Long non-coding RNA linc01433 promotes tumorigenesis and progression in esophageal squamous cell carcinoma by sponging miR-1301.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have emerged as pivotal participants of various tumors. This manuscript focuses on the function of lncRNA linc01433 (linc01433) in esophageal squamous cell carcinoma (ESCC) development. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect expressions of linc01433 and microRNA-1301 (miR-1301) in ESCC tissues and cells. Cell counting kit-8 (CCK-8) and colony formation assays were used to verify proliferative ability changes in ESCC influenced by linc01433 and miR-1303. Wound healing and transwell assays were chosen to determine migratory ability in ESCC cells. RESULTS: Linc01433 was abnormally up-regulated in ESCC tissues and cells. High level of linc01433 was positively correlated with tumor size and lymph node metastasis in ESCC patients. Up-regulation of linc01433 promoted cell proliferation and migration. MiR-1301 was a potential target of linc01433, and its level was negatively regulated by linc01433. MiR-1301 was responsible for linc01433-regulated proliferation and migration of ESCC. CONCLUSIONS: Linc01433 participated in ESCC progression by regulating miR-1301 and it could function as a novel biomarker in ESCC diagnosis and treatment.

LncRNA ANRIL impacts the progress of osteoarthritis via regulating proliferation and apoptosis of osteoarthritis synoviocytes.

OBJECTIVE: Long noncoding RNAs (lncRNAs) have been indicated to play an important role in many different diseases. Osteoarthritis (OA) is a disease which causes a change of morphology and function in articular cartilage and synovium, leading to cartilage degradation. Synovitis is a common pathological feature of OA, owing to the proliferation of synoviocytes. In this research, we want to verify the role of lncRNA ANRIL in osteoarthritis. PATIENTS AND METHODS: qRT-PCR was used to detect the expression of lncRNA ANRIL in normal synoviocytes and osteoarthritis synoviocytes. The cell proliferation in normal synoviocytes and osteoarthritis synoviocytes after transfection with lncRNA-NC or lncRNA-ANRIL were tested. The apoptosis rate and cell cycle in normal synoviocytes and osteoarthritis synoviocytes were detected by the Flow Cytometry analysis. Western blot was used to analyze the possible mechanism that ANRIL regulated the cells' proliferation in osteoarthritis. RESULTS: We indicated that the expression of ANRIL was significantly improved in OAS compared to NS. The expression of ANRIL was decreased and the cell proliferation was reduced in OAS after transfected with siRNA. And the cell cycle was suspended in G0/G1 phase and the cell apoptosis was improved in OAS after transfected with siRNA. Moreover, ANRIL could regulate the proliferation and apoptosis of OAS via miR-122-5p/DUSP4 axis. CONCLUSIONS: We suggest that lncRNA ANRIL was closely related to osteoarthritis. ANRIL may be involved in the development and progression of osteoarthritis and become a potential target for diagnosis and treatment in OA.

[Selective tarsometatarsal arthrodesis for old Lisfranc injury].

Objective: To discuss the methods and clinical outcomes of selective tarsometatarsal (TMT) arthrodesis for old Lisfranc injury. Methods: The clinical data of 36 cases with old Lisfranc injury treated by selective arthrodesis from January 2010 to October 2016 in the Department of Orthopedics in Shanghai Sixth People's Hospital were analyzed retrospectively. There were 16 males and 20 females in this group with a mean age of (40±6) years. The information of pre-operative and post-operative X-ray, American Orthopaedics Foot and Ankle Society (AOFAS) midfoot score and pain Visual Analogue Scale (VAS) score was collected. The complications were also recorded. The pre- and post-operative data were compared with t test. Results: The 36 patients got a follow-up for at-least 2 years (averaged (4.3±1.6) years, ranged from 2 to 8 years). The post-operative AOFAS midfoot score was improved from (44±7)(28-60) to (83±7)(76-97)(t=-37.1, P<0.05), and the VAS score decreased from (6.3±2.5)(5-9) to (1.6±1.3)(0-3)(t=23.7, P<0.05). Implant breakage occurred in two patients and the symptom was relieved after the removal of implants. Conclusion: The selective TMT arthrodesis for old Lisfranc injury may relieve the symptoms, improve the function and life quality of patients by restoring the medial arch and midfoot and forefoot alignment.

The influence of palatable high-energy diet in diet-induced obesity pregnant rats on offspring oxidative stress in liver.

OBJECTIVE: We established an animal model of diet-induced obesity pregnant rats and their offsprings, and explored the effect of high-energy feeding on oxidative stress in filial rat liver, as well as the underlying mechanism. MATERIALS AND METHODS: Pregnant female Sprague-Dawley (SD) rats were randomly assigned into two groups: control group and palatable high-energy diet (PHED) group. Liver tissues were obtained 12 days after offspring rats were born for further study. The expressions of malondialdehyde (MDA), reduced glutathione (GSH) and antioxidative enzyme activities were measured, and pathological change of liver tissues was examined by HE staining. In addition, the expressions of inflammatory factors, tumor necrosis factor-α (TNF-α), IL-1ß, and mRNA level of Heme oxygenase-1 (HO-1), were examined by ELISA and RT-PCR, respectively. Furthermore, COX-2 and nuclear factor kappa B (NF-κB) expressions were also examined by Western Blot. RESULTS: Offspring rats of PHED group displayed a significantly higher level of MDA than the control group, and significantly lower level of GSH. Significant reductions in the activities of a number of antioxidant enzymes, such as glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), were found in the PHED group offspring rats compared to the control group offspring rats. HE staining showed the liver cells in the control group offspring rats showed normal histopathological appearance, such as well-aligned cell patterning and unchanged cellular structure, but in the PHED group offspring rats showed slight structure deformation and misalignment. HO-1 mRNA in PHED group offspring rats is significantly higher than that in the control group offspring rats. Also, the expression of COX-2 and p-NF-κB-p65 in PHED group offspring rat liver is 72% and 38% higher than in the control group offspring rat liver, respectively. Expression of NF-κB-p65 in PHED group offspring rats is also significantly higher than that in the control group offspring rats. CONCLUSIONS: Palatable high-energy intake of obesity pregnant rats could lead to reduced antioxidant function in offspring rat liver, even increase the chance of chronical liver disease in the early ages of offsprings. The underlying mechanism is associated with the activity of NF-κB protein.

[Effect of preoperative monocyte-lymphocyte ratio on prognosis of patients with resectable esophagogastric junction cancer].

Objective: To investigate the associations between various blood test parameters including MLR (monocyte-lymphocyte ratio) and prognosis in post-operative esophagogastric junction cancer patients. Methods: We retrospectively studied the preoperative and postoperative data of 309 patients who underwent radical surgery for esophagogastric junction cancer. The relationship between MLR, neutrophil lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and overall survival (OS) was analyzed. Results: The cutoff values of MLR、NLR and PLR were 0.201, 1.697 and 96.960, respectively. The median OS was 51.4 months for all the patients in the study group (n=309). MLR in patients with esophagogastric junction carcinoma was associated with gender, depth of invasion, histological grade, TNM stage, NLR and PLR (P<0.05). PLR was associated with tumor size, TNM stage, NLR and MLR (P<0.05). NLR was associated with gender, tumor size, TNM stage, PLR and MLR (both P<0.05). Univariate analysis showed that tumor size, depth of tumor invasion, metastasis of lymph nodes, pathological grading, nerve infiltration, lymphovascular invasion, TNM staging, PLR and MLR were associated with the median overall survival time (P<0.05). Multivariate analysis showed that TNM stage, nerve infiltration and MLR were independent prognostic predictors for patients with esophagogastric junction cancer (P<0.05), but not PLR or NLR. Setting the optimal cut-off value of the MLR in 0.201, the area under the curve was 0.603, significantly larger than that of PLR and NLR (P<0.05). Conclusions: Preoperative MLR is a very useful predictor of patients with esophagogastric junction cancer who underwent radical rescetion. Preoperative MLR> 0.201 is an independent risk factor for postoperative survival in patients with esophagogastric cancer, and PLR> 96.960 may predict a poor prognosis risk.

Prognostic significance of tumor-associated macrophage infiltration in gastric cancer: a meta-analysis.

Tumor-associated macrophages (TAMs), which play a crucial role in the tumor microenvironment, can be divided into M1 and M2 phenotypes, these phenotypes may exert opposite effects on the prognoses of patients with gastric cancer (GC). The association between TAMs and GC is contentious. Thus, a meta-analysis of 12 studies (incorporating 1388 patients) retrieved from the Cochrane Library, PubMed, and Embase databases was conducted in order to evaluate the relationship between TAMs and GC prognosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled to explore the effect of these cells on survival of GC patients. Our results implied that high total TAM infiltration levels correspond to worse overall survival (OS) in patients with GC (HR = 1.70, 95%CI = 1.39-2.09; P < 0.001), and a similar result was observed in relation to M2 macrophage infiltration (HR = 1.71, 95%CI = 1.19-2.45; P = 0.004). In contrast, elevated M1 macrophage density in GC patients was associated with better OS (HR = 0.46, 95%CI = 0.33-0.65; P < 0.001). This meta-analysis showed that the numbers of infiltrating M2 macrophages and total TAMs might be negative prognostic factors for patients with GC, while M1 macrophage infiltration may be associated with a favorable survival rate.

[Pathologic response and changes of serum VEGF during chemoradiotherapy may predict prognosis in non-surgical patients with esophageal carcinoma].

OBJECTIVE: To observe the pathological response in the tumor tissue and the changes of serum level of vascular endothelial growth factor (VEGF) in esophageal cancer patients receiving concurrent chemoradiotherapy, in order to study the impacts of these two factors on the prognosis of patients. METHODS: One hundred pathologically confirmed esophageal cancer patients were treated with radiotherapy including 72 patients with concurrent chemoradiotherapy. After 4 weeks, gastroscopy was performed to collect tumor biopsies for examination of pathological changes. The responses to radiotherapy were classified into three degrees: mild, moderate and intensive. Moreover, serum samples were collected from the patients prior to, at the fourth week during radiotherapy, and one week after radiotherapy, and serum VEGF level was determined. The changes of serum VEGF were classified as increased, unchanged and decreased. Serum samples from 30 healthy subjects were collected and represented as VEGF healthy control. RESULTS: Among the eighty-nine patients evaluable, the 1- and 3-year overall survival (OS) rates were 70.8% and 33.3%, respectively; 1-year and 3-year progression-free survival (PFS) rates were 61.8% and 28.2%, respectively; and 1-year and 3-year local control (LC) rates were 76.9% and 50.0%, respectively. The 1-year OS rates in the patients with mild, moderate and intensive pathological responses were 50.0%, 76.9% and 78.0%, respectively. The 1-year OS rate in the mild response group was significantly lower than that in the intensive response group (P<0.05). The 1-year and 3-year PFS rates in the three groups were 36.4%, 73.1%, 68.3%, and 0.0%, 40.0% and 38.9%, respectively, showing that the rate in the mild response group was significantly lower than that in the moderate and intensive response groups (P<0.05 for both). The PFS rate in the mild response group was significantly lower than that in the moderate and intensive response groups(P<0.05 for both). Moreover, the 1-year local control (LC) rates in the three groups were 52.9%, 83.3% and 83.8%, and the three-year LC rates were 0.0%, 64.3% and 64.0%, respectively, showing that the lowest LC rates in the mild response group were significantly lower than that in the moderate and intensive response groups (P<0.05 for both). The average serum VEGF levels in the patients prior to, during and after radiotherapy were (109.6±33.7) ng/L, (101.2±24.3) ng/L and (99.5±22.9) ng/L, respectively, all significantly higher than that in the healthy subjects [(79.6±39.2) ng/L, P<0.05 for both]. The level of serum VEGF was decreased during and after radiotherapy compared with that before radiotherapy (F=6.124, P=0.004). The 1-year OS rates in the VEGF-increased, unchanged and decreased groups were 50.0%, 67.4% and 86.7%, respectively, and the 3-year OS rates in these three groups were 15.4%, 27.0% and 50.0%, respectively. The OS rates in the increased group were significantly lower than that in the VEGF-decreased group (P<0.05). Moreover, the 3-year PFS rates in the three groups were 7.7%, 21.6% and 46.4%, respectively, and the rate in the VEGF-increased group was significantly lower than that in the VEGF-decreased group (P<0.05). The multi-variate analysis showed that TNM stage, pathological response and serum VEGF were independent factors affecting the survival in the non-surgical patients with esophageal cancer (P<0.05 for all). CONCLUSIONS: Tumor tissue pathological response and variation of serum VEGF level in response to chemoradiotherapy can be used to predict the efficacy of chemoradiotherapy in non-surgical patients with esophageal cancer. Hence, monitoring the pathological response and VEGF changes during the course of therapy is of utmost importance to evaluate and perform an individualized therapy in clinical practice.

[Route and preparation of 5-Fu administration as preoperative adjuvant chemotherapy in rectal cancer. I. Concentration and distribution of 5-Fu in tissues monitored by 14C-isotopically tagged 5-Fu].

Experimental studies on more rational route and preparation of preoperative administration of 5-Fu were undertaken from March 1981 to June 1985. The experimental observation shows that intrarectal administration of radioisotope 14C tagged 5-Fu (suppository and emulsion) produces a much higher concentration in the rectal wall and mesenteric lymph nodes compared with its intravenous administration (40 rabbits) and produces a much higher concentration in cancer tissue than in surrounding tissues and in mesenteric lymph nodes than in the inferior mesenteric veins (4 patients). These findings favor the attenuation or destruction of cancer cells in the tumor and regional lymph nodes-the main route of spread. Also, after intrarectal administration of 14C tagged 5-Fu, its concentration in the lung, liver and bone marrow is much lower than that after intravenous administration (40 rabbits), and hence systemic toxicity is decreased. The above results indicate that the intrarectal route stands better than the conventional intravenous route for 5-Fu preoperative adjuvant chemotherapy in rectal cancer. Administration of 5-Fu emulsion produces a higher concentration in the rectal wall and mesenteric lymph nodes than that of 5-Fu suppository and peak concentration also appears earlier, i.e. 2 hours after the administration of 5-Fu emulsion. This will lessen the interference of 5-Fu absorption owing to its premature evacuation, indicating that emulsion is a better form for intrarectal 5-Fu.