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Background: Cisplatin is one of the first-line drugs for urothelial bladder cancer (UBC) treatment. However, its considerable side effects and the emergence of drug resistance are becoming major limitations for its application. This study aimed to investigate whether matrine and cisplatin could present a synergistic anti-tumor effect on UBC cells. Methods: Cell viability assay was used to assess the suppressive effect of matrine and cisplatin on the proliferation of the UBC cells. Wound healing assay and transwell assay were applied respectively to determine the migration and invasion ability of the cells. The distribution of cell cycles, the generation of reactive oxygen species (ROS) and the apoptosis rate were detected by flow cytometry (FCM). The expressions of the relative proteins in apoptotic signal pathways and the epithelial-mesenchymal transition (EMT) related genes were surveyed by western blotting. The binding modes of the drugs within the proteins were detected by CDOCKER module in DS 2.5. Results: Both matrine and cisplatin could inhibit the growth of the UBC cells in a time- and dose-dependent manner. When matrine combined with cisplatin at the ratio of 2000:1, they presented a synergistic inhibitory effect on the UBC cells. The combinative treatment could impair cell migration and invasion ability, arrest cell cycle in the G1 and S phases, increase the level of ROS, and induce apoptosis in EJ and T24 cells in a synergistic way. In all the treated groups, the expressions of E-cadherin, β-catenin, Bax, and Cleaved Caspase-3 were up-regulated, while the expressions of Fibronectin, Vimentin, Bcl-2, Caspase-3, p-Akt, p-PI3K, VEGFR2, and VEGF proteins were down-regulated, and among them, the combination of matrine and cisplatin showed the most significant difference. Molecular docking algorithms predicted that matrine and cisplatin could be docked into the same active sites and interact with different residues within the tested proteins. Conclusions: Our results suggested that the combination of matrine and cisplatin could synergistically inhibit the UBC cells' proliferation through down-regulating VEGF/PI3K/Akt signaling pathway, indicating that matrine may serve as a new option in the combinative therapy in the treatment of UBC. [ABSTRACT FROM AUTHOR]

Background: The study was designed to develop a platform to verify whether the extract of herbs combined with chemotherapy drugs play a synergistic role in anti-tumor effects, and to provide experimental evidence and theoretical reference for finding new effective sensitizers. Methods: Inhibition of tanshinone IIA and adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8 assays. The combination index (CI) was calculated with the Chou-Talalay method, based on the median-effect principle. Migration and invasion ability of A549 cells were determined by wound healing assay and transwell assay. Flow cytometry was used to detect the cell apoptosis and the distribution of cell cycles. TUNEL staining was used to detect the apoptotic cells. Immunofluorescence staining was used to detect the expression of Cleaved Caspase-3. Western blotting was used to detect the proteins expression of relative apoptotic signal pathways. CDOCKER module in DS 2.5 was used to detect the binding modes of the drugs and the proteins. Results: Both tanshinone IIA and adriamycin could inhibit the growth of A549, PC9, and HLF cells in a dose- and time-dependent manner, while the proliferative inhibition effect of tanshinone IIA on cells was much weaker than that of adriamycin. Different from the cancer cells, HLF cells displayed a stronger sensitivity to adriamycin, and a weaker sensitivity to tanshinone IIA. When tanshinone IIA combined with adriamycin at a ratio of 20:1, they exhibited a synergistic anti-proliferation effect on A549 and PC9 cells, but not in HLF cells. Tanshinone IIA combined with adriamycin could synergistically inhibit migration, induce apoptosis and arrest cell cycle at the S and G2 phases in A549 cells. Both groups of the single drug treatment and the drug combination up-regulated the expressions of Cleaved Caspase-3 and Bax, but down-regulated the expressions of VEGF, VEGFR2, p-PI3K, p-Akt, Bcl-2, and Caspase-3 protein. Compared with the single drug treatment groups, the drug combination groups were more statistically significant. The molecular docking algorithms indicated that tanshinone IIA could be docked into the active sites of all the tested proteins with H-bond and aromatic interactions, compared with that of adriamycin. Conclusions: Tanshinone IIA can be developed as a novel agent in the postoperative adjuvant therapy combined with other anti-tumor agents, and improve the sensibility of chemotherapeutics for non-small cell lung cancer with fewer side effects. In addition, this experiment can not only provide a reference for the development of more effective anti-tumor medicine ingredients, but also build a platform for evaluating the anti-tumor effects of Chinese herbal medicines in combination with chemotherapy drugs. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) has become one of the mainstays of treatment for early gastric cancer (EGC). Radical surgery is also a classical treatment method for EGC. There have been no systematic clinical studies of the curative effects and adverse events associated with ESD vs. radical surgery for EGC. This study investigated the therapeutic efficacy and safety of ESD and radical surgery for EGC. Methods: Twenty-nine patients with EGC underwent ESD, and 59 underwent radical surgery at Weihai Municipal Hospital. The pathological characteristics, postoperative outcomes, hospital course, morbidity and mortality were retrospectively compared between the two groups. Results: The oncological clearance was 93.1 % (27/29) in the ESD group. Postoperative delayed haemorrhage occurred in two patients. The hospital stay ranged from 10 to 23 days, and the average stay was 14.3 ± 3.7 days. The patients were followed-up for 1 to 5 years, with a mean follow-up of 26.9 ± 8.5 months. Regular endoscopic examinations showed that the wound had healed with no cancer recurrence in all of the patients. In the radical surgery group, the oncological clearance was 100 % (59/59). The hospital stay ranged from 11 to 55 days, and the average stay was 21.7 ± 9.3 days. The patients were followed-up for 1 to 3.7 years, with a mean follow-up of 22.3 ± 9.4 months. Nine patients developed complications, including acute postoperative adhesive ileus (1/59) and symptomatic residual gastritis (3/59). These complications were improved by an additional operation, drainage, gastrointestinal decompression and comprehensive therapy. Conclusions: ESD achieved similar efficacy and had many advantages compared with radical surgery for the treatment of EGC. [ABSTRACT FROM AUTHOR]

Background: Hypertension is one of the major risk factors for cardiovascular diseases. Research on the patient classification of hypertension has become an important topic because Traditional Chinese Medicine lies primarily in "treatment based on syndromes differentiation of the patients". Methods: Clinical data of hypertension was collected with 12 syndromes and 129 symptoms including inspection, tongue, inquiry, and palpation symptoms. Syndromes differentiation was modeled as a patient classification problem in the field of data mining, and a new multi-label learning model BrSmoteSvm was built dealing with the class-imbalanced of the dataset. Results: The experiments showed that the BrSmoteSvm had a better results comparing to other multi-label classifiers in the evaluation criteria of Average precision, Coverage, One-error, Ranking loss. Conclusions: BrSmoteSvm can model the hypertension's syndromes differentiation better considering the imbalanced problem. [ABSTRACT FROM AUTHOR]

Background: Our previous study found that suppression of TRPM7 reduced neuronal death in adult rat ischemic brain injury. It was reported that carvacrol blocked TRPM7 and attenuated brain injury in an adult rat MCAO model. The effects of carvacrol on neonatal stroke remain unknown. This study investigated the effects of carvacrol on neuronal injury and behavioral impairment after hypoxia-ischemia in neonatal mice and the potential signaling pathway underlying these effects. Results: Carvacrol inhibited TRPM7 current in HEK293 cells over-expressing TRPM7 and TRPM7-like current in hippocampal neurons in a dose-dependent manner. Carvacrol (>200 μM) reduced OGD-induced neuronal injury in cortical neurons. 24 hours after HI, TRPM7 protein level in the ipsilateral hemisphere was significantly higher than in the contralateral hemisphere. Carvacrol (30 and 50 mg/kg) pre-treatment reduced brain infarct volume 24 hours after HI in a dose-dependent manner. Carvacrol pre-treatment also improved neurobehavioral outcomes. Furthermore, animals pre-treated with carvacrol had fewer TUNEL-positive cells in the brain compared to vehicle-treated animals 3 days after HI. Carvacrol pre-treatment also increased Bcl-2/Bax and p-Akt/t-Akt protein ratios and decreased cleaved caspase-3 protein expression 24 hours after HI. Conclusions: Carvacrol pre-treatment protects against neonatal hypoxic-ischemic brain injury by reducing brain infarct volume, promoting pro-survival signaling and inhibiting pro-apoptotic signaling, as well as improving behavioral outcomes. The neuroprotective effect may be mediated by the inhibition of TRPM7 channel function. Carvacrol is a potential drug development target for the treatment of neonatal stroke. [ABSTRACT FROM AUTHOR]

Background: Although hypoxia is known to promote hepatoma cell invasion and migration, little is known regarding the molecular mechanisms of this process. Our previous research showed that loss of Tg737 is associated with hepatoma cell invasion and migration; therefore, we hypothesized that the Tg737 signal might be required for hypoxia-enhanced invasion and migration. Methods: We established in vitro normoxic or hypoxic models to investigate the role of Tg737 in the hypoxia-enhanced invasion and migration of hepatoma cells. The hepatoma cell lines HepG2 and MHCC97-H were subjected to normoxic or hypoxic conditions, and the cell adhesion, invasion, and migration capabilities were tested. The expression of Tg737 under normoxia or hypoxia was detected using western blot assays; cell viability was determined using flow cytometry. Furthermore, we created HepG2 and MHCC97-H cells that over expressed Tg737 prior to incubation under hypoxia and investigated their metastatic characteristics. Finally, we analyzed the involvement of critical molecular events known to regulate invasion and migration. Results: In this study, Tg737 expression was significantly inhibited in HepG2 and MHCC97-H cells following exposure to hypoxia. The down regulation of Tg737 expression corresponded to significantly decreased adhesion and increased invasion and migration. Hypoxia also decreased the expression/secretion of polycystin-1, increased the secretion of interleukin-8 (IL-8), and increased the levels of active and total transforming growth factor β 1 (TGF-β1), critical regulators of cell invasion and migration. Moreover, the decrease in adhesiveness and the increase in the invasive and migratory capacities of hypoxia-treated hepatoma cells were attenuated by pcDNA3.1-Tg737 transfection prior to hypoxia. Finally, following the up regulation of Tg737, the expression/secretion of polycystin-1 increased, and the secretion of IL-8 and the levels of active and total TGF-β1 decreased correspondingly. Conclusions: These data provide evidence that Tg737 contributes to hypoxia-induced invasion and migration, partially through the polycystin-1, IL-8, and TGF-β1 pathway. Taken together, this work suggests that Tg737 is involved in the invasion and migration of hepatoma cells under hypoxia, with the involvement of the polycystin-1, IL-8, and TGF-β1 signaling pathway. Tg737 is a potential therapeutic target for inhibiting the high invasion and migration potential of hepatoma cells in hypoxic regions. [ABSTRACT FROM AUTHOR]

Background: Measure Yourself Medical Outcome Profile (MYMOP) is a patient generated outcome instrument applicable in the evaluation of both allopathic and complementary medicine treatment. This study aims to adapt MYMOP into Chinese, and to assess its validity, responsiveness and minimally important change values in a sample of patients using Chinese medicine (CM) services. Methods: A Chinese version of MYMOP (CMYMOP) is developed by forward-backward-forward translation strategy, expert panel assessment and pilot testing amongst patients. 272 patients aged 18 or above with subjective symptoms in the past 2 weeks were recruited at a CM clinic, and were invited to complete a set of questionnaire containing CMYMOP and SF-36. Follow ups were performed at 2nd and 4th week after consultation, using the same set of questionnaire plus a global rating of change question. Criterion validity of CMYMOP was assessed by its correlation with SF-36 at baseline, and responsiveness was evaluated by calculating the Cohen effect size (ES) of change at two follow ups. Minimally important difference (MID) values were estimated via anchor based method, while minimally detectable difference (MDC) figures were calculated by distribution based method. Results: Criterion validity of CMYMOP was demonstrated by negative correlation between CMYMOP Profile scores and all SF-36 domain and summary scores at baseline. For responsiveness between baseline and 4th week follow up, ES of CMYMOP Symptom 1, Activity and Profile reached the moderate change threshold (ES>0.5), while Symptom 2 and Wellbeing reached the weak change threshold (ES>0.2). None of the SF-36 scores reached the moderate change threshold, implying CMYMOP's stronger responsiveness in CM setting. At 2nd week follow up, MID values for Symptom 1, Symptom 2, Wellbeing and Profile items were 0.894, 0.580, 0.263 and 0.516 respectively. For Activity item, MDC figure of 0.808 was adopted to estimate MID. Conclusions: The findings support the validity and responsiveness of CMYMOP for capturing patient centred clinical changes within 2 weeks in a CM clinical setting. Further researches are warranted (1) to estimate Activity item MID, (2) to assess the test-retest reliability of CMYMOP, and (3) to perform further MID evaluation using multiple, item specific anchor questions. [ABSTRACT FROM AUTHOR]

Background: The downstream of tyrosine kinase/docking protein (Dok) adaptor protein family has seven members, Dok1 to Dok7, that act as substrates of multiple receptor tyrosine kinase and non-receptor tyrosine kinase. The tropomyosin-related kinase (Trk) receptor family, which has three members (TrkA, TrkB and TrkC), are receptor tyrosine kinases that play pivotal roles in many stages of nervous system development, such as differentiation, migration, axon and dendrite projection and neuron patterning. Upon related neurotrophin growth factor stimulation, dimerisation and autophosphorylation of Trk receptors can occur, recruiting adaptor proteins to mediate signal transduction. Results: In this report, by using yeast two-hybrid assays, glutathione S-transferase (GST) precipitation assays and coimmunoprecipitation (Co-IP) experiments, we demonstrate that Dok6 selectively binds to the NPQY motif of TrkC through its phosphotyrosine-binding (PTB) domain in a kinase activity-dependent manner. We further confirmed their interaction by coimmunoprecipitation and colocalisation in E18.5 mouse cortex neurons, which provided more in vivo evidence. Next, we demonstrated that Dok6 is involved in neurite outgrowth in mouse cortex neurons via the RNAi method. Knockdown of Dok6 decreased neurite outgrowth in cortical neurons upon neurotrophin 3 (NT-3) stimulation. Conclusions: We conclude that Dok6 interacts with the NPQY motif of the TrkC receptor through its PTB domain in a kinase activity-dependent manner, and works as a novel substrate of the TrkC receptor involved in NT-3-mediated neurite outgrowth in mouse cortex neurons. [ABSTRACT FROM AUTHOR]

Background: Disorders of the metabolism and absorption of vitamin B12 can lead to decrease in activity of methionine synthetase and methylmalonate coenzyme A mutase (MMUT), which results in increased levels of methylmalonic acid and homocysteine in blood and urine. Often, combined methylmalonic acidemia (MMA) and homocysteinemia is misdiagnosed due to a lack of specific symptoms. The clinical manifestations are diverse, but proteinuria as the initial presentation is rare. Case presentation: Two cases of MMA with homocysteinemia in children are reported. Proteinuria were a primary presenting symptom, followed by anemia and neurologic symptoms (frequent convulsions and unstable walking, respectively). Screening of amino acids and acyl carnitine in serum showed that the propionyl carnitine:acetylcarnitine ratio increased. Profiling of urinary organic acids by gas chromatography–mass spectrometry revealed high levels of methylmalonic acid. Homocysteine content in blood was increased. Comprehensive genetic analyses of peripheral blood-derived DNA demonstrated heterozygous variants of methylmalonic aciduria type C and homocystinuria (MMACHC) and amnionless (AMN) genes in our two patients, respectively. After active treatment, the clinical manifestations in Case 1 were relieved and urinary protein ceased to be observed; Case 2 had persistent proteinuria and was lost to follow-up. Conclusions: Analyses of the organic acids in blood and urine suggested MMA combined with homocysteinemia. In such diseases, reports of renal damage are uncommon and proteinuria as the initial presentation is rare. Molecular analysis indicated two different genetic causes. Although the pathologic mechanisms were related to vitamin B12, the severity and prognosis of renal lesions were different. Therefore, gene detection provides new insights into inherited metabolic diseases. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence recognizes that DNA methylation abnormalities play critical roles in cancer development. Our previous genome-wide methylation profile showed that tumor necrosis factor-alpha-induced protein 8 like 3 (TIPE3) was hypermethylated in nasopharyngeal carcinoma (NPC). However, the relationship between TIPE3 methylation and its mRNA expression, as well as its biological roles in NPC are unknown. Methods: Bisulfite pyrosequencing and quantitative RT-PCR were performed to quantify the TIPE3 methylation and expression levels. Kaplan-Meier curves and Cox regression analysis were used to estimate the correlation between TIPE3 methylation levels and survival in two patient cohorts collected from two hospitals (n = 441). The MTT, colony formation, Transwell migration and invasion assays, and xenograft tumor growth and lung metastatic colonization models were used to identify the functions of TIPE3 on NPC cells. Results: We found that TIPE3 CpG island (CGI) was hypermethylated and its mRNA levels were downregulated in many cancers, including NPC. TIPE3 downregulation was associated with its CGI hypermethylation. Furthermore, NPC patients with high TIPE3 CGI methylation levels had poorer clinical outcomes than those with low methylation levels. The TIPE3 CGI methylation level was an independent prognostic factor. Moreover, restoring TIPE3 expression significantly inhibited NPC cell proliferation, migration and invasion in vitro, and suppressed tumor growth and lung metastatic colonization in vivo, while silencing TIPE3 acted in an opposite way. Conclusions: TIPE3 downregulation correlates with its CGI hypermethylation in several solid cancers. TIPE3 acts as a tumor suppressor in NPC, providing a further insight into NPC progression and representing a potential prognostic biomarker for NPC. [ABSTRACT FROM AUTHOR]

Background: Cisplatin is one of the first-line drugs for urothelial bladder cancer (UBC) treatment. However, its considerable side effects and the emergence of drug resistance are becoming major limitations for its application. This study aimed to investigate whether matrine and cisplatin could present a synergistic anti-tumor effect on UBC cells., Methods: Cell viability assay was used to assess the suppressive effect of matrine and cisplatin on the proliferation of the UBC cells. Wound healing assay and transwell assay were applied respectively to determine the migration and invasion ability of the cells. The distribution of cell cycles, the generation of reactive oxygen species (ROS) and the apoptosis rate were detected by flow cytometry (FCM). The expressions of the relative proteins in apoptotic signal pathways and the epithelial-mesenchymal transition (EMT) related genes were surveyed by western blotting. The binding modes of the drugs within the proteins were detected by CDOCKER module in DS 2.5., Results: Both matrine and cisplatin could inhibit the growth of the UBC cells in a time- and dose-dependent manner. When matrine combined with cisplatin at the ratio of 2000:1, they presented a synergistic inhibitory effect on the UBC cells. The combinative treatment could impair cell migration and invasion ability, arrest cell cycle in the G1 and S phases, increase the level of ROS, and induce apoptosis in EJ and T24 cells in a synergistic way. In all the treated groups, the expressions of E-cadherin, β-catenin, Bax, and Cleaved Caspase-3 were up-regulated, while the expressions of Fibronectin, Vimentin, Bcl-2, Caspase-3, p-Akt, p-PI3K, VEGFR2, and VEGF proteins were down-regulated, and among them, the combination of matrine and cisplatin showed the most significant difference. Molecular docking algorithms predicted that matrine and cisplatin could be docked into the same active sites and interact with different residues within the tested proteins., Conclusions: Our results suggested that the combination of matrine and cisplatin could synergistically inhibit the UBC cells' proliferation through down-regulating VEGF/PI3K/Akt signaling pathway, indicating that matrine may serve as a new option in the combinative therapy in the treatment of UBC.

Background: The study was designed to develop a platform to verify whether the extract of herbs combined with chemotherapy drugs play a synergistic role in anti-tumor effects, and to provide experimental evidence and theoretical reference for finding new effective sensitizers., Methods: Inhibition of tanshinone IIA and adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8 assays. The combination index (CI) was calculated with the Chou-Talalay method, based on the median-effect principle. Migration and invasion ability of A549 cells were determined by wound healing assay and transwell assay. Flow cytometry was used to detect the cell apoptosis and the distribution of cell cycles. TUNEL staining was used to detect the apoptotic cells. Immunofluorescence staining was used to detect the expression of Cleaved Caspase-3. Western blotting was used to detect the proteins expression of relative apoptotic signal pathways. CDOCKER module in DS 2.5 was used to detect the binding modes of the drugs and the proteins., Results: Both tanshinone IIA and adriamycin could inhibit the growth of A549, PC9, and HLF cells in a dose- and time-dependent manner, while the proliferative inhibition effect of tanshinone IIA on cells was much weaker than that of adriamycin. Different from the cancer cells, HLF cells displayed a stronger sensitivity to adriamycin, and a weaker sensitivity to tanshinone IIA. When tanshinone IIA combined with adriamycin at a ratio of 20:1, they exhibited a synergistic anti-proliferation effect on A549 and PC9 cells, but not in HLF cells. Tanshinone IIA combined with adriamycin could synergistically inhibit migration, induce apoptosis and arrest cell cycle at the S and G2 phases in A549 cells. Both groups of the single drug treatment and the drug combination up-regulated the expressions of Cleaved Caspase-3 and Bax, but down-regulated the expressions of VEGF, VEGFR2, p-PI3K, p-Akt, Bcl-2, and Caspase-3 protein. Compared with the single drug treatment groups, the drug combination groups were more statistically significant. The molecular docking algorithms indicated that tanshinone IIA could be docked into the active sites of all the tested proteins with H-bond and aromatic interactions, compared with that of adriamycin., Conclusions: Tanshinone IIA can be developed as a novel agent in the postoperative adjuvant therapy combined with other anti-tumor agents, and improve the sensibility of chemotherapeutics for non-small cell lung cancer with fewer side effects. In addition, this experiment can not only provide a reference for the development of more effective anti-tumor medicine ingredients, but also build a platform for evaluating the anti-tumor effects of Chinese herbal medicines in combination with chemotherapy drugs.

Background: Whether the ABO blood group is associated with the survival of patients with laryngeal cancer remains unknown. The purpose of this study was to investigate the association between the ABO blood group and clinicopathologic characteristics of patients with laryngeal cancer and assess whether the ABO blood group was associated with prognosis., Methods: We analyzed the records of 1260 patients with laryngeal cancer who underwent curative treatment at Sun Yat-sen University Cancer Center between January 1993 and December 2009. The Chi-square test was used to assess the relationship between the ABO blood group and clinicopathologic characteristics. The Kaplan-Meier method was used to estimate 3-, 5-, and 10-year overall survival (OS) rates. The Cox proportional hazards model was used in univariate and multivariate analyses of OS., Results: No significant association was found between the ABO blood group and clinicopathologic characteristics except for primary tumor site. The median OS for patients with blood groups A, B, AB, and O were 87.0, 80.0, 90.0, and 72.5 months, respectively. The 3-, 5-, and 10-year OS rates were 82.4%, 76.0%, and 67.5% for patients with blood group A; 77.4%, 69.8%, and 58.4% for patients with blood group B; 82.2%, 73.1%, and 65.6% for patients with blood group AB; and 71.7%, 66.4%, and 55.5% for patients with blood group O, respectively. Univariate and multivariate analyses showed that the ABO blood group had significant effects on prognosis in patients with laryngeal cancer., Conclusions: The ABO blood group is associated with survival in patients with laryngeal cancer. Patients with blood group O had significantly shorter OS than patients with other ABO blood groups.

Background: Endoscopic submucosal dissection (ESD) has become one of the mainstays of treatment for early gastric cancer (EGC). Radical surgery is also a classical treatment method for EGC. There have been no systematic clinical studies of the curative effects and adverse events associated with ESD vs. radical surgery for EGC. This study investigated the therapeutic efficacy and safety of ESD and radical surgery for EGC., Methods: Twenty-nine patients with EGC underwent ESD, and 59 underwent radical surgery at Weihai Municipal Hospital. The pathological characteristics, postoperative outcomes, hospital course, morbidity and mortality were retrospectively compared between the two groups., Results: The oncological clearance was 93.1 % (27/29) in the ESD group. Postoperative delayed haemorrhage occurred in two patients. The hospital stay ranged from 10 to 23 days, and the average stay was 14.3 ± 3.7 days. The patients were followed-up for 1 to 5 years, with a mean follow-up of 26.9 ± 8.5 months. Regular endoscopic examinations showed that the wound had healed with no cancer recurrence in all of the patients. In the radical surgery group, the oncological clearance was 100 % (59/59). The hospital stay ranged from 11 to 55 days, and the average stay was 21.7 ± 9.3 days. The patients were followed-up for 1 to 3.7 years, with a mean follow-up of 22.3 ± 9.4 months. Nine patients developed complications, including acute postoperative adhesive ileus (1/59) and symptomatic residual gastritis (3/59). These complications were improved by an additional operation, drainage, gastrointestinal decompression and comprehensive therapy., Conclusions: ESD achieved similar efficacy and had many advantages compared with radical surgery for the treatment of EGC.

Background: Hypertension is one of the major risk factors for cardiovascular diseases. Research on the patient classification of hypertension has become an important topic because Traditional Chinese Medicine lies primarily in "treatment based on syndromes differentiation of the patients"., Methods: Clinical data of hypertension was collected with 12 syndromes and 129 symptoms including inspection, tongue, inquiry, and palpation symptoms. Syndromes differentiation was modeled as a patient classification problem in the field of data mining, and a new multi-label learning model BrSmoteSvm was built dealing with the class-imbalanced of the dataset., Results: The experiments showed that the BrSmoteSvm had a better results comparing to other multi-label classifiers in the evaluation criteria of Average precision, Coverage, One-error, Ranking loss., Conclusions: BrSmoteSvm can model the hypertension's syndromes differentiation better considering the imbalanced problem.

Background: MicroRNAs (miRNAs) regulate many biological processes by post-translational gene silencing. Analysis of miRNA expression profiles is a reliable method for investigating particular biological processes due to the stability of miRNA and the development of advanced sequencing methods. However, this approach is limited by the broad specificity of miRNAs, which may target several mRNAs., Result: In this study, we developed a method for comprehensive annotation of miRNA array or deep sequencing data for investigation of cellular biological effects. Using this method, the specific pathways and biological processes involved in Alzheimer's disease were predicted with high correlation in four independent samples. Furthermore, this method was validated for evaluation of cadmium telluride (CdTe) nanomaterial cytotoxicity. As a result, apoptosis pathways were selected as the top pathways associated with CdTe nanoparticle exposure, which is consistent with previous studies., Conclusions: Our findings contribute to the validation of miRNA microarray or deep sequencing results for early diagnosis of disease and evaluation of the biological safety of new materials and drugs.

Background: The aim of the study was to test for human papilloma virus (HPV) infection and human telomerase RNA component (hTERC) gene amplification in tissues derived from esophageal cancer, in esophagus displaying atypical hyperplasia and in normal tissue, and to analyze the relationship between them and discuss whether HPV infection and hTERC gene amplification play a role in the duration of survival of esophageal cancer patients., Methods: To test for HPV infection, surface plasma resonance was used after extracting and subjecting the DNA to PCR amplification. Measurement of hTERC gene amplification was performed by the fluorescence in situ hybridization technique., Results: The rates of HPV infection in the normal group, the atypical esophageal hyperplasia group and the cancer group were 0% (0/40), 10.00% (1/10) and 20.65% (19/92), respectively, with a statistically significant difference of P < 0.01. The hTERC gene amplification rate in normal tissue, grade I atypical hyperplastic tissue, grade II/III atypical hyperplastic tissue and esophageal cancer tissue were 0% (0/89), 15.38% (4/26), 47.06% (8/17) and 89.13% (82/92), respectively, with a statistically significant difference of P < 0.01. On follow-up of 92 patients, survival curves of the HPV-positive and HPV-negative groups were not significantly different (P > 0.05). Survival curves of the hTERC gene amplification-positive and hTERC gene amplification-negative groups were statistically significant (P < 0.05). A matching chi-square test showed that there was no correlation between HPV infection and hTERC gene amplification (P > 0.05)., Conclusion: HPV infection may be one of many factors contributing to the development of esophageal cancer, but it does not influence prognosis. Amplification of the hTERC gene appears to influence certain features associated with postoperative survival in esophageal carcinoma patients.

Background: The downstream of tyrosine kinase/docking protein (Dok) adaptor protein family has seven members, Dok1 to Dok7, that act as substrates of multiple receptor tyrosine kinase and non-receptor tyrosine kinase. The tropomyosin-related kinase (Trk) receptor family, which has three members (TrkA, TrkB and TrkC), are receptor tyrosine kinases that play pivotal roles in many stages of nervous system development, such as differentiation, migration, axon and dendrite projection and neuron patterning. Upon related neurotrophin growth factor stimulation, dimerisation and autophosphorylation of Trk receptors can occur, recruiting adaptor proteins to mediate signal transduction., Results: In this report, by using yeast two-hybrid assays, glutathione S-transferase (GST) precipitation assays and coimmunoprecipitation (Co-IP) experiments, we demonstrate that Dok6 selectively binds to the NPQY motif of TrkC through its phosphotyrosine-binding (PTB) domain in a kinase activity-dependent manner. We further confirmed their interaction by coimmunoprecipitation and colocalisation in E18.5 mouse cortex neurons, which provided more in vivo evidence. Next, we demonstrated that Dok6 is involved in neurite outgrowth in mouse cortex neurons via the RNAi method. Knockdown of Dok6 decreased neurite outgrowth in cortical neurons upon neurotrophin 3 (NT-3) stimulation., Conclusions: We conclude that Dok6 interacts with the NPQY motif of the TrkC receptor through its PTB domain in a kinase activity-dependent manner, and works as a novel substrate of the TrkC receptor involved in NT-3-mediated neurite outgrowth in mouse cortex neurons.