BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 target...BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
In this article,a comprehensive survey of deep learning-based(DLbased)human pose estimation(HPE)that can help researchers in the domain of computer vision is presented.HPE is among the fastest-growing research domains...In this article,a comprehensive survey of deep learning-based(DLbased)human pose estimation(HPE)that can help researchers in the domain of computer vision is presented.HPE is among the fastest-growing research domains of computer vision and is used in solving several problems for human endeavours.After the detailed introduction,three different human body modes followed by the main stages of HPE and two pipelines of twodimensional(2D)HPE are presented.The details of the four components of HPE are also presented.The keypoints output format of two popular 2D HPE datasets and the most cited DL-based HPE articles from the year of breakthrough are both shown in tabular form.This study intends to highlight the limitations of published reviews and surveys respecting presenting a systematic review of the current DL-based solution to the 2D HPE model.Furthermore,a detailed and meaningful survey that will guide new and existing researchers on DL-based 2D HPE models is achieved.Finally,some future research directions in the field of HPE,such as limited data on disabled persons and multi-training DL-based models,are revealed to encourage researchers and promote the growth of HPE research.展开更多
BACKGROUND The co-occurrence of Anti-phospholipase A2 receptor-associated membranous nephropathy(anti-PLA2R-MN)and human immunodeficiency virus(HIV)infection is a rare clinical scenario,presenting significant challeng...BACKGROUND The co-occurrence of Anti-phospholipase A2 receptor-associated membranous nephropathy(anti-PLA2R-MN)and human immunodeficiency virus(HIV)infection is a rare clinical scenario,presenting significant challenges in terms of management and treatment.CASE SUMMARY A 32-year-old Chinese male diagnosed with HIV infection presented with a clinical history of proteinuria persisting for over two years.A kidney biopsy demonstrated subepithelial immune complex deposition and a thickened glomerular basement membrane,indicative of stage I-II membranous nephro-pathy.Immunofluorescence staining revealed granular deposition of PLA2R(3+)along the glomerular capillary loops,corroborated by a strongly positive anti-PLA2R antibody test(1:320).Initial treatment involving losartan potassium,rivaroxaban,tacrolimus,and rituximab was discontinued due to either poor effec-tiveness or the occurrence of adverse events.Following a regimen of weekly subcutaneous injections of telitacicept(160 mg),a marked decline in the 24 h urine protein was observed within a three-month period,accompanied by a rise in serum albumin level.No significant reductions in peripheral blood CD3+CD4+T and CD3+CD8+T cell counts were detected.The patient's physical and psychological conditions showed significant improvements,with no adverse events reported during the treatment course.CONCLUSION Telitacicept might offer a potential therapeutic avenue for patients diagnosed with anti-PLA2R-MN concomitant with HIV infection.展开更多
Objective:To construct a secretory eukaryotic expression vector of DSG2 fused with the Fc region of the human IgG,to validate its expression in 293T cells,and to purify the secretory protein with biological activity.M...Objective:To construct a secretory eukaryotic expression vector of DSG2 fused with the Fc region of the human IgG,to validate its expression in 293T cells,and to purify the secretory protein with biological activity.Methods:The DSG2 extracellular domain fragment gene(DSG2ex),was amplified by PCR,and was inserted into the eukaryotic expression plasmid pCMV3-IgG1 to construct the recombinant eukaryotic expression plasmid-pCMV3-DSG2ex-IgG1.The successfully constructed eukaryotic expression plasmid was transfected into 293T cells to express and secrete DSG2 extracellular domain protein.The targeted protein was purified from the cell culture supernatant by Protein A affinity chromatography and confirmed by Western Blotting and ELISA.Results:The pCMV3-DSG2ex-IgG1 eukaryotic expression plasmid was successfully constructed.The highest protein expression level was obtained with 293T cells after 96 h of transfection.The relative molecular mass of the purified product was between 100 and 130 kDa was estimated by SDS-PAGE,which was consistent with the expectation.The yield of the purified protein reached 0.8 mg/ml with a purity over 90%.The purified DSG2 extracellular domain protein with IgG1 tag was recognized by IgG monoclonal antibodies by Western blotting.Moreover,the ELISA results showed that the prepared DSG2 extracellular domain protein had significant binding activity to human type 55 adenovirus Fiber Knob protein(HAdV-55).Conclusion:A simple and efficient method for eukaryotic expression and purification of human soluble DSG2 extracellular domain protein was successfully established,and biologically active DSG2 extracellular domain protein was purified,which laid the foundation for the later study of its protein function and anti-adenovirus drugs.展开更多
基金Supported by the Science and Technology Innovation Development Project of Tai’an,No.2021NS160the Medical and Health Science and Technology Development Plan of Shandong Province,No.202102010647。
文摘BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
基金supported by the[Universiti Sains Malaysia]under FRGS Grant Number[FRGS/1/2020/STG07/USM/02/12(203.PKOMP.6711930)]FRGS Grant Number[304PTEKIND.6316497.USM.].
文摘In this article,a comprehensive survey of deep learning-based(DLbased)human pose estimation(HPE)that can help researchers in the domain of computer vision is presented.HPE is among the fastest-growing research domains of computer vision and is used in solving several problems for human endeavours.After the detailed introduction,three different human body modes followed by the main stages of HPE and two pipelines of twodimensional(2D)HPE are presented.The details of the four components of HPE are also presented.The keypoints output format of two popular 2D HPE datasets and the most cited DL-based HPE articles from the year of breakthrough are both shown in tabular form.This study intends to highlight the limitations of published reviews and surveys respecting presenting a systematic review of the current DL-based solution to the 2D HPE model.Furthermore,a detailed and meaningful survey that will guide new and existing researchers on DL-based 2D HPE models is achieved.Finally,some future research directions in the field of HPE,such as limited data on disabled persons and multi-training DL-based models,are revealed to encourage researchers and promote the growth of HPE research.
文摘BACKGROUND The co-occurrence of Anti-phospholipase A2 receptor-associated membranous nephropathy(anti-PLA2R-MN)and human immunodeficiency virus(HIV)infection is a rare clinical scenario,presenting significant challenges in terms of management and treatment.CASE SUMMARY A 32-year-old Chinese male diagnosed with HIV infection presented with a clinical history of proteinuria persisting for over two years.A kidney biopsy demonstrated subepithelial immune complex deposition and a thickened glomerular basement membrane,indicative of stage I-II membranous nephro-pathy.Immunofluorescence staining revealed granular deposition of PLA2R(3+)along the glomerular capillary loops,corroborated by a strongly positive anti-PLA2R antibody test(1:320).Initial treatment involving losartan potassium,rivaroxaban,tacrolimus,and rituximab was discontinued due to either poor effec-tiveness or the occurrence of adverse events.Following a regimen of weekly subcutaneous injections of telitacicept(160 mg),a marked decline in the 24 h urine protein was observed within a three-month period,accompanied by a rise in serum albumin level.No significant reductions in peripheral blood CD3+CD4+T and CD3+CD8+T cell counts were detected.The patient's physical and psychological conditions showed significant improvements,with no adverse events reported during the treatment course.CONCLUSION Telitacicept might offer a potential therapeutic avenue for patients diagnosed with anti-PLA2R-MN concomitant with HIV infection.
基金Nanjing Science and Technology Plan Project(No.ZX20200009)Jiangsu Province Postgraduate Research and Practice Innovation Program(No.SJCX22-0895)。
文摘Objective:To construct a secretory eukaryotic expression vector of DSG2 fused with the Fc region of the human IgG,to validate its expression in 293T cells,and to purify the secretory protein with biological activity.Methods:The DSG2 extracellular domain fragment gene(DSG2ex),was amplified by PCR,and was inserted into the eukaryotic expression plasmid pCMV3-IgG1 to construct the recombinant eukaryotic expression plasmid-pCMV3-DSG2ex-IgG1.The successfully constructed eukaryotic expression plasmid was transfected into 293T cells to express and secrete DSG2 extracellular domain protein.The targeted protein was purified from the cell culture supernatant by Protein A affinity chromatography and confirmed by Western Blotting and ELISA.Results:The pCMV3-DSG2ex-IgG1 eukaryotic expression plasmid was successfully constructed.The highest protein expression level was obtained with 293T cells after 96 h of transfection.The relative molecular mass of the purified product was between 100 and 130 kDa was estimated by SDS-PAGE,which was consistent with the expectation.The yield of the purified protein reached 0.8 mg/ml with a purity over 90%.The purified DSG2 extracellular domain protein with IgG1 tag was recognized by IgG monoclonal antibodies by Western blotting.Moreover,the ELISA results showed that the prepared DSG2 extracellular domain protein had significant binding activity to human type 55 adenovirus Fiber Knob protein(HAdV-55).Conclusion:A simple and efficient method for eukaryotic expression and purification of human soluble DSG2 extracellular domain protein was successfully established,and biologically active DSG2 extracellular domain protein was purified,which laid the foundation for the later study of its protein function and anti-adenovirus drugs.
