AIM： To assess whether the effectiveness of a combination of transarterial chemoembolization （TACE） and percutaneous ethanol injection （PEI） in the treatment of unresectable hepatocellular carcinoma （HCC） is su...AIM： To assess whether the effectiveness of a combination of transarterial chemoembolization （TACE） and percutaneous ethanol injection （PEI） in the treatment of unresectable hepatocellular carcinoma （HCC） is superior to TACE alone a randomized controlled trial was performed. METHODS： The effect of combination therapy on longterm survival rates and duration of hospitalization was evaluated in 52 previously untreated HCCs, randomly allocated to TACE-PEI （27 pts） or TACE alone （25 pts）. RESULTS： The cumulative survival rate of the TACE group was 75.8% at 6 mo, 62.9% at 12 mo, and 18.0% at 24 mo and of the TACE-PEI group 76.9%, 61.5%, and 38.7%, respectively. Comparison of overall survival in both groups showed no statistically significant difference. Regarding the patients with HCCs Okuda stage I （n = 26）, the median survival of the TACE-PEI group was significantly longer （〉24 mo, median not yet reached in the study period） compared to the TACE group （18.4 mo [range 11.6-21.7 mo]; P = 0.04）. TACE-PEI reduced the relative risk for mortality to 0.4 （95% CI 0.15-0.96） compared to patients who received TACE alone. Median survival in patients with HCCs Okuda stage Ⅱ or Ⅲ was 5.0 mo in the TACE group （1.7 rno-not defined） compared to 10.4 mo in the TACE-PEI group. CONCLUSION： The combination TACE-PEI improved survival time compared to TACE alone. Our study revealed a statistically significant improved survival in HCCs Okuda stage I. Side effects were minor and the combination therapy did not prolong duration of hospitalization considerably.展开更多
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatoc...Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, ＜5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC develop展开更多
AIM: To further analyze the interaction of tupaia CD81 with hepatitis C virus (HCV) envelope protein E2. METHODS: A tupaia CD81 large extracellular loop (CD81 LEL), which binds to HCV E2 protein, was cloned and expres...AIM: To further analyze the interaction of tupaia CD81 with hepatitis C virus (HCV) envelope protein E2. METHODS: A tupaia CD81 large extracellular loop (CD81 LEL), which binds to HCV E2 protein, was cloned and expressed as a GST-fusion protein, and interaction of HCV E2 protein with a tupaia CD81 LEL was evaluated by enzyme-linked immunosorbent assay (EIA). RESULTS: Although tupaia and human CD81 LEL differed in 6 amino acid changes, tupaia CD81 LEL was strongly recognized by anti-CD81 antibodies against human CD81 LEL conformation-dependent epitopes. Investigating LEL CD81-E2 interactions by EIA, we demonstrated that binding of tupaia CD81 LEL GST fusion protein to recombinant HCV E2 protein was markedly reduced compared to binding of human CD81 LEL GST fusion protein to recombinant HCV E2 protein. CONCLUSION: These data suggest that the structural differences in-between the tupaia and human CD81 may alter the interaction of the large extracellular loop with HCV envelope glycoprotein E2. These findings may be important for the understanding of the mechanisms of binding and entry of HCV to PTHs.展开更多
AIM： Different strains of bifidobacteria were analysed for their effects on HT-29 intestinal epithelial cells （IECs） in in vitro models both of the non-inflamed and inflamed intestinal epithelium. METHODS： A repor...AIM： Different strains of bifidobacteria were analysed for their effects on HT-29 intestinal epithelial cells （IECs） in in vitro models both of the non-inflamed and inflamed intestinal epithelium. METHODS： A reporter gene system in HT-29 cells was used to measure levels of NF-KB activation after challenge with bifidobacteria or after bacterial pre-treatment following LPS challenge. IL-8 protein and pro-inflammatory gene expression was investigated using normal HT-29 cells. RESULTS： None of the bifidobacteria tested induced activation of nuclear factor κB （NF-κB） indicating that bifidobacteria themselves do not induce inflammatory events in IECs. However, six out of eight bifidobacteria tested inhibited lipopolysaccharide- （LPS-） induced NF-κB activation in a dose- and strain-dependent manner. In contrast, NF-κB activation in response to challenge with tumor necrosis factor-α （TNF-α） was affected by none of the tested bifidobacteria, indicating that the inhibitory effect of bifidobacteria is specific for LPS-induced inflammation in IECs. As shown with two of the six inhibitionpositive bifidobacteria, LPS-induced inhibition of NF-κB activation was accompanied by a dose-dependent decrease of interleukin 8 （IL-8） secretion and by lower mRNA levels for IL-8, TNF-α, cyclooxygenase 2 （Cox-2）, and intercellular adhesion molecule 1（ICAM-1）. CONCLUSION： Some strains of bifidobacteria are effective in inhibiting LPS-induced inflammation and thus might be appropriate candidates for probiotic intervention in chronic intestinal inflammation.展开更多
AIM: To assess the anti-inflammatory effect of the probiotic Bifidobacterium lactis (B. lactis) in an adoptive transfer model of colitis. METHODS: Donor and recipient mice received either B. lactis or bacterial cultur...AIM: To assess the anti-inflammatory effect of the probiotic Bifidobacterium lactis (B. lactis) in an adoptive transfer model of colitis. METHODS: Donor and recipient mice received either B. lactis or bacterial culture medium as control (deMan Rogosa Sharpe) in drinking water for one week prior to transfer of a mix of naive and regulatory T cells until sacrifice. RESULTS: All recipient mice developed signs of colonic inflammation, but a significant reduction of weight loss was observed in B. lactis-fed recipient mice compared to control mice. Moreover, a trend toward a diminution of mucosal thickness and attenuated epithelial damage was revealed. Colonic expression of pro-inflammatory and T cell markers was significantly reduced in B. lactis-fed recipient mice compared to controls. Concomitantly, forkhead box protein 3, a marker of regulatory T cells, was significantly up-regulated by B. lactis. CONCLUSION: Daily oral administration of B. lactis was able to reduce inflammatory and T cells mediators and to promote regulatory T cells specific markers in a mouse model of colitis.展开更多
Gastric cancer represents a serious health problem on a global scale. It is the second leading cause of cancer-related death worldwide. Novel therapeutic targets are desperately needed because the meager improvement i...Gastric cancer represents a serious health problem on a global scale. It is the second leading cause of cancer-related death worldwide. Novel therapeutic targets are desperately needed because the meager improvement in the cure rate of about 10% realized by adjunctive treatments to surgery is unacceptable as > 50% patients with localized gastric cancer succumb to their disease. Either postoperative chemoradiotherapy (United States), pre-and post-operative chemotherapy (Europe), and adjuvant chemotherapy after a D2 resection (Asia) can all be regarded as standards of care in the localized gastric cancer management. In metastatic disease the addition of trastuzumab to chemotherapy is standard of care in Her2 positive disease. In the HER2 negative population, the treatments remain limited. In the first line setting, the standard of care is a combination of fluoropyrimidine and platinum containing chemotherapy, with or without epirubicin or docetaxel. The results of targeted therapy trials have by and large been disappointing, but none of these trials looked at an appropriately enriched population. Finally there is a meager overall survival benefit in treating patients with metastatic disease in the second line setting, with either irinotecan, docetaxel or ramucirumab however none of these drugs have been compared head to head in a well-powered randomized controlled trial.展开更多
Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and ...Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and TNFα occur. Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. For virtually all HCV proteins, pro- and anti-apoptotic effects have been described, especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or anti- apoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades.展开更多
The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK...The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK^(+)mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification.Moreover,the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals.Based on these advantages,the detection efficiency for the proton decay via p→νK^(+)is 36.9%±4.9%with a background level of 0.2±0.05(syst)±0.2(stat)events after 10 years of data collection.The estimated sensitivity based on 200 kton-years of exposure is 9.6×1033 years,which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies.展开更多
Ultrasonic vibration-assisted laser surface processing that involves application of vertical ultrasonic vibrations to the Ti-6 Al-4 V alloy substrates while being irradiated with a CO_2 laser was performed for the dev...Ultrasonic vibration-assisted laser surface processing that involves application of vertical ultrasonic vibrations to the Ti-6 Al-4 V alloy substrates while being irradiated with a CO_2 laser was performed for the development of laser melted and textured surfaces with potential applications in biomedical implants.The laser processing resulted in very consistent repeating undulating grooved surfaces, and the undulations were significantly more pronounced in the samples processed with higher ultrasonic power outputs.The phase evolution, studied by x-ray diffraction, confirmed that the laser processing triggered transformation of globular α→ acicular α and martensitic α' as well as increased amounts of retained α phases,which were also reflected in the microscopic analysis. The surface texture developed by laser processing resulted in increased surface wettability with increasing ultrasonic power output. The textured surfaces exhibited marked decrease in coefficients of friction during sliding wear testing performed under simulated body fluid due to lubricant entrainment within the textured grooves. The texturing also resulted in significant reduction in surface contact area during the wear process, which considerably reduced the overall wear rates due to abrasive wear.展开更多
We refute the controversial statement that addiction is not a brain disorder. Extensive peer-reviewed studies support the underlying neurobiological and neurogenetic basis of addiction’s “disease model”. In the 70s...We refute the controversial statement that addiction is not a brain disorder. Extensive peer-reviewed studies support the underlying neurobiological and neurogenetic basis of addiction’s “disease model”. In the 70s and 80s, a few clinical scientists suggested that it is possible to use behavioral training to teach controlled drinking. However, this controversial model failed drastically and increased labeling and stigmatization. Additionally, it was unhelpful in the search for treatment. Instead, we assert that addiction is a neuropsychiatric disorder characterized by a recurring desire to continue taking substances despite harmful physical and mental consequences. Work from our laboratory in 1995 supported the Reward Deficiency Syndrome (RDS) concept based on a common neurogenetic mechanism (hypodopaminergia) that underlies all substance and non-substance addictions. Non-substance addictions include behaviors like pathological gambling, internet addiction, and mobile phone addiction. Certain impulsive and compulsive behaviors or the acute intake of psychoactive substances result in heightened dopaminergic activity, while the opposite, hypodopaminergia, occurs following chronic abuse. Patients with Substance Use Disorder (SUD) can have a genetic predisposition compounded by stress or other epigenetic insults that can impact recovery. Relapse will occur post-short-term recovery if dopaminergic dysfunction remains untreated. Addiction, a brain disorder, requires treatment with DNA-directed pro-dopamine regulation and rehabilitation.展开更多
Immunotherapy has attracted tremendous attention due to the remarkable clinical successes for treating a broad spectrum of tumors. One challenge for cancer immunotherapy is the inability to control localization and su...Immunotherapy has attracted tremendous attention due to the remarkable clinical successes for treating a broad spectrum of tumors. One challenge for cancer immunotherapy is the inability to control localization and sustain concentrations of therapeutics at tumor sites. Local drug delivery systems(LDDSs) like the biomaterial scaffold-based drug delivery systems have emerged as a promising approach for delivering immunotherapeutic agents facilely and intensively in situ with reduced systemic toxicity. In this review, recent advances in biomaterial scaffold-based LDDSs for the administration of immunotherapeutic agents including vaccines, immunomodulators, and immune cells are summarized. Moreover, codelivery systems are also evaluated for local immunotherapy-involving combination anti-tumor therapy,including chemotherapy-immunotherapy, photothermal-immunotherapy, and other combination therapies. Finally, the current challenges and future perspectives on the development of next-generation LDDSs for cancer immunotherapy are discussed.展开更多
Umbilical hernia occurs in 20% of the patients with liver cirrhosis complicated with ascites. Due to the enormous intraabdominal pressure secondary to the ascites, umbilical hernia in these patients has a tendency to ...Umbilical hernia occurs in 20% of the patients with liver cirrhosis complicated with ascites. Due to the enormous intraabdominal pressure secondary to the ascites, umbilical hernia in these patients has a tendency to enlarge rapidly and to complicate. The treatment of umbilical hernia in these patients is a surgical challenge. Ascites control is the mainstay to reduce hernia recurrence and postoperative complications, such as wound infection, evisceration, ascites drainage, and peritonitis. Intermittent paracentesis, temporary peritoneal dialysis catheter or transjugular intrahepatic portosystemic shunt may be necessary to control ascites. Hernia repair is indicated in patients in whom medical treatment is effective in controlling ascites. Patients who have a good perspective to be transplanted within 3-6 mo, herniorrhaphy should be performed during transplantation. Hernia repair with mesh is associated with lower recurrence rate, but with higher surgical site infection when compared to hernia correction with conventional fascial suture. There is no consensus on the best abdominal wall layer in which the mesh should be placed: Onlay, sublay, or underlay. Many studies have demonstrated several advantages of the laparoscopic umbilical herniorrhaphy in cirrhotic patients compared with open surgical treatment.展开更多
Background:Patients with inflatable penile prostheses(IPP)may experience erosions after years of use or after indwelling Foley catheter placement.IPP erosions should be managed as an infection with the entire IPP remo...Background:Patients with inflatable penile prostheses(IPP)may experience erosions after years of use or after indwelling Foley catheter placement.IPP erosions should be managed as an infection with the entire IPP removed.Replacing IPPs in erosion patients can be challenging due to extensive scarring development.Using proper graft materials may be necessary to close and reinforce the corporal defect after difficult corporal dilation or significant scar removal for the long‐term success of IPP reimplantation.Case Presentation:Herein we report a patient with a history of IPP placement in 2007 for erectile dysfunction and Peyronie's disease,presenting in 2018 with dysuria and a feeling of IPP displacement following Foley catheter placement for coronary artery bypass graft surgery.The left cylinder of the IPP was observed by physical examination and a defect near the fossa navicularis was discovered during office cystoscopy.A complete explantation of IPP was then performed.Reimplantation of the IPP was performed in 2021 which required excision of corporal scar tissue and repair of a left distal corporal defect using a Tutoplast®pericardium allograft.The procedure was successful with proper IPP position and good function without any penile deformity.Conclusion:The use of graft materials in the management of corporeal defects should be considered in the setting of complex IPP revision.The Tutoplast®pericardium allograft reinforcement can provide long‐term durability,flexibility,and a lower risk of infection.展开更多
JUNO is a multi-purpose neutrino observatory under construction in the south of China.This publication presents new sensitivity estimates for the measurement of the △m_(31)^(2),△m_(21)^(2),sin^(2)θ_(12),and sin^(2)...JUNO is a multi-purpose neutrino observatory under construction in the south of China.This publication presents new sensitivity estimates for the measurement of the △m_(31)^(2),△m_(21)^(2),sin^(2)θ_(12),and sin^(2)θ_(13) oscillation parameters using reactor antineutrinos,which is one of the primary physics goals of the experiment.The sensitivities are obtained using the best knowledge available to date on the location and overburden of the experimental site,the nuclear reactors in the surrounding area and beyond,the detector response uncertainties,and the reactor antineutrino spectral shape constraints expected from the TAO satellite detector.It is found that the △m_(21)^(2) and sin^(2)θ_(12) oscillation parameters will be determined to 0.5%precision or better in six years of data collection.In the same period,the △m_(31)^(2) parameter will be determined to about 0.2%precision for each mass ordering hypothesis.The new precision represents approximately an order of magnitude improvement over existing constraints for these three parameters.展开更多
We present a new approach for predicting spatial phase signals originating from photothermally excited metallic nanoparticles of arbitrary shapes and sizes.The heat emitted from such a nanoparticle affects the measure...We present a new approach for predicting spatial phase signals originating from photothermally excited metallic nanoparticles of arbitrary shapes and sizes.The heat emitted from such a nanoparticle affects the measured optical phase signal via changes in both the refractive index and thickness of the nanoparticle surroundings.Because these particles can be bio-functionalized to bind certain biological cell components,they can be used for biomedical imaging with molecular specificity,as new nanoscopy labels,and for photothermal therapy.Predicting the ideal nanoparticle parameters requires a model that computes the thermal and phase distributions around the particle,thereby enabling more efficient phase imaging of plasmonic nanoparticles and avoiding trial-and-error experiments while using unsuitable nanoparticles.The proposed nonlinear model is the first to enable the prediction of phase signatures from nanoparticles with arbitrary parameters.The model is based on a finite-volume method for geometry discretization and an implicit backward Euler method for solving the transient inhomogeneous heat equation,followed by calculation of the accumulative phase signal.To validate the model,we compared its results with experimental results obtained for gold nanorods of various concentrations,which we acquired using a custom-built wide-field interferometric phase microscopy system.展开更多
应用科技大学(FH-University of applied sciences)是德国的一类以培养应用型高级人才为目标的高等学校。本文通过讨论其准确的译名,介绍它的历史和现状,以及它目前正在实施的种种改革,廓清目前存在于中国的有关FH的不准确理解,并对中...应用科技大学(FH-University of applied sciences)是德国的一类以培养应用型高级人才为目标的高等学校。本文通过讨论其准确的译名,介绍它的历史和现状,以及它目前正在实施的种种改革,廓清目前存在于中国的有关FH的不准确理解,并对中国高等院校应借鉴德国FH的经验,培养应用型人才提出了有关建议。展开更多
This paper presents a procedure from which information contained in 3-Dimensional single energy X-ray computed tomography (XR-CT) images of sedimentary rocks is converted into sub-mm scale resolution core scalar and c...This paper presents a procedure from which information contained in 3-Dimensional single energy X-ray computed tomography (XR-CT) images of sedimentary rocks is converted into sub-mm scale resolution core scalar and core image logs. This new data provide a quantitative and compact (data volume reduction of ~90%) description of the XR-CT images. Density-related outputs are calibrated through automatic integration with continuous digital visual core description (VCD) and discrete moisture and density (MAD) property index measurements of selected samples. After lithology-based calibration of the X-ray attenuation coefficients into density values, quantitative displays include: 1) histogram of the distribution of density values and its related statistical parameters, 2) radial and angular distributions of core density values, 3) volume, average density and mass contributions of three core fractions defined by density thresholds corresponding to voids or vugs (VV, density ≤ ~1 g<span style="white-space:nowrap;">•</span>cm<sup><span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>3</sup>), and a break in the histogram of distribution of the density values showing the limit between the damaged (DM) and non-damaged (ND) fractions of the core material, and so, 4) providing a sub-mm scale bulk density core log free of any drilling disturbance. The procedure is illustrated on data from the 365 m deep Hole C9001C drilled off-shore Shimokita (northeast coast of Honshu, Japan). Usage of the outputs include: 1) derivation of sub-mm scale porosity core log, 2) correction of volume sensitive measurements in case of poor core quality and partially filled core liner, and 3) seismic modeling and well ties.展开更多
文摘AIM： To assess whether the effectiveness of a combination of transarterial chemoembolization （TACE） and percutaneous ethanol injection （PEI） in the treatment of unresectable hepatocellular carcinoma （HCC） is superior to TACE alone a randomized controlled trial was performed. METHODS： The effect of combination therapy on longterm survival rates and duration of hospitalization was evaluated in 52 previously untreated HCCs, randomly allocated to TACE-PEI （27 pts） or TACE alone （25 pts）. RESULTS： The cumulative survival rate of the TACE group was 75.8% at 6 mo, 62.9% at 12 mo, and 18.0% at 24 mo and of the TACE-PEI group 76.9%, 61.5%, and 38.7%, respectively. Comparison of overall survival in both groups showed no statistically significant difference. Regarding the patients with HCCs Okuda stage I （n = 26）, the median survival of the TACE-PEI group was significantly longer （〉24 mo, median not yet reached in the study period） compared to the TACE group （18.4 mo [range 11.6-21.7 mo]; P = 0.04）. TACE-PEI reduced the relative risk for mortality to 0.4 （95% CI 0.15-0.96） compared to patients who received TACE alone. Median survival in patients with HCCs Okuda stage Ⅱ or Ⅲ was 5.0 mo in the TACE group （1.7 rno-not defined） compared to 10.4 mo in the TACE-PEI group. CONCLUSION： The combination TACE-PEI improved survival time compared to TACE alone. Our study revealed a statistically significant improved survival in HCCs Okuda stage I. Side effects were minor and the combination therapy did not prolong duration of hospitalization considerably.
文摘Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, ＜5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC develop
基金Supported by Grants from Health Department of Hubei Province (JX2B09)NSFC (30771911)National 973 Key Program (2009CB522502), and Tongji Hospital
文摘AIM: To further analyze the interaction of tupaia CD81 with hepatitis C virus (HCV) envelope protein E2. METHODS: A tupaia CD81 large extracellular loop (CD81 LEL), which binds to HCV E2 protein, was cloned and expressed as a GST-fusion protein, and interaction of HCV E2 protein with a tupaia CD81 LEL was evaluated by enzyme-linked immunosorbent assay (EIA). RESULTS: Although tupaia and human CD81 LEL differed in 6 amino acid changes, tupaia CD81 LEL was strongly recognized by anti-CD81 antibodies against human CD81 LEL conformation-dependent epitopes. Investigating LEL CD81-E2 interactions by EIA, we demonstrated that binding of tupaia CD81 LEL GST fusion protein to recombinant HCV E2 protein was markedly reduced compared to binding of human CD81 LEL GST fusion protein to recombinant HCV E2 protein. CONCLUSION: These data suggest that the structural differences in-between the tupaia and human CD81 may alter the interaction of the large extracellular loop with HCV envelope glycoprotein E2. These findings may be important for the understanding of the mechanisms of binding and entry of HCV to PTHs.
文摘AIM： Different strains of bifidobacteria were analysed for their effects on HT-29 intestinal epithelial cells （IECs） in in vitro models both of the non-inflamed and inflamed intestinal epithelium. METHODS： A reporter gene system in HT-29 cells was used to measure levels of NF-KB activation after challenge with bifidobacteria or after bacterial pre-treatment following LPS challenge. IL-8 protein and pro-inflammatory gene expression was investigated using normal HT-29 cells. RESULTS： None of the bifidobacteria tested induced activation of nuclear factor κB （NF-κB） indicating that bifidobacteria themselves do not induce inflammatory events in IECs. However, six out of eight bifidobacteria tested inhibited lipopolysaccharide- （LPS-） induced NF-κB activation in a dose- and strain-dependent manner. In contrast, NF-κB activation in response to challenge with tumor necrosis factor-α （TNF-α） was affected by none of the tested bifidobacteria, indicating that the inhibitory effect of bifidobacteria is specific for LPS-induced inflammation in IECs. As shown with two of the six inhibitionpositive bifidobacteria, LPS-induced inhibition of NF-κB activation was accompanied by a dose-dependent decrease of interleukin 8 （IL-8） secretion and by lower mRNA levels for IL-8, TNF-α, cyclooxygenase 2 （Cox-2）, and intercellular adhesion molecule 1（ICAM-1）. CONCLUSION： Some strains of bifidobacteria are effective in inhibiting LPS-induced inflammation and thus might be appropriate candidates for probiotic intervention in chronic intestinal inflammation.
文摘AIM: To assess the anti-inflammatory effect of the probiotic Bifidobacterium lactis (B. lactis) in an adoptive transfer model of colitis. METHODS: Donor and recipient mice received either B. lactis or bacterial culture medium as control (deMan Rogosa Sharpe) in drinking water for one week prior to transfer of a mix of naive and regulatory T cells until sacrifice. RESULTS: All recipient mice developed signs of colonic inflammation, but a significant reduction of weight loss was observed in B. lactis-fed recipient mice compared to control mice. Moreover, a trend toward a diminution of mucosal thickness and attenuated epithelial damage was revealed. Colonic expression of pro-inflammatory and T cell markers was significantly reduced in B. lactis-fed recipient mice compared to controls. Concomitantly, forkhead box protein 3, a marker of regulatory T cells, was significantly up-regulated by B. lactis. CONCLUSION: Daily oral administration of B. lactis was able to reduce inflammatory and T cells mediators and to promote regulatory T cells specific markers in a mouse model of colitis.
文摘Gastric cancer represents a serious health problem on a global scale. It is the second leading cause of cancer-related death worldwide. Novel therapeutic targets are desperately needed because the meager improvement in the cure rate of about 10% realized by adjunctive treatments to surgery is unacceptable as > 50% patients with localized gastric cancer succumb to their disease. Either postoperative chemoradiotherapy (United States), pre-and post-operative chemotherapy (Europe), and adjuvant chemotherapy after a D2 resection (Asia) can all be regarded as standards of care in the localized gastric cancer management. In metastatic disease the addition of trastuzumab to chemotherapy is standard of care in Her2 positive disease. In the HER2 negative population, the treatments remain limited. In the first line setting, the standard of care is a combination of fluoropyrimidine and platinum containing chemotherapy, with or without epirubicin or docetaxel. The results of targeted therapy trials have by and large been disappointing, but none of these trials looked at an appropriately enriched population. Finally there is a meager overall survival benefit in treating patients with metastatic disease in the second line setting, with either irinotecan, docetaxel or ramucirumab however none of these drugs have been compared head to head in a well-powered randomized controlled trial.
文摘Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and TNFα occur. Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. For virtually all HCV proteins, pro- and anti-apoptotic effects have been described, especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or anti- apoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades.
基金supported by the Chinese Academy of Sciencesthe National Key R&D Program of China+22 种基金the CAS Center for Excellence in Particle PhysicsWuyi Universitythe Tsung-Dao Lee Institute of Shanghai Jiao Tong University in Chinathe Institut National de Physique Nucléaire et de Physique de Particules (IN2P3) in Francethe Istituto Nazionale di Fisica Nucleare (INFN) in Italythe Italian-Chinese collaborative research program MAECI-NSFCthe Fond de la Recherche Scientifique (F.R.S-FNRS)FWO under the "Excellence of Science-EOS" in Belgiumthe Conselho Nacional de Desenvolvimento Científico e Tecnològico in Brazilthe Agencia Nacional de Investigacion y Desarrollo in Chilethe Charles University Research Centrethe Ministry of Education,Youth,and Sports in Czech Republicthe Deutsche Forschungsgemeinschaft (DFG)the Helmholtz Associationthe Cluster of Excellence PRISMA+ in Germanythe Joint Institute of Nuclear Research (JINR)Lomonosov Moscow State University in Russiathe joint Russian Science Foundation (RSF)National Natural Science Foundation of China (NSFC) research programthe MOST and MOE in Taiwan,Chinathe Chulalongkorn UniversitySuranaree University of Technology in Thailandthe University of California at Irvine in USA
文摘The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK^(+)mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification.Moreover,the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals.Based on these advantages,the detection efficiency for the proton decay via p→νK^(+)is 36.9%±4.9%with a background level of 0.2±0.05(syst)±0.2(stat)events after 10 years of data collection.The estimated sensitivity based on 200 kton-years of exposure is 9.6×1033 years,which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies.
基金supported by the U.S. National Science Foundation (NSF CAREER Award No. CMMI-1149079)
文摘Ultrasonic vibration-assisted laser surface processing that involves application of vertical ultrasonic vibrations to the Ti-6 Al-4 V alloy substrates while being irradiated with a CO_2 laser was performed for the development of laser melted and textured surfaces with potential applications in biomedical implants.The laser processing resulted in very consistent repeating undulating grooved surfaces, and the undulations were significantly more pronounced in the samples processed with higher ultrasonic power outputs.The phase evolution, studied by x-ray diffraction, confirmed that the laser processing triggered transformation of globular α→ acicular α and martensitic α' as well as increased amounts of retained α phases,which were also reflected in the microscopic analysis. The surface texture developed by laser processing resulted in increased surface wettability with increasing ultrasonic power output. The textured surfaces exhibited marked decrease in coefficients of friction during sliding wear testing performed under simulated body fluid due to lubricant entrainment within the textured grooves. The texturing also resulted in significant reduction in surface contact area during the wear process, which considerably reduced the overall wear rates due to abrasive wear.
文摘We refute the controversial statement that addiction is not a brain disorder. Extensive peer-reviewed studies support the underlying neurobiological and neurogenetic basis of addiction’s “disease model”. In the 70s and 80s, a few clinical scientists suggested that it is possible to use behavioral training to teach controlled drinking. However, this controversial model failed drastically and increased labeling and stigmatization. Additionally, it was unhelpful in the search for treatment. Instead, we assert that addiction is a neuropsychiatric disorder characterized by a recurring desire to continue taking substances despite harmful physical and mental consequences. Work from our laboratory in 1995 supported the Reward Deficiency Syndrome (RDS) concept based on a common neurogenetic mechanism (hypodopaminergia) that underlies all substance and non-substance addictions. Non-substance addictions include behaviors like pathological gambling, internet addiction, and mobile phone addiction. Certain impulsive and compulsive behaviors or the acute intake of psychoactive substances result in heightened dopaminergic activity, while the opposite, hypodopaminergia, occurs following chronic abuse. Patients with Substance Use Disorder (SUD) can have a genetic predisposition compounded by stress or other epigenetic insults that can impact recovery. Relapse will occur post-short-term recovery if dopaminergic dysfunction remains untreated. Addiction, a brain disorder, requires treatment with DNA-directed pro-dopamine regulation and rehabilitation.
基金supported by the National Natural Science Foundation of China (31900945)Basic Research Program of Shenzhen(JCYJ20170412111100742, JCYJ20180507182413022)+2 种基金Fok YingTong Education Foundation for Young Teachers in the Higher Education Institutions of China (161032)Postdoctoral Science Foundation of China (2018M643175)Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (2018B030308003)。
文摘Immunotherapy has attracted tremendous attention due to the remarkable clinical successes for treating a broad spectrum of tumors. One challenge for cancer immunotherapy is the inability to control localization and sustain concentrations of therapeutics at tumor sites. Local drug delivery systems(LDDSs) like the biomaterial scaffold-based drug delivery systems have emerged as a promising approach for delivering immunotherapeutic agents facilely and intensively in situ with reduced systemic toxicity. In this review, recent advances in biomaterial scaffold-based LDDSs for the administration of immunotherapeutic agents including vaccines, immunomodulators, and immune cells are summarized. Moreover, codelivery systems are also evaluated for local immunotherapy-involving combination anti-tumor therapy,including chemotherapy-immunotherapy, photothermal-immunotherapy, and other combination therapies. Finally, the current challenges and future perspectives on the development of next-generation LDDSs for cancer immunotherapy are discussed.
文摘Umbilical hernia occurs in 20% of the patients with liver cirrhosis complicated with ascites. Due to the enormous intraabdominal pressure secondary to the ascites, umbilical hernia in these patients has a tendency to enlarge rapidly and to complicate. The treatment of umbilical hernia in these patients is a surgical challenge. Ascites control is the mainstay to reduce hernia recurrence and postoperative complications, such as wound infection, evisceration, ascites drainage, and peritonitis. Intermittent paracentesis, temporary peritoneal dialysis catheter or transjugular intrahepatic portosystemic shunt may be necessary to control ascites. Hernia repair is indicated in patients in whom medical treatment is effective in controlling ascites. Patients who have a good perspective to be transplanted within 3-6 mo, herniorrhaphy should be performed during transplantation. Hernia repair with mesh is associated with lower recurrence rate, but with higher surgical site infection when compared to hernia correction with conventional fascial suture. There is no consensus on the best abdominal wall layer in which the mesh should be placed: Onlay, sublay, or underlay. Many studies have demonstrated several advantages of the laparoscopic umbilical herniorrhaphy in cirrhotic patients compared with open surgical treatment.
文摘Background:Patients with inflatable penile prostheses(IPP)may experience erosions after years of use or after indwelling Foley catheter placement.IPP erosions should be managed as an infection with the entire IPP removed.Replacing IPPs in erosion patients can be challenging due to extensive scarring development.Using proper graft materials may be necessary to close and reinforce the corporal defect after difficult corporal dilation or significant scar removal for the long‐term success of IPP reimplantation.Case Presentation:Herein we report a patient with a history of IPP placement in 2007 for erectile dysfunction and Peyronie's disease,presenting in 2018 with dysuria and a feeling of IPP displacement following Foley catheter placement for coronary artery bypass graft surgery.The left cylinder of the IPP was observed by physical examination and a defect near the fossa navicularis was discovered during office cystoscopy.A complete explantation of IPP was then performed.Reimplantation of the IPP was performed in 2021 which required excision of corporal scar tissue and repair of a left distal corporal defect using a Tutoplast®pericardium allograft.The procedure was successful with proper IPP position and good function without any penile deformity.Conclusion:The use of graft materials in the management of corporeal defects should be considered in the setting of complex IPP revision.The Tutoplast®pericardium allograft reinforcement can provide long‐term durability,flexibility,and a lower risk of infection.
基金Supported by the Chinese Academy of Sciencesthe National Key R&D Program of China+18 种基金the CAS Center for Excellence in Particle Physics,Wuyi Universitythe Tsung-Dao Lee Institute of Shanghai Jiao Tong University in Chinathe Institut National de Physique Nucléaire et de Physique de Particules(IN2P3)in Francethe Istituto Nazionale di Fisica Nucleare(INFN)in Italythe Italian-Chinese collaborative research program MAECI-NSFCthe Fond de la Recherche Scientifique(F.R.S-FNRS)FWO under the“Excellence of Science-EOS in Belgium”the Conselho Nacional de Desenvolvimento Científico e Tecnològico in Brazilthe Agencia Nacional de Investigacion y Desarrollo and ANID-Millennium Science Initiative Program-ICN2019_044 in Chilethe Charles University Research Centre and the Ministry of Education,Youth,and Sports in Czech Republicthe Deutsche Forschungsgemeinschaft(DFG)the Helmholtz Associationthe Cluster of Excellence PRISMA+in Germanythe Joint Institute of Nuclear Research(JINR)and Lomonosov Moscow State University in Russiathe joint Russian Science Foundation(RSF)National Natural Science Foundation of China(NSFC)research programthe MOST and MOE in Taiwanthe Chulalongkorn University and Suranaree University of Technology in Thailand,University of California at Irvinethe National Science Foundation in USA。
文摘JUNO is a multi-purpose neutrino observatory under construction in the south of China.This publication presents new sensitivity estimates for the measurement of the △m_(31)^(2),△m_(21)^(2),sin^(2)θ_(12),and sin^(2)θ_(13) oscillation parameters using reactor antineutrinos,which is one of the primary physics goals of the experiment.The sensitivities are obtained using the best knowledge available to date on the location and overburden of the experimental site,the nuclear reactors in the surrounding area and beyond,the detector response uncertainties,and the reactor antineutrino spectral shape constraints expected from the TAO satellite detector.It is found that the △m_(21)^(2) and sin^(2)θ_(12) oscillation parameters will be determined to 0.5%precision or better in six years of data collection.In the same period,the △m_(31)^(2) parameter will be determined to about 0.2%precision for each mass ordering hypothesis.The new precision represents approximately an order of magnitude improvement over existing constraints for these three parameters.
基金This work was supported by the FP7 Marie Curie Career Integration Grant(CIG)No.303559.
文摘We present a new approach for predicting spatial phase signals originating from photothermally excited metallic nanoparticles of arbitrary shapes and sizes.The heat emitted from such a nanoparticle affects the measured optical phase signal via changes in both the refractive index and thickness of the nanoparticle surroundings.Because these particles can be bio-functionalized to bind certain biological cell components,they can be used for biomedical imaging with molecular specificity,as new nanoscopy labels,and for photothermal therapy.Predicting the ideal nanoparticle parameters requires a model that computes the thermal and phase distributions around the particle,thereby enabling more efficient phase imaging of plasmonic nanoparticles and avoiding trial-and-error experiments while using unsuitable nanoparticles.The proposed nonlinear model is the first to enable the prediction of phase signatures from nanoparticles with arbitrary parameters.The model is based on a finite-volume method for geometry discretization and an implicit backward Euler method for solving the transient inhomogeneous heat equation,followed by calculation of the accumulative phase signal.To validate the model,we compared its results with experimental results obtained for gold nanorods of various concentrations,which we acquired using a custom-built wide-field interferometric phase microscopy system.
文摘应用科技大学(FH-University of applied sciences)是德国的一类以培养应用型高级人才为目标的高等学校。本文通过讨论其准确的译名,介绍它的历史和现状,以及它目前正在实施的种种改革,廓清目前存在于中国的有关FH的不准确理解,并对中国高等院校应借鉴德国FH的经验,培养应用型人才提出了有关建议。
文摘This paper presents a procedure from which information contained in 3-Dimensional single energy X-ray computed tomography (XR-CT) images of sedimentary rocks is converted into sub-mm scale resolution core scalar and core image logs. This new data provide a quantitative and compact (data volume reduction of ~90%) description of the XR-CT images. Density-related outputs are calibrated through automatic integration with continuous digital visual core description (VCD) and discrete moisture and density (MAD) property index measurements of selected samples. After lithology-based calibration of the X-ray attenuation coefficients into density values, quantitative displays include: 1) histogram of the distribution of density values and its related statistical parameters, 2) radial and angular distributions of core density values, 3) volume, average density and mass contributions of three core fractions defined by density thresholds corresponding to voids or vugs (VV, density ≤ ~1 g<span style="white-space:nowrap;">•</span>cm<sup><span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>3</sup>), and a break in the histogram of distribution of the density values showing the limit between the damaged (DM) and non-damaged (ND) fractions of the core material, and so, 4) providing a sub-mm scale bulk density core log free of any drilling disturbance. The procedure is illustrated on data from the 365 m deep Hole C9001C drilled off-shore Shimokita (northeast coast of Honshu, Japan). Usage of the outputs include: 1) derivation of sub-mm scale porosity core log, 2) correction of volume sensitive measurements in case of poor core quality and partially filled core liner, and 3) seismic modeling and well ties.
