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Lu Zhu,1,&ast; Jing Li,1,&ast; Zhao-Qin Wang,1,2,&ast; Yun-Jia Gu,1 Guo-Na Li,3 Wen-Jia Wang,1 Guang-Bin Pen,1 Qi Li,1 Meng-Die Wu,1 Hui-Rong Liu,1,2 Yan Huang,1,2 Lu-Yi Wu1 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3School of Acupuncture, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu-Yi Wu, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai City, 200437, People’s Republic of China, Email luyitcm@163.com Yan Huang, Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, No. 650 Wanping South Road, Xuhui District, Shanghai City, 200030, People’s Republic of China, Email huangyan@shutcm.edu.cnObjective: Moderate-to-severe pain is the most common clinical symptom in patients with hepatocellular carcinoma (HCC).This trial aimed to analyze the clinical efficacy of Transcutaneous electrical acupoint stimulation (TEAS) in patients of HCC with severe pain and provide a reliable reference for optimizing the clinical diagnostic and therapeutic strategies of HCC.Methods: A total of 104 eligible patients were randomly allocated to experimental and control groups in a ratio of 1:1.The treatment was administered for 1 week continuously. Patients in both groups were followed up 1 week after the end of the treatment.The primary outcome measure was the Numerical Rating Scale (NRS) score, whereas the secondary outcome measures included Brief Pain Inventory BPI-Q3, Q4, Q5 scores, analgesic dose, frequency of opioid-induced gastrointestinal side effects, Karnofsky Performance Status (KPS), Quality of Life Scale - Liver Cancer (QOL-LC), and Brief Fatigue Inventory (BFI) scores.Results: The NRS scores of experimental group was significantly lower after treatment and at the follow-up than baseline (average P< 0.01), there were also statistical differences between the groups at the above time points (average P< 0.01). BPI-Q3, -Q4, and -Q5 scores in the experimental group were decreased after treatment when compared with those before treatment (average P< 0.01). Furthermore, there were significant improvements of gastrointestinal side effects, KPS, QOL-LC and BPI in the experimental group after treatment, and the above results were statistically significant compared to the control group.Conclusion: 7-day TEAS treatment can significantly enhance the analgesic effect and maintain for the following week, also reduce the incidence of gastrointestinal side effects caused by opioids, and improve the quality of life of patients with moderate-to-severe HCC-related pain, which has reliable safety and certain clinical promotion value.Keywords: hepatocellular carcinoma pain, transcutaneous electrical acupoint stimulation, cancer pain, randomized controlled trial

Wei Wang,&ast; Fei Teng,&ast; Shi Bu, Wei Xu, Qing-Chun Cai, Yue-Quan Jiang, Zhi-Qiang Wang Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing, 400030, China&ast;These authors contributed equally to this workCorrespondence: Yue-Quan Jiang; Zhi-Qiang Wang, Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, No. 181 of Hanyu Road, Shapingba District, Chongqing, 400030, China, Tel +86 13708335256 ; +86 15215023098, Email jiangyuequanjyq1@126.com; wangzhiqiangwzq9@126.comObjective: This study aimed to design a nomogram survival prediction by means of the figures retrieved from the Surveillance, Epidemiology, and End Results (SEER) source bank, and to predict the overall survival (OS) of patients with stage IIA non-small cell lung cancer (NSCLC) after surgery.Methods: Data for 4511 patients who had been diagnosed with postoperative stage IIA NSCLC were collected from the SEER databank, while information on 528 patients was acquired from the Chongqing University Cancer Hospital for the external validation cohort. The independent risk factors that affected the prognosis were identified using a multivariate Cox proportional hazards regression model (also used to conduct a nomogram). A survival analysis between the low- and the high-risk groups was performed using the Kaplan–Meier method. Furthermore, a subgroup analysis was conducted of the two groups using the Kaplan–Meier method to determine whether the patients had received adjuvant chemotherapy.Results: The following five variables were integrated into the nomogram: sex (female: HR 1.73, 95% CI 0.64– 0.83), age (≥ 60: HR 1.61, 95% CI 1.39– 1.87), differentiation grade (grade II: HR 2.19, 95% CI 1.66– 2.88; grade III: HR 2.65, 95% CI 2.00– 3.51; grade IV: HR 3.17, 95% CI 1.99– 5.03), surgery (lobectomy: HR 0.72, 95% CI 0.59– 0.86), and lymph node resection (> 12: HR 0.82, 95% CI 0.70– 0.96). Furthermore, the patients selected were categorized into high- and low-risk groups. The OS rate was significantly lower in the high-risk group than in the low-risk group (P < 0.001). Finally, adjuvant chemotherapy was highly correlated with OS in the high-risk set (P = 0.035); however, adjuvant chemotherapy was not related to OS in the low-risk set.Conclusion: A nomogram was created as a reliable, convenient scheme that could predict OS, and it was determined that the high-risk feature patients identified by the nomogram gained benefits from adjuvant chemotherapy.Keywords: nomogram, stage IIA non-small cell lung cancer, adjuvant chemotherapy, OS prediction

Yong Liu,1 Yan-Ping Zhu,2 Ming-Zhi Cai,1 Bin Ke,1 Bin Li,1 Ning Liu,1 Qiang Xue,1 Hong-Jie Zhan,1 Jing-Yu Deng,1 Li Zhang,1 Yan-Peng Hao,2 Zhi-Qiang Wang,2 Li Wang,2 Han Liang1 1Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of China; 2Nanjing Personal Oncology Biological Technology Co. Ltd., Nanjing 211100, Jiangsu, People’s Republic of ChinaCorrespondence: Han LiangDepartment of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, Tianjin 300060, People’s Republic of ChinaTel +86 22 2334 0123-1061Fax +86 22 2334 0123Email liangh95247@163.comObjective: The current study aims to explore the establishment of the patient-derived tumor xenograft (PDTX) model.Materials and Methods: Twenty patients with gastric cancer, 10 males and 10 females, were enrolled in the current study. Firstly, the volume, invasion and metastasis of the xenografts were observed. Subsequently, the correlation between tumor tissues of the PDTX mouse model and the patients’ primary tumor tissues was evaluated by pathological H&E staining and immunohistochemistry.Results: The results showed that the PDTX models corresponding to 15 of the 20 patients were successfully established, and the success rate of PDTX model establishment was 75%. Furthermore, the PDTX models maintained the differentiation degree, morphological characteristics and structural characteristics of tumor cells.Conclusion: A PDTX model can be used as a substitute for cancer patients in clinical practice and may be suitable for clinical pharmacodynamic screening and new drug development.Keywords: gastric tumor, PDTX, xenotransplantation model

JY Ren,* DM Lin,* CB Wang, YL Yang, ZQ Wang, BQ Cui, J Ma Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: J MaDepartment of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, No.2 Anzhen Road, Chaoyang District, Beijing 100029, People’s Republic of ChinaTel +8613370103571Email majuntongxun@sohu.comBackground/Aims: To investigate the postconditioning protective effect of penehyclidine hydrochloride (PHC) against anoxia/reoxygenation (A/R) injury in H9c2 cells along with the involved mechanism and timing effect.Methods: We divided H9c2 cells into 7 groups: control group, A/R group and PHC+A/R groups at 0 min, 5 mins, 10 mins, 20 mins, 30 mins, respectively (treated with 0.1 μm/L PHC at 0 min, 5 mins, 10 mins, 20 mins, 30 mins after the reoxygenation procedure began). Cell apoptosis, oxidative stress, intracellular Ca2+ concentration, mitochondrial membrane potential and mitochondrial permeability transition pore (MPTP) opening were explored. Bcl-2, Bax, Cyt C, caspase-3 and caspase-9 levels were measured.Results: A/R significantly increased both cell injury and cell apoptosis. PHC showed postconditioning protective effect by attenuating superoxide production, decreasing Ca2+ overload, restraining MPTP activities, restoring mitochondrial membrane potential, regulating cell apoptosis proteins and modulation of mitochondrial pathway. Earlier administration of PHC offered greater postconditioning protective effect.Conclusion: H9c2 cells were protected by PHC from A/R injury regardless of timing of PHC administration (0 min, 5 mins, 10 mins, 20 mins, 30 mins). However, earlier administration of PHC resulted in better PHC postconditioning protection.Keywords: penehyclidine hydrochloride, PHC, anoxia/reoxygenation injury, A/R injury, cell apoptosis, oxidative stress, mitochondrial pathway

Lu-Ping Yang,1 Zi-Xian Wang,1 Ming-Ming He,1 Hao-Xiang Wu,1 Shu-Qiang Yuan,2 Wei Wang,2 Ying Jin,1 Chao Ren,1 Zhi-Qiang Wang,1 Feng-Hua Wang,1 Yu-Hong Li,1 Feng Wang,1 Rui-Hua Xu11Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of China; 2Department of Gastric and Pancreatic Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of ChinaBackground: The benefit of palliative gastrectomy for patients with metastatic gastric cancer (mGC) is controversial, and suitable candidates for surgery and treatment strategies remain unclear. The present study aimed to investigate the efficacy of palliative gastrectomy plus chemotherapy among patients with mGC and to identify the potential patients for such treatment using real-world data.Methods: A dataset of 236 patients with mGC diagnosed at the Sun Yat-Sen University Cancer Center from January 1, 2006 to December 31, 2012 were analyzed retrospectively. The cohort comprised 80 patients who had palliative gastrectomy plus chemotherapy (SC) and 156 patients who had chemotherapy only (CO). Propensity score matching (PSM) was employed to minimize the influence of confounders.Results: The median overall survival of the SC group was significantly better than that of the CO group (Before PSM: 17.0 months vs 12.0 months, P=0.038; after PSM: 17.0 months vs 13.0 months, P=0.017). In the multivariate analysis, SC (Before PSM: hazard ratio (HR) =0.68, P=0.023; after PSM: HR =0.64, P=0.021) was favored for better survival after adjustment for sex, age, year of diagnosis, primary tumor location, and tumor grade. Total gastrectomy (P=0.026) was associated with worse survival for the SC group. The significant survival advantage of SC over CO was retained in patients with single organ metastasis (P=0.016), peritoneal seedings (P=0.039), and those receiving taxane-based chemotherapy (P=0.011).Conclusion: SC could improve the overall survival of patients with mGC as compared with CO. The chemotherapy regimen and type of resection were proven to influence efficacy. Patients who received taxane-based regimens might be suitable for palliative gastrectomy.Keywords: first-line chemotherapy, metastatic gastric cancer, palliative gastrectomy, propensity score matching, survival

Yuan Ding,1,* Wei Cui,2,* Dan Sun,1 Gui-Ling Wang,1 Yu Hei,1 Shuai Meng,1 Jian-Hua Chen,3 Ying Xie,1 Zhi-Qiang Wang4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, 2School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 3School of Medicine, Jianghan University, Wuhan, People’s Republic of China; 4Department of Chemistry and Biochemistry, Kent State University Geauga, Burton, OH, USA *These authors contributed equally to this work Abstract: In vivo evaluation of drug delivery vectors is essential for clinical translation. In BALB/c nude mice bearing human breast cancer tumors, we investigated the biocompatibility, pharmacokinetics, and pharmacodynamics of doxorubicin (DOX)-loaded novel cell-penetrating peptide (CPP)-modified pH-sensitive liposomes (CPPL) (referred to as CPPL(DOX)) with an optimal CPP density of 4%. In CPPL, a polyethylene glycol (PEG) derivative formed by conjugating PEG with stearate via acid-degradable hydrazone bond (PEG2000-Hz-stearate) was inserted into the surface of liposomes, and CPP was directly attached to liposome surfaces via coupling with stearate to simultaneously achieve long circulation time in blood and improve the selectivity and efficacy of CPP for tumor targeting. Compared to PEGylated liposomes, CPPL enhanced DOX accumulation in tumors up to 1.9-fold (p

Yuan Ding,1,* Dan Sun,1,* Gui-Ling Wang,1 Hong-Ge Yang,1 Hai-Feng Xu,1 Jian-Hua Chen,2 Ying Xie,1,3 Zhi-Qiang Wang4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 2School of Medicine, Jianghan University, Wuhan, 3State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People’s Republic of China; 4Department of Chemistry and Biochemistry, Kent State University Geauga, Burton, OH, USA *These authors contributed equally to this work Abstract: Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future. Keywords: long circulation, pharmacokinetics, lysosome escape, nanocarrier, pH-sensitive liposomes

Kai Liu,1 Zhi-qi Wang,2 Shi-jiang Wang,3 Ping Liu,4 Yue-hong Qin,5 Yan Ma,3 Xiao-Chen Li,6 Zhi-Jun Huo7 1Department of Gastrointestinal Surgery, 2Department of Head and Neck Surgery, 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute, 4Department of Pharmacy, 5Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, 6Department of Internal Medicine, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, 7Department of Breast Disease Center, Shandong Cancer Hospital and Institute, Jinan, People’s Republic of China Abstract: Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU) is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA)-conjugated silica nanoparticles (SiNPs) to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP) was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage) compared with only 20% for 5-FU/silica nanoparticles (SNP)-treated group. The HA-conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer therapy. Keywords: colon cancer, 5-fluorouracil, nanoparticles, hyaluronic acid, apoptosis

Xiao-zhen Zhao,1,* Yu Liu,1,* Li-juan Zhou,1,* Zhong-qi Wang,1 Zhong-hua Wu,2 Xiao-yuan Yang31Department of Tumor, Longhua Hospital, 2Center of Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA*These authors contributed equally to this workBackground/aim: Estrogen is reported to promote the occurrence and development of several human cancers. Increasing evidence shows that most human lung tumors exert estrogen receptor expression. In the present study, we investigated the underlying mechanism of estrogen effect in lung cancer through estrogen receptor-epithelial–mesechymal-transition signaling pathways for the first time.Materials and methods: A total of 36 inbred C57BL/6 mice (18 male and 18 female) were injected subcutaneously with human lung adenocarcinoma cell line, Lewis. After the lung tumor model was established, mice with lung adenocarcinoma were randomly divided into three groups for each sex (n=6), such as vehicle group, estrogen group, and estrogen plus tamoxifen group. The six groups of mice were sacrificed after 21 days of drug treatment. Tumor tissue was stripped and weighed, and tumor inhibition rate was calculated based on average tumor weight. Protein and messenger RNA (mRNA) expressions of estrogen receptor α (ERα), estrogen receptor β (ERβ), phosphatidylinositol 3'-kinase (PI3K), AKT, E-cadherin, and vimentin were detected in both tumor tissue and lung tissue by using immunohistochemistry and real-time reverse transcription-polymerase chain reaction.Results: 1) For male mice: in the estrogen group, estrogen treatment significantly increased ERα protein and mRNA expressions in tumor tissue and protein expression of PI3K, AKT, and vimentin in both tumor tissue and lung tissue compared with the vehicle-treated group. Besides, mRNA expression of E-cadherin was significantly reduced in estrogen-treated tumor tissues than that in vehicle-treated tissues. In the estrogen plus tamoxifen group, protein and mRNA expressions of ERα and AKT were dramatically reduced by tamoxifen treatment in tumor tissue compared with the estrogen group; mRNA expression of E-cadherin was increased in tumor tissue; protein expression of vimentin and PI3K were downregulated in tumor tissue; protein expression of E-cadherin increased in lung tissue; protein expression of ERα and PI3K were downregulated in lung tissue compared with the estrogen group. 2) For female mice: in the estrogen group, estrogen treatment significantly increased mRNA expression of ERβ and PI3K, and protein expression of ERβ, PI3K, AKT, and vimentin in both tumor tissue and lung tissue compared with the vehicle-treated group. mRNA expression of E-cadherin was downregulated in tumor tissue, and mRNA expression of AKT was increased in lung tissues compared with the vehicle-treated group. In the estrogen plus tamoxifen group, tamoxifen treatment dramatically reduced protein expression of ERα, ERβ, AKT, and vimentin but significantly increased protein expression of E-cadherin in tumor tissues and lung tissue compared with the estrogen group. mRNA expression of ERβ, PI3K, and AKT was dramatically reduced by tamoxifen treatment in lung tissues compared with the estrogen group.Conclusion: Estrogen promoted lung adenocarcinoma cell metastasis by inducing lung epithelial mesenchymal cells and reducing intercellular adhesion force through PI3K/AKT signaling pathway.Keywords: Lewis lung carcinoma, estrogen, estrogen receptor, epithelial–mesenchymal transition

Zhong Q Wang,1,2 Yongmei Yu,1,2 Xian H Zhang,1,2 Z Elizabeth Floyd,3 Anik Boudreau,2 Kun Lian,4 William T Cefalu1,21Nutrition and Diabetes Research Laboratory, 2Botanical Research Center, 3Ubiquitin Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA; 4The Center for Energy and Environmental Studies, Southern University, Baton Rouge, LA, USAAim: To compare the effects of dietary fibers on hepatic cellular signaling in mice.Methods: Mice were randomly divided into four groups (n = 9/group): high-fat diet (HFD) control, cellulose, psyllium, and sugarcane fiber (SCF) groups. All mice were fed a HFD with or without 10% dietary fiber (w/w) for 12 weeks. Body weight, food intake, fasting glucose, and fasting insulin levels were measured. At the end of the study, hepatic fibroblast growth factor (FGF) 21, AMP-activated protein kinase (AMPK) and insulin signaling protein content were determined.Results: Hepatic FGF21 content was significantly lowered, but βKlotho, fibroblast growth factor receptor 1, fibroblast growth factor receptor 3, and peroxisome proliferator-activated receptor alpha proteins were significantly increased in the SCF group compared with those in the HFD group (P < 0.01). SCF supplementation also significantly enhanced insulin and AMPK signaling, as well as decreased hepatic triglyceride and cholesterol in comparison with the HFD mice. The study has shown that dietary fiber, especially SCF, significantly attenuates lipid accumulation in the liver by enhancing hepatic FGF21, insulin, and AMPK signaling in mice fed a HFD.Conclusion: This study suggests that the modulation of gastrointestinal factors by dietary fibers may play a key role in both enhancing hepatic multiple cellular signaling and reducing lipid accumulation.Keywords: dietary fiber, FGF21, insulin signaling, AMPK, GLP-1, PI 3K

Magnetic topological phases of quantum matter are an emerging frontier in physics and materials science, of which kagome magnets appear as a highly promising platform. Here, we explore magnetic correlations in the recently identified topological kagome system TbMn6Sn6 using muon spin rotation, combined with local field analysis and neutron diffraction. Our studies identify an out-of-plane ferrimagnetic structure with slow magnetic fluctuations which exhibit a critical slowing down below TC1* ≃ 120 K and finally freeze into static patches with ideal out-of-plane order below TC1 ≃ 20 K. We further show that hydrostatic pressure of 2.1 GPa stabilises the static out-of-plane topological ferrimagnetic ground state in the whole volume of the sample. Therefore the exciting perspective arises of a magnetically-induced topological system whose magnetism can be controlled through external parameters. The present results will stimulate theoretical investigations to obtain a microscopic understanding of the relation between the low-temperature volume-wise magnetic evolution of the static c-axis ferrimagnetic patches and the topological electronic properties in TbMn6Sn6.

We report muon spin rotation (μSR) experiments together with first-principles calculations on microscopic properties of superconductivity in the kagome superconductor LaRu3Si2 with Tc≃ 7K. Below Tc, μSR reveals type-II superconductivity with a single s-wave gap, which is robust against hydrostatic pressure up to 2 GPa. We find that the calculated normal state band structure features a kagome flat band, and Dirac as well as van Hove points formed by the Ru-dz2 orbitals near the Fermi level. We also find that electron-phonon coupling alone can only reproduce a small fraction of Tc from calculations, which suggests other factors in enhancing Tc such as the correlation effect from the kagome flat band, the van Hove point on the kagome lattice, and the high density of states from narrow kagome bands. Our experiments and calculations taken together point to nodeless moderate coupling kagome superconductivity in LaRu3Si2.

Aim: Perineal wound complications after abdominoperineal resection (APR) have become a major clinical challenge. Myocutaneous flap closure has been proposed in place of primary closure to improve wound healing. We conducted this comprehensive meta‐analysis to evaluate the current scientific evidence of primary closure vs myocutaneous flap closure of perineal defects following APR for colorectal disease. Methods: We systematically searched the MEDLINE, Embase, PubMed, Web of Science and Cochrane Library databases to identify all relevant studies. After data extraction from the included studies, meta‐analysis was performed to compare perioperative outcomes of primary closure and myocutaneous flap closure. Results: Eighteen studies with a total of 17 913 patients (16 346 primary closure vs 1567 myocutaneous flap closure) were included. We found that primary closure was significantly associated with higher total perineal wound complications (P = 0.007), major perineal wound complications (P < 0.001) and perineal wound infection (P = 0.001). On the other hand, myocutaneous flap closure takes more operation time (P < 0.001) and increases the risk of perineal wound dehiscence (P = 0.01), deep surgical site infection (P < 0.001), enterocutaneous fistulas (P = 0.03) and return to the operating room (P = 0.0005). There were no significant differences between the two groups for other outcomes. Conclusions: This is the first systematic review with meta‐analysis comparing primary closure with myocutaneous flap closure of perineal defects after APR for colorectal disease. Although taking more operation time and an increased risk of specific complications, the pooled results have validated the use of myocutaneous flaps for reducing total/major perineal wound complications. More investigations are needed to draw definitive conclusions on this dilemma. [ABSTRACT FROM AUTHOR]

Ectopic lipids in peripheral tissues have been implicated in attenuating insulin action in vivo. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is not known. We sought to determine whether the mechanism by which PMI 5011 improves insulin signaling is through regulation of lipid metabolism. After differentiation, cells were separately preincubated with free fatty acids (FFAs) and ceramide C2, and the effects on glycogen content, insulin signaling, and ceramide profiles were determined. The effect of PMI 5011 on ceramide accumulation and ceramide-induced inhibition of insulin signaling was evaluated. FFAs resulted in increased levels of total ceramides and ceramide species in L6 myotubes. Saturated FFAs and ceramide C2 inhibited insulin-stimulated phosphorylation of protein kinase B/Akt and reduced glycogen content. PMI 5011 had no effect on ceramide formation or accumulation but increased insulin sensitivity via restoration of Akt phosphorylation. PMI 5011 also attenuated the FFA-induced upregulation of a negative inhibitor of insulin signaling, i.e., protein tyrosine phosphatase 1B (PTP1B), and increased phosphorylation of PTP1B. PMI 5011 attenuates the reduction in insulin signaling induced by ceramide accumulation, but the mechanism of improved insulin signaling is independent of ceramide formation. [ABSTRACT FROM AUTHOR]

An ethanolic extract of Artemisia dracunculus L. (PMI 5011) has been observed to decrease glucose and insulin levels in animal models, but the cellular mechanisms by which insulin action is enhanced in vivo are not precisely known. In this study, we evaluated the effects of PMI 5011 to modulate gene expression and cellular signaling through the insulin receptor in skeletal muscle of KK-A(y) mice. Eighteen male KK-A(y) mice were randomized to a diet (w/w) mixed with PMI 5011 (1%) or diet alone for 8 weeks. Food intake, adiposity, glucose and insulin were assessed over the study, and at study completion, vastus lateralis muscle was obtained to assess insulin signaling parameters and gene expression. Animals randomized to PMI 5011 were shown to have enhanced insulin sensitivity and increased insulin receptor signaling, i.e., IRS-associated PI-3 kinase activity, Akt-1 activity and Akt phosphorylation, in skeletal muscle when compared to control animals (P<.01, P<.01 and P<.001, respectively). Gene expression for insulin signaling proteins, i.e., IRS-1, PI-3 kinase and Glut-4, was not increased, although a relative increase in protein abundance was noted with PMI 5011 treatment. Gene expression for specific ubiquitin proteins and specific 20S proteasome activity, in addition to skeletal muscle phosphatase activity, i.e., PTP1B activity, was significantly decreased in mice randomized to PMI 5011 relative to control. Thus, the data demonstrate that PMI 5011 increases insulin sensitivity and enhances insulin receptor signaling in an animal model of insulin resistance. PMI 5011 may modulate skeletal muscle protein degradation and phosphatase activity as a possible mode of action. [ABSTRACT FROM AUTHOR]

Background.Mesangial cell (MC) proliferation and matrix expansion are characteristics of many glomerulopathies. Heparin has been shown to inhibit MC proliferation in vitro and mitigate cell proliferation, matrix expansion, proteinuria, renal insufficiency, and hypertension in experimental glomerulonephritis and subtotal renal ablation. We examined the effect of standard heparin on MC proliferation and matrix protein expression in vitro which necessarily excludes the confounding influences of haemodynamic, inflammatory, heamostatic, and various other processes that are present in vivo. [ABSTRACT FROM PUBLISHER]

OBJECTIVES: Platinum-based chemotherapy is the recognized first-line treatment for metastatic nasopharyngeal carcinoma (NPC). However there is no standard second-line treatment. This study was designed to evaluate the efficacy and safety of a gemcitabine and vinorelbine combination (GV) in patients with metastatic NPC previously treated with platinum-based chemotherapy. METHODS: A total of 61 patients with metastatic NPC after prior platinum-based chemotherapy were enrolled. Gemcitabine (1000mg/m(2)) and vinorelbine (25mg/m(2)) were administered intravenously on Day 1 and Day 8 every 3weeks. RESULTS: In this study, the overall response rate was 37.7% (95% CI, 25.5-49.9%) one complete response (1.6%) and 22 partial responses (36.1%). The median progression-free survival was 5.2months (95% CI, 3.4-7.0months) and the median overall survival was 14.1months (95% CI, 11.1-17.1months). Grade 3/4 toxicity including leucopenia (19.7%), neutropenia (18%), anemia (4.9%) and thrombocytopenia (6.5%) were tolerable. Univariate and multivariate analyses indicated age and salvage treatment after failure of GV treatment were independently significant prognostic factors. CONCLUSION: Our preliminary result shows gemcitabine and vinorelbine combination is effective and safe for the patients with advanced NPC pretreated with platinum-based chemotherapy. Further clinical study is warranted. [ABSTRACT FROM AUTHOR]

Purpose: This study is to investigate the value of double contrast-enhanced ultrasonography (DCEU) in assessing microcirculation of colorectal adenocarcinomas and to describe the perfusion features of the tumours. Material and Methods: DCEUS was performed in 42 patients with adenocarcinoma. The time-intensity curve parameters (arrival time (AT), time-to-peak (TTP), peak intensity (PI) and area under the curve (AUC)) within the tumours were extracted. The parameters were compared among the tumours with different CEUS features and stages. Results: The mean values of AT, TTP, PI and AUC of the colorectal adenocarcinomas were 13.68±13.36s, 32.61±19.56s, 19.82±16.54dB and 271.10±159.19dBs, respectively. In the adenocarcinomas with necrosis, the mean values of AUC was significantly lower than that of the adenocarcinomas without (231.10±219.27dBs, 278.10±123.20dBs, p=0.004). In the adenocarcinomas with necrosis, the AUC and PI of the non-necrotic part were significantly higher than that of the necrotic part (p=0.007, 0.0025, respectively). AUC increased progressively in the subgroups of T2, T3 and T4 and the difference of AUC between T2 and T4 subgroup was significant (p=0.008). Conclusions: Double contrast-enhanced ultrasonography is a valuable technique for quantifying tumour vascularity of colorectal adenocarcinomas. AUC was significantly different in the subgroups of different T stage. AUC and PI could reflect the different perfusion status of tumours with or without necrosis. [ABSTRACT FROM AUTHOR]