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SHR-A1811(antibody-drug conjugate)in advanced HER2-mutant non-small cell lung cancer:a multicenter,open-label,phase 1/2 study

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3483-3492页

作者： Ziming Li Zhengbo Song Wei hong Nong yang Yongsheng Wang hong Jian Zibin Liang Sheng Hu Min Peng yan Yu yan Wang Zicong Jiao Kaijing Zhao Ke Song You Li Wei Shi Shun Lu Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiaotong University School of MedicineShanghai 200030China Phase I Clinical Trial Ward Zhejiang Cancer HospitalHangzhou 310000China Department of Thoracic Oncology Zhejiang Cancer HospitalHangzhou 310000China Department of Lung&Gastrointestinal Oncology Hunan Cancer HospitalChangsha 410031China Thoracic Oncology Ward/Cancer Center West China Hospital of Sichuan UniversityChengdu 610041China Department of Thoracic Oncology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 51900China Department of Medical Oncology Hubei Cancer HospitalWuhan 43000China Department of Oncology Renmin Hospital of Wuhan UniversityWuhan 430200China Department of Thoracic Medicine Harbin Medical University Cancer HospitalHarbin 150081China Department of Medical Oncology Cancer HospitalChinese Academy of Medical SciencesBeijing 100021China Geneplus-Beijing CoLtd.Beijing 102206China Jiangsu Hengrui Pharmaceuticals Co.Ltd.Shanghai 200120China

A dose-escalation and expansion,phase 1/2 study(***,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer(NSCLC).Here,we report results from the phase 1 *** who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 *** escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose ***,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/*** patients had HER2-mutant ***-limiting toxicity occurred in one patient in the 8.0 mg/kg dose ***≥3 treatment-related adverse events occurred in 29(46.0%)*** patient in the 6.4 mg/kg cohort died due to interstitial lung *** of April 11,2023,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 27.0-57.9),and a disease control rate of 95.3%(95%Cl 84.2-99.4).The median duration of response was 13.7 months,with 13 of 18 responses *** median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutantNSCLC.

关键词： SHR HER2 doses

Tuning the membrane rejection behavior by surface wettability engineering for an effective water-in-oil emulsion separation

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Chinese Chemical Letters 2024年第6期35卷 480-485页

作者： yan Zou Yin-Shuang Hu Deng-Hui Tian hong Wu Xiaoshu Lv Guangming Jiang Yu-Xi Huang Engineering Research Center for Waste Oil Recovery Technology and Equipment Ministry of EducationChongqing Technology and Business UniversityChongqing 400067China School of Environmental Science and Engineering Sun Yat-sen UniversityGuangzhou 510275China Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology(Sun Yat-sen University) Guangzhou 510275China

Membrane-based separation is a promising technology to eliminate water impurities from the oil ***,it remains a great challenge to separate water from highly emulsified viscous oil owing to the high stability of the water droplets in *** we report a surface wettability engineering on an alumina ceramic membrane to achieve an efficient separation of a water-in-oil(W/O)*** with different carbon chain lengths and fluorinated status were introduced to endow the alumina membrane with different surface *** all the modified membranes exhibited excellent separation of the W/O without Span 80(surfactant),the one with amphiphobic wettability and lowest surface energy failed to separate the Span 80 stabilized W/*** presence of Span 80 reduced the interfacial tension of water droplets,making them easier to deform and penetrate the modified membrane with the lowest surface *** reveals that engineering proper surface wettability is the key to separating the oil and water ***,the modified membranes maintained decent separation performance and stability under long-term run separation of the emulsified W/O.

关键词： Water-in-oil emulsion Ceramic membrane Membrane separation Surface wettability

Ileal collision tumor associated with gastrointestinal bleeding: A case report and review of literature

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 628-634页

作者： Yu-Qi Wu hong-yan Wang Mu-Min Shao Lin Xu Xiao-yan Jiang Shao-Ju Guo Department of Gastroenterology Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Chinese MedicineShenzhen 518033Guangdong ProvinceChina Department of Pathology Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Chinese MedicineShenzhen 518033Guangdong ProvinceChina

BACKGROUND Collision tumors involving the small intestine,specifically the combination of a hamartomatous tumor and a lipoma,are extremely *** our knowledge,no previous case report has described a collision tumor composed of two benign tumors of different origins in the small *** SUMMARY Here,we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm×32 mm×30 mm in the terminal *** on computed tomography scan findings,the mass was initially suspected to be a lipoma.A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line.A biopsy of the upper portion suggested a juvenile polyp(JP).Owing to the patient’s advanced age,multiple comorbidities,and poor surgical tolerance,a modified endoscopic submucosal dissection was *** examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top,demonstrating evidence of rupture and associated *** patient’s overall health remained satisfactory,with no recurrence of hematochezia during the six-month follow-up *** This case report provides new evidence for the understanding of gastrointestinal collision tumors,emphasizing their diverse clinical presentations and histopathological *** also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.

关键词： Collision tumor Gastrointestinal bleeding Hamartomatous tumor Lipoma Modified endoscopic submucosal dissection Case report

Hydrogen production from hydrolysis of NaBH_(4) solution over Co-Fe-B@g-C_(3)N_(4)/NF thin film catalyst

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Rare Metals 2024年第6期43卷 2648-2659页

作者： yan Wang Jia-Xin Ma Jian Ren Di Zhang Feng-yan Xu Ke Zhang Zhong-Qiu Cao Qiu-Ju Sun Guo-De Li Shi-Wei Wu hong-Hui Chen College of Chemistry and Chemical Engineering Shenyang Normal UniversityShenyang 110034China Experimental Center Shenyang Normal UniversityShenyang 110034China Hunan Shande Energy Storage New Materials Research Institute Limited Company Changde 415000China

In this study,the double loaded Co-Fe-B@g-C_(3)N_(4)/NF(NF:Ni foam)thin film catalysts were prepared for the first time via chemical deposition method at room *** optimizing the reducing agent concentration to 0.9 mol·L^(-1),the as-obtained Co-Fe-B@g-C_(3)N_(4)/NF exhibited the twisted ribbon structure with more distinct three-dimensional hierarchy and the smaller particle size,showing the good catalytic property for the hydrolysis of NaBH_(4)*** H_(2)generation rate of Co-Fe-B@g-C_(3)N_(4)/NF and binary Co-B@g-C_(3)N_(4)/NF under visible light irradiation surpassed the value under natural *** apparent activation energy of Co-Fe-B@g-C_(3)N_(4)/NF(45.0 kJ·mol^(-1))under visible light irradiation was obviously reduced when compared with the natural condition(48.4 kJ·mol^(-1))and binary Co-B@g-C_(3)N_(4)/NF(60.6 kJ·mol^(-1))under visible light ***,the catalytic performance of the optimized Co-Fe-B@g-C_(3)N_(4)/NF thin film catalyst was superior to most of the reported non-noble metal and even noble metal ***,it illustrated that the catalytic H_(2)production performance of Co-Fe-B@g-C_(3)N_(4)/NF thin film was distinctly improved after the introduction of light and multicomponent recombination.

关键词： Sodium borohydride Co-Fe-B@g-C_(3)N_(4)/NF catalyst Chemical deposition Hydrogen production

Clinical and genetic heterogeneity of adult polyglucosan body disease caused by GBE1 biallelic mutations in China

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Genes & Diseases 2024年第5期11卷 17-20页

作者： Yikun Chen yan Shi Yuan Gao yan Hu Linying Zhou Jingmei hong Shirui Gan Xiang Lin Wanjin Chen Guorong Xu Jin He Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350005China Fujian Key Laboratory of Molecular Neurology Institute of NeuroscienceFujian Medical UniversityFuzhouFujian 350005China Electron Microscopy Lab of Public Technology Service Center Fujian Medical UniversityFuzhouFujian 350005China

Adult polyglucosan body disease(APBD)is a rare and highly heterogeneous glycogen storage disorder due to biallelic variants in GBE1.1 Typical APBD presentations include gait abnormalities with polyneuropathy,leukodystrophy,neurogenic bladder,and mild cognitive *** diagnosis of APBD encompasses a large spectrum of conditions including axonal and demyelinating sensorimotor polyneuropathy,progressive spastic paraparesis,and leukodystrophies.

关键词： GBE bladder diagnosis

Parotid metastasis of rare lung adenocarcinoma:A case report

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World Journal of Clinical Cases 2024年第6期12卷 1182-1189页

作者： Ru-Xi yan Lin-Bo Dou Zi-Jia Wang Xue Qiao hong-Hai Ji yan-Cong Zhang School of Stomatology Weifang Medical UniversityWeifang 261000Shandong ProvinceChina Department of Stomatology Dezhou People’s HospitalDezhou 253000Shandong ProvinceChina Department of Stomatology Dezhou Women and Children's HospitalDezhou 253000Shandong ProvinceChina

BACKGROUND Lung cancer(LC)is the leading cause of malignancy-related deaths *** most common sites of metastasis include the nervous system,bone,liver,respiratory system,and adrenal *** metastasis in the parotid gland is very rare,and its diagnosis presents a ***,we report a case of parotid metastasis in primary *** SUMMARY The patient was a 74-year-old male who was discovered to have bilateral facial asymmetry inadvertently two years *** right earlobe was slightly swollen and without pain or *** tomography(CT)examination showed bilateral lung space-occupying *** biopsy was performed and revealed adenocarcinoma(right-upper-lung nodule tissue).Positron emission tomography-CT examination showed:(1)Two hypermetabolic nodules in the right upper lobe of the lung,enlarged hy-permetabolic lymph nodes in the right hilar and mediastinum,and malignant space-occupying lesion in the right upper lobe of the lung and possible metastasis to the right hilar and mediastinal lymph nodes;and(2)multiple hypermetabolic nodules in bilateral parotid *** puncture biopsy was performed considering lung adenocarcinoma *** detection of lung biopsy specimens revealed an EGFR gene 21 exon L858R *** This case report highlights the challenging diagnosis of parotid metastasis in LC given its rare *** lesions should be differentiated from primary tumors of the parotid *** radiological imaging is unreliable,and puncture biopsy is needed for final diagnosis of this condition.

关键词： Lung cancer Metastasis Parotid gland Pathology Positron emission tomography/computed tomography Case report

Therapeutic effects of Lingguizhugan decoction in a rat model of high-fat diet-induced insulin resistance

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World Journal of Diabetes 2024年第6期15卷 1291-1298页

作者： Xiao-Ming Liu Shi-Qing Yuan Ying Ning Shi-Jia Nie Xu-qiong Wang hong-Yi Jia Xiu-Li Zheng Department of Basic Medicine School of Basic Medicine Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina Department of Clinical Medicine Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina

BACKGROUND Lingguizhugan(LGZG)decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet(HFD)-induced insulin resistance(IR)in animal *** To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying *** To establish an IR rat model,a 12-wk HFD was administered,followed by a 4-wk treatment with *** determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance *** a targeted metabolomics platform to analyze changes in serum metabolites,quantitative real-time PCR(qRT-PCR)was used to assess the gene expression of the ribosomal protein S6 kinase beta 1(S6K1).RESULTS In IR rats,LGZG decreased body weight and indices of hepatic *** effectively controlled blood glucose and food intake while protecting islet *** analysis revealed significant differences between the HFD and HFDLGZG *** intervention reduced branched-chain amino acid *** of IR-related metabolites such as tryptophan,alanine,taurine,and asparagine decreased *** may be linked to amino acids due to the contemporaneous increase in S6K1 expression,as shown by *** Our study strongly suggests that LGZG decoction reduces HFD-induced *** may activate S6K1 via metabolic *** findings lay the groundwork for the potential of LGZG as an IR treatment.

关键词： Lingguizhugan decoction High-fat diet-induced insulin resistance Amino acid metabolism S6K1

The light and hypoxia induced gene ZmPORB1 determines tocopherol content in the maize kernel

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Science China(Life Sciences) 2024年第3期67卷 435-448页

作者： Nannan Liu Yuanhao Du Shijuan yan Wei Chen Min Deng Shutu Xu hong Wang Wei Zhan Wenjie Huang yan Yin Xiaohong yang Qiao Zhao Alisdair R.Fernie Jianbing yan National Key Laboratory of Crop Genetic Improvement Huazhong Agricultural UniversityWuhan 430070China Hubei hongshan Laboratory Wuhan 430070China Agro-biological Gene Research Center Guangdong Academy of Agricultural SciencesGuangzhou 510640China College of Agronomy Hunan Agricultural UniversityChangsha 410128China College of Agronomy Northwest A&F UniversityXi'an 710000China State Key Laboratory of North China Crop Improvement and Regulation Hebei Sub-center of National Maize Improvement Center of ChinaCollege of AgronomyHebei Agricultural UniversityBaoding 071001China College of Life Sciences South-Central Minzu UniversityWuhan 430070China Plant Science Facility of the Institute of Botany Chinese Academy of SciencesBeijing 100093China National Maize Improvement Center of China Beijing Key Laboratory of Crop Genetic ImprovementChina Agricultural UniversityBeijing 100093China Shenzhen Key Laboratory of Synthetic Genomics Guangdong Provincial Key Laboratory of Synthetic GenomicsShenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Max Planck Institute of Molecular Plant Physiology Potsdam-Golm 14476Germany

Tocopherol is an important lipid-soluble antioxidant beneficial for both human health and plant growth. Here, we fine mapped a major QTLqVE1 affecting γ-tocopherol content in maize kernel, positionally cloned and confirmed the underlying gene ZmPORB1(por1), as a protochlorophyllide oxidoreductase. A 13.7 kb insertion reduced the tocopherol and chlorophyll content, and the photosynthetic activity by repressing ZmPORB1 expression in embryos of NIL-K22, but did not affect the levels of the tocopherol precursors HGA(homogentisic acid)and PMP(phytyl monophosphate). Furthermore, ZmPORB1 is inducible by low oxygen and light, thereby involved in the hypoxia response in developing embryos. Concurrent with natural hypoxia in embryos, the redox state has been changed with NO increasing and H_(2)O_(2) decreasing, which lowered γ-tocopherol content via scavenging reactive nitrogen species. In conclusion, we proposed that the lower lightharvesting chlorophyll content weakened embryo photosynthesis, leading to fewer oxygen supplies and consequently diverse hypoxic responses including an elevated γ-tocopherol consumption. Our findings shed light on the mechanism for fine-tuning endogenous oxygen concentration in the maize embryo through a novel feedback pathway involving the light and low oxygen regulation of ZmPORB1 expression and chlorophyll content.

关键词： maize tocopherol hypoxia photosynthesis ZmPORB1

Generation of mitochondrial replacement monkeys by female pronucleus transfer

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Zoological Research 2024年第2期45卷 292-298页

作者： Chun-yang Li Xing-Chen Liu Yu-Zhuo Li yan Wang yan-hong Nie Yu-Ting Xu Xiao-Tong Zhang Yong Lu Qiang Sun Institute of Neuroscience Center for Excellence in Brain Science and Intelligence TechnologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai 200031China Key Laboratory of Genetic Evolution and Animal Models Chinese Academy of SciencesKunming 650201China University of Chinese Academy of Sciences Beijing 100049China

Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe *** replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA *** pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously *** this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear *** individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during *** successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

关键词： Non-human primates Mitochondrial replacement Female pronuclear transfer