Poly(A)-specific ribonuclease protein promotes the proliferation, invasion and migration of esophageal cancer cells.

BACKGROUND: Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear. AIM: To investigate the relationship between PARN and the proliferation, migration and invasion of EC cells. METHODS: The EC tissues of 91 patients after EC surgery and 63 paired precancerous healthy tissues were collected. PARN mRNA levels were measured using a tissue microarray, and the PARN expression level was evaluated using immunohistochemistry to analyze the relationship between PARN expression and clinicopathologic features as well as the survival and prognosis of patients. In addition, the effects of PARN gene knockout on tumor cell proliferation, invasion and migration were studied by using shRNA during the in vitro culture of EC cell lines Eca-109 and TE-1, and the effects of the PARN gene on tumor growth in vivo were verified by a xenotransplantation nude mice model. RESULTS: The expression of PARN in EC tissues was higher than that in adjacent normal tissues, and the level of PARN expression was significantly positively correlated with lymphatic metastasis. Patients with high PARN levels had poor overall survival. BIM, IGFBP-5 and p21 levels were significantly increased in the PARN knockout group, while the expression levels of the antiapoptotic proteins Survivin and sTNF-R1 were significantly decreased in the apoptotic antibody array data. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 in the downstream signaling pathway regulating EC progression were significantly decreased. The culture of EC cell lines confirmed that the apoptosis rate of EC cells was significantly increased, the growth and proliferation of tumor cells were significantly inhibited, and the invasion and migration ability of tumor cells were significantly decreased after PARN gene knockout. In vivo experiments of BALB/c nude mice transfected with Eca-109 cells expressing control shRNA (sh-NC) and PARN shRNA (sh-PARN) showed that the tumor volume and weight of nude mice treated with sh-PARN were significantly decreased compared with those of nude mice treated with sh-NC, indicating that PARN knockdown significantly inhibited tumor growth in vivo. CONCLUSION: PARN has antiapoptotic effects on EC cells and promotes their proliferation, invasion and migration, which is associated with the development of EC and poor patient prognosis. PARN may become a potential target for the diagnosis, prognosis prediction and treatment of EC.

The efficacy and safety of two low-dose peri-operative dexamethasone on pain and recovery following total hip arthroplasty: a randomized controlled trial.

PURPOSE: To evalute the efficacy and safety of two low-dose peri-operative dexamethasone on pain and recovery following total hip arthroplasty (THA). METHODS: One hundred ten patients received two-dose of 10 mg IV-dexamethasone (group dexa) or IV-isotonic saline (group placebo). The level of C-reactive protein (CRP) and interleukin-6 (IL-6), pain at rest and during mobilization, incidence of post-operative nausea and vomiting (PONV), intensity of nausea, post-operative fatigue, consumption of analgesic and antiemetic rescue, range of motion (ROM), post-operative length of stay (post-operative LOS), wound problems and complications were recorded and compared. RESULTS: The level of inflammation markers (CRP, IL-6) in group dexa was lower than group placebo at 24, 48, 72 hours post-operatively. Dynamic pain VAS score at 24 hours was lower in group dexa (P = 0.002), however, there was no significant effect on pain at rest. In group dexa, patients had a lower incidence of PONV (P = 0.003), as well as a lower VAS score of nausea (P = 0.044). The post-operative fatigue (P < 0.001) was relieved and the consumption of analgesic and antiemetic rescues were reduced. Furthermore, patients had better maximum hip flexion (P < 0.001) and abduction (P = 0.017), with shorter post-operative LOS (P = 0.006). There is no difference between groups in wound problems. No surgical site infection or gastrointestinal haemorrhage was detected in both groups. CONCLUSIONS: The administration of two low-dose peri-operative dexamethasone can effectively reduce the post-operative level of CRP and IL-6, provide additional pain and nausea control, ameliorate post-operative fatigue, enhance mobility, and shorten post-operative LOS following THA, without increasing the risk of infection and gastrointestinal hemorrhage. LEVEL OF EVIDENCE: I.

Copper(I)-Catalyzed Enantioselective Addition of Enynes to Ketones.

A copper(I)-catalyzed enantioselective addition of enynes to ketones was developed. The method allows facile construction of enantiomerically enriched tertiary alcohols using skipped enynes as stable hydrocarbon pronucleophiles. The combination of a soft copper(I)-conjugated Brønsted base catalyst with a chiral diphosphine ligand, (S,S)-Ph-BPE, enabled chemoselective deprotonation of the skipped enynes in the presence of ketones bearing intrinsically more acidic α-protons. The catalytically generated chiral allylcopper species enantio-, diastereo-, regio-, and chemoselectively reacted with ketones, thereby demonstrating excellent substrate generality with functional group tolerance. The skipped enyne moieties of the pronucleophiles were exclusively converted to cis-conjugated enynes, which will eventually allow for further versatile transformations.

Clinical Evaluation of Tumor Markers for Diagnosis in Patients with Non-small Cell Lung Cancer in China.

BACKGROUND: To evaluate the value of combined detection of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and carbohydrateantigen 125 (CA125) for the clinical diagnosis of non- small cell lung cancer (NSCLC). MATERIALS AND METHODS: Serum CEA, CYFRA21-1 and CA125 were assessed in 140 patients with NSCLC, 90 patients with benign lung disease and 90 normal control subjects, and differences of expression were compared in each group, and joint effects of these tumor markers in the diagnosis of NSCLC were analyzed. RESULTS: Serum CEA, CYFRA21-1 and CA125 in patients with NSCLC were significantly higher than those with benign lung disease and normal controls (P<0.05). The sensitivity of CEA, CYFRA21-1 and CA125 were 49.45%, 59.67%, and 44.87% respectively. As expected, combinations of these tumor markers improved their sensitivity for NSCLC. The combined detection of CEA+CYFRA21-1 was the most cost-effective combination which had higher sensitivity and specificity in NSCLC. Elevation of serum CEA and CYFRA21-1 was significantly associated with pathological types (P<0.05) and elevation of serum CEA, CYFRA21-1 and CA125 was significantly associated with TNM staging (P<0.05). CONCLUSIONS: Single measurement of CEA, CYFRA21-1 and CA125 is of diagnostic value in the diagnosis of lung cancer, and a joint detection of these three tumor markers, could greatly improve the sensitivity of diagnosis on NSCLC. Combined detection of CEA+CYFRA21-1 proved to be the most economic and practical strategy in diagnosis of NSCLC, which can be used to screen the high-risk group.