[摘 要] 目的：为解决野生型B细胞成熟抗原（BCMA）被γ分泌酶切割导致表达不稳定的问题，构建抵抗γ分泌酶切割的BCMA突变体并构建靶细胞，用于评价BCMA CAR-T细胞的杀伤功能。方法：将野生型BCMA的穿膜域替换为人CD8α穿膜域，构建抵抗γ分泌酶切割的BCMA突变体（BCMA-CD8α TM），构建过表达该突变体的U266（U266BCMA Mut）、K562（K562BCMA Mut）、SKOV3（SKOV3BCMA Mut）和CHO（CHOBCMA Mut）细胞；构建装载NFAT-EGFP报告基因的BCMA CAR Jurkat细胞（BCMA-CAR-Jurkat-Reporter）与U266BCMA Mut细胞共培养，采用FCM检测该细胞中EGFP表达水平以指示NFAT激活水平，荧光素酶法检测BCMA CAR-T细胞对Luciferase标记的K562BCMA Mut细胞的杀伤作用，实时无标记动态细胞分析技术（RTCA）检测BCMA CAR-T细胞对SKOV3BCMA Mut和CHOBCMA Mut细胞的杀伤作用。结果：应用γ分泌酶抑制剂LY411575抑制γ分泌酶活性，显著增强野生型U266细胞表面BCMA表达水平，平均荧光强度上调10倍以上；但撤除抑制剂后BCMA表达水平逐渐降低（P<0.01）；BCMA-CD8α TM突变体可抵抗γ分泌酶的切割作用，在U266细胞表面稳定表达（P>0.05）；U266细胞及过表达BCMA-CD8α TM的U266细胞与BCMA-CAR-Jurkat-Reporter细胞共培养后都可激活Reporter系统、增强EGFP表达，但该效应在BCMA-CD8α TM过表达的U266细胞中更显著（P<0.01）；BCMA-CD8α TM在BCMA表达阴性的K562、SKOV3和CHO 3种靶细胞中成功过表达，且在LY411575处理下该突变体的表达水平仅有小幅度升高；荧光素酶法检测结果显示，不同效靶比下，BCMA CAR-T细胞均可特异、高效杀伤过表达BCMA-CD8α TM的K562细胞；RTCA结果显示，不同效靶比下，BCMA CAR-T细胞均可有效识别、杀伤过表达BCMA-CD8α TM的SKOV3和CHO细胞，但同等效靶比下的Mock-T细胞无此效应。结论：本实验构建的BCMA-CD8α TM突变体能够抵抗γ分泌酶的切割，在多种靶细胞表面稳定表达，为评价BCMA CAR-T细胞体外杀伤的有效性和特异性提供多种检测手段。

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

Radical gastrectomy combined with perioperative comprehensive treatment is the main curable strategy for gastric cancer patients, and postoperative complications are the issue that gastric surgeons have to face. Complications not only affect the short-term postoperative recovery, but also facilitate tumor recurrence or metastasis, thus resulting in poor prognosis. Therefore, unifying the diagnostic criteria for postoperative complications, bringing the surgeons' attention to complications, and understanding the potential mechanism of complications undermining long-term survival, will be helpful to the future improvement of the clinical diagnosis and treatment as well as prognosis for gastric cancer patients in China. Meanwhile, surgeons should constantly hone their operative skills, improve their sense of responsibility and empathy, and administer individualized perioperative management based on patients' general conditions, so as to minimize the occurrence of postoperative complications and their influence on prognosis.
Humans ; Stomach Neoplasms/pathology* ; Empathy ; Neoplasm Recurrence, Local/surgery* ; Prognosis ; Gastrectomy/methods* ; Postoperative Complications/etiology* ; Surgeons ; Retrospective Studies

Humans ; Stomach Neoplasms/pathology* ; Carcinoma, Signet Ring Cell/pathology* ; Adenocarcinoma/pathology*

OBJECTIVE: To analyze the distribution characteristics of emerging and reemerging Oncomelania hupensis snails after the criteria for transmission control of schistosomiasis were achieved in China, so as to provide insights into assessment of schistosomiasis transmission risk and formulation of snail control strategies during the elimination phase. METHODS: O. hupensis survey data in China from 2015 to 2021 were collected from the National Schistosomiasis Pevention and Control Information Management System, and the distribution characteristics of emerging and reemerging O. hupensis snails were descriptively analyzed. RESULTS: Emerging and reemerging O. hupensis snails were identified in China each year from 2015 to 2021, with relatively larger areas with emerging and reemerging O. hupensis snail habitats in 2016 and 2021, and relatively higher numbers of counties (districts) where emerging and reemerging O. hupensis snails were detected in 2016 and 2021. A total of 4 586.30 hm² of emerging O. hupensis snail habitats were found in 10 schistosomiasis-endemic provinces of China (except Fujian and Yunnan Provinces) from 2015 to 2021, with 96.80% in Anhui, Hunan and Hubei provinces, where marshland and lake endemic foci were predominant. A total of 21 023.90 hm² of reemerging O. hupensis snail habitats were found in 12 schistosomiasis-endemic provinces of China from 2015 to 2021, with 97.67% in six provinces of Hubei, Sichuan, Jiangxi, Jiangsu, Yunnan and Anhui, where marshland and lake and hilly endemic regions were predominant. Emerging snail habitats were found in 15.08% of all schistosomiasisendemic counties (districts) in China from 2015 to 2021, and 78.75% of all emerging snail habitats were identified in 11 schistosomiasis-endemic counties (districts), with the largest area of emerging snail habitats found in Lixian County, Hunan Province (645.00 hm²). Reemerging snail habitats were found in 47.67% of all schistosomiasis-endemic counties (districts) in China from 2015 to 2021, and 43.29% of all reemerging snail habitats were identified in 11 schistosomiasis-endemic counties (districts), with the largest area of reemerging snail habitats found in Weishan Li and Hui Autonomous County of Hunan Province (1 579.70 hm²). CONCLUSIONS Emerging and reemerging O. hupensis snails were identified in China each year from 2015 to 2021, with much larger areas of reemerging snail habitats than emerging snail habitats, and larger numbers of schistosomiasis-endemic provinces and counties (districts) with reemerging snails were found that those of provinces and counties (districts) with emerging snails. Specific snail control interventions are required tailored to the causes of emerging and reemerging snail habitats. Both emergence and reemergence of O. hupensis snails should be paid attention to in marshland and lake endemic areas, and Guangxi Zhuang Autonomous Region, Shanghai Municipality and Zhejiang Province where schistosomiasis had been eliminated, and reemergence of O. hupensis snails should be given a high priority in hilly areas. In addition, monitoring of O. hupensis snails should be reinforced in snail-free areas after flooding.
Humans ; China/epidemiology* ; Schistosomiasis/prevention & control* ; Cities ; Ecosystem ; Lakes

OBJECTIVE: To establish a snail control approach for spraying chemicals with drones against Oncomelania hupensis in complex snail habitats in hilly regions, and to evaluate its molluscicidal effect. METHODS: The protocol for evaluating the activity of spraying chemical molluscicides with drones against O. hupensis snails was formulated based on expert consultation and literature review. In August 2022, a pretest was conducted in a hillside field environment (12 000 m²) north of Dafengji Village, Dacang Township, Weishan County, Yunnan Province, which was assigned into four groups, of no less than 3 000 m² in each group. In Group A, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with drones at a dose of 40 g/m², and in Group B, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with drones at a dose of 40 g/m², while in Group C, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with knapsack sprayers at a dose of 40 g/m², and in Group D, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with knapsack sprayers at a dose of 40 g/m². Then, each group was equally divided into six sections according to land area, with Section 1 for baseline surveys and sections 2 to 6 for snail surveys after chemical treatment. Snail surveys were conducted prior to chemical treatment and 1, 3, 5, 7 days post-treatment, and the mortality and corrected mortality of snails, density of living snails and costs of molluscicidal treatment were calculated in each group. RESULTS: The mortality and corrected mortality of snails were 69.49%, 69.09%, 53.57% and 83.48%, and 68.58%, 68.17%, 52.19% and 82.99% in groups A, B, C and D 14 days post-treatment, and the density of living snails reduced by 58.40%, 63.94%, 68.91% and 83.25% 14 days post-treatment relative to pre-treatment in four groups, respectively. The median concentrations of chemical molluscicides were 37.08, 35.42, 42.50 g/m² and 56.25 g/m² in groups A, B, C and D, and the gross costs of chemical treatment were 0.93, 1.50, 0.46 Yuan per m² and 1.03 Yuan per m² in groups A, B, C and D, respectively. CONCLUSIONS The molluscicidal effect of spraying 5% niclosamide ethanolamine salt granules with drones against O. hupensis snails is superior to manual chemical treatment without environmental cleaning, and chemical treatment with drones and manual chemical treatment show comparable molluscicidal effects following environmental cleaning in hilly regions. The cost of chemical treatment with drones is slightly higher than manual chemical treatment regardless of environmental cleaning. Spraying 5% niclosamide ethanolamine salt granules with drones is recommended in complex settings with difficulty in environmental cleaning to improve the molluscicidal activity and efficiency against O. hupensis snails.
Niclosamide/pharmacology* ; Ethanolamine/pharmacology* ; Unmanned Aerial Devices ; China ; Molluscacides/pharmacology* ; Ethanolamines

[Abstract] Objective: To investigate the effect of lncRNA SNHG11 on the proliferation, invasion and migration of non-small cell lung cancer (NSCLC) A549 cells and its possible mechanisms. Methods: qPCR was used to detect the levels of lncRNA SNHG11 and miR-193a-5p in human embryonic lung cells (HEL-1) and lung cancer cells (A549, H1299, and HCC827). A549 cells were transfected with SNHG11 small interfering RNA (si-SNHG11), miR-193a mimic or miR-193a inhibitor. The proliferation of A549 cells was detected by CCK-8 assay, migration and invasion of A549 cells were detected by Wound healing and Transwell assay, the protein expression of Ki67 and Cyclin D1 was determined by Western blot, and the targeting relationship between lncRNA SNHG11 and miR-193a-5p was verified by Dual-luciferase reporter experiment. Results: Compared with HEL-1 cells, the expression level of lncRNA SNHG11 was significantly increased while the expression of miR-193a-5p was decreased in lung cancer A549, H1299 and HCC827 cells (all P<0.05). Silencing lncRNA SNHG11 inhibited the proliferation, migration and invasion of A549 cells and reduced the protein expression of Ki67 and Cyclin D1 (all P<0.05). Over-expression of miR-193a-5p inhibited the proliferation, migration and invasion of A549 cells (all P<0.05). lncRNA SNHG11 could targetedly adsorb miR-193a-5p. miR-139a-5p inhibition could partially reverse the effect of silencing lncRNA SNHG11 on the proliferation, invasion and migration of A549 cells (all P<0.05). Conclusion: lncRNA SNHG11 promotes the proliferation, invasion and migration of NSCLC cells by adsorbing miR-193a-5p.

Allyl Compounds ; Animals ; Lung ; Male ; Paraquat/pharmacology* ; Poisons ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sulfides

Adult ; Brain ; Brain Diseases ; Heat Stroke ; Humans ; Magnetic Resonance Imaging ; Male ; Retrospective Studies