目的 通过基于基因表达综合(GEO)数据集的生物信息学方法筛选和分析甲型H1N1流感病毒性肺炎的潜在生物标志物.方法 从GEO数据库获取甲型H1N1流感病毒性肺炎的数据集,并筛选差异表达基因,使用STRING 12.0数据库和Cytoscape 3.9.1软件对这些差异表达基因进行分析并筛选出Hub基因,使用DAVID数据库对这些差异表达基因进行功能富集分析.结果 筛选出1 019个差异表达基因,其中上调基因522个,下调基因497个.富集结果显示,这些差异表达基因的功能主要富集于细胞质、蛋白质磷酸化、免疫应答、补体成分、激酶活性、T细胞受体信号通路及FoxO信号通路等.最终确定了 CDK1、CCNA2、CCNB2、CDC20、TOP2A、KIF20A、DLGAP5、BUB1、KIF11和TPX2为Hub基因.结论 本研究阐明了 10个Hub基因(CDK1、CCNA2、CCNB2、CDC20、TOP2A、KIF20A、DLGAP5、BUB1、KIF11 和 TPX2)有可能作为甲型H1N1流感病毒性肺炎诊断和治疗的潜在生物标志物,但仍需更多的实验来进一步探索这些Hub基因在甲型H1N1流感病毒性肺炎中的具体机制.

目的:了解台州市新报告HIV/AIDS病例的流行特征。方法:采用描述性流行病学方法对国家艾滋病防治信息系统中2018-2019年台州市新报告HIV/AIDS病例资料进行人群、时间和地区分布以及传播途径、发现途径等分析。结果:台州市2018-2019年新报告HIV/AIDS病例751例，男女比例为5.06∶1；年龄主要为20~49岁（80.03%）；职业主要为农民、工人及商业服务，分别占30.89%、21.30%、14.38%；文化程度以初中以下为主（74.57%）；未婚、已婚、离异或丧偶患者比例分别为27.16%、54.19%、18.64%。感染途径以性传播和注射吸毒为主，不同性别、年龄段和婚姻状况的HIV/AIDS病例感染途径比较，差异均有统计学意义（ P<0.05）。HIV/AIDS病例检测报告发现途径主要为各医疗机构、疾控中心为主。 结论:2018-2019年台州市新报告HIV/AIDS病例以男性、中青年、已婚、初中及以下文化程度为主，以性传播为主，主要通过医疗机构和疾控中心检测发现。

目的:探索吸烟肺腺癌组织中和自噬相关联的基因，并确定吸烟导致肺腺癌的潜在的自噬相关因素和预后因素。方法:从GEO数据库下载2个数据集(GSE32863和GSE75037)的基因表达谱，同时下载来自TCGA数据库的吸烟肺腺癌患者的数据集。采用R中的微阵列数据包的线性模型探索来自吸烟的肺腺癌患者的样本与癌旁肺组织之间的差异基因。采用数据库DAVID进行差异基因的富集分析。采用相互作用基因/蛋白质检索的搜索工具和Cytoscape软件获得蛋白质-蛋白质相互作用网络并识别关键基因。此外，构建自噬相关基因和差异基因之间的网络。采用Kaplan-Meier分析总生存率。结果:在GSE32863数据集确定了71个差异基因，在GSE75037数据集确定了641个差异基因，在TCGA数据集中确定了4 070个差异基因。3个数据集的交集显示了52个差异基因，并选择这些数据进行进一步研究。采用GO基因功能注释将52个差异基因分为生物学过程、分子功能和细胞组分3个类别，进行京都基因和基因组百科全书分析。总共有17个差异基因和自噬相关基因密切关联，其中LYVE1、RGCC、FOSB、ETV4、CDC20与自噬基因关联最为密切。LYVE1、CDC20的表达量在吸烟肺腺癌人群和不吸烟肺腺癌中比较，差异均有统计学意义( P值均<0.05)，且与肺腺癌患者总生存率相关( P值均<0.05)，RGCC、FOSB、ETV4表达量在吸烟肺腺癌人群和不吸烟肺腺癌中比较，差异均无统计学意义( P值均>0.05)。 结论:确定了LYVE1，CDC20为吸烟肺腺癌患者特异性的自噬相关基因。这些基因与患者的预后密切相关，可能为肺腺癌的治疗提供新的靶点。

目的:分析镇江市不同方式招募的男男同性性行为人群（MSM）的HIV感染高危性行为差异，为艾滋病的精准防控提供数据支持。方法:2020年4 - 6月通过疾病预防控制中心（CDC）自愿咨询检测（VCT）门诊和社区组织（CBO）两种方式在镇江范围内招募MSM人群作为研究对象，采用统一调查问卷收集目标人群的一般人口学特征、药物滥用、HIV检测史和高危性行为等信息。卡方检验或Fisher确切概率法检验分析不同途径招募的MSM人群之间相关特征的差异。结果:两种方式共招募641例MSM，其中CBO招募442例占68.95%，CDC招募199例占31.05%；CBO招募的MSM中，20岁以下占比（6.56%）显著高于CDC招募方式（1.01%， χ2 = 9.20， P = 0.002）；CDC招募的MSM人群使用卫生专业机构和新型网络媒体接受毒品潜在危害信息宣教的比例分别为7.54%（15例）和16.58%（33例），均显著高于CBO组[3.39%（15例）， χ2 = 5.28， P = 0.022；9.50%（42例）， χ2 = 6.66， P = 0.010]。CBO招募的MSM群交性行为发生率为25.21%（30例），与女性发生无保护性行为的比例为47.51%（210例），均显著高于CDC招募组[7.50%（6例）， χ2 = 10.13， P = 0.001；27.64%（55例）， χ2 = 22.35， P < 0.001]，而CBO招募者中异性恋的比例（2.04%，9例）、不清楚性伴HIV感染状态的比例（22.40%，99例）、无保护肛交性行为发生率（39.82%，176例）均显著低于CDC招募的MSM人群[6.53%（13例）， χ2 = 8.37， P = 0.004；39.70%（79例）， χ2 = 20.48， P < 0.001；57.29%（114例）， χ2 = 16.90， P < 0.001]。CBO招募的MSM曾经做过HIV检测的比例为74.43%（329例），最近1次HIV检测途径为CDC的比例为23.10%（76例），HIV感染率为5.20%（23例），均显著低于CDC组[80.90%（161例）， χ2 = 3.19， P = 0.074；57.14%（92例）， χ2 = 99.41， P < 0.001；13.07%（26例）， χ2 = 21.85， P < 0.001]。 结论:通过CBO和CDC两种方式招募的MSM人群在人口学、行为学上互补，具有一般MSM人群的代表性，应根据人群的不同特点制定艾滋病具体防控措施。

目的:探讨纺锤体和动粒相关蛋白2(SKA2)和细胞分裂周期蛋白20(CDC20)在乳腺癌中的表达及其与乳腺癌患者临床病理特征的关系。方法:收集2015年5月至2021年3月临沂市人民医院107例乳腺癌组织和癌旁组织标本，应用免疫组织化学方法检测以上组织中SKA2和CDC20的表达，采用 χ2检验行相关分析。 结果:乳腺癌组织中SKA2表达率为67.29%(72/107)，明显高于癌旁组织中SKA2表达率15.89%(17/107)，两者差异有统计学意义( χ2＝62.928， P<0.01)。SKA2表达水平与乳腺癌TNM分期、肿瘤大小、淋巴结转移明显相关( χ2＝6.889、6.348、5.752， P<0.05)，差异有统计学意义。SKA2表达水平与乳腺癌年龄、组织学分型、组织学分级无相关( χ2＝0.015、0.008、0.157， P>0.05)，差异无统计学意义。乳腺癌组织中CDC20表达率为47.66%(51/107)，明显高于癌旁组织中CDC20表达率12.15%(13/107)，两者差异有统计学意义( χ2＝32.189， P<0.01)。CDC20表达水平与乳腺癌TNM分期、组织学分级、淋巴结转移明显相关( χ2＝7.330、5.888、4.275， P<0.05)，差异有统计学意义。CDC20表达水平与乳腺癌年龄、肿瘤大小、组织学分型无相关( χ2＝0.002、0.205、0.094， P>0.05)，差异无统计学意义。 结论:SKA2和CDC20在乳腺癌中表达异常增高、并与乳腺癌患者的不良预后密切相关，提示SKA2和CDC20可能是乳腺癌患者预后的重要生物标志物。

目的:基于生物信息学方法挖掘分析恶性胸膜间皮瘤（MPM）的差异表达基因，研究其在MPM中的预后价值及其在免疫治疗中的潜在作用。方法:于2022年1月，从GEO数据库下载数据集GSE51024，获得MPM（55例）和正常组织（41例）样本。利用R软件结合HMDD和miRNet数据库筛选MPM相关差异基因并确定共表达基因。对共表达基因进行富集和功能注释，使用STRING数据库和Cytoscape软件构建蛋白质-蛋白质相互作用（PPI）网络并确定关键基因。利用TRRUST、GEPIA数据库预测关键基因的转录因子及预后生存分析。使用TIMER分析关键基因和免疫细胞浸润程度的相关性。结果:共获得435个共表达基因，主要富集于细胞外基质组织、细胞黏附分子信号通路。结合PPI和TRRUST数据库，确定7个MPM预后相关的关键基因，其中细胞周期蛋白20（CDC20）、细胞周期检测点激酶1（CHEK1）、Zeste基因增强子同源物2（EZH2）、核糖核苷酸还原酶亚基M2（RRM2）、拓扑异构酶2A（TOP2A）、泛素样含植物同源结构域和环指域1（UHRF1）在MPM中的表达上调，周期调节蛋白A1（CCNA1）表达下调；CCNA1、CDC20、CHEK1、EZH2、RRM2、TOP2A、UHRF1基因表达与MPM总体生存率有明显关联（ P<0.05）。CDC20、CHEK1、EZH2、RRM2、TOP2A基因表达与B细胞、树突状细胞均呈正相关（ P<0.05），与中性粒细胞均呈负相关（ P<0.05）。 结论:CCNA1、CDC20、CHEK1、EZH2、RRM2、TOP2A、UHRF1可能是MPM患者潜在的预后标志物，其表达可能与MPM肿瘤免疫相关。

Background::Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL.Methods::The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens.Results::We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F lowTAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo. Conclusion::Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.

Background::Spinal injuries are an urgent public health priority; nevertheless, no China-wide studies of these injuries exist. This study measured the incidence, prevalence, causes, regional distribution, and annual trends of spinal injuries in China from 1990 to 2019.Methods::We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 to estimate the incidence and prevalence of spinal injuries in China. The data of 33 provincial-level administrative regions (excluding Taiwan, China) provided by the National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention (CDC) were use to systematically analyze the provincial etiology, geographical distribution, and annual trends of spinal injuries. The Bayesian meta-regression tool DisMod-MR 2.1 was used to ensure the consistency among incidence, prevalence, and mortality rates in each case.Results::From 1990 to 2019, the number of living patients with spinal injuries in China increased by 138.32%, from 2.14 million to 5.10 million, while the corresponding age-standardized prevalence increased from 0.20% (95% uncertainty interval [UI]: 0.18-0.21%) to 0.27% (95% UI: 0.26-0.29%). The incidence of spinal injuries in China increased by 89.91% (95% UI: 72.39-107.66%), and the prevalence increased by 98.20% (95% UI: 89.56-106.82%), both the most significant increases among the G20 countries; 71.00% of the increase could be explained by age-specific prevalence. In 2019, the incidence was 16.47 (95% UI: 12.08-22.00, per 100,000 population), and the prevalence was 358.30 (95% UI: 333.96-386.62, per 100,000 population). Based on the data of 33 provincial-level administrative regions provided by CDC, age-standardized incidence and prevalence were both highest in developed provinces in Eastern China. The primary causes were falls and road injuries; however, the prevalence and specific causes differed across provinces.Conclusions::In China, the overall disease burden of spinal injuries increased significantly during the past three decades but varied considerably according to geographical location. The primary causes were falls and road injuries; however, the prevalence and specific causes differed across provinces.

目的：:探讨MicroRNA-96（miR-96）对人视网膜色素上皮（RPE）细胞增殖和迁移的影响。方法：:实验研究。通过RNA原位杂交检测人胚胎眼（20周）石蜡切片中RPE层miR-96的表达情况。将miR-96和随机序列寡核苷酸链[阴性对照（NC）]通过阳离子脂质体介导转染人眼RPE细胞，采用细胞增殖实验（MTS）、流式细胞术和Transwell实验分别检测细胞增殖、细胞周期以及细胞迁移能力。通过生物信息学及Western blot法确定miR-96作用的靶基因。应用Western blot检测miR-96对细胞增殖迁移相关信号通路蛋白（Akt、ERK）及细胞周期相关蛋白（p-Cdc2、CyclinD2、p-Rb）表达的影响。组间数据比较采用独立样本 t检验。 结果：:miR-96在人眼RPE细胞中有表达。MTS结果显示，转染NC、miR-96后，人眼RPE细胞的相对增殖速率分别为100%、74%±2%，差异有统计学意义（ t=42.174， P=0.002）。流式细胞术检测结果显示，转染miR-96后阻滞在G1期的RPE细胞明显多于转染NC后，且差异有统计学意义（ t=-18.444， P=0.003）。Transwell实验结果显示，与转染NC相比，转染miR-96能显著抑制RPE细胞的迁移，差异具有统计学意义（ t=6.754， P=0.002）。进而，明确了 MITF是miR-96作用的靶基因。Western blot检测结果显示，转染miR-96后细胞中细胞周期相关蛋白p-Rb（ t=11.211， P=0.002）、p-Cdc2（ t=9.133， P=0.003）、CyclinD2（ t=7.542， P=0.005）以及迁移相关信号通路蛋白p-ERK（ t=16.699， P<0.001）、p-Akt（ t=23.552， P<0.001）的表达水平均降低。 结论：:miR-96通过作用于靶基因 MITF，调控细胞周期和迁移相关蛋白的表达从而抑制人RPE细胞的增殖和迁移。

Background::The chaperonin containing t-complex (CCT) proteins play an important role in cell cycle-related protein degradation in yeast and mammals. The role of the chaperonin containing t-complex 4 (CCT4), one subtype of CCT proteins, in the progress of hepatocellular carcinoma (HCC) was not fully elucidated. Here, we aimed to explore the mechanisms of CCT4 in HCC.Methods::In this study, we used the UALCAN platform to analyze the relationship between CCT4 and HCC, and the association of CCT4 with the overall survival (OS) of HCC patients was also analyzed. CCT4 expression in HCC tumor tissues and normal tissues was also determined by western blot (WB) assay. Lentivirus vector was used to knock down the CCT4 expression, and quantitative polymerase chain reaction and WB were used to determine the level of CCT4 in HCC cell lines. Cell counting kit-8 (CCK-8) and 5-ethynyl-2 ＇-deoxyuridine (EdU) assays were used to detect the cell proliferation, and flow cytometry (FCM) was performed to evaluate the effect of CCT4 on the apoptosis of HCC cells. Co-immunoprecipitation (co-IP) assay and WB were used to explore the mechanisms of CCT4 regulating the growth of HCC. Data were calculated from at least three replicate experiments and expressed as mean ± standard deviation. Student’s t test, paired t test, and Kaplan-Meier analysis were used to compare across different groups. Results::We found CCT4 was upregulated in HCC tissues compared with normal tissues, and its high expression was associated with poor prognosis ( P < 0.001). CCT4 was significantly increased in HCC tumor tissues compared with normal tissues (0.98 ± 0.12 vs. 0.23 ± 0.05, t = 7.73, P < 0.001). After being transfected with CCT4 short-hairpin RNA (shRNA), CCT4 was decreased in mRNA level and protein level in both Huh7 (mRNA level: 0.41 ± 0.07 vs. 1.01 ± 0.11, t = 8.09, P = 0.001; protein level: 0.61 ± 0.03 vs. 0.93 ± 0.07, t = 7.19, P = 0.002) and Hep3b cells (mRNA level: 0.55 ± 0.11 vs. 1.04 ± 0.15, t = 4.51, P = 0.011; protein level: 0.64 ± 0.10 vs. 0.95 ± 0.08, t = 4.32, P = 0.012). CCK8 assay indicated that CCT4 knockdown inhibited cell proliferation in both Huh7 (OD value of 3 days: 0.60 ± 0.14 vs. 0.97 ± 0.16, t = 3.13, P = 0.036; OD value of 4 days: 1.03 ± 0.07 vs. 1.50 ± 0.12, t = 5.97, P = 0.004) and Hep3b (OD value of 3 days: 0.69 ± 0.14 vs. 1.10 ± 0.11, t = 3.91, P = 0.017; OD value of 4 days: 1.12 ± 0.12 vs. 1.48 ± 0.13, t = 3.55, P = 0.024) cells. EdU assay showed that CCT4 knockdown inhibited the cell proliferation in both Huh7 (EdU positive rate: [31.25 ± 3.41]% vs. [58.72 ± 3.78]%, t = 9.34, P = 0.001) and Hep3b cells (EdU positive rate: [44.13 ± 7.02]% vs. [61.79 ± 3.96]%, t = 3.79, P = 0.019). FCM assay suggested that CCT4 knockdown induced apoptosis in HCC cells (apoptosis rate of Huh7: [9.10 ± 0.80]% vs. [3.66 ± 0.64]%, t = -9.18, P = 0.001; apoptosis rate of Hep3b: [6.69 ± 0.72]% vs. [4.20 ± 0.86]%, t = -3.84, P = 0.018). We also found that CCT4 could regulate anaphase-promoting complex (APC) Cdc20 activity via interacting with Cdc20. Furthermore, CCT4 knockdown induced securin (0.65 ± 0.06 vs. 0.44 ± 0.05, t = -4.69, P = 0.009) and B-cell lymphoma-2 (Bcl-2) interacting mediator of cell death (Bim; 0.96 ± 0.06 vs. 0.61 ± 0.09, t = -5.65, P = 0.005) accumulation. The upregulation of securin inhibited cell growth by downregulating cyclin D1 (0.65 ± 0.05 vs. 1.04 ± 0.07, t = 8.12, P = 0.001), and the accumulation of Bim inhibited Bcl-2 (0.77 ± 0.04 vs. 0.87 ± 0.04, t = 3.00, P = 0.040) and activated caspase 9 (caspase 9: 0.77 ± 0.04 vs. 0.84 ± 0.05, t = 1.81, P = 0.145; cleaved caspase 9: 0.64 ± 0.06 vs. 0.16 ± 0.07, t = 1.81, P = 0.001), which led to elevated apoptosis. Conclusions::Overall, these results showed that CCT4 played an important role in HCC pathogenesis through, at least partly, interacting with Cdc20.