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Laparoscopic surgery with natural orifice specimen extraction (La-NOSE) is being performed more frequently for the minimally invasive management of sigmoid and rectal cancer. The objective of this meta-analysis was to compare the clinical and oncological safety and efficacy of La-NOSE versus conventional laparoscopy (CL). A search of the PubMed, Web of Science, and Cochrane databases was performed for studies that compared clinical or oncological outcomes of conventional laparoscopic resection using NOSE with conventional laparoscopic resection for sigmoid and rectal cancer. Compared with CL group, the length of hospital stay and the pain score on the first day were shorter in the La-Nose group. The La-NOSE group had a lower incidence of total perioperative complications (OR 0.46; 95% CI [0.32 to 0.66]; I2 = 0%; P

HCC (hepatocellular carcinoma) is a major health threat for the Chinese population and has poor prognosis because of strong resistance to chemotherapy in patients. For instance, a considerable challenge for the treatment of HCC is sorafenib resistance. The aberrant glucose metabolism in cancer cells aerobic glycolysis is associated with resistance to chemotherapeutic agents. Drug-resistance cells and tumors were exposed to sorafenib to establish sorafenib-resistance cell lines and tumors. Western blotting and real-time PCR or IHC staining were used to analyze the level of CLCF1 in the sorafenib resistance cell lines or tumors. The aerobic glycolysis was analyzed by ECAR assay. The mechanism mediating the high expression of CLCF1 in sorafenib-resistant cells and its relationships with miR-130-5p was determined by bioinformatic analysis, dual luciferase reporter assays, real-time PCR, and western blotting. The in vivo effect was evaluated by xenografted with nude mice. The relation of CLCF1 and miR-30a-5p was determined in patients’ samples. In this study, we report the relationship between sorafenib resistance and increased glycolysis in HCC cells. We also show the vital role of CLCF1 in promoting glycolysis by activating PI3K/AKT signaling and its downstream genes, thus participating in glycolysis in sorafenib-resistant HCC cells. Furthermore, we also show that miR-30a-5p directly targets CLCF1 and that sorafenib-mediated suppression of miR-30a-5p results in the upregulation of CLCF1 in HCC cells resistant to sorafenib. We also found that when a cholesterol modified agomiR-30a-5p was delivered systemically to mice harboring sorafenib-resistant HCC tumors, tumor growth decreased significantly. There is an uncharacterized mechanism of biochemical resistance to hormone therapies orchestrated by the miR-30a-5p/CLCF1 axis to mediate sorafenib resistance and aerobic glycolysis in HCC. Therefore, this study indicates that targeting the miR-30a-5p/CLCF1 axis may hold promise for therapeutic intervention in HCC sorafenib resistance patients.

Naoxintong Capsule (NXT) is a Traditional Chinese Medicine formulation which has been widely applied in treating cardiovascular and cerebrovascular diseases. Previous studies also reported the potential effects of NXT against diabetes and certain complications, yet its mechanisms remain largely obscured. Herein, in this study, we investigated the anti-diabetic effects of NXT as well as its potential mechanisms. Type 2 diabetes (T2D) was induced in rats by 10-week high-fat diet in companion with a low-dose streptozotocin injection. NXT was administrated for additional 8 weeks. The results showed that NXT exerted potent efficacy against T2D by alleviating hyperglycemia and hyperlipidemia, ameliorating insulin resistance, mitigating inflammation, relieving hypertension, and reducing myocardial injuries. To investigate its mechanisms, by integrating sequencing of gut microbiota and serum untargeted metabolomics, we showed that NXT could significantly recover the disturbances of gut microbiota and metabolic phenotypes in T2D rats. Several feature pathways, such as arachidonic acid metabolism, fatty acid β-oxidation and glycerophospholipid metabolism, were identified as the potential mechanisms of NXT in vivo. In summary, our study has comprehensively revealed the anti-diabetic effects of NXT which could be considered as a promising strategy for treating metabolic disorders, T2D and diabetic related complications in clinical practice.

Flavonoids are an important class of phytopharmaceuticals in plants. Naringin (naringenin- 7-O-rhamnoglucoside) is a flavanone glycoside isolated from folk herbal medicine Exocarpium Citri grandis (called Huajuhong in Chinese). Massive experimental works have been performed on naringin describing its phytochemical, pharmacokinetic, and bioactive properties. Naringin was found to possess multiple pharmacological activities in relieving inflammation, diabetes, neurodegeneration, cardiovascular disorders, and metabolic syndrome. Recently, it has been approved as a potential antitussive and expectorant for clinical trials. However, the pharmacokinetic aspects of naringin and its therapeutic potentials in respiratory diseases have not been comprehensively reviewed. The present review provides highlights of naringin with respect to its absorption, distribution, metabolism, excretion and its therapeutic effects on cough, phlegm, and pulmonary inflammation. This review would be helpful for the interpretation of pharmacokinetics and pharmacodynamics of naringin in clinical trials.

Naoxintong Capsule (NXT), a Chinese medicine, has been widely used for the treatment of cardiovascular diseases in clinic. The present study was designed to clarify the effects of NXT on haemorheology, blood coagulation, hepatic function, antioxidant capacity and inflammatory responses in a rat model of blood stasis syndrome. Rats were placed in ice-cold water for 5 min during the time interval of two adrenaline injections to induce blood circulation disorders after intragastric administration of 10 consecutive days. Blood was collected from abdominal aorta to determine whole blood viscosity (WBV), plasma viscosity (PV), activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), malonaldehyde (MDA), alanine transaminase (ALT), aspartate transaminase (AST), interleukin-1β (IL-1β), interleukin-6 (IL-6), platelet activating factor (PAF). The results showed that NXT could significantly decrease the WBV, PV, FIB and prolong the APTT and PT. Meanwhile, NXT significantly decreased the serum contents of MDA, IL-1β, IL-6, ALT, AST and PAF, while elevating T-AOC and SOD levels. These results indicate that NXT could improve coagulation function, enhance antioxidant capacity and suppress inflammation, which might partly account for its mechanisms of action in preventing and treating cardiovascular diseases.

Context Naoxintong Capsule (NXT), a Chinese medicine, has been widely used for the treatment of coronary heart disease (CHD) in clinics. Objective This study evaluated the cardioprotective effects of NXT alone and in combination with ticagrelor (TIC) and atorvastatin (ATO). Materials and methods Qi deficiency and blood stasis rats were established by 8 weeks high fat diet feeding and 16 days exhaustive swimming and randomly divided into seven groups, that is, NXT (250, 500 and 1000 mg/kg/d), TIC (20 mg/kg/d), ATO (8 mg/kg/d), NXT (500 mg/kg/d)+TIC (20 mg/kg/d) and NXT (500 mg/kg/d)+ATO (8 mg/kg/d) group, with oral administration for 12 weeks. The contents of TC, TG, LDL-C, HDL-C, IL-1β, IL-6, IL-8, TNF-α, AST, ALT, SOD, MDA, CK-MB, LDH, TXA2, PGI2, IgA, IgG, IgM and C3 in serum were measured. Results NXT + TIC group was significantly superior to the TIC group in decreasing the levels of TC (4.34 vs. 5.54), TG (3.37 vs. 4.66), LDL-C (1.21 vs. 1.35), LDH (4919.71vs. 5367.19) and elevating SOD level (248.54 vs. 192.04). NXT + ATO group was significantly superior to the ATO group in decreasing the levels of AST (195.931 vs. 241.63), ALT (71.26 vs. 83.16), LDH (4690.05 vs. 5285.82), TXA2 (133.73 vs. 158.67), IgG (8.08 vs. 9.80), C3 (2.03 vs. 2.35) and elevating the levels of HDL-C (1.19 vs. 0.91), SOD (241.91vs. 209.49). Conclusions The present findings demonstrate that the combined use of NXT with TIC and ATO had better integrated regulating effects than TIC and ATO, respectively. The mechanism of action requires further research.

Summary Drugs and therapies available for the treatment of inflammatory bowel disease (IBD) are not satisfactory. Our previous study has established the inhibitor of apoptosis-stimulating p53 protein (iASPP) as an oncogenic regulator in colorectal cancer by forming a regulatory axis or feedback loop with miR-124, p53, or p63. As iASPP could target and inhibit nuclear factor kappa B (NF-κB) activation, in this study the role and mechanism of iASPP in IBD was investigated. The aberrant up-regulation of iASPP in IBD was subsequently confirmed, based on online data sets, clinical sample examinations and 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis mice models. TNBS or DSS stimulation successfully induced colon shortness, body weight loss, mice colon oxidative stress and inflammation. In both types of colitis mice models, iASPP over-expression improved, whereas iASPP knockdown aggravated TNBS or DSS stimulation-caused colon shortness, body weight loss and mice colon oxidative stress and inflammation. Meanwhile, in both types of colitis mice models, iASPP over-expression inhibited p65 phosphorylation and decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, C-X-C motif chemokine ligand (CXCL)1 and CXCL2 in mice colons, whereas iASPP knockdown exerted opposite effects.

In this paper, a combination algorithm for diagnosing rotor crack fault is presented. Firstly, the nonlinear output frequency response functions (NOFRFs) are used to analyze the severity of crack damage in the rotor system qualitatively. The NOFRFs are obtained by processing the vibration signal through the nonlinear output frequency response functions. Further analysis of the NOFRFs can determine the crack depth qualitatively. Secondly, the position of the crack is then located using the crack position index (CPI) λ based on the higher harmonic response (HHR) and the dynamic compliance matrix. The simulation and experimental results show that the G2(j2wF) in NOFRFs is very sensitive to crack depth, and the crack position index (CPI) λ can determine the shaft segment effectively where the crack is located. The advantage of this combination algorithm is that it can detect the crack faults by measuring the vibration signal of the cracked rotor at two speeds, which makes the measurement process more simplified and reduces the measurement time for real-time monitoring. At each speed only the vibration response of the two nodes need to be measured, which greatly reduces the number of sensor used in the measurement process and reduces the cost of monitoring. The combination algorithm can diagnose cracked rotor faults effectively and has certain application value in the diagnosis of cracked rotor fault.

BACKGROUND The rate of positive resection margins (R1) in patients with low rectal cancer is substantial. Recommended remedies such as extended resection or chemoradiotherapy have their own serious drawbacks. It has been reported that photodynamic therapy (PDT) as a remedial treatment for esophageal cancer. Colorectal cancer and esophageal cancer has many similarities, however, PDT as a salvage therapy for rectal cancer is rare. CASE SUMMARY Here, we describe a 56-year-old man who was admitted to the hospital due to a 6-mo history of hemafecia, which had been aggravated for 1 mo. Colonoscopy revealed a 3 cm × 4 cm ulcerated mass in the rectum 4 cm from the anus. Preoperative pathological examination showed villous adenoma, moderate-to-high-grade dysplasia, good differentiation, and invasion of the mucosal muscle. The patient had R1 after ultra-low anterior resection, but he refused extended resection and experienced severe liver function impairment after 3 cycles of chemotherapy. Ultimately, the patient underwent PDT to remove R1. After five years of follow-up, there was no liver function impairment, recurrence, metastasis, sexual dysfunction, or abnormal defecation function. CONCLUSION This is the first case worldwide in which R1 of rectal cancer were successfully treated by PDT.

Natural orifice specimen extraction surgery (NOSES) is especially suitable for colorectal surgery. Until now, most of the reports published were about laparoscopic NOSES, the reports about robotic NOSES are extremely rare. This study aims to explore the safety and feasibility of robotic NOSES for colorectal neoplasms. All patients underwent robotic NOSES from March 2016 to October 2019 in our hospital were enrolled for retrospective analysis. Clinicopathological data including patient characteristics, perioperative information and pathological information were collected and analyzed. According to the distance between tumor and anus or whether neoadjuvant chemoradiotherapy (nRCT) is performed, we grouped the cases and studied its influence on robotic NOSES. Also, we compared the previous reports on laparoscopic NOSES with our study and revealed advantages of robotic NOSES in terms of safety and feasibility. A total of 180 patients were enrolled. The average distance from the lower edge of the tumor to the anus was (8.64 ± 3.64) cm and maximum circumferential diameter (CDmax) of specimen was (3.5 ± 1.6) cm. In terms of safety, the average operation time, intraoperative blood loss, and postoperative hospital stay were (187.5 ± 78.3) min, (47.4 ± 34) mL, and (11.3 ± 7.5) days, respectively. In terms of feasibility, the average number of lymph node harvested was (14.8 ± 5). Robotic NOSES shows advantages in terms of safety and feasibility compared with laparoscopic NOSES. This procedure could not only be a safe procedure but also could achieve good oncological outcomes.

Transanal specimen extraction is an alternative approach to remove the specimen from the abdominal cavity after minimally invasive colorectal surgery, which is associated with better cosmetic results and lighter postoperative pain. The single stapling anastomosis is not only as safe as conventional double stapling anastomosis but also able to avoid the “dog ears” and achieve a longer distal margin. Although transanal specimen extraction with single stapling anastomosis has been performed by some experienced surgeons in laparoscopic surgery, the technical limitations of laparoscopic approach make it challenging to create a single stapling anastomosis laparoscopically after performing low anterior resection, especially ultralow anterior resection.

Although the survival rate of patients with cancer have increased due to the use of current chemotherapeutic agents, adverse effects of cancer therapy remain a concern. The reversal of drug resistance, reduction in harmful side effects and accelerated increase in efficiency have often been addressed in the development of combination therapeutics. Tazemetostat (EPZ-6438), a histone methyltransferase EZH2 selective inhibitor, was approved by the FDA for the treatment of advanced epithelioid sarcoma. However, the effect of tazemetostat on colorectal cancer (CRC) and 5-FU sensitivity remains unclear. In this study, the enhancement of tazemetostat on 5-FU sensitivity was examined in CRC cells. Our findings demonstrated that tazemetostat combined with 5-FU exhibits synergistic antitumor function in vitro and in vivo in CRC cells. In addition, tazemetostat promotes PUMA induction through the ROS/ER stress/CHOP axis. PUMA depletion attenuates the antitumor effect of the combination therapy. Therefore, tazemetostat may be a novel treatment to improve the sensitivity of tumors to 5-FU in CRC therapy. In conclusion, the combination of 5-FU and tazemetostat shows high therapeutic possibility with reduced unfavorable effects.

The dosages of valaciclovir used for herpes zoster treatment recommended by Chinese pharmaceutical companies can differ considerably from those reported in the literature. This randomized clinical study compares the efficacy and safety of different oral valaciclovir doses for the treatment of herpes zoster in adults.A total of 214 patients with herpes zoster were enrolled and randomized into two groups according to age: 98 patients in the 18-44-year group (younger patients) and 116 patients in the 45-74-year group (middle-aged and elderly patients). Patients in the two age groups were then prescribed different doses of valaciclovir. The high-dose group was administered 900 mg of valaciclovir, three times daily for 10 days, whereas the low-dose group was administered 300 mg of valaciclovir, two times daily for 10 days. The efficacy and side effects of these regimens were recorded on days 6, 11 and 30.In total, 207 (of 214 enrolled) patients completed the study. Of the seven patients who discontinued the study, five discontinued because their follow-up time was not fixed and two withdrew after moving to other cities. At the 11th day after treatment, the clinical effect of high-dose valaciclovir groups were significantly better than that of the low-dose valaciclovir groups in middle-aged and elderly patients (p 0.05). The difference in visual analog scale (VAS) pain scores between the two dose groups was statistically significant in middle-aged and elderly patients at the 6th day(p 0.05), whereas there was no difference in younger patients (p 0.05). The VAS scores were significantly lower in high-dose group than in low-dose group at day 11 in both groups of patients(p 0.05).There was no statistically significant difference in the time to skin scab improvement between the two different dose groups in younger patients (p 0.05). Among middle-aged and elderly patients, the incidence of postherpetic neuralgia (PHN) was significantly lower in the high-dose group than in the low-dose group (p 0.05). The difference in the incidence of adverse reactions between the high-dose and low-dose groups was not statistically significant (p 0.05). Overall, the main side effect was headache.The present study indicates that early treatment with high-dose valaciclovir can significantly reduce pain in patients, especially in elderly patients, in whom it can also reduce the incidence of PHN. In terms of safety, no significant difference was noted in the incidence of adverse reactions between high- and low-dose groups.

Aim: To analyze the learning curve (LC) for robotic natural orifice specimen extraction surgery (NOSES) for colorectal neoplasms and evaluate safety and feasibility during the initial LC.Method: Patients who consecutively underwent robotic NOSES performed by two surgeons between March 2016 and October 2019 were analyzed retrospectively. The operation time was evaluated using the cumulative sum method to analyze the LC. The clinicopathological data before and after the completion of LC were extracted and compared to evaluate safety and feasibility.Results: In total, 99 and 66 cases were scheduled for robotic NOSES by Prof. Yao and Prof. Li, respectively. The peak points of LC were observed at the 42nd and 15th cases of Yao and Li, respectively, then operation time began to decrease. Only the operation time for Yao before the completion of LC (213.3 ± 67.0 min) was longer than that after the completion of LC (143.8 ± 33.3 min). For Yao nor for Li, other indices, such as postoperative hospital stay, intraoperative blood loss, conversion to laparotomy, incidence of anastomotic leakage, reoperation rate, and 90-day mortality rate lacked significant statistical differences(P > 0.05). In terms of feasibility, the number of lymph nodes harvested, positive resection margin rate, and total cost before and after the completion of LC had no significant statistical difference (P > 0.05).Conclusion: The cases before the completion of LC for robotic NOSES in colorectal neoplasms varied from 15 cases to 42 cases. Robotic NOSES is safe and feasible during the initial LC.

Background: PIK3CA mutations are common genomic alterations in estrogen receptor (ER)-positive breast cancers, currently, the development of selective PI3Kα (phosphatidylinositol 3-kinase α) inhibitors is ongoing. The mechanisms contributing to the anticancer activity of alpelisib in PIK3CA-mutant breast cancer cells and the mechanism of acquired resistance to alpelisib remain elusive. Methods: Drug-sensitive cell lines were exposed to alpelisib to establish alpelisib-resistant cell lines. Western blotting was used to assess changes in protein expression. Apoptosis was evaluated by flow cytometry. In vivo with mouse xenograft models and in vitro colony formation and MTS and assay were carried out to determine the growth inhibitory effects of the tested drugs. Protein half-lives were examined and proteasome inhibitors were used to estimate protein degradation. Gene knockdown was carried out using shRNA or siRNA. Results: In the present study, we report the potent induction of apoptosis by alpelisib in PIK3CA-mutant breast cancer cell lines. AKT phosphorylation suppression, AKT/Foxo3a-dependent Bim induction, and AKT/GSK-3β-dependent Mcl-1 degradation were observed. Apoptosis induced by alpelisib was attenuated by Mcl-1 (4A) overexpression or Bim suppression. Furthermore, alpelisib could not modulate Mcl-1 or Bim levels in cell lines that were resistant to alpelisib. AKT inhibitor and alpelisib combination restored the sensitivity of alpelisib-resistant cells to growth inhibition and apoptosis in vitro and in vivo. Conclusions: Therefore, modulation of Mcl-1 degradation and AKT-dependent Bim induction are crucial for mediating the resistance and sensitivity of PIK3CA-mutant breast tumor cells to alpelisib, thus making it a productive strategy for overcoming acquired resistance to alpelisib.

Oral ulcers are the most prevalent oral mucosal diseases globally, and no specific treatment schemes are currently available due to the complexity of oral ulcer diseases. Sleep deprivation increases the risk of a deterioration in oral health. Kouyanqing Granule (KYQG) has been used for decades in China to treat inflammatory diseases of the mouth and throat associated with the hyperactivity of fire due to yin deficiency syndrome. However, the mechanisms underlying the effects of KYQG in the treatment of oral ulcers are still unclear. The aims of this study were to investigate whether KYQG treatment could attenuate the symptoms of oral ulcers worsened by sleep deprivation and identify the involved metabolic pathways. First, we conducted chemical profiling of KYQG via UPLC–MS analysis. We then combined pharmacological and metabolomics approaches in a phenol-induced rat model of oral ulcers worsened by sleep deprivation. A total of 79 compounds were initially identified. Our observations showed that KYQG treatment induced a significantly higher healing rate in oral ulcers worsened by sleep deprivation. KYQG significantly reduced the levels of 5-HT and GABA in serum, and only decreased the 5-HT level in brain tissue after phenol injury followed by sleep deprivation. Moreover, KYQG administration significantly suppressed systemic inflammation by inhibiting TNF-α, IL-1β, IL-6, IL-18, and MCP-1. Immunohistochemical analysis further revealed that KYQG inhibited IL-6 expression in buccal mucosa tissues. KYQG treatment also significantly decreased the serum levels of ACTH, CORT, IgM, and 8-OHdG. Serum metabolomics analysis showed that a total of 30 metabolites showed significant differential abundances under KYQG intervention, while metabolic pathway analysis suggested that the altered metabolites were associated with the dysregulation of eight metabolic pathways. Taken together, our results indicated that KYQG attenuates the symptoms of oral ulcers worsened by sleep deprivation probably through the regulation of the neuroimmunoendocrine system, oxidative stress levels, and tryptophan metabolism. This study also provides a novel approach for addressing the increased health risks resulting from sleep deficiency using an herbal medicine formula.

Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series. A total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed. A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien–Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384, P

T-cell immunoglobulin domain and mucin domain-4 (Tim-4) is overexpressed in several tumors and is correlated with enhanced tumor development and metastasis. In this study, we investigated the physiological alterations and molecular events related to Tim-4 overexpression in a mouse model of colorectal cancer (CRC). In the current study, we observed that Tim-4 is upregulated in CRC tissues compared with neighboring normal tissues. In addition, statistical analysis revealed that elevated Tim-4 expression was strongly linked to distant metastasis, TNM stage and reduced overall survival duration in CRC patients. An orthotopic model was employed to explore the function of Tim-4 in CRC development through the implantation of Tim-4-overexpressing CT26 murine colon adenocarcinoma cells. It was observed that Tim-4 overexpression considerably enhanced CRC tumorigenesis in vivo and promoted angiogenesis through the upregulation of vascular endothelial growth factor (VEGF). In CT26 cells, Tim-4 overexpression increased the aldehyde dehydrogenase-1 (ALDH1) level, indicating an increase in cancer stem cell (CSC)-like properties. Furthermore, we determined that Tim-4 activates PI3K/AKT/mTOR signaling in CRC cells. Tim-4-overexpressing cancer cells recruited tumor-associated macrophages (TAMs), thereby accelerating cancer development. Therefore, our results strongly indicate that Tim-4 overexpression promotes proliferation and tumor stroma remodeling in CRC. PI3K/AKT/mTOR activation might be crucial in Tim-4-linked tumor development. This finding might offer a new strategy for therapeutic intervention.

Purposes: To explore the safety and feasibility of totally robotic distal gastrectomy (TRDG) for gastric cancer patients who undergo distal gastrectomy. Methods: Consecutive patients with gastric cancer who underwent TRDG (TRDG group) and robotic-assisted distal gastrectomy (RADG) (RADG group) were systematically reviewed at the Second Xiangya Hospital of Central South University from October 2015 to August 2018. Data were collected and statistically analyzed. Results: A total of 161 consecutive patients were included in this study: 84 cases in the TRDG group and 77 in the RADG group. Clinical characteristics and pathological results were mostly similar in both groups. The TRDG group had a significantly longer anastomotic time (20.6 ± 3.3 vs. 17.5 ± 4.0 min, p ˂ 0.001) but showed no difference in total operating time (167.0 ± 18.0 vs. 162.9 ± 17.6 min, p = 0.159). The postoperative hospitalization in the TRDG group was shorter than that in the RADG group (6.7 ± 1.2 vs. 7.2 ± 1.7 days, p = 0.019). Conversion rate, estimated blood loss, and postoperative complications were similar in both groups. There were no statistical differences in the estimated 2-year disease-free survival and overall survival rate between both groups. Conclusions: Although our current results need to be verified in further studies, TRDG represents a safe and feasible approach to distal gastrectomy and embodies the theory of minimally invasive surgery.

Background Situs inversus totalis (SIT) refers to an unusual condition involving reversal of abdominal and thoracic viscera, with an incidence rate of 1/5000–20,000 adults. Minimally invasive surgeries for SIT patients are technically challenging, while the surgical experience for SIT patients is quite limited. Case presentation A 61-year-old man, previously diagnosed as SIT, came to our hospital for 6 months history of hematochezia and altered bowel habit. A diagnosis of rectal cancer was made in view of colonoscopic biopsy which confirmed an irregular circumferential lump of well differentiated adenocarcinoma at 10 cm from the anal verge. The computed tomography contrast-enhanced (thorax + abdomen + pelvis) scan revealed a total transposition of abdominal and thoracic organs and an enhanced eccentric mass of rectal but with no evidence of distant metastasis. Robotic low anterior resection (LAR) plus transanal natural orifice specimen extraction (NOSE) was performed after obtaining informed consent. The procedure was performed successfully and the patient convalesced nicely without any complications. The postoperative pathological diagnosis revealed a 4x4x0.6 cm3 moderately differentiated adenocarcinoma and circumferential clearance. Conclusions Robotic LAR plus transanal NOSE for rectal cancer patients with SIT can be performed safely and may be an effective approach in contrast to open or laparoscopic approach, despite the unconventional anatomy.

A tunable dynamic vibration absorber for unbalanced rotor system which is made up of coil springs and magnetic spring is presented. The structure of the absorber is introduced and the stiffness tuning mechanism of the magnetic spring is explained. A finite element model of the rotor-absorber system was built and the influencing factors to the appearance of the absorber were studied numerically. Finally, experiments were carried out to verify the numerical results, and PID control strategy was tested. The numerical and experimental results show that the present absorber is effective for vibration suppression of an unbalanced rotor system, and the control strategy is effective.

// Kuijie Liu 1 , Hongliang Yao 1 , Sanlin Lei 1 , Li Xiong 1 , Haizhi Qi 1 , Ke Qian 1 , Jiqiang Liu 1 , Peng Wang 1 , Hua Zhao 1 1 Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China Correspondence to: Hua Zhao, email: drzhaohua2012@163.com Keywords: miR-124, p63, feedback loop, cell growth, colorectal cancer Received: May 26, 2016 Accepted: February 20, 2017 Published: March 16, 2017 ABSTRACT Among the diverse co-regulatory relationships between transcription factors (TFs) and microRNAs (miRNAs), feedback loops have received the most extensive research attention. The co-regulation of TFs and miRNAs plays an important role in colorectal cancer (CRC) growth. Here, we show that miR-124 can regulate two isoforms of p63, TAp63 and ΔNp63, via iASPP, while p63 modulates signal transducers and activators of transcription 1 (STAT1) expression by targeting miR-155. Moreover, STAT1 acts as a regulator of CRC growth by targeting miR-124. Taken together, these results reveal a feedback loop between miRNAs and TFs. This feedback loop comprises miR-124, iASPP, STAT1, miR-155, TAp63 and ΔNp63, which are essential for CRC growth. Moreover, this feedback loop is perturbed in human colon carcinomas, which suggests that the manipulation of this microRNA-TF feedback loop has therapeutic potential for CRC.

OBJECTIVE Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with metastasis in most patients at diagnosis. The molecular mechanisms associated with its high malignancy have not been fully elucidated. This study investigated the clinicopathological significances of GPC3 and KRT19 expression in PDAC. METHODS GPC3, KRT19, and CA19-9 protein expression were measured by immunohistochemistry. RESULTS GPC3 and KRT19 protein levels were overexpressed in PDAC tumors compared to normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P< 0.01). The percentage of positive GPC3 and KRT19 expression were significantly higher in PDAC patients with larger tumor size, poorly differentiated tumor, lymph node metastasis, invasion, and TNM stage III/IV disease than in patients with small tumor size, well-differentiated tumor, no lymph node metastasis and invasion, as well as TNM stage I/II stage disease (P< 0.05 or P< 0.01). Benign pancreatic lesions with positive GPC3 and KRT19 protein expression exhibited dysplasia or intraepithelial neoplasia. Kaplan-Meier survival analysis showed that PDAC patients with positive GPC3 and KRT19 expression survived significantly shorter than patients with negative GPC3 and KRT19 expression (P < 0.05 or P< 0.001). Cox multivariate analysis revealed that positive GPC3 and KRT19 expression were independent poor prognosis factors in PDAC patients. CONCLUSIONS GPC3 and KRT19 overexpression are associated with carcinogenesis, progression, and poor prognosis in patients with PDAC and a valuable biomarker for diagnosis of PDAC.

Background Oral ulcer diseases are complex inflammatory diseases caused by multi-factors, which severely impact patient quality of life. Kouyanqing Granule (KYQG) has been used to treat inflammatory diseases of the mouth and throat, including recurrent aphthous stomatitis (RAS), traumatic ulcers, oral leukoplakia and so on. However, the underlying molecular mechanisms of KYQG in treating these diseases are still unclear. We aimed to explore the possible mechanisms in KYQG for the treatment of oral ulcers. Methods An innovative network pharmacology method was established by incorporating targets searching and fishing, network analysis, and silico validation to discover the pharmacological mechanisms of action of KYQG for the treatment of oral ulcers. Then, we verified the reliability of this method by an animal experiment. Results Our data indicated that a total of 47 key targets were screened, which mainly involved in three function modules including the inhibition of inflammation, the regulation of immunological response, and the suppression of oxidative stress. The implementation of these functions relies on the complex multi-pathways network, especially TNF signaling pathway and HIF-1 signaling pathway. The results of the experimental verification indicated that KYQG significantly inhibited the serum levels of cyclooxygenase-2 (COX2), matrix metalloproteinase 9 (MMP9) and tumor necrosis factor-alpha (TNF-α) in rats with oral ulcer. Conclusion KYQG exhibited the therapeutic effects on oral ulcers probably by inhibiting inflammation, regulating immunological response, and suppressing oxidative stress through a complex multi-pathways network. Particularly, TNF signaling pathway and HIF-1 signaling pathway may play crucial roles in the protection of KYQG against oral ulcers. This work not only offers a method for understanding the functional mechanisms of KYQG for treating oral ulcer diseases from a multi-scale perspective but also may provide an efficient way for research and development of complex composition formula.

Sleep deficiency has been reported to be associated with some oral health problems. Oral ulcers are very common lesions of the oral mucosa, which severely impact patients' quality of life. However, the association between sleep deficiency and the oral ulcer remains unknown. The present study aims to explore the effects of sleep deficiency on oral ulcers.Rats were divided into normal control group (n = 30) and oral ulcer group (OU group, n = 50). Model rats with phenol-induced oral ulcers were deprived of sleep for 72 h by using the modified multiple platform technique.Sleep deprivation worsened oral ulcers and delayed healing process in rats. In addition, sleep deprivation increased the γ-aminobutyric acid (GABA, P 0.01) and 5-hydroxytryptamine (5-HT, P 0.05) levels in serum and brain, the corticotrophin (ACTH, P 0.05), corticosterone (CORT, P 0.01), immunoglobulin (Ig)M (P 0.01), tumor necrosis factor-alpha (TNF-α) (P 0.01), interleukin (IL)-1β (P 0.01), IL-6 (P 0.01), IL-8 (P 0.01), monocyte chemoattractant protein-1 (MCP-1) (P 0.01), and 8-hydroxy-deoxyguanosine (8-OHdG, P 0.01) levels in serum. Sleep deprivation also up-regulated malonaldehyde (MDA) (P 0.05), TNF-α (P 0.05), and IL-1β (P 0.01) levels in oral mucosa tissue and delayed superoxide dismutase (SOD, P 0.05) activity recovery.These data suggest that sleep deprivation impaired the oral ulcer healing in rat oral mucosa, and the mechanisms of this effect are probably related to neuro-immuno-endocrine system and oxidative stress.

This paper presents a study of a novel nonlinear damper on vibration control of rotor system with variable damping by using a smart material- shear thickening fluid (STF), whose viscosity and damping will dramatically increase with shear rate. A STF damper was self-developed and dynamic model of the STF damper-rotor system was established by using the Bouc-Wen model as mechanical model of the smart material damper. The incremental harmonic balance (IHB) method combined with the arc-length method was presented to investigate the dynamic response of rotor system with hysteresis nonlinear damping force theoretically. Experimental study of STF damper on suppressing vibration of rotor system was carried out by using a Bently rotor test rig with two STF dampers. The damping effect under different damper installation direction, vibration frequency and amplitude were investigated theoretically and experimentally. Study shows that the nonlinear damper exhibits larger damping force and fuller hysteresis characteristics, so it has better effect on resonance energy absorption compared with the traditional linear damper; and its output damping force can increase dramatically with the change of frequency and amplitude. It is verified that the unbalance vibration, especially the resonance amplitude of rotor system can be effectively suppressed by nonlinear damping of STF damper. The study shows the feasibility and advantages of using the STF damper for potential applications of adaptive or semi-active vibration control of rotating machinery.

The paper focuses on investigating the lateral inertia effect in dynamic impact testing of ultra-high performance concrete (UHPC) using a Split-Hopkinson pressure bar (SHPB), based on numerical analysis. The assigned material parameters of the UHPC are obtained by calibrating the parameters of the Karagozian and Case concrete (KCC) model in LS-DYNA software. An impact analysis model of UHPC using SHPB technology is established and calibrated by the test results. A parametric study is performed to estimate the influences of the diameter and aspect ratio (AR) of the UHPC specimen, and the strain rate on the lateral inertia effect in the SHPB testing. The numerical simulation results show that: (1) the impact analysis model can predict the test results of UHPC specimens using the SHPB technique with reasonable accuracy; (2) to reduce the lateral inertia effect, the suggested diameter and AR of the UHPC specimen is 0.9–0.95 times the diameter of the bar, and 0.35–0.45 at a 100 s−1 strain rate or lower, respectively; (3) the lateral inertia effect of UHPC in the SHPB testing is more noticeable with an increase in strain rate, and the diameter of the UHPC specimen is recommended to be 0.95 times the diameter of the bar, as the strain rate is higher than 100 s−1.

4538 Background: Gastric cancer remains the 3rd leading cancer related death worldwide due to early disease recurrence. We hypothesize that hyperthermic intraperitoneal chemotherapy (HIPEC) may effectively prevent local regional recurrence for locally advanced gastric cancer patients who received curative intent surgery. Methods: Pathology proven gastric cancer patients with clinical T3/T4NxM0 disease are eligible for the study and will be randomized to either control group, who will receive standard radical gastrectomy and D2 lymph node dissection or HIPEC group, who will receive the same surgery and HIPEC with paclitaxel x 2 within the first week after surgery. All patients will receive either XELOX or SOX adjuvant chemotherapy. The primary end point is overall survival. Results: 648 patients from 16 high volume gastric medical centers were enrolled between May, 2015 and March, 2019. 331 and 317 patients were randomized to control and HIPEC groups respectively. The median follow-up time is 12.1 months. The common grade 3/4 toxicities ( > 5%) in control and HIPEC groups are anemia 6% vs. 4.1%, intraabdominal infection 5.4% vs. 3.8%, pneumonia 9.7% vs. 9.8%, fever 10.6% vs. 11.4% and hypoalbunemia 15.1% vs. 16.7% respectively. All three perioperative death (within 30 days after surgery) occurred in control group. One patient died from duodenum stump leak which led to multiple organ failure. One patient died from anastomotic led to intraabdominal infection and shock. The 3rd death was suicide caused by severe depression. At the time of this report, the number of event has not reached for final efficacy analysis. Conclusions: It is safe to administer HIPEC to patients received radical gastrectomy with D2 lymph node dissection within one week of surgery. The primary analysis will be expected in one year. Clinical trial information: NCT02356276 .

Currently, the prevention and treatment of hypertensive crises especially when it occurs with serious adverse outcomes have led to worldwide controversy. Despite of clinical possibilities of multiple agents, clinical failures still occur frequently. Therefore, early evaluations and observations of different therapies on appropriate animals should be emphasized. In the present study, an animal model for hypertensive crises emergencies was firstly established and experimentally testified. Five-month-male spontaneously hypertensive rat was consecutively fed with 60%-Kcal fat diet for four, six, and eight weeks with body weight and blood pressure monitored every two weeks, and then followed by an acute vasoconstriction stress of 5-min ice-bath treatment in the 4-h time interval of two adrenaline injections (0.8 mg/kg). Forty-four biochemical parameters were detected, covering hepatic and renal function, blood glucose and lipid levels, myocardial enzymes and energy metabolisms, blood coagulative and anti-coagulative system, oxidative stress and anti-inflammatory cytokine, blood viscosity, and RAAS system. Six tissues including heart, brain, liver, kidney, coronary arteries, and mesenteries were removed for pathological observations with hematoxylin–eosin staining. As a result, multi-organ dysfunctions in the heart, brain, liver, kidney, vascular endothelium, and blood system were testified in the modeling rats at weeks 6 and 8. In conclusion, severe consequences of this animal model were highly similar to those in hypertensive crises emergencies, which could be further utilized in the early intervention of hypertensive crises emergencies including the possible risk factors control and efficient therapies assessment.Impact statementIn the late 90s, numerous reports predicted that 1–2% of hypertensive individuals would undergo hypertensive crises (HPC) and figures reached as high as 7% when no antihypertensive therapies were administrated. Currently, clinical failures appear frequently due to the improper or excessive medication regimen instead of the illness itself. Therefore, early evaluations and observations of HPC on appropriate animal models ahead of patients should be discussed and emphasized more widely. In the present study, an appropriate animal model for HPC emergencies was firstly established, in which the consequences of long-term high-fat diet feeding followed by an acute vasoconstriction stress on the spontaneously hypertensive rats were experimentally testified. The proposed model would have a wide application prospects in early intervention of HPC emergencies including the controls of possible risk factors and assessments of efficient therapies.

We propose a novel method with an ultrasonically excited structure as a vibration limiter to control the vibration of rotor systems. The friction between the rotor and the limiter is significantly reduced by ultrasonic lubrication, thereby preventing the occurrence of rubbing-induced thermal bowing, which is commonly observed in traditional vibration limiters. In our study, the friction reduction mechanism of the ultrasonically excited vibration limiter was first examined based on tribology theory and Hertz contact theory. The vibration control effects and the alleviation of thermal bowing were then investigated by numerical simulation. Finally, vibration control experiments were performed on a Bentley test rig with the ultrasonically excited vibration limiter. The consistency between theoretical and experimental results confirmed the effectiveness of the proposed method.

Blade-rotor systems frequently encounter the problem of blade-to-case rubbing, which affects their safety and stability. Numerical simulation can be used to predict the steady-state response of these systems. However, such simulation is frequently computationally expensive because of the high dimensions of the dynamic model of a blade-rotor system. To overcome this problem, a new method that combines the receptance-based dimension-reduction approach with the incremental harmonic balance (IHB) method is presented in this study. First, a dynamic model of a blade-rotor system is developed using the finite element method, and the number of dimensions of the model is reduced by the receptance method. Subsequently, the steady-state response is obtained by the improved IHB method to conveniently manage the large number of super-harmonic components of the local rubbing system. Finally, the precision and efficiency of the proposed method is verified by comparing its results with those obtained by the Newmark-β method. The proposed method is found to be efficient in analyzing local rubbing blade-rotor systems with high dimensions, local nonlinearities, and rich super-harmonics.

Since traditional Chinese medicine (TCM) is a complex mixture of multiple components, the application of methodologies for evaluating single-components Western medicine in TCM studies may have certain limitations. Appropriate strategies that recognize the integrality of TCM and connect to TCM theories remain to be developed. Here we use multiple unique approaches to study the scientific connotation of a TCM formula Dan-hong injection (DHI) without undermining its prescription integrity. The blood circulation improving and healing promoting effects of DHI were assessed by a qi stagnation blood stasis rat model and a mouse model of laser irradiation induced cerebral microvascular thrombosis. By UFLC-PDA-Triple Q-TOF-MS/MS and relevance analysis between chemical characters and biological effects, 82 chemical constituents and nine core components, whose blood circulation promoting effects were found comparable to that of whole DHI, were successfully identified. What’s more, the rationality of DHI prescription compatibility could be reflected not only in the maximum efficacy of the original ratio, but also in the interactions of compounds from different ingredient herbs, such as complementary activities and facilitating tissues distribution. This study provides scientific evidences in explanation of the clinical benefits of DHI, and also gives a good demonstration for the comprehensive evaluation of other TCM.

Latent variables often play an important role in improving the quality of the lea rned Bayesian networks and understanding the nature of interactions in the model. The dimensionality of latent variables h as significant effect on the representation quality and complexity of the model. The maximum possible dimensionality of a latent variable is a Cartesian product of the state space of its Markov blanket variables. In order to obtain the dimensionality of the latent variable, we need to calculate the network score for every possible dimensionality of the latent variable, and the calculations of this task a re substantial. Besides, we do not know the data and condition probability table of the latent variable which makes the task difficult. I n this paper, we propose a novel method to learn the dimensionality of the latent variable when the network structure is known. Firstly, we use the latent variable and its Markov blanket variables to extract a local network from original network. Then, we score the local network instead of the original network which reduces the running time of the task. Secondly, we utilize a state-clustering m ethod to score the network for each dimensionality of the latent variable, where a simulated annealing strategy is introduced to avo id local optimum. Finally, based on the above stages, we choose the dimensionality of the latent variable which can make the network get the best score. This new method has excellent learning performance and can deal with complex networks. Extensive experiments validate the effectiveness of our method against other algorithms.

To suppress the vibration of a rotor system, a vibration absorber combining negative stiffness with positive stiffness together is proposed in this paper. Firstly, the negative stiffness producing mechanism using ring type permanent magnets is presented and the characteristics of the negative stiffness are analyzed. Then, the structure of the absorber is proposed; the principles and nonlinear dynamic characteristics of the absorber-rotor system are studied numerically. Finally, experiments are carried out to verify the numerical conclusions. The results show that the proposed vibration absorber is effective to suppress the vibration of the rotor system, the nonlinearity of the negatives stiffness affects the vibration suppression effect little, and the negative stiffness can broaden the effective vibration control frequency range of the absorber.

A detection strategy for the rubbing locations in a rotor system based on the super-harmonic responses is developed. Firstly, the dy- namics of the rotor system with rubbing fault is investigated based on the theory of nonlinear output frequency response function. Then, the relationship between the super-harmonic components of the vibrations of fault rotor system and the receptance matrix of the fault-free rotor system is established. The detection method is then set up for rubbing location along the rotor. With this approach, the rubbing loca- tion can be determined by using super-harmonic responses measured at only two nodes under one case of operating speed. Finally, nu- merical simulations and experimental observations are carried out to verify the efficiency of the proposed detection method for rubbing location in a rotor system.

This paper presents an experimental study of the dynamic performance of a self-developed shear thickening fluid (STF) damper and its mechanical model was proposed by nonlinear fitting. First, STF samples with different mass fraction and dispersion medium were fabricated by nano fumed silica and polyethylene glycol, and its rheological properties were investigated by a rheometer. Second, a smart STF damper was developed and manufactured. Its dynamic properties were experimentally investigated by establishing a vibration test bench, and results indicated that the STF damper can output variable damping force by controlling the loading frequency, loading amplitude and fluid gap. Third, the Bouc–Wen model was proposed to address the dynamic properties of STF damper, and mechanical model analysis was carried out by comparing several fitting functions. It verified that the Bouc–Wen hysteresis model can be better used to describe the nonlinear stiffness, nonlinear damping and rate-dependence characteristics of the STF damper. All these investigations can offer an effective guidance for further theoretical and application study of the smart STF damper in energy dissipation fields.

As intervened edges are difficult to be determined when intervention method is used for learning the causal relationships of probability model, an active learning method (Structural Intervention Learning of Sensitivity Analysis –SILSA Algorithm) is proposed. SILSA algorithm obtains original network structure based on k2 algorithm, then uses junction tree algorithm to decompose original networks structure and takes local intervention learning in every clique of junction tree, which can decrease the searching extension of intervened edges. Causal Bayesian networks can be learned by Edge-based Interventions when intervened edges are selected. In order to get appropriate intervened edge, sensitivity analysis is used to select the important edge in SILSA algorithm. The efficient of selecting intervened edge is improved. Experimental results show that the effectiveness and performance of SILSA algorithm are better than intervened edges with choosing randomly and passive learning method.

The HFE gene has been suggested to play an important role in the pathogenesis of colorectal cancer. However, the results have been conflicting. In this study, we performed a meta-analysis to clarify the association of HFE gene C282Y variant with colorectal cancer. PubMed and Embase were retrieved to identify the potential literature. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. A total of eight papers including nine studies (7,588 colorectal cancer cases and 81,571 controls) for HFE gene C282Y variant were included in the meta-analysis. The result indicated that HFE gene C282Y variant was significantly associated with colorectal cancer under recessive model (OR = 2.00, 95 % CI = 1.32-3.04), with no evidence of between-study heterogeneity (I (2) = 0.2 %, p = 0.432). Further subgroup analysis by number of cases suggested the effect was significant in studies with more than 500 cases (OR = 2.51, 95 % CI = 1.58-3.98, I (2) = 0.0 %, p = 0.921), but not in studies with less than 500 cases (OR = 0.75, 95 % CI = 0.28-1.97, I (2) = 0.0 %, p = 0.622). The current meta-analysis supported the positive association of HFE gene C282Y variant with colorectal cancer. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

To investigate the association between p53 codon 72 polymorphisms and gastric cancer risk, a meta-analysis published in 2007 was updated with new data. Relevant literature was retrieved by searching PubMed and statistical analysis conducted using Review Manager software. Twenty-eight case–control studies were included in this meta-analysis, with 6,859 cases and 9,277 controls. The pooled results for all included studies showed that patients with gastric cancer had a borderline lower frequency of the Arg/Arg phenotype (odds ratio (OR) = 0.91, 95 % CI = 0.83–1.00, p = 0.04). When stratified for race, the difference in Arg/Arg frequency was significant among Asians (OR = 0.87, 95 % CI = 0.78–0.97, p = 0.01). On stratifying the various studies we found that, among Asians: (i) patients with cardial gastric cancer had a significantly higher frequency of the Pro/Pro genotype (OR = 1.35, 95 % CI = 1.03–1.77, p = 0.04) than those with non-cardial gastric cancer; (ii) patients with advanced (stage III/IV) gastric cancer had a significantly higher frequency of Arg/Arg (OR = 1.30, 95 % CI = 1.06–1.61, p = 0.01) than those with early (stage I/II) cancer; and (iii) patients with metastasis had a significantly higher frequency of Pro/Pro (OR = 3.31, 95 % CI = 1.31–8.41) than those without metastasis. Our study suggests that, among Asians, the p53 codon 72 Arg/Arg genotype is associated with a modestly decreased risk of gastric cancer, and that this difference in genotype distribution may be associated with cancer stage, location, differentiation and metastasis.

Cyclin D1 is aberrantly expressed in many types of cancers, including breast cancer. High levels of cyclin D1b, the truncated isoform of cyclin D1, have been reported to be associated with a poor prognosis for breast cancer patients. In the present study, we used siRNA to target cyclin D1b overexpression and assessed its ability to suppress breast cancer growth in nude mice. Cyclin D1b siRNA effectively inhibited overexpression of cyclin D1b. Depletion of cyclin D1b promoted apoptosis of cyclin D1b-overexpressing cells and blocked their proliferation and transformation phenotypes. Notably, cyclin D1b overexpression is correlated with triple-negative basal-like breast cancers, which lack specific therapeutic targets. Administration of cyclin D1b siRNA inhibited breast tumor growth in nude mice and cyclin D1b siRNA synergistically enhanced the cell killing effects of doxorubicin in cell culture, with this combination significantly suppressing tumor growth in the mouse model. In conclusion, the results indicate that cyclin D1b, which is overexpressed in breast cancer, may serve as a novel and effective therapeutic target. More importantly, the present study clearly demonstrated a very promising therapeutic potential for cyclin D1b siRNA in the treatment of cyclin D1b-overexpressing breast cancers, including the very malignant triple-negative breast cancers. (Cancer Sci 2011; 102: 1537‐1544)

Learning a Bayesian network classifier from data is an active research topic in data mining. The key problem for constructing a Bayesian network classifier is to learn an accurate Bayesian network structure which is a difficult task. The K2 algorithm, as one of the most efficient Bayesian network learning methods can deal with this difficult task. However, K2 requires a variable ordering in advance. Existing methods for establishing this ordering neglect information of the variables selected. To address this problem, in this paper, we propose an L1 regularized Bayesian network classifier (L1-BNC). L1-BNC defines a variable ordering by the LARS (Least Angle Regression) method, and then with this ordering it uses K2 to construct a Bayesian network classifier. In comparison with seven Bayesian network classifiers, L1-BNC outperforms those classifiers on most datasets Refereed/Peer-reviewed

Associative classifiers have received considerable attention due to their easy to understand models and promising performance. However, with a high dimensional dataset, associative classifiers inevitably face two challenges: (1) how to extract a minimal set of strong predictive rules from an explosive number of generated association rules; and (2) how to deal with the highly sensitive choice of the minimal support threshold. In order to address these two challenges, we introduce causality into associative classification, and propose a new framework of causal associative classification. In this framework, we use causal Bayesian networks to bridge irrelevant and redundant features with irrelevant and redundant rules in associative classification. Without loss of prediction power, the feature space involved with the antecedent of a classification rule is reduced to the space of the direct causes, direct effects, and direct causes of the direct effects, a.k.a. the Markov blanket, of the consequent of the rule in causal Bayesian networks. The proposed framework is instantiated via baseline classifiers using emerging patterns. Experimental results show that our framework significantly reduces the model complexity while outperforming the other state-of-the-art algorithms. Refereed/Peer-reviewed

There exist different vibration patterns when a rotor system runs up and down through its critical speed, in one of them, is the interesting phenomenon called frequency capture. Based on a specially designed rotor system which is supported by elastic supports, the resonance vibrations of frequency capture and pass-through are discussed both in time and frequency domains. The nonlinear dynamical equations are described in details for the system. The vibrations of capture, when the rotating speed is locked, are compared with normal pass-through by numerical simulations and experiments. Also the instantaneous displacement trajectories, 3D FFT waterfalls and phase space portraits are calculated and demonstrated for the above two resonance vibrations. In addition, the periodical motions are discussed for capture motions using both amplitude spectra and pseudo-Poincare mappings of simulation and experiment data.

A dynamical model of a four-span rotor system with multi-discs is built up, considering nonlinear oil-film forces, based on a 300 thousand kilowatt turbine-generator test rig. The bifurcation features of the system are studied with numerical integration technique. It is revealed that the proposed multi-span rotor model can express the fundamental dynamic characteristics of such a nonlinear system. Some bifurcations and chaotic motions may occur according to the calculated results. In coupling analyses, each rotor span also affects dynamically on the other, and the second span affects on the whole system in a serious way.Copyright © 2006 by ASME

Lile Wu, Zhongqiang Zhang, Hongliang Yao, Kuijie Liu, Yu Wen, Li Xiong Department of General Surgery, Second Xiangya Hospital of Central South University, Changsha, People's Republic of China Background: Primary and secondary resistance to imatinib, a selective receptor tyrosine kinase inhibitor (TKI), is a serious clinical problem in the control of advanced gastrointestinal stromal tumors (GIST). Here we report on a meta-analysis we performed to evaluate the efficacy of second-generation TKIs in the treatment of patients with imatinib-resistant GIST.Methods: Randomized controlled trials evaluating the clinical efficacy of second-generation TKIs were identified by searching PubMed and EMBASE from 2000 to February 2014. Outcomes subjected to analysis were progression-free survival and overall survival. Statistical analyses were performed using Review Manager version 5.1.0 (Cochrane Collaboration, Oxford, UK). Weighted hazard ratios (HR) with 95% confidence intervals (CIs) were calculated for the outcomes. Fixed-effects or random-effects models were used, depending on the degree of heterogeneity across the selected studies.Results: Three randomized controlled trials were selected for meta-analysis. Among imatinib-resistant or imatinib-intolerant patients, 541 received second-generation TKIs (sunitinib, nilotinib, or regorafenib) and 267 controls received placebo or best supportive care. Progression-free survival was significantly improved in the TKI-treated group (HR 0.38; 95% CI 0.24–0.59; P

Background: Photodynamic therapy(PDT) is a non-invasive treatment modality for selective destruction of cancer and other diseases.PDT has several potential advantages over surgery and radiotherapy, It requires three elements: a photosensitizer(PS), light and oxygen, Nanoparticles are efficient means to deliver photosensitizers for photodynamic therapy. However, it is largely unknown if Photosan-II can be efficiently delivered by hollow silica nanoparticles (HSNP). We investigated the effects and functional mechanisms of photodynamic therapy (PDT) mediated by a nanocrystallized photosensitizer (Photosan-loaded hollow silica nanoparticles) on the human colon carcinoma cell line HT29. Methods: HT29 cells were treated with nanocrystallized photosensitizer-mediated PDT, and the rate of cell survival and effects on apoptosis or cell necrosis were investigated with tetrazolium (MTT) assays and flow cytometry, respectively. We quantified the variation of Bcl-2 and Bax expression in nude mice transplanted with HT29 cells before and after PDT with quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: MTT assays revealed that cell growth was inhibited in an obvious manner, and there was a dramatic decline in the rate of survival (P Conclusion: PDT mediated by Photosan-loaded hollow silica nanoparticles inhibits the growth of human colon carcinoma HT29 cells with predominant induction of apoptosis. It can also downregulate the Bcl-2/Bax expression ratio, thereby inducing apoptosis in HT29 cells.