[ASPIRE guidelines and their enlightenment on application of sham acupuncture in clinical researches].

Reasonable and standard application of sham acupuncture control is the key to determine the quality of acupuncture clinical trials, and is also a difficult problem faced by acupuncture clinical research. The UK National Institute for Health Research and the Medical Research Council jointly published the Applying Surgical Placebo in Randomised Evaluation (ASPIRE) guidelines on the application of placebo surgical operation in randomized evaluation, which includes 4 parts: rationale and ethics, design, conduct, and interpretation and translation, providing comprehensive guidance for the application of placebo controls in surgical trials. As an operational intervention, acupuncture is similar to surgery, so, ASPIRE guidelines can also provide certain guidance for the application of sham acupuncture. In the present paper, we introduce the ASPIRE guidelines, and put forward its enlightenment and reference to the application of sham acupuncture control in combination with retrospecting the current situations of sham acupuncture research. We hold that future studies should strengthen the consideration of the rationality and ethics of sham acupuncture, standardize the design of sham acupuncture control, and convey the information related to sham acupuncture to patients with appropriate descriptions.

Modified pedicle screw-rod versus anterior subcutaneous internal pelvic fixation for unstable anterior pelvic ring fracture: a retrospective study and finite element analysis.

OBJECTIVES: This study compared the stability and clinical outcomes of modified pedicle screw-rod fixation (MPSRF) and anterior subcutaneous internal pelvic fixation (INFIX) for the treatment of anterior pelvic ring fractures using the Tornetta and Matta grading system and finite element analyses (FEA). METHODS: In a retrospective review of a consecutive patient series, 63 patients with Orthopaedic Trauma Association (OTA)/Arbeitsgemeinschaft für Osteosynthesefragen (AO) type B or C pelvic ring fractures were treated by MPRSF (n = 30) or INFIX (n = 33). The main outcome measures were the Majeed score, incidence of complications, and adverse outcomes, and fixation stability as evaluated by finite element analysis. RESULTS: Sixty-three patients were included in the study, with an average age of 34.4 and 36.2 in modified group and conventional group, respectively. Two groups did not differ in terms of the injury severity score, OTA classification, cause of injury, and time to pelvic surgery. However, the MPSRF group had a rate of higher satisfactory results according to the Tornetta and Matta grading system than the conventional group (73.33% vs 63.63%) as well as a higher Majeed score (81.5 ± 10.4 vs 76.3 ± 11.2), and these differences were statistically significant at 6 months post-surgery. FEA showed that MPSRF was stiffer and more stable than INFIX and had a lower risk of implant failure. CONCLUSIONS: Both MPSRF and INFIX provide acceptable biomechanical stability for the treatment of unstable anterior pelvic ring fractures. However, MPSRF provides better fixation stability and a lower risk of implant failure, and can thus lead to better clinical outcomes. Therefore, MPSRF should be more widely applied to anterior pelvic ring fractures.

LAMB3 mediates apoptotic, proliferative, invasive, and metastatic behaviors in pancreatic cancer by regulating the PI3K/Akt signaling pathway.

The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is partially attributed to the invasive and metastatic behavior of this disease. Laminin subunit beta-3 (LAMB3) encodes one of the three subunits of LM-332, an extracellular matrix protein secreted by cultured human keratinocytes. In addition, LAMB3 is involved in the invasive and metastatic abilities of some types of cancer, including colon, pancreas, lung, cervix, stomach, and prostate cancer, but the role and mechanism of LAMB3 in PDAC have not been previously determined. Herein, we tentatively investigated the role of LAMB3 in the malignant biological behavior of PDAC. In this study, we demonstrated that LAMB3 is upregulated in PDAC. Inhibition of LAMB3 abrogated the tumorigenic outcomes of PI3K/Akt signaling pathway activation, including those involving cell cycle arrest, cell apoptosis, proliferation, invasion and migration in vitro, and tumor growth and liver metastasis in vivo. Our results showed that LAMB3 could mediate cell cycle arrest and apoptosis in PDAC cells and alter the proliferative, invasive, and metastatic behaviors of PDAC by regulating the PI3K/Akt signaling pathway. LAMB3 may be a novel therapeutic target for the treatment of PDAC in the future.

Depletion of STYK1 inhibits intrahepatic cholangiocarcinoma development both in vitro and in vivo.

Intrahepatic cholangiocarcinoma (ICC) has been reported to be the second most common primary hepatic carcinoma worldwide, and very limited therapies are currently available. Serine threonine tyrosine kinase (STYK1), a member of the receptor tyrosine kinase family, exhibits tumorigenicity in many types of cancers and is a potential therapeutic target for ICC. In this study, STYK1 was knocked down in the ICC cell lines HCCC-9810 and RBE via a lentivirus-mediated system using short hairpin RNA (shRNA). Next, cell proliferation, colony formation, cell cycle progression, tumor formation in nude mice, migration and invasion, and the expression levels of cell cycle proteins in Lv-sh STYK1- or Lv-sh Con-infected cells were analyzed by CCK-8 assay, colony formation evaluation, flow cytometry, tumor formation evaluation, wound scratch assay, transwell assay, and western blotting. The results indicated that depletion of STYK1 inhibits ICC development both in vitro and in vivo.

Tumor suppressor Fbxw7 antagonizes WNT signaling by targeting ß-catenin for degradation in pancreatic cancer.

Pancreatic cancer is one of the deadliest solid malignancies associated with aberrant Wnt signaling activation. Fbxw7 mutations have been implicated in the development of pancreatic cancer, whereas the exact mechanism of this ubiquitin ligase as a tumor suppressor remains unclear in pancreatic carcinogenesis. Here, we describe that Fbxw7 is downregulated upon pancreatic cancer development. Depletion of Fbxw7 results in tumor suppression in pancreatic cancer cells, while Fbxw7 overexpression inhibits pancreatic cancer cell proliferation and invasion. Considering the negative correlation between Fbxw7 and ß-catenin, we find that Fbxw7 antagonizes Wnt signaling through targeting ß-catenin for its degradation. Moreover, the inhibitory effect of Fbxw7 on pancreatic cancer cell proliferation is mainly executed by the destruction of the Wnt/ß-catenin signaling pathway. We also reveal that c-myc, a widely accepted target of Fbxw7, is also transcriptionally regulated by the Fbxw7/ß-catenin axis in pancreatic cancer cells. Collectively, our results demonstrate that Fbxw7 is a novel regulator of Wnt/ß-catenin signaling-dependent regulation of pancreatic cancer cell growth and invasion, and inactivation of Fbxw7 in pancreatic cancer tissues might be the reason for the aberrant activation of Wnt signaling.

Insights into significant pathways and gene interaction networks in peripheral blood mononuclear cells for early diagnosis of hepatocellular carcinoma.

BACKGROUND: Early diagnosis of hepatocellular cancer (HCC) significantly helps improve patient survival. However, high specific and sensitive tests for screening patients with early stage of HCC are not yet available. Novel HCC biomarkers based on gene expression profiles of peripheral blood mononuclear cells (PBMCs) might change the situation. Recently, a three gene-based signature for the non-invasive detection of early HCC was reported. OBJECTIVE: To compare the differences in global gene expression profiles in PBMCs of healthy individuals and HCC patients, with a specific aim to uncover the significantly altered biological pathways and important hub genes. MATERIALS AND METHODS: Two groups of data were extracted from Affymetrix microarray expression dataset GSE49515. One group had 10 PBMCs samples from healthy control individuals, and the other had 10 PBMCs samples from patients with HCC. Gene expression profiles of both groups were analyzed and compared. Furthermore, ribonucleic acid (RNA) levels of seven of the identified differentially expressed genes (DEGs) were further confirmed by quantitative reverse transcription polymerase chain reaction (QRT-PCR). RESULTS: Significant differences were uncovered in gene expression profiles in PBMCs of healthy individuals and HCC patients. Three hundred and seventy-five up-regulated and 169 down-regulated DEGs were identified. Three hundred and eighty-seven gene ontology (GO) biological processes and 15 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were over-represented by the identified DEGs. CONCLUSIONS: Using identified DEGs, significantly changed biological processes such as nucleic acid metabolic process and KEGG pathways such as cytokine-cytokine receptor interaction in PBMCs of HCC patients were identified. In addition, several important hub genes, for example, CUL4A, and interleukin (IL) 8 were also uncovered.

Hypoxia disrupts the expression levels of circadian rhythm genes in hepatocellular carcinoma.

Disturbance in the expression of circadian rhythm genes is a common feature in certain types of cancer, however the mechanisms mediating this disturbance remain to be elucidated. The present study aimed to investigate the effect of hypoxia on the expression of circadian rhythm genes in liver cancer cells and to identify the mechanisms underlying this effect in hepatocellular carcinoma (HCC). The HCC cell line, PLC/PRF/5. was treated with either a vehicle control or CoCl2 at 50, 100 or 200 µΜ for 24 h. Following treatment, the protein expression levels of hypoxia­inducible factor (HIF)­1α and HIF­2α were detected by western blotting and the mRNA expression levels of circadian rhythm genes, including circadian locomotor output cycles kaput (Clock), brain and muscle Arnt­like 1 (Bmal1), period (Per)1, Per2, Per3, cryptochrome (Cry)1, Cry2 and casein kinase Iε (CKIε), were detected by reverse transcription quantitative polymerase chain reaction (RT­qPCR). Expression plasmids containing HIF­1α or HIF­2α were transfected into the PLC/PRF/5 cells using liposomes and RT­qPCR was used to determine the effects of the transfections on the expression levels of circadian rhythm genes. Following treatment with CoCl2, the protein expression levels of HIF­1α and HIF­2α were upregulated in a CoCl2 concentration­dependent manner. The mRNA expression levels of Clock, Bmal1 and Cry2 were increased, and the mRNA expression levels of Per1, Per2, Per3, Cry1 and CKIε were decreased following CoCl2 treatment (P<0.05). In the PLC/PRF/5 cells transfected with the plasmid containing HIF­1α, the mRNA expression levels of Clock, Bmal1 and Cry2 were increased, and the mRNA expression levels of Per1, Per2, Per3, Cry1 and CKIε were decreased. In the PLC/PRF/5 cells transfected with the plasmid containing HIF­2α, the mRNA expression levels of Clock, Bmal1, Per1, Cry1, Cry2 and CKIε were upregulated, and the mRNA expression levels of Per2 and Per3 were downregulated (P<0.05). A hypoxic microenvironment may contribute to the disturbance in the expression of circadian genes in HCC. HIF­1α and HIF­2α are involved in this process and have redundant, but not identical effects.

Overexpression of microRNA-125b sensitizes human hepatocellular carcinoma cells to 5-fluorouracil through inhibition of glycolysis by targeting hexokinase II.

5-fluorouracil (5-FU)-based chemotherapy is widely used in the treatment of human hepatocellular carcinoma. However, despite impressive initial clinical responses, the majority of patients eventually develop resistance to 5-FU. The microRNA (miR)-125 family has been implicated in a variety of carcinomas as either a tumor suppressor or promoter. In the present study, the role of miR-125b in acquired 5-FU resistance in multiple human hepatocellular carcinoma cell lines was investigated using transfection of miR-125b. Compared with 5-FU?sensitive cells, 5?FU?resistant cells exhibited reduced expression levels of miR?125b. Furthermore, transfection of pre?miR-125b into liver cancer cells resulted in sensitization of 5-FU?resistant cells to 5-FU. In addition, the glucose uptake and lactate production in 5-FU?resistant liver cancer cells were demonstrated to be significantly increased compared with 5?FU?sensitive cells (P<0.05), indicating that targeting glycolytic pathways may overcome chemoresistance in human liver cancer cells. Notably, miR-125 was found to downregulate glucose metabolism by directly targeting hexokinase II. Since drug resistance is a common phenotype of malignant cancer cells, the finding that miR-125b expression levels are negatively correlated with 5-FU resistance in hepatocellular carcinoma cells is consistent with the reported functions of miR-125b. In conclusion, the present study identified miR-125b as a tumor suppressor-like microRNA, which exhibits great potential as a diagnostic and prognostic biomarker in hepatocellular carcinoma.

Expression of the bcl-2 gene and its significance in human pancreatic carcinoma.

OBJECTIVE: To elucidate the expression of the bcl-2 gene in association with both biological characteristics of human primary pancreatic carcinoma and patient's prognosis. METHODS: The s-p immunohistochemistry assay was used to detect the expression of the bcl-2 gene on paraffin-embedded sections from 97 cases of primary pancreatic carcinoma, 32 cases of pancreatitis, and 21 cases of normal pancreas. RESULTS: Among the 97 cases of pancreatic carcinoma, 70 (72.2%) showed positive staining for the bcl-2 protein. In the 32 cases of pancreatitis, 3 (9.4%) showed positive immunostaining for the bcl-2, and in the normal pancreas cases, 1 (4.8%) showed positive immunostaining for the bcl-2. However, the positive staining rates of the bcl-2 protein were lower in tumor tissue from the patients with metastases and tumor-node-metastasis (TNM) stages III, IV than in those from those with non-metastases, well differentiation, non-invasion and TNM stages I, II. The patients with positive immunostaining of bcl-2 have a longer postoperative survival than those with negative staining. CONCLUSIONS: Pancreatic carcinoma expressed a high positivity for bcl-2. Findings suggested that the overexpression of bcl-2 is related to the carcinogenesis and progression of human pancreatic carcinoma. Bcl-2 might be one of the parameters in terms of biological characteristics and good prognosis in patients with pancreatic carcinoma.