following simultaneous melatonin injection, using the method of morphological evaluation. These results suggest that melatonin protects against gentamicin ototoxicity by interfering with cytotoxic mechanisms.

Dual silencing of type 1 insulin-like growth factor and epidermal growth factor receptors to induce apoptosis of nasopharyngeal cancer cells.

OBJECTIVE: The epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (type 1 IGF receptor or IGF1R) have played an important role in the growth and apoptosis of cancer. The RNA interference (RNAi) technique can suppress gene expression, but the effects of dual silencing of EGFR and type 1 IGF receptor have not been well understood. METHODS: pU6-EGFR-shRNA-1, pU6-EGFR-shRNA-2, pU6-IGF1R-shRNA-1 and pU6-IGF-1R-shRNA-2 plasimd vectors were transfected to the nasopharyngeal cancer cells. Seven groups were selected for the study. The protein and downstream protein expression were assessed by Western blot. Apoptosis was determined via flow cytometry. Meanwhile, chemosensitivity of nasopharyngeal cancer cell lines transfeced to chemotherapeutic drugs were carried out by MTT. RESULTS: In dual silencing of EGFR and IGF-1R, the protein expression much more was decreased than single silencing of EGFR or IGF-1R, but the cell apoptosis much more is increased than single silencing EGFR or IGF-1R. Dual silencing of EGFR and IGF-1R enhanced chemosensitivity to anticancer drugs, compared with single silencing of EGFR or IGF-1R. CONCLUSION: Dual silencing of EGFR and IGF-1R are capable of suppressing EGFR and IGF-1R expression of the nasopharyngeal cancer cell and can promote apoptosis and increase the cell sensitivity of anticancer drug. The dual silencing of genes RNAi technique is significantly better than a single gene.