目的:探讨微环境中Ⅸ型胶原α1(collagen type IX alpha 1 chain,COL9A1)在结直肠腺癌中的表达及其与肿瘤进展的相关性和临床意义。方法:收集2012年1月至2021年1月手术切除的结直肠癌标本408例,采用免疫组织化学检测结直肠腺癌肿瘤组织...目的:探讨微环境中Ⅸ型胶原α1(collagen type IX alpha 1 chain,COL9A1)在结直肠腺癌中的表达及其与肿瘤进展的相关性和临床意义。方法:收集2012年1月至2021年1月手术切除的结直肠癌标本408例,采用免疫组织化学检测结直肠腺癌肿瘤组织及癌旁正常组织中COL9A1表达,同时检测肿瘤组织中肿瘤蛋白53(tumor protein 53,P53)和错配修复(mismatch repair,MMR)蛋白MLH1、MSH6和PMS2的表达,统计分析COL9A1的表达与各临床病理特征参数的关系,以及与P53突变和MMR状态的相关性,并分析COL9A1阳性表达患者的预后情况。结果:COL9A1在结直肠腺癌肿瘤组织中表达显著低于癌旁正常组织(P<0.001);COL9A1的表达与肿瘤浸润深度、临床分期和肠系膜淋巴结转移有关(χ^(2)=16.943、89.031和84.814;均P<0.001),而与P53突变和MMR状态无关(χ^(2)=0.677、1.260,均P>0.05);Log-rank检验显示COL9A1阴性表达患者的无进展生存期(progression free survival,PFS)和总体生存期(overall survival,OS)显著低于COL9A1阳性表达患者(分别P<0.001,P=0.040)。结论:结直肠腺癌中COL9A1蛋白的表达缺失与肿瘤浸润及转移密切相关,并提示不良预后,这可为结直肠癌预后评估、药物筛选等提供可能的分子标志物和治疗策略。展开更多
BACKGROUND At present,the enhanced recovery after surgery(ERAS)protocol is widely implemented in the field of gastric surgery.However,the effect of the ERAS protocol on the long-term prognosis of gastric cancer has no...BACKGROUND At present,the enhanced recovery after surgery(ERAS)protocol is widely implemented in the field of gastric surgery.However,the effect of the ERAS protocol on the long-term prognosis of gastric cancer has not been reported.AIM To compare the effects of ERAS and conventional protocols on short-term outcomes and long-term prognosis after laparoscopic gastrectomy.METHODS We retrospectively analyzed the data of 1026 consecutive patients who underwent laparoscopic gastrectomy between 2012 and 2015.The patients were divided into either an ERAS group or a conventional group.The groups were matched in a 1:1 ratio using propensity scores based on covariates that affect cancer survival.The primary outcomes were the 5-year overall and cancer-specific survival rates.The secondary outcomes were the postoperative short-term outcomes and inflammatory indexes.RESULTS The patient demographics and baseline characteristics were similar between the two groups after matching.Compared to the conventional group,the ERAS group had a significantly shorter postoperative hospital day(7.09 d vs 8.67 d,P<0.001),shorter time to first flatus,liquid intake,and ambulation(2.50 d vs 3.40 d,P<0.001;1.02 d vs 3.64 d,P<0.001;1.47 d vs 2.99 d,P<0.001,respectively),and lower medical costs($7621.75 vs$7814.16,P=0.009).There was a significantly higher rate of postoperative complications among patients in the conventional group than among those in the ERAS group(18.1 vs 12.3,P=0.030).Regarding inflammatory indexes,the C-reactive protein and procalcitonin levels on postoperative day 3/4 were significantly different between the two groups(P<0.001 and P=0.025,respectively).The ERAS protocol was associated with significantly improved 5-year overall survival and cancer-specific survival rates compared with conventional protocol(P=0.013 and 0.032,respectively).When stratified by tumour stage,only the survival of patients with stage III disease was significantly different between the two groups(P=0.044).CONCLUSION Adherence to the ERAS protocol improves both the short-term outcomes and the 5-year overall survival and cancer-specific survival of patients after laparoscopic gastrectomy.展开更多
Black phosphorus(BP)nano-materials,especially BP quantum dots(BPQDs),performs outstanding photothermal antitumor effects,excellent biocompatibility and biodegradability.However,there are several challenges to overcome...Black phosphorus(BP)nano-materials,especially BP quantum dots(BPQDs),performs outstanding photothermal antitumor effects,excellent biocompatibility and biodegradability.However,there are several challenges to overcome before offering real benefits,such as poor stability,poor dispersibility as well as difficulty in tailoring other functions.Here,a“three-in-one”mitochondria-targeted BP nano-platform,called as BPQD-PEG-TPP,was designed.In this nano-platform,BPQDs were covalently grafted with a heterobifunctional PEG,in which one end was an aryl diazo group capable of reacting with BPQDs to form a covalent bond and the other end was a mitochondria-targeted triphenylphosphine(TPP)group.In addition to its excellent near-infrared photothermal properties,BPQD-PEG-TPP had much enhanced stability and dispersibility under physiological conditions,efficient mitochondria targeting and promoted ROS production through a photothermal effect.Both in vitro and in vivo experiments demonstrated that BPQD-PEG-TPP performed much superior photothermal cytotoxicity than BPQDs and BPQD-PEG as the mitochondria targeted PTT.Thus this“three-in-one”nanoplatform fabricated through polymer grafting,with excellent stability,dispersibility and negligible side effects,might be a promising strategy for mitochondria-targeted photothermal cancer therapy.展开更多
Dynamic spectrum access (DSA) scheme in Cognitive Radio (CR) can solve the current problem of scarce spectrum resource effectively, in which the unlicensed users (i.e. Second Users, SUs) can access the licensed spectr...Dynamic spectrum access (DSA) scheme in Cognitive Radio (CR) can solve the current problem of scarce spectrum resource effectively, in which the unlicensed users (i.e. Second Users, SUs) can access the licensed spectrum in opportunistic ways without interference to the licensed users (i.e. Primary Users, PUs). However, SUs have to vacate the spectrum because of PUs coming, in this case the spectrum switch occurs, and it leads to the increasing of SUs’ delay. In this paper, we proposed a Variable Service Rate (VSR) scheme with the switch buffer as to real-time traffic (such as VoIP, Video), in order to decrease the average switch delay of SUs and improve the other performance. Different from previous studies, the main characteristics of our studying of VSR in this paper as follows: 1) Our study is on the condition of real-time traffic and we establish three-dimension Markov model;2) Using the internal optimization strategy, including switching buffer, optimizing buffer and variable service rate;3) As to the real-time traffic, on the condition of meeting the Quality of Service(QoS) on dropping probability, the average switch delay is decreased as well as improving the other performance. By extensive simulation and numerical analysis, the performance of real-time traffic is improved greatly on the condition of ensuring its dropping probability. The result fully demonstrates the feasibility and effectiveness of the variable service rate scheme.展开更多
Protein therap34 wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of e...Protein therap34 wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of efficient strategies for delivering proteins and the rapid clearance of therapeutic proteins in vivo after their administration. Here, we demonstrate a novel strategy that can significantly prolong the circulation time of therapeutic proteins as well as minimize their immunogenicity. This is achieved by encapsulating individual protein molecules with a thin layer of crosslinked phosphorylcholine polymer that resists protein adsorption. Through extensive cellular studies, we demonstrate that the crosslinked phosphorylcholine polymer shell effectively prevents the encapsulated protein from being phagocytosed by macrophages, which play an essential role in the clearance of nanoparfides in vivo. Moreover, the polymer shell prevents the encapsulated protein from being identified by immune cells. As a result, immune responses against the therapeutic protein are effectively suppressed. This work describes a feasible method to prolong the circulation time and reduce the immunogenicity of therapeutic proteins, which may promote the development and application of novel protein therapies in the treatment of diverse diseases.展开更多
Short in vivo circulation is a major hindrance to the widespread adoption of protein therapeutics. Protein nanocapsules generated by encapsulating proteins with a thin layer of phosphorylcholine-based polymer via a tw...Short in vivo circulation is a major hindrance to the widespread adoption of protein therapeutics. Protein nanocapsules generated by encapsulating proteins with a thin layer of phosphorylcholine-based polymer via a two-step encapsulation process exhibited significantly prolonged plasma half-life. Furthermore, by constructing nanocapsules with similar sizes but different surface charges and chemistry, we demonstrated a generic strategy for prolonging the plasma half-life of therapeutic proteins. In an in vitro experiment, four types of bovine serum albumin （BSA） nanocapsules were incubated with fetal bovine serum （FBS） in phosphate buffer saline （PBS）; the cell uptake by HeLa cells was monitored to systematically evaluate the characteristics of the surface chemistry during drculation. Single positron emission tomography-computed tomography （SPECT） was employed to allow real-time observation of the BSA nanoparticle distribution in vivo, as well as quantification of the plasma concentration after intravenous administration. This study offers a practical method for translating a broad range of proteins for clinical use.展开更多
A series of new oxyapatite red phosphors Ca_(3) Y_(7)(BO_(4)) (SiO_(4))_(5) O doped with different concentrations of Eu^(3+)were successfully synthesized by high temperature solid state method.The X-ray diffraction(XR...A series of new oxyapatite red phosphors Ca_(3) Y_(7)(BO_(4)) (SiO_(4))_(5) O doped with different concentrations of Eu^(3+)were successfully synthesized by high temperature solid state method.The X-ray diffraction(XRD)Rietveld refinement results show that the structure of the phosphor belongs to space group P6_(3)/m and Eu^(3+)ion replaces Y^(3+)ion.The emission spectrum consists of the characteristic emission peaks corresponding to Eu^(3+)under the excitation of 274 nm and the dominant emission peak is at 614 nm(^(5)D_(0)→^(7)F_(2) of Eu^(3+)).The concentration quenching effect occurs and the optimized Eu^(3+)concentration is 4.0 mol%.The energy level diagram for luminous mechanism is also given and the non-radiative energy transfer mechanism between Eu^(3+)is mainly exchange interaction.The CIE coordinate is close to the ideal red light and the color purity is higher than 99.79%.Moreover,the phosphor exhibits moderate thermal stability because the photoluminescence intensity at 423 K is still maintained at higher than 78.97%of that at room temperature.The internal quantum efficiency of Ca_(3) Y_(7)(BO_(4)) (SiO_(4))_(5) O:4.0 mol%Eu^(3+)phosphor is 58.2%.A red light emitting diode(LED)device based on it can emit bright red light.The CCT values of the device are basically unchanged when driven by various bias current.The results show that Ca_(3) Y_(7)(BO_(4)) (SiO_(4))_(5) O:Eu^(3+)is a new type of oxyapatite red fluorescent material with good comprehensive performances.展开更多
Moderate level of exposure to the solar irradiation containing UV component is essential for health care. To incorporate the UV-emitting phosphors into the commercial YAG-based white light-emitting diode introduces th...Moderate level of exposure to the solar irradiation containing UV component is essential for health care. To incorporate the UV-emitting phosphors into the commercial YAG-based white light-emitting diode introduces the possibilities of healthy illumination to individuals＇ daily lives. 1 mol.% E3＊-doped BaGd2ZnO5（BGZ） particles were synthesized via sol-gel method and efficient up-converted luminescence peaked at 380 nm was detected under 480 nm excitation. The mixed phosphors with varied mass ratio of Er3＋：BGZ and Ce3＋：YAG particles were encapsulated to form LEDs. The study of the LEDs indicated that the introduction of BGZ component favored the enhancement of color-rendering index and the neutralization of the white light emitting. The WLED with the BGZ/YAG ratio of 8：2 was recommendable for its excellent overall white light luminous performances and UV intensity of 84.55 mW/cm2. The UV illumination dose of the WLEDs with mixed YAG and BGZ was controllable by adjusting the ratio, the illumination distance and the illumination time. Er3＋：BGZ phosphors are promising UV- emitting phosphors for healthy indoor illumination.展开更多
文摘目的:探讨微环境中Ⅸ型胶原α1(collagen type IX alpha 1 chain,COL9A1)在结直肠腺癌中的表达及其与肿瘤进展的相关性和临床意义。方法:收集2012年1月至2021年1月手术切除的结直肠癌标本408例,采用免疫组织化学检测结直肠腺癌肿瘤组织及癌旁正常组织中COL9A1表达,同时检测肿瘤组织中肿瘤蛋白53(tumor protein 53,P53)和错配修复(mismatch repair,MMR)蛋白MLH1、MSH6和PMS2的表达,统计分析COL9A1的表达与各临床病理特征参数的关系,以及与P53突变和MMR状态的相关性,并分析COL9A1阳性表达患者的预后情况。结果:COL9A1在结直肠腺癌肿瘤组织中表达显著低于癌旁正常组织(P<0.001);COL9A1的表达与肿瘤浸润深度、临床分期和肠系膜淋巴结转移有关(χ^(2)=16.943、89.031和84.814;均P<0.001),而与P53突变和MMR状态无关(χ^(2)=0.677、1.260,均P>0.05);Log-rank检验显示COL9A1阴性表达患者的无进展生存期(progression free survival,PFS)和总体生存期(overall survival,OS)显著低于COL9A1阳性表达患者(分别P<0.001,P=0.040)。结论:结直肠腺癌中COL9A1蛋白的表达缺失与肿瘤浸润及转移密切相关,并提示不良预后,这可为结直肠癌预后评估、药物筛选等提供可能的分子标志物和治疗策略。
文摘BACKGROUND At present,the enhanced recovery after surgery(ERAS)protocol is widely implemented in the field of gastric surgery.However,the effect of the ERAS protocol on the long-term prognosis of gastric cancer has not been reported.AIM To compare the effects of ERAS and conventional protocols on short-term outcomes and long-term prognosis after laparoscopic gastrectomy.METHODS We retrospectively analyzed the data of 1026 consecutive patients who underwent laparoscopic gastrectomy between 2012 and 2015.The patients were divided into either an ERAS group or a conventional group.The groups were matched in a 1:1 ratio using propensity scores based on covariates that affect cancer survival.The primary outcomes were the 5-year overall and cancer-specific survival rates.The secondary outcomes were the postoperative short-term outcomes and inflammatory indexes.RESULTS The patient demographics and baseline characteristics were similar between the two groups after matching.Compared to the conventional group,the ERAS group had a significantly shorter postoperative hospital day(7.09 d vs 8.67 d,P<0.001),shorter time to first flatus,liquid intake,and ambulation(2.50 d vs 3.40 d,P<0.001;1.02 d vs 3.64 d,P<0.001;1.47 d vs 2.99 d,P<0.001,respectively),and lower medical costs($7621.75 vs$7814.16,P=0.009).There was a significantly higher rate of postoperative complications among patients in the conventional group than among those in the ERAS group(18.1 vs 12.3,P=0.030).Regarding inflammatory indexes,the C-reactive protein and procalcitonin levels on postoperative day 3/4 were significantly different between the two groups(P<0.001 and P=0.025,respectively).The ERAS protocol was associated with significantly improved 5-year overall survival and cancer-specific survival rates compared with conventional protocol(P=0.013 and 0.032,respectively).When stratified by tumour stage,only the survival of patients with stage III disease was significantly different between the two groups(P=0.044).CONCLUSION Adherence to the ERAS protocol improves both the short-term outcomes and the 5-year overall survival and cancer-specific survival of patients after laparoscopic gastrectomy.
基金We are grateful for the financial support from National Natural Science Foundation of China(51703258,81772449 and 81971081)Guangzhou science technology and innovation commission(201804010309 and 201803010090)Science,Technology&Innovation Commission of Shenzhen Municipality(JCYJ20180307154606793 and JCYJ20180507181654186).
文摘Black phosphorus(BP)nano-materials,especially BP quantum dots(BPQDs),performs outstanding photothermal antitumor effects,excellent biocompatibility and biodegradability.However,there are several challenges to overcome before offering real benefits,such as poor stability,poor dispersibility as well as difficulty in tailoring other functions.Here,a“three-in-one”mitochondria-targeted BP nano-platform,called as BPQD-PEG-TPP,was designed.In this nano-platform,BPQDs were covalently grafted with a heterobifunctional PEG,in which one end was an aryl diazo group capable of reacting with BPQDs to form a covalent bond and the other end was a mitochondria-targeted triphenylphosphine(TPP)group.In addition to its excellent near-infrared photothermal properties,BPQD-PEG-TPP had much enhanced stability and dispersibility under physiological conditions,efficient mitochondria targeting and promoted ROS production through a photothermal effect.Both in vitro and in vivo experiments demonstrated that BPQD-PEG-TPP performed much superior photothermal cytotoxicity than BPQDs and BPQD-PEG as the mitochondria targeted PTT.Thus this“three-in-one”nanoplatform fabricated through polymer grafting,with excellent stability,dispersibility and negligible side effects,might be a promising strategy for mitochondria-targeted photothermal cancer therapy.
文摘Dynamic spectrum access (DSA) scheme in Cognitive Radio (CR) can solve the current problem of scarce spectrum resource effectively, in which the unlicensed users (i.e. Second Users, SUs) can access the licensed spectrum in opportunistic ways without interference to the licensed users (i.e. Primary Users, PUs). However, SUs have to vacate the spectrum because of PUs coming, in this case the spectrum switch occurs, and it leads to the increasing of SUs’ delay. In this paper, we proposed a Variable Service Rate (VSR) scheme with the switch buffer as to real-time traffic (such as VoIP, Video), in order to decrease the average switch delay of SUs and improve the other performance. Different from previous studies, the main characteristics of our studying of VSR in this paper as follows: 1) Our study is on the condition of real-time traffic and we establish three-dimension Markov model;2) Using the internal optimization strategy, including switching buffer, optimizing buffer and variable service rate;3) As to the real-time traffic, on the condition of meeting the Quality of Service(QoS) on dropping probability, the average switch delay is decreased as well as improving the other performance. By extensive simulation and numerical analysis, the performance of real-time traffic is improved greatly on the condition of ensuring its dropping probability. The result fully demonstrates the feasibility and effectiveness of the variable service rate scheme.
基金This work is supported by the National Natural Science Foundation of China （NSFC, Nos. 91127045, 51390483, 51473319, 51303025, 81401439 and 51343007）, YG2012MS38 and China Postdoctoral Science Foundation （No. 2014M551399）.
文摘Protein therap34 wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of efficient strategies for delivering proteins and the rapid clearance of therapeutic proteins in vivo after their administration. Here, we demonstrate a novel strategy that can significantly prolong the circulation time of therapeutic proteins as well as minimize their immunogenicity. This is achieved by encapsulating individual protein molecules with a thin layer of crosslinked phosphorylcholine polymer that resists protein adsorption. Through extensive cellular studies, we demonstrate that the crosslinked phosphorylcholine polymer shell effectively prevents the encapsulated protein from being phagocytosed by macrophages, which play an essential role in the clearance of nanoparfides in vivo. Moreover, the polymer shell prevents the encapsulated protein from being identified by immune cells. As a result, immune responses against the therapeutic protein are effectively suppressed. This work describes a feasible method to prolong the circulation time and reduce the immunogenicity of therapeutic proteins, which may promote the development and application of novel protein therapies in the treatment of diverse diseases.
基金This work is supported by the National Natural Science Foundation of China （NSFC, Nos. 51343007, 81271612 and 81401439）, Shanghai Pujiang Program （No. 13PJD022）, and Shanghai Health Bureau Fund （No. 20124016）.
文摘Short in vivo circulation is a major hindrance to the widespread adoption of protein therapeutics. Protein nanocapsules generated by encapsulating proteins with a thin layer of phosphorylcholine-based polymer via a two-step encapsulation process exhibited significantly prolonged plasma half-life. Furthermore, by constructing nanocapsules with similar sizes but different surface charges and chemistry, we demonstrated a generic strategy for prolonging the plasma half-life of therapeutic proteins. In an in vitro experiment, four types of bovine serum albumin （BSA） nanocapsules were incubated with fetal bovine serum （FBS） in phosphate buffer saline （PBS）; the cell uptake by HeLa cells was monitored to systematically evaluate the characteristics of the surface chemistry during drculation. Single positron emission tomography-computed tomography （SPECT） was employed to allow real-time observation of the BSA nanoparticle distribution in vivo, as well as quantification of the plasma concentration after intravenous administration. This study offers a practical method for translating a broad range of proteins for clinical use.
基金Project supported by the National Natural Science Foundation of China(51972213,61605116,51972208,51802196).
文摘A series of new oxyapatite red phosphors Ca_(3) Y_(7)(BO_(4)) (SiO_(4))_(5) O doped with different concentrations of Eu^(3+)were successfully synthesized by high temperature solid state method.The X-ray diffraction(XRD)Rietveld refinement results show that the structure of the phosphor belongs to space group P6_(3)/m and Eu^(3+)ion replaces Y^(3+)ion.The emission spectrum consists of the characteristic emission peaks corresponding to Eu^(3+)under the excitation of 274 nm and the dominant emission peak is at 614 nm(^(5)D_(0)→^(7)F_(2) of Eu^(3+)).The concentration quenching effect occurs and the optimized Eu^(3+)concentration is 4.0 mol%.The energy level diagram for luminous mechanism is also given and the non-radiative energy transfer mechanism between Eu^(3+)is mainly exchange interaction.The CIE coordinate is close to the ideal red light and the color purity is higher than 99.79%.Moreover,the phosphor exhibits moderate thermal stability because the photoluminescence intensity at 423 K is still maintained at higher than 78.97%of that at room temperature.The internal quantum efficiency of Ca_(3) Y_(7)(BO_(4)) (SiO_(4))_(5) O:4.0 mol%Eu^(3+)phosphor is 58.2%.A red light emitting diode(LED)device based on it can emit bright red light.The CCT values of the device are basically unchanged when driven by various bias current.The results show that Ca_(3) Y_(7)(BO_(4)) (SiO_(4))_(5) O:Eu^(3+)is a new type of oxyapatite red fluorescent material with good comprehensive performances.
基金This work was supported by the National Natural Science Foundation of China （Grant Nos. 51472263 and 51572175）, the Jiangsu Planned Projects for Postdoctoral Research Funds （1501131C）, and the Shanghai Planned Projects for Young Teacher Training of Universities （ZZyy15087）.
文摘Moderate level of exposure to the solar irradiation containing UV component is essential for health care. To incorporate the UV-emitting phosphors into the commercial YAG-based white light-emitting diode introduces the possibilities of healthy illumination to individuals＇ daily lives. 1 mol.% E3＊-doped BaGd2ZnO5（BGZ） particles were synthesized via sol-gel method and efficient up-converted luminescence peaked at 380 nm was detected under 480 nm excitation. The mixed phosphors with varied mass ratio of Er3＋：BGZ and Ce3＋：YAG particles were encapsulated to form LEDs. The study of the LEDs indicated that the introduction of BGZ component favored the enhancement of color-rendering index and the neutralization of the white light emitting. The WLED with the BGZ/YAG ratio of 8：2 was recommendable for its excellent overall white light luminous performances and UV intensity of 84.55 mW/cm2. The UV illumination dose of the WLEDs with mixed YAG and BGZ was controllable by adjusting the ratio, the illumination distance and the illumination time. Er3＋：BGZ phosphors are promising UV- emitting phosphors for healthy indoor illumination.
