BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value...BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.展开更多
目的评估在骨质疏松条件下,行L5/S1节段斜外侧椎间融合术(oblique lateral interbody fusion at L5/S1,OLIF51)及其联合双侧皮质骨轨迹螺钉(cortical bone trajectory screw,CBT)和双侧椎弓根螺钉(bilateral pedicle screw,BPS)的生物...目的评估在骨质疏松条件下,行L5/S1节段斜外侧椎间融合术(oblique lateral interbody fusion at L5/S1,OLIF51)及其联合双侧皮质骨轨迹螺钉(cortical bone trajectory screw,CBT)和双侧椎弓根螺钉(bilateral pedicle screw,BPS)的生物力学性能。方法招募1名健康青年男性作为志愿者,获得其腰骶椎三维CT数据,在有限元分析软件中完成L4~S1三维模型,采用前路钛板(titanium plate,TP)固定的OLIF51手术模型、OLIF51+CBT和OLIF51+BPS手术模型的构建,分别命名为A、B、C、D模型。通过赋值、设定条件、施加载荷,分析不同条件下的生物力学特性。结果顺利完成4种有限元模型的构建。4种模型在所有运动中的平均活动度(range of motion,ROM)变化趋势为A模型>B模型>C模型>D模型;其中,与A模型相比,B模型降幅为84.21%~94.42%,C模型降幅为88.12%~96.40%,D模型降幅为90.07%~96.49%(P均<0.05);与B模型相比,C模型降幅为7.41%~52.38%,D模型降幅为27.78%~58.33%(P均<0.05)。3种手术模型在所有运动中的融合器(Cage)平均最大应力变化趋势为B模型>C模型>D模型;其中,与B模型相比,C模型降幅为12.89%~57.62%,D模型降幅为36.43%~73.11%;D模型和C模型相比,除左侧弯外差异均有统计学意义(P均<0.05);D模型降幅为21.83%~37.67%。3种手术模型在所有运动中的内固定平均最大应力变化趋势为B模型>C模型>D模型;与B模型相比,C模型降幅为3.55%~65.47%,D模型降幅为18.58%~84.41%;CBT应力大于BPS应力(P<0.05)。结论在OLIF51手术中,补充后路内固定可以增强融合节段的稳定性并减轻TP上的应力。不建议对骨质疏松症患者单独进行OLIF51手术,使用BPS辅助固定可达到最佳生物力学特性。接受CBT辅助内固定的患者术后需要佩戴支具,并尽量避免融合部位的右侧弯曲运动。展开更多
Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation...Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.展开更多
Except for positive transfer, the first language has a bad effect on people's second language learning undoubtedly, which is the very thing all second language learners ought to pay attention to and overcome.
基金Supported by National Nature Science Foundation of China,No.82060450,No.82360517,No.81460374,and No.31460304Nature Science Foundation of Jiangxi Province of China,No.20232BAB206086,No.20192BAB205072,No.20203BBGL73206,No.2017BCB23086,No.2017BAB205062,and No.20181BAB205050.
文摘BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.
文摘目的评估在骨质疏松条件下,行L5/S1节段斜外侧椎间融合术(oblique lateral interbody fusion at L5/S1,OLIF51)及其联合双侧皮质骨轨迹螺钉(cortical bone trajectory screw,CBT)和双侧椎弓根螺钉(bilateral pedicle screw,BPS)的生物力学性能。方法招募1名健康青年男性作为志愿者,获得其腰骶椎三维CT数据,在有限元分析软件中完成L4~S1三维模型,采用前路钛板(titanium plate,TP)固定的OLIF51手术模型、OLIF51+CBT和OLIF51+BPS手术模型的构建,分别命名为A、B、C、D模型。通过赋值、设定条件、施加载荷,分析不同条件下的生物力学特性。结果顺利完成4种有限元模型的构建。4种模型在所有运动中的平均活动度(range of motion,ROM)变化趋势为A模型>B模型>C模型>D模型;其中,与A模型相比,B模型降幅为84.21%~94.42%,C模型降幅为88.12%~96.40%,D模型降幅为90.07%~96.49%(P均<0.05);与B模型相比,C模型降幅为7.41%~52.38%,D模型降幅为27.78%~58.33%(P均<0.05)。3种手术模型在所有运动中的融合器(Cage)平均最大应力变化趋势为B模型>C模型>D模型;其中,与B模型相比,C模型降幅为12.89%~57.62%,D模型降幅为36.43%~73.11%;D模型和C模型相比,除左侧弯外差异均有统计学意义(P均<0.05);D模型降幅为21.83%~37.67%。3种手术模型在所有运动中的内固定平均最大应力变化趋势为B模型>C模型>D模型;与B模型相比,C模型降幅为3.55%~65.47%,D模型降幅为18.58%~84.41%;CBT应力大于BPS应力(P<0.05)。结论在OLIF51手术中,补充后路内固定可以增强融合节段的稳定性并减轻TP上的应力。不建议对骨质疏松症患者单独进行OLIF51手术,使用BPS辅助固定可达到最佳生物力学特性。接受CBT辅助内固定的患者术后需要佩戴支具,并尽量避免融合部位的右侧弯曲运动。
文摘Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.
文摘Except for positive transfer, the first language has a bad effect on people's second language learning undoubtedly, which is the very thing all second language learners ought to pay attention to and overcome.
