The identification of novel functional biomarkers is crucial in recognizing high-risk colorectal cancer (CRC) patients. Despite this need, no prognostic biomarker has been implemented in clinical practice for CRC. To address this gap, we utilized integrated transcriptomic data from public databases alongside our original multi-omics data, including proteome and chromatin accessibility datasets. Bioinformatics studies on transcriptomic datasets from 487 CRC patients led us to identify three Golgi apparatus prognostic genes: NIPAL1, ZYG11B, and PARP10. We found that decreased expression of NIPAL1 and ZYG11B, as well as increased expression of PARP10, elevated the risk of CRC. These genes are potentially involved in cellular processes such as nucleotide excision repair and DNA replication. Additionally, our original multi-omics datasets, encompassing proteomic data and chromatin accessibility profiling from assay for transposase-accessible chromatin with sequencing (ATAC-Seq), identified alterations in protein levels of potential upstream transcription factors CDX2 and YY1 for three genes. Furthermore, chromatin accessibility at DNA binding regions corresponding to transcription factors such as SPI1 and JUND changed, potentially explaining the observed variations in mRNA levels for these genes. Our findings highlight the biological activities of these genes, including NIPAL1, PARP10, and ZYG11B, and their upstream regulators, offering a functional context for future in-depth mechanistic studies.

The objective of this study was to construct a prognostic model and medicine therapeutic response by utilizing mitochondrial energy metabolism-related genes (MMRGs), thus establishing a risk score for colorectal cancer (CRC). Based on the TCGA-CRC and GEO data set, MMRGs expression levels were identified by clustering analysis. 10 differential expression genes were used to construct RiskScore by Cox regression. GSE 39582 data set was used for validation. The clinical characteristics,survival characteristics,SNV,CNV,methylation, immune features, and potential benefits of chemotherapy drugs were analyzed for two risk groups. RiskScore was constructed based on the genes ACOX1, ATP6V1G2, COX7A1, CPT2, DLAT, ECGS1, ECI2, NDUFA1, PPA2, and SUCLG2. Patients in the low risk group exhibited a superior overall survival. In addition, Univariate Cox regression analysis and Multivariate Cox regression analysis demonstrated that the risk score, stage and lymphatic invasion can serve as the independent prognostic factors.Trametinib exhibited positive correlations between IC50 values and MMRGs expression levels,which may be more sensitive to chemotherapy drugs. Mitochondrial Energy -Related Genes was a promising biomarker that can be used to distinguish CRC prognosis, immune features, and sensitivity to chemotherapy drugs.

Kidney stone disease (KSD) is a common urological disease entailing the formation of minerals and salts that form inside the urinary tract, caused by diabetes, high blood pressure, hypertension, and monogenetic components in most patients.

目的 考察抗氧化剂N乙酰半胱氨酸(NAC)对四氯化碳(CCl4)所致的大鼠急性肝损伤的保护机制研究.方法 将4～6周龄的SPF级SD雄性大鼠随机分为A、B、C三组,分别为模型组、对照组和NAC治疗组.本实验制备经典CCl4大鼠急性肝损伤模型,通过腹腔注射浓度为10％的CCl4橄榄油溶液10ml/kg建立SPF级SD大鼠急性肝损伤的模型,CCl4注射前30 min、给药后6、12h分别给腹腔注射等体积生理盐水,共三次.通过生化仪器检测血清中天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、血清碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)、血清总胆红素(TBil)、白蛋白(ALB)、谷氨酸脱氢酶(GLDH)、谷氨酰转肽酶(GGTP)、血清铁、丙二醛(MDA)和超氧化物歧化酶(SOD)的水平.留取每只大鼠肝脏相同部位,4％多聚甲醛固定,进行石蜡包埋,石蜡切片,每组织切1张,并进行HE染色及全景扫描.观察肝组织病理学变化.结果 NAC治疗组的GLDH水平低于模型组,差异有统计学意义(P＜0.01);NAC治疗组的血清铁与SOD水平高于模型组,差异有统计学意义(P＜0.000 1);NAC治疗组的TBil、MDA水平低于模型组,差异有统计学意义(P＜0.000 1).NAC治疗组能够降低模型组大鼠血清中GLDH水平,增加肝组织SOD的水平,降低肝组织TBil和MDA水平,可减少肝细胞坏死.结论 NAC通过抗氧化应激途径,能够有效改善CCl4所致大鼠急性肝损伤,对肝损伤有积极作用.

Background: Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by recurring bone fractures. Some OI patients have other clinical manifestations such as growth retardation, dental abnormalities, blue sclera, and hearing loss. The relationship between the phenotype and genotype of OI is indistinct, and there is no cure for OI. Therefore, an appropriate disease model is urgently needed to understand the pathophysiology of OI. Induced pluripotent stem cells (iPSCs) are capable of developing into three germ layers and have the same genetic background as the donor cells they were derived from; thus, they are an appropriate disease model. Methods: Blood samples collected from the proband and her affected children and one unaffected child were used forgenotyping by whole genome sequencing. A patient-specific iPSC line and a healthy donor iPSC line were generated by reprogramming peripheral blood mononuclear cells with episomal plasmids containing seven transcription factors, namely, OCT4, SOX2, NANOG, LIN28, cMYC, KLF4, and SV40LT. Results: The proband and her two affected children were homozygous for a mutation in collagen type I alpha 1 exon 10, c.725G>T, predicting a p.G242V substitution. A patient-specific iPSC line and a healthy donor iPSC line were generated and characterized in terms of their human embryonic stem cell-like morphology, expression of pluripotency markers, and the ability to differentiate into cells of three germ layers. Conclusions: Here, we report the phenotyping and iPSC disease modeling of an OI family. The detailed phenotyping of the OI family and establishment of iPSCs from an OI patient and healthy family member will provide a powerful tool to evaluate the pathophysiology of OI and develop targeted therapies.

目的 了解深圳市坪山区健康体检人幽门螺杆菌(Hp)感染特点,为开展健康管理提供参考.方法 采用13C呼气试验检测985名健康体检者是否感染Hp.结果 在985名体检者中,按年龄分为A、B、C、D、E共5组.检出Hp阳性386例,感染率为39.2％,其中男性Hp阳性222例,感染率40.6％,女性Hp阳性164例,感染率37.4％;A组感染率(男性35.1％、女性33.9％),B组感染率(男性42.9％、女性28.6％),C组感染率(男性42.7％、女性41.7％),D组感染率(男性37.0％、女性49.3％,E组感染率(男性35.7％、女性57.7％).男性30～39岁感染率最高(42.9％).女性30～39岁感染率最低(28.6％),40岁以后逐步增高,50～59岁感染率达到49.3％;30～39岁时,男性感染率显著高于同年龄段女性,而50～59岁人群,女性感染率高于同年龄段男性12.3％.结论 深圳市坪山区体检人群Hp感染率与年龄、性别有关.50岁以上人群,女性感染率高于同年龄段男性的原因,有待于大样本流行病学和分子生物学研究.

目的 筛选肝细胞癌(HCC)组织表达下调蛋白,探索生物标志物.方法 采用在中国人民解放军某三甲医院8例住院患者HCC组织及癌旁组织标本,使用同位素标记相对和绝对定量(iTRAQ)蛋白标记技术和液相串联质谱分析对这些标本进行蛋白表达水平研究.结果 共筛选出下调蛋白71个,结合蛋白覆盖度、可信度及文献,发现蛋白谷胱甘肽转移酶(GSTM1)、B淋巴细胞瘤-2蛋白(Bcl-2)、细胞色素氧化酶(CYP)2C8、CYP2A6、氨基酰化酶1(ACY1)明显下调.结论 HCC组织下调蛋白对该病的诊断、预后判断有重要价值,下调蛋白迫切需要大样本进行验证,并开展关键蛋白机制研究,为HCC的防治提供新的信息.

目的 探讨原发性肝癌(PLC)患者外周血中环状RNAs(circRNAs)作为PLC分子标志物的临床诊断价值.方法 利用circRNAs微阵列芯片技术检测4例PLC患者(PLC组)和4例健康对照者(对照组)外周血circRNAs的表达谱,并进行组间差异分析,基因本体/基因功能(GO/KEGG)分析差异表达的circRNAs明显富集的潜在功能和信号通路.结果 与对照组比较,PLC组中共有26种circRNAs具有差异表达,包括上调的14种circRNAs和下调的12种circRNAs,亲本基因为:NFATC3、UBQLN1、SKA3、OAT、DENND4A、MGEA5、N4BP2L2、MKLN1、RANBP9、PICALM、SPECC1、LRP5、FAM64A、RPS8、FLI1、PCNXL2、RPL13、LINC00340、KIF26B、WBSCR17、NUP214、GPI、GRB10.GO/KEGG分析发现,亲本基因多涉及转录因子活性、RNA转运RT及通过内质网蛋白质加工、泛素介导的蛋白质水解和参与cGM P-PKG信号通路等功能.结论 PLC患者外周血存在明显差异表达的circRNAs,其亲本基因可能参与PLC复杂的发病机制.

BACKGROUND:Autosomal dominant osteopetrosis type II (ADO2) is a genetically and phenotypically metabolic bone disease, caused by osteoclast abnormalities. The pathways dysregulated in ADO2 could lead to the defects in osteoclast formation and function. However, the mechanism remains elusive.MATERIALS AND METHODS:To systematically explore the molecular characterization of ADO2, we performed a multi-omics profiling from the autosomal dominant osteopetrosis type II iPSCs (ADO2-iPSCs) and healthy normal control iPSCs (NC-iPSCs) using whole genome re-sequencing, DNA methylation and N6-methyladenosine (m6A) analysis in this study.RESULTS:Totally, we detected 7,095,817 single nucleotide polymorphisms (SNPs) and 1,179,573 insertion and deletions (InDels), 1,001,943 differentially methylated regions (DMRs) and 2984 differential m6A peaks, and the comprehensive multi-omics profile was generated from the two cells. Interestingly, the ISG15 m6A level in ADO2-iPSCs is higher than NC-iPSCs by IGV software, and the differentially expressed m6A-modified genes (DEMGs) were highly enriched in the osteoclast differentiation and p53 signaling pathway, which associated with the development of osteopetrosis. In addition, combining our previously published transcriptome and proteome datasets, we found that the change in DNA methylation levels correlates inversely with some gene expression levels.CONCLUSION:Our results indicate that the global multi-omics landscape not only provides a high-quality data resource but also reveals a dynamic pattern of gene expression, and found that the pathogenesis of ADO2 may begin early in life.

Background: Primary torsion dystonia (PTD) is a group of related movement disorders characterized by abnormal repetitive, twisting postures due to the involuntary co-contraction of opposing muscle groups. The research is based on whole genome sequencing technology of PTD patients to analyze the pathogenic genes and mutation sites in patients with primary dystonia, the relationship among genotype, clinical phenotype and prognosis. Methods: In order to investigate the association between the familial disease and its molecular mechanisms, 100 normal Han Chinese donors were also examined. The DNA of all the samples was sequenced using whole genome sequencing technique.The participants was conducted and submitted to the Macrogen Group (Seoul, Korea) for analysis. Results: We had detected the data output of precursor is 112.91G, throughut mean depth is 39.50X, mappable mean depth is 35.70X, genome coverage ratio is 99.50%.A novel heterozygous missense variant of uncertain significance (VUS) in ANO3 of Primary Torsion Dystonia had be found, but not in healthy control groups. Conclusions: Together, our results report a new mutation that may be similar in phenotype to known pathogenic genes, which will lay the foundation for future work. More families will be sequenced to identify more informations, which can help us to make the correct molecular diagnosis of the disease and to provide better genetic information.

已有大量研究发现了炎症与肾结石形成的相关性.炎症在草酸钙结石的形成过程中发挥了作用,这是由于尿液中的草酸和草酸钙晶体成分可引起上皮细胞损伤,进而导致炎症的发生.本文综述与肾结石形成相关的一些炎性细胞因子研究进展,并提出存在的一些问题和进一步的研究方向.

胃癌是消化道常见的恶性肿瘤之一,也是我国致死率最高的四大癌症之一,其发病机制仍是当今人类探索的热点之一.染色质三维构象的变化能在一定程度上影响正常基因的表达和功能,进而诱导疾病的发生发展.为加深对胃癌发生机制的理解,本文从细胞染色质三维构象角度,探讨其与胃癌发生发展之间的关联,同时展望了细胞染色质三维结构在胃癌临床诊治中的应用前景.

Background Autosomal dominant osteopetrosis type II (ADO2) is a rare human genetic disease that has been broadly studied as an important osteopetrosis model; however, there are no disease-specific induced pluripotent stem cells (ADO2-iPSCs) that may be valuable for understanding the pathogenesis and may be a potential source of cells for autologous cell-based therapies. Methods To generate the first human ADO2-iPSCs from a Chinese family with ADO2 and to identify their characteristics, blood samples were collected from the proband and his parents and were used for genotyping by whole-exome sequencing (WES); the urine-derived cells of the proband were reprogrammed with episomal plasmids that contained transcription factors, such as KLF4, OCT4, c-MYC, and SOX2. The proteome-wide protein quantification and lysine 2-hydroxyisobutyrylation detection of the ADO2-iPSCs and normal control iPSCs (NC-iPSCs) were performed by high-resolution LC-MS/MS and bioinformatics analysis. Results WES with filtering strategies identified a mutation in CLCN7 (R286W) in the proband and his father, which was absent in the proband’s mother and the healthy controls; this was confirmed by Sanger sequencing. The ADO2-iPSCs were successfully generated, which carried a normal male karyotype (46, XY) and the mutation of CLCN7 (R286W); the ADO2-iPSCs positively expressed alkaline phosphatase and other surface markers; and no vector and transgene were detected. The ADO2-iPSCs could differentiate into all three germ cell layers, both in vitro and in vivo. The proteomic profiling revealed similar expression of pluripotency markers in the two cell lines and identified 7405 proteins and 3664 2-hydroxyisobutyrylated peptides in 1036 proteins in the ADO2-iPSCs. Conclusions Our data indicated that the mutation CLCN7 (R286W) may be a cause of the osteopetrosis family. The generated vector-free and transgene-free ADO2-iPSCs with known proteomic characteristics may be valuable for personalized and cell-based regenerative medicine in the future.

目的 筛选IgA肾病患者的DNA N6-甲基腺嘌呤(N6-methyladenine,6mA)异常甲基化谱,探讨IgA肾病的发病机制,为其诊断和治疗寻找新靶标.方法 采用N6-腺嘌呤甲基化免疫共沉淀高通量测序技术(N6-methyladenosine immunoprecipitation sequencing,6mA-IPSeq)检测10例IgA肾病患者和10例健康人全基因组的6mA水平,筛选出差异的DNA甲基化谱,通过基因本体功能注释、富集分析和KEGG信号转导通路富集分析,初步对IgA肾病患者基因甲基化情况进行分析.结果 共检测IgA肾病组中6mA位点61465个,主要分布在内含子上,其中上调基因2550个,下调基因1563个.生物信息学分析结果提示,差异基因组主要参与线粒体呼吸链复合体Ⅳ、多囊肾蛋白复合体、核常染色质、细胞器内膜等组成;主要涉及调节肾小管和上皮细胞形态发生、ATP生物合成、细胞周期等生物过程;IgA肾病差异基因在胞吞通路富集程度最高,该通路中MHC、TGB1、PIP5K、PLD1、RAB、CLB等基因6mA表达水平显著下调.结论 IgA肾病的发生、发展可能与胞吞功能失调有关.

The present study aimed to investigate the complexity and diversity of the T lymphocyte immune repertoire in patients with bladder cancer. To do so, the immune state of patients was assessed. The study also aimed to elucidate the aetiology and pathogenesis of bladder cancer to provide a novel theoretical basis for disease prevention, diagnosis, treatment and prognosis monitoring. Cancerous and paracancerous (control) tissue samples were collected from five patients diagnosed with muscle-invasive bladder cancer. Multiplex polymerase chain reaction and Illumina high-throughput sequencing were used to determine the characteristics and clonal diversity of the T-cell receptor (TCR) β-chain complementarity-determining region 3 (CDR3) gene in the cancerous and paracancerous tissues of patients with bladder cancer. The degree of clonal expansion in malignant samples was significantly higher than in adjacent samples. Furthermore, ΤCRβ variable (TRBV), ΤCRβ diversity (TRBD) and ΤCRβ joining (TRBJ) repertoires were significantly different in cancerous samples compared with adjacent samples. In addition, 13 identified V-J pairs were highly expressed in cancerous samples whereas they had low expression in control samples. In conclusion, the degree of T-cell clonal expansion in bladder cancerous tissue was higher than in paracancerous tissue, whereas the immune diversity of the tissues of patients with bladder cancer was significantly lower. The DNA sequence and amino acid sequences, and V-J combination level may be used to comprehensively understand the diversity and characteristics of TCR CDR3 in bladder cancer and paracancerous tissues, and to evaluate the immune status of bladder cancer to develop therapeutic targets and biomarkers for prognosis monitoring.

Background Retinitis pigmentosa (RP) is one of the major types of hereditary retinal dystrophies with extreme genotypic heterogeneity. To date, more than 80 genes have been identified to be associated with RP in human. Method Here, we presented a clinical genetic study of three Chinese man manifested with night vision blindness and complete loss of midperipheral visual field. All of these three probands have been identified with loss of both central vision and far peripheral visual field. Gradual loss of rod cells followed by subsequent loss of cone cells have been identified in these probands. Targeted next generation sequencing and Sanger sequencing have been performed to understand the pathogenic variants underlying the disease phenotype in these three unrelated Chinese probands. Results Targeted next generation sequencing and Sanger sequencing identified three homozygous novel mutations (c.1880C>A; c.1459_1460delGA, and c.392G>A) in the MERTK gene in these three unrelated Chinese proband. In the first proband, the identified mutation (c.1880C>A) leads to the formation of a premature stop codon followed by the formation of a truncated mer-tyrosine kinase (MERTK) protein (p.Ser627*) product which predicted to be disease causing. In the second proband, the identified deletion (c.1459_1460delGA) leads to the formation of a frameshift which also finally results in the formation of a truncated MERTK protein (p.Asp487Leufs*57) product which also predicted to be disease causing. In the third proband, the identified mutation (c.392G>A) leads to the formation of a premature stop codon followed by the formation of a truncated MERTK protein (p.Trp131*) product which also predicted to be disease causing. Hence, these three mutations are loss-of-function mutations. These three mutations were absent in unaffected family members and in 100 normal healthy controls. Conclusion Our present study also demonstrates the significance of targeted next generation sequencing in determining the genetic basis of RP.

目的 探讨胸腔积液和血液γ-干扰素释放试验(IGRA)在结核性胸膜炎患者中的诊断价值.方法 选取2016年1～12月深圳市人民医院临床症状有胸腔积液的患者151例,按临床诊断将其分为结核性胸膜炎组77例,非结核性胸膜炎组74例,分别收集患者的血液和胸腔积液样本开展IGRA,利用统计学软件分析试验对血液和胸腔积液样本的灵敏度、特异性、阴性预测值、阳性预测值以及结果的一致性.结果 胸腔积液IGRA灵敏度为97.4％,特异性为73.1％;血液灵敏度为83.1％,特异性为87.7％,胸腔积液灵敏度高于血液(x2=8.94,P＜0.05),但特异性小于血液(x2=4.74,P＜0.05);胸腔积液阳性预测值为80.6％,阴性预测值为96.1％;血液阳性预测值为87.7％,阴性预测值为83.1％,胸腔积液的阳性预测值与血液的比较,差异无统计学意义(x2=1.48,P＞0.05),而胸腔积液的阴性预测值高于血液(x2=4.98,P＜0.05);两种样本检测结果一致性一般(Kappa=0.57).结论 胸腔积液和血液IGRA在结核性胸膜炎中均有一定诊断价值,胸腔积液IGRA对鉴别诊断结核性胸膜炎更有意义.

目的 探讨胸腔积液γ-干扰素释放试验(IG RA)在结核性胸膜炎诊断中的价值.方法 选取2016年1-12月胸腔积液患者105例,经临床诊断为结核性胸膜炎患者52例纳入结核组;非结核性胸膜炎患者53例,其中42例IGRA结果阴性的非结核患者纳入IGRA阴性-非结核组,11例IGRA结果阳性的非结核患者纳入IGRA阳性-非结核组.收集患者胸腔积液标本进行体外IGRA试验,并对结果进行比较.结果 结核组阴性对照干扰素水平明显高于IGRA阴性-非结核组(t=0.0016)和IGRA阳性-非结核组(t=0.0017)阴性对照干扰素水平;结核组结核刺激剂干扰素水平明显高于IGRA阴性-非结核组(t=6.32761×10-8)和IGRA阳性-非结核组(t=5.90637×10-7)结核刺激剂干扰素水平,差异均有统计学意义(P<0.05).结论 综合分析胸腔积液IGRA检测阴性对照及结核刺激剂干扰素水平能够有效诊断结核性胸膜炎.

Objective: various prenatal diagnosis examinations greatly contribute to predicting chromosome abnormalities, cordocentesis is one of the important methods for prenatal diagnosis in China. Materials and methods: Pregnant women underwent serum screening and sonographic screening, who were conducted on umbilical cord blood because of high-risk pregnancy abnormalities, the umbilical cord blood was brought up to culture medium, lymphocytes were collected for karyotype analysis. Results: we found that a total of 112 (4.8%) cases were diagnosed with chromosomal abnormalities, including 72 cases (64.3%) of trisomy syndrome, 15 cases (13.4%) of sex chromosome aneuploidy, 12 cases (10.7%) of translocation, 7 cases (6.3%) of mosaic and 6 other types (5.4%). In the serum screening abnormalities, compared to the abnormalities of multi-markers and single markers, the multi-markers showed statistically significant difference in chromosome abnor malities. In the abnormal group of ultrasound screening, the structural anomalies showed statistically significant difference in chromosome abnormalities compared to anomalies of sonographic marker (14.8%vs.3.5%). Patients without abnormalities were found in groups with rare characteristics. the high-risk compound and abnormalities of single and multiple serum markers were important in predicting chromosomal disorders. Compared with sonographic markers, fetal structural abnormalities were more effective in predicting chromosomal abnormalities. Conclusion: cordocentesis is crucial significance for the diagnosis of fetal chromosome abnormalities, especially for those gravidas with advanced maternal age who have not received regular prenatal examinations.

采用静态法从10种大孔树脂中筛选纯化银杏叶黄酮的最佳树脂,并通过动态吸附考察最佳大孔树脂的吸附性能和最优洗脱参数,同时研究银杏叶黄酮提取物对α-葡萄糖苷酶的抑制活性.确定LX-68大孔树脂纯化银杏叶黄酮的最佳工艺条件为:提取液pH值为4.0,上柱流速为2 BV·h-1,先以4 BV 10％乙醇洗脱杂质,再用70％乙醇洗脱,洗脱流速为3 BV·h-1.在此条件下,银杏叶提取物总黄酮含量达27.3％.纯化的银杏叶黄酮提取物具有餐后降血糖的作用,作用优于阿卡波糖,表明银杏叶黄酮提取物是一种优质的降血糖产品.