[摘 要] 目的：探讨核仁小RNA（snoRNA）71A通过TLR3/PD-L1通路对食管鳞状细胞癌（ESCC）细胞增殖、迁移及侵袭能力的影响。方法：qPCR检测52例ESCC患者的配对肿瘤组织、癌旁组织，以及人ESCC细胞中SNORA71A的表达情况。将反义寡核苷酸（SNORA71A-ASO-29、SNORA71A-ASO-102和NC-ASO）或小干扰RNA（siTLR3、siTLR3-NC）分别转染至人ESCC TE-1细胞，分别记为SNORA71A-ASO1组、SNORA71A-ASO2组、NC-ASO组及siTLR3组、siNC组。另外将过表达质粒pcDNA3.1-SNORA71A和pcDNA3.1空载体质粒分别转染至TE-1细胞，分别记为SNORA71A组和Vector组。细胞功能学实验（MTS实验、划痕愈合实验，以及Transwell侵袭实验）评估各组细胞在敲低或过表达SNORA71A后增殖、迁移和侵袭能力的变化。高通量转录组测序筛选SNORA71A下游作用靶基因，基因本体论（GO）和京都基因与基因组百科全书（KEGG）功能富集分析预测SNORA71A下游作用靶基因可能参与的生物学过程和信号通路。qPCR检测测序筛选出的下游作用靶基因TLR3在ESCC组织以及细胞中的表达。同时，qPCR和WB检测TE-1细胞在敲低或过表达TLR3后PD-L1 mRNA和蛋白质表达变化。细胞功能学实验检测TLR3敲低对SNORA71A所促进的TE-1细胞恶性生物行为（增殖、迁移、侵袭）的影响。结果：在52例ESCC患者的肿瘤组织以及ESCC细胞中SNORA71A表达均呈高水平（P < 0.01或P < 0.05）。敲低SNORA71A抑制TE-1细胞增殖、迁移和侵袭（P < 0.01或P < 0.05），过表达SNORA71A则促进TE-1细胞增殖、迁移和侵袭（P < 0.01或P < 0.05）。高通量转录组测序筛选到TLR3为SNORA71A下游作用靶基因。TLR3在ESCC组织以及TE-1细胞中呈低表达（P < 0.01或P < 0.05）。TLR3正向调控PD-L1 mRNA和蛋白质表达（P < 0.01或P < 0.05）。细胞功能学实验中，TLR3可以部分削弱SNORA71A对PD-L1表达的调控（P < 0.01）。结论：SNORA71A通过调控TLR3/PD-L1通路调节TE-1细胞增殖、迁移和侵袭。

[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.

［摘要］ 目的：探讨miR-627-3p 在食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）组织中的表达及其对ESCC 细胞生物学行为的影响。方法：收集2015 年1 月至2015 年10 月河北医科大学第四医院胸外科手术切除的ESCC组织86 例及对 应的癌旁组织标本20 例。通过qPCR法检测miR-627-3p 在86 例ESCC组织及癌旁组织中的表达，分析其表达与ESCC患者临床 病理学指标及预后的关系；利用Kaplan-Meier Plotter 在线数据库进一步分析数据库中hsa-miR-627 的表达与ESCC患者预后的关 系；通过qPCR法检测miR-627-3p 在4 株ESCC细胞系中的表达，选取表达水平最低的食管癌细胞转染miR-627-3p mimic，选取表 达水平最高的ESCC细胞转染miR-627-3p inhibitor，采用CCK-8 法检测细胞的增殖，采用Transwell 实验检测细胞迁移和侵袭；采 用KEGG分析探讨miR-627-3p 可能介导的信号转导通路，并采用qPCR法验证miR-627-3p 对信号通路中关键基因表达的影响。 结果：miR-627-3p 在ESCC组织中的表达明显低于在癌旁组织中的表达，miR-627-3p 的表达与ESCC患者淋巴结转移和临床分 期相关（均P<0.05）；miR-627-3p 高表达的ESCC 患者的5 年生存率明显高于miR-627-3p 低表达的食管癌患者（P<0.05）。ESCC 细胞系KYSE170 中miR-627-3p 表达最低，KYSE30 中miR-627-3p 表达最高；在KYSE170 细胞中转染miR-627-3p mimic 后，细胞 的增殖能力无明显变化（P>0.05），但细胞的迁移（P<0.05）和侵袭能力（P<0.05）显著降低；在KYSE30 细胞中转染miR-627-3p inhibitor 后，细胞的增殖能力无明显变化（P>0.05），但细胞的迁移（P<0.05）和侵袭能力（P<0.05）显著增高。KEGG分析结果显 示，miR-627-3p 介导了多条与肿瘤相关的信号转导通路。结论：miR-627-3p 在ESCC组织中的表达明显低于在癌旁组织中的表 达，其低表达与ESCC患者的不良预后相关，miR-627-3p 抑制ESCC细胞的迁移和侵袭，可能是通过干扰多条与肿瘤相关的信号 通路发挥生物学功能。