Background Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. MethodsIn this pilot study, we administered six preoperative doses of each 2-week cycle of the anti-PD-1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5-FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, <= 10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. Results By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow-up was 24.7 months (IQR: 21.1-26.1). All patients underwent R0 surgical resection without treatment-related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence-free. Treatment-related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 x 10(-8)). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non-pCR tumors (p = 0.038 and p = 0.015, respectively). Conclusions Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non-pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD-1 blockade-enhanced targeted chemotherapy require further investigation.

Purpose:Both Ku80 and Ku70 are promising drug targets for hepatocellular carcinoma (HCC) and crucial for immune regulation. However, their correlation with HCC immune signatures has not yet been investigated. Therefore, we aimed to investigate the relationship between Ku80, Ku70, and immune signatures in HCC and validate their significance in cytotoxic lymphocyte (CTL) immunotherapy. Patients and Methods:Analyses of Ku70, Ku80, and immune signatures in public datasets was performed using R software, an online Kaplan-Meier plotter, g:Profiler, GeneTrail, and Metascape. Uniform manifold approximation and projection, correlation chord diagrams, Pearson's correlation tests, and Spearman correlation tests were used to describe various correlation levels. HCC mRNA sequencing data (n=373 tumor samples and n=50 para-tumor samples) were drawn from The Cancer Genome Atlas (TCGA) public database. Immunofluorescent staining was used to validate Ku70/Ku80 and CD8+CTL expression in 120 HCC patients from our center. Survival analysis was performed using the Kaplan-Meier survival analysis with the Log rank test and was adopted to analyze immunotherapy outcomes correlated with Ku70/Ku80 expression in various solid tumors. Multivariate analysis of HCC patient data from our center was performed using a Cox proportional hazards model. Results:Increased Ku70/Ku80 expression positively correlated with more enriched immune microenvironment signatures, indicating increased immune infiltration in HCC. Upregulation of Ku70/Ku80 indicated better anti-PD1 and anti-PDL1 treatment outcomes in various solid tumors. Higher Ku70/Ku80 expression with lower CD8+CTL signatures indicated worse survival outcomes, whereas lower Ku70/Ku80 expression with higher CD8+CTL signatures indicated the best prognosis. Conclusion:Higher Ku70/Ku80 expression indicated an immune-hot infiltration signature in HCC. Patients with increased Ku70/Ku80 expression and high CD8+CTL signatures may potentially benefit from CTL-centered immunotherapies.

Objective: To explore the active substances and targets of Danbie Capsules in Endometriosis therapy. Methods: This study was conducted through TCMSP and published literature screened and obtained 183 active substances of Danbie Capsules, combined and intersected with Endometriosis target genes collected and screened in the GEO database, obtained 24 target genes for Endometriosis treatment, and mapped the target network map of Danbie Capsules active substances against Endometriosis. The network was analyzed with the aid of Cytoscape version 3.9.1. With the aid of the platform of the STRING data analysis, PPI network analysis was conducted on 24 anti-Endometriosis targets of the Danbie Capsules. Results: The research results obtained three critical active substances, namely, Quercetin, beta-sitosterol, and Luteolin. Seven critical targets were identified, and two representative genes (TP53 and AKT1) have been verified in Macromolecular docking and immunohistochemical verification. Conclusion: The active substances of Danbie Capsules in the treatment of Endometriosis are Quercetin, beta-sitosterol and Luteolin, and the main targets are TP53 and AKT1.

Prostate cancer (PCa) is the second most frequently diagnosed cancer among men, causing a huge number of deaths each year. Traditional chemotherapy for PCa mostly focused on targeting androgen receptors. However, some of the patients would develop resistance to hormonal therapy. In these cases, it is suggested for these patients to administer treatments in combination with other chemotherapeutics. Current chemotherapeutics for metastatic castration-resistant PCa could hardly reach satisfying effects, therefore it is crucial to explore novel agents with low cytotoxicity. Herein, a common drug against the human immunodeficiency virus (HIV), the dolutegravir (DTG) was modified to become a series of dolutegravir-1,2,3-triazole derivatives. Among these compounds, the 4d and 4q derivatives were verified with high anti-tumor efficiency, suppressing the proliferation of the prostate cancer cells PC3 and DU145. These compounds function by binding to the poly (adenosine diphosphate-ribose) polymerase (PARP), inactivating the PARP and inducing DNA damage in cancer cells. It is noteworthy that the 4d and 4q derivatives showed almost no impact on normal cells and mice. Thereby, the results reveal that these dolutegravir-1,2,3-triazole compounds are potential chemotherapeutics for PCa treatment.

Background: Gliomas are highly refractory intracranial cancers characterized by genetic and transcriptional heterogeneity. However, therapeutic options are limited. In the last years, copper-induced cell death is becoming a prospective treatment strategy for gliomas and other solid tumors, but copper metabolism-related genes associated with cancer development remain unclear.Methods: We first collected gene expression data from The Cancer Genome Atlas (TCGA) to identify significantly differentially expressed copper metabolism-related genes in gliomas. Using these genes, we performed COX regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression to construct the prognostic model. The prognostic value of the model was further validated by CGGA testing set. Subsequently, functional analyses were carried out, including gene set enrichment analysis (GSEA), immune infiltration analysis, and mutation analysis. Finally, the expression levels of these genes were verified by immunohistochemical analysis.Results: The prognostic model consisted of 7 genes: CDK1, LOXL2, LOXL3, NFE2L2, SLC31A1, SUMF1 and FDX1. According to this prognosis model, glioma patients could be split into the high-risk group or low-risk group, and the low-risk group showed significantly better prognostic survival (p < 0.001). Moreover, the high-risk group had higher levels of immune cell infiltration, immune checkpoint genes expression, and higher tumor mutational burden (TMB), which indicates that they might benefit more from immunotherapy. Finally, we confirmed the expression level of FDX1, SUMF1, and SLC31A1 protein as significantly different in glioblastoma, lower-grade glioma, and non-tumor brain tissues by immunohistochemical analysis, and the high expression of FDX1 and SLC31A1 protein was related to poor survival in glioma patients.Conclusions: Our study could contribute to the prognosis prediction and decision-making in patients with gliomas.

Background:Heart transplantation is now widely performed in China, but the current entry criteria for heart transplantation donors are simple and lack reliable standards; there are still no studies on the effect of preoperative echocardiographic parameters of heart transplantation donors on the prognosis of the recipient. Therefore, the aim of this study is twofold: (I) to observe the characteristics of changes in echocardiographic parameters of the donor's heart before and after heart transplantation and (II) to study the relationship between the changes in echocardiographic parameters of the donor's heart pre- and post-transplant and transplant recipient survival.Methods:A total of 29 patients who underwent orthotopic heart transplant in our hospital from October 2016 to October 2019 were enrolled in this study. All recipients were followed up until April 2020. Echocardiographic data were collected pre-transplantation (donor) and at 1 week and 1 month post-transplant (recipient).Results:Compared with the pretransplanted donor's heart, there was an increase in the interventricular septal diameter, left ventricular posterior wall diameter, right atrium diameter and right ventricular diameter, while a decrease was found in the tricuspid annular systolic displacement and tricuspid annular peak systolic velocity at 1 week post-transplant. The survival curve showed that the postoperative survival time in the right atrium/ventricle ≥32 mm group was better than that in the right atrium/ventricle <32 mm group. The survival curve also showed that the postoperative survival time in the right atrium/ventricle enlargement <2 mm group was better than that in the right atrium/ventricle enlargement ≥2 mm group.Conclusions:In the early post-transplant period, ventricular myocardial thickening, right heart enlargement and a decrease in right heart function were observed in the post-transplanted heart compared to the pretransplanted donor's heart. Postoperative survival was higher among heart transplant patients who received a heart with right atrium/ventricle ≥32 mm. Postoperative survival was lower among heart transplant patients whose right atrium/ventricle was dilated ≥2 mm at 1 month postoperatively compared with the pretransplanted donor's heart.

患者38岁,孕4产2,因"孕27+3周,双下肢水肿3周,发现血压升高1 d"于2019年6月24日急诊收入中山大学附属第三医院产科.患者末次月经不详,根据超声推算预产期2019年9月18日.孕期未进行规律产科检查,未监测血压.

Background. With the progress of shock therapy and the establishment and promotion of methods such as thrombolytic therapy and percutaneous coronary intervention (PCI), many tissues and organs have been reperfused after ischemia which may cause even worse disorder called ischemia-reperfusion injury (IRI). mRNAs have been found to have significant impacts on ischemia-reperfusion through various mechanisms. In view of the accessibility of mRNAs from blood, we aimed to find the association between mRNA and ischemia-reperfusion. Methods. We used the GSE83472 dataset from the Gene Expression Omnibus (GEO) database to find differential RNA expression between ischemia-reperfusion tissue and control samples. In addition, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to find the biological property of 449 RNAs from GSE83472 via the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Besides, Gene Set Enrichment Analysis (GSEA), a tool to find the pathway orientation of a gene set, was used for further study in the four most significant KEGG pathways. Furthermore, we constructed a protein-protein interaction (PPI) network. In the end, we used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting to measure and compare the expression of Spp1 in patients who accepted percutaneous coronary intervention. Results. The bioinformatics analyses suggested that Spp1 was a hub gene in reperfusion after ischemia. The qRT-PCR result showed that the Spp1 expression was significantly downregulated in ischemia-reperfusion cells after PCI compared with normal samples and so as the western blotting. Conclusion. Spp1 might play an essential role in acute myocardial infarction after ischemia and reperfusion injury.

Atherosclerosis (AS) is a chronic metabolic disease in arterial walls, characterized by lipid deposition and persistent aseptic inflammation. AS is regarded as the basis of a variety of cardiovascular and cerebrovascular diseases. It is widely acknowledged that macrophages would become foam cells after internalizing lipoprotein particles, which is an initial factor in atherogenesis. Here, we showed the influences of Bruton's tyrosine kinase (BTK) in macrophage-mediated AS and how BTK regulates the inflammatory responses of macrophages in AS. Our bioinformatic results suggested that BTK was a potential hub gene, which is closely related to oxidative stress, ER stress, and inflammation in macrophage-induced AS. Moreover, we found that BTK knockdown could restrain ox-LDL-induced NK-κB signaling activation in macrophages and repressed M1 polarization. The mechanistic studies revealed that oxidative stress, mitochondrial injury, and ER stress in macrophages were also suppressed by BTK knockdown. Furthermore, we found that sh-BTK adenovirus injection could alleviate the severity of AS in ApoE-/- mice induced by a high-fat diet in vivo. Our study suggested that BTK promoted ox-LDL-induced ER stress, oxidative stress, and inflammatory responses in macrophages, and it may be a potential therapeutic target in AS.

Human papillomavirus (HPV)-mediated cervical carcinogenesis is a multistep progressing from persistent infection, precancerous lesion to cervical cancer (CCa). Although molecular alterations driven by viral oncoproteins are necessary in cervical carcinogenesis, the key regulators behind the multistep process remain not well understood. It is pivotal to identify the key genes involved in the process for early diagnosis and treatment of this disease. Here we analyzed the mRNA expression profiles in cervical samples including normal, cervical intraepithelial neoplasia (CIN), and CCa. A co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to reveal the crucial modules in the dynamic process from HPV infection to CCa development. Furthermore, the differentially expressed genes (DEGs) that could distinguish all stages of progression of CCa were screened. The key genes involved in HPV-CCa were identified. It was found that the genes involved in DNA replication/repair and cell cycle were upregulated in CIN compared with normal control, and sustained in CCa, accompanied by substantial metabolic shifts. We found that upregulated fibronectin type III domain-containing 3B (FNDC3B) and downregulated bisphosphoglycerate mutase (BPGM) could differentiate all stages of CCa progression. In patients with CCa, a higher expression of FNDC3B or lower expression of BPGM was closely correlated with a shorter overall survival (OS) and disease-free survival (DFS). A receiver operating characteristic (ROC) analysis of CIN and CCa showed that FNDC3B had the highest sensitivity and specificity for predicting CCa development. Taken together, the current data showed that FNDC3B and BPGM were key genes involved in HPV-mediated transformation from normal epithelium to precancerous lesions and CCa.

Ketogenic diet (KD) is popular in diabetic patients but its cardiac safety and efficiency on the heart are unknown. The aim of the present study is to determine the effects and the underlined mechanisms of KD on cardiac function in diabetic cardiomyopathy (DCM). We used db/db mice to model DCM, and different diets (regular or KD) were used. Cardiac function and interstitial fibrosis were determined. T-regulatory cell (Treg) number and functions were evaluated. The effects of ketone body (KB) on fatty acid (FA) and glucose metabolism, mitochondria-associated endoplasmic reticulum membranes (MAMs), and mitochondrial respiration were assessed. The mechanisms via which KB regulated MAMs and Tregs were addressed. KD improved metabolic indices in db/db mice. However, KD impaired cardiac diastolic function and exacerbated ventricular fibrosis. Proportions of circulatory CD4+CD25+Foxp3+ cells in whole blood cells and serum levels of IL-4 and IL-10 were reduced in mice fed with KD. KB suppressed the differentiation to Tregs from naive CD4+ T cells. Cultured medium from KB-treated Tregs synergically activated cardiac fibroblasts. Meanwhile, KB inhibited Treg proliferation and productions of IL-4 and IL-10. Treg MAMs, mitochondrial respiration and respiratory complexes, and FA synthesis and oxidation were all suppressed by KB while glycolytic levels were increased. L-carnitine reversed Treg proliferation and function inhibited by KB. Proportions of ST2L+ cells in Tregs were reduced by KB, as well as the production of ST2L ligand, IL-33. Reinforcement expressions of ST2L in Tregs counteracted the reductions in MAMs, mitochondrial respiration, and Treg proliferations and productions of Treg cytokines IL-4 and IL-10. Therefore, despite the improvement of metabolic indices, KD impaired Treg expansion and function and promoted cardiac fibroblast activation and interstitial fibrosis. This could be mainly mediated by the suppression of MAMs and fatty acid metabolism inhibition via blunting IL-33/ST2L signaling.

例1 患者31 岁,孕2产0,因"停经39 +3周,下腹阵痛6 h"于2014年8月8 日收入中山大学附属第三医院产科.患者孕期定期产前检查,妊娠期血常规提示血红蛋白波动在100～110 g/L,其余各项检查均正常,否认既往高血压、糖尿病、心脏病、癫痫等病史.入院诊断:(1 )妊娠39 +3周,先兆临产;(2)轻度贫血.入院后患者生命体征平稳顺利进入产程,第一产程14小时零5 分钟,患者无不适,第二产程指导用力15 min后患者突然出现抽搐,呼之不应,口吐白沫,呼吸困难和低氧血症.立即启动多学科[神经内科、神经外科、心血管内科、麻醉科、新生儿科、重症监护病房(intensive care unit,ICU)]急会诊,怀疑羊水栓塞,按照羊水栓塞抢救并气管插管,抢救期间血压最高148/86 mmHg,检测尿蛋白(-),胎心率100～110 次/min,钳产助产娩出一足月女婴,出生体重4000 g,Apgar评分9-10-10分,因代谢性酸中毒转新生儿科.分娩后患者行头颅CT平扫(图1 A)、计算机断层扫描动脉造影(computed tomography angiography,CTA)及计算机断层扫描静脉造影(computed tomography venography, CTV)检查,左侧大脑中动脉M1 段可见一球状突起,大小约24 mm ×22 mm,左侧大脑中动脉M1段动脉瘤破裂伴广泛蛛网膜下腔出血,双侧侧脑室后角及第四脑室积血(图1B,C).产后24 h阴道出血约300 ml.产后患者处于轻度昏迷,呼吸机辅助呼吸,格拉斯哥昏迷指数评分(Glasgow Coma Scale,GCS)为7分(唤醒能睁眼、伴呻吟、对外界刺激四肢可屈曲有反应),Hunt-Hess分级属于Ⅳ级.因患者浅昏迷伴肺部感染、广泛的蛛网膜下腔出血和脑水肿,动脉瘤2. 5 cm开颅手术难度较大,死亡率极高,全院大会诊和与患者家属沟通后,家属考虑手术风险,强烈要求保守治疗.

Atherosclerosis (AS) is one of the most serious and common cardiovascular diseases affecting human health. AS is featured by the accumulation of plaques in vessel walls. The pathophysiology of AS is relevant in the low-density lipoprotein (LDL) uptake by macrophages, as well as the conversion of macrophages to foam cells. However, the mechanisms about how macrophages regulate AS have not been fully elucidated. In this study, we aimed to illuminate the roles of ZBTB20 and to excavate the underlying regulative mechanisms of ZBTB20 in AS. The microarray analysis revealed that ZBTB20 was a hub gene in the oxidative stress and inflammatory responses induced by oxidized LDL (ox-LDL) in AS. Correspondingly, our validation studies showed that ZBTB20 increased in either the human atherosclerotic lesion or the ox-LDL-stimulated macrophages. Moreover, the knockdown of ZBTB20 decreased M1 polarization, suppressed the proinflammatory factors, inhibited mitochondrial fission, and reduced the oxidative stress level of macrophages induced by ox-LDL. The mechanistic studies revealed that the ZBTB20 knockdown suppressed NF-κB/MAPK activation and attenuated the mitochondrial fission possibly via regulating the nucleus translocation of NRF2, a pivotal transcription factor on redox homeostasis. Our in vivo studies showed that the sh-ZBTB20 adenovirus injection could reduce the progression of AS in apolipoprotein E-deficient (ApoE-/-) mice. All in all, these results suggested that ZBTB20 positively regulated the oxidative stress level, mitochondrial fission, and inflammatory responses of macrophages induced by ox-LDL, and the knockdown of ZBTB20 could attenuate the development of AS in ApoE-/- mice.

Objective:To explore the effects of gestational diabetes mellitus (GDM) on the perinatal outcomes in twin pregnancies, and analyze the risk factors of twin pregnancies complicated with GDM.Methods:Retrospective analysis was performed on 757 patients of twin pregnancies who had delivered in the Third Affiliated Hospital of Sun Yat-sen University during January 2015 to June 2020. According to the results of 75 g oral glucose tolerance test (OGTT), 196 cases were in the GDM group, and 561 cases were inthe non-GDM group. The clinical characteristics of the subjects were recorded, the perinatal outcomes of the two groups were compared by using t test, Mann-Whitney U test, χ 2 test or Fisher exact probability method;the risk factors related to GDM were analyzed by multivariate-logistic stepwise regression. Results:Compared with the non-GDM group, 75 g OGTT-fasting plasma glucose (FPG), 1 h plasma glucose (PG), 2 h PG in GDM group were higher, gestational weeks and birth weight of newborn in GDM group were lower, the rate of preterm birth(<37 weeks) was higher. The incidence of neonatal respiratory distress syndrome, infection and anemia in the GDM group was higher than that in the non-GDM group (all P<0.05). There were statistically significant differences in age, pre-pregnancy body mess index (pre-BMI), gravidity, parity, proportion of in vitro fertilization and embryo transfer (IVF-ET), chorionicity, polycystic ovary syndrome (PCOS) history and family history of diabetes (all P<0.05). Risk factors were analyzed by multivariate-logistic stepwise regression, age ≥35 years (OR=2.335), pre-BMI ≥24.0 kg/m 2 (OR=2.356), PCOS history (OR=1.932) and family history of diabetes (OR=3.127) were independent risk factors for GDM in twin pregnancies (all P<0.05). Conclusions:GDM increased the incidence of preterm birth less than 37 weeks, neonatal respiratory distress syndrome, infection and anemia in twin pregnancies. Age ≥35 years, pre-BMI ≥24.0 kg/m 2, PCOS history and family history of diabetes were independent risk factors for GDM in twin pregnancies.

Objective:To explore whether thyroid stimulating hormone (TSH) treat-to-target during early pregnancy had an impact on the incidence of gestational diabetes mellitus (GDM) in women with hypothyroidism.Methods:A retrospective analysis was performed on naturally conceived singleton pregnant women who had accepted routinely prenatal services at the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to December 2018. The gestational weeks of the first obstetric examination were before 13 weeks and 6 days of gestation. Data of 6 978 subjects were analyzed, including 186 cases in the hypothyroidism group and 6 792 cases in the normal group. In the hypothyroidism group, according to whether TSH levels were<2.5 mU/L in the first prenatal examination, 124 cases were in the under control group and 62 cases in the non-control group. Basic information was collected at first visit, and laboratory tests were performed with fasting samples, including thyroid function [TSH, free thyroxine (FT4), thyroid peroxidase antibody (TPOAb)] and fasting plasma glucose (FPG). The 75-gram oral glucose tolerance test (OGTT) was performed at 24 to 28 weeks. The incidence of GDM and the impact of TSH levels on it between the hypothyroidism group and the normal group were explored by using χ2 test. The risk factors of GDM were analyzed by logistic regression. Results:The incidence of GDM in the hypothyroidism group was higher than that in the under-control group [21.5% (40/186) vs. 13.7% (929/6 792), P=0.002]. The incidences of GDM in the under-control group [20.2% (25/124)] and the non-control group [24.2% (15/62)] were higher than that of the control group (all P<0.05). Multivariate logistic regression analysis for risk factors of incidence of GDM was performed, and finally age, pregestational body mass index, history of hypothyroidism, FPG, positive TPOAb, and triglyceride were considered to be independent risk factors for incidence of GDM ( P<0.05). Whether TSH met the standard was ruled out from the equation. Conclusion:Compared with women with normal thyroid function, women with hypothyroidism still are at higher risk of developing GDM, whether TSH levels are under control or not.

Micro/nanotextured topographies (MNTs) can modulate cell-biomaterial interactions mostly by their controllable geometrics. Among them, TiO2 nanotubes, regarded as having a highly controllable nanoscale geometry, have been extensively investigated and applied and significantly affect diameter-dependent cell biological behaviors. In this study, we used five typical MNTs decorated with TiO2 nanotubes with diameters of 30, 50, 70, 100 and 120 nm to explore the optimal nanotube diameter for improving the biofunctional properties and to more deeply understand the underlying mechanisms by which these MNTs affect osteogenic differentiation by revealing the effect of beta1-integrin/Hedgehog-Gli1 signaling on this process. The MNTs affected MG63 osteoblast-like cell spreading, osteogenic gene expression (BMP-2, Runx2 and ALP), mineralization and ALP activity in a diameter-dependent pattern, and the optimal TiO2 nanotube diameter of 70 nm provided the best microenvironment for osteogenic differentiation as well as beta1-integrin/Hedgehog-Gli1 signaling activation. This enhanced osteogenic differentiation by the optimal-diameter TiO2 nanotubes of 70 nm was attenuated via suppression of the beta1-integrin/ Hedgehog-Gli1 signaling, which indicated a significant role of this pathway in mediating the diameter-dependent osteogenic differentiation promotional effect of MNTs with different TiO2 nanotube diameters. These results might provide deeper insights into the signal transduction mechanisms by which different nanoscale geometries influence cellular functions for biomaterial modification and biofunctionalization.

Colorectal cancer (CRC) is a major cause of cancer deaths worldwide. Unfortunately, many CRC patients are still being diagnosed at an advanced stage of the cancer, and the 5-year survival rate is only ~30%. Effective prognostic markers of CRC are therefore urgently needed. To address this issue, we performed a detailed bioinformatics analysis based on the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases to identify prognostic biomarkers for CRC, which in turn help in exploring potential drug-repurposing. We identified five hub genes (PGM2, PODXL, RHNO1, SCD, and SEPHS1), which had good performance in survival prediction and might be involved in CRC through three key pathways (“Cell cycle,” “Purine metabolism,” and “Spliceosome” KEGG pathways) identified by a KEGG pathway enrichment analysis. What is more, we performed a co-expression analysis between five hub genes and transcription factors to explore the upstream regulatory region. Furthermore, we screened the potential drug-repurposing for the five hub genes in CRC according to the Binding DB and ZINC15 databases. Taking together, we constructed a five-gene signature to predict overall survival of CRC and found the potential drug-repurposing, which may improve the outcome of CRC in the future.

目的:探讨早期集束化护理对食管癌术后吸入性肺炎合并急性呼吸窘迫综合征(ARDS)的预后高危因素的影响及其临床应用价值。方法:纳入2016年至2017年中山大学肿瘤防治中心胸外科接受手术治疗后发生吸入性肺炎合并ARDS的食管癌患者90例，术后根据患者及其家属的自愿选择分为对照组(44例)和观察组(46例)。对照组给予常规的护理干预，观察组在常规护理的基础上给予早期集束化护理干预，利用Logistic多因素回归分析分析食管癌术后吸入性肺炎合并ARDS的预后高危因素，对比常规护理与早期集束化护理在食管癌术后吸入性肺炎合并ARDS患者护理中的效果及两种护理方式对患者预后的影响。结果:多因素Logistic回归分析结果显示，食管癌术后吸入性肺炎合并ARDS的预后危险因素包括氧合指数不足、呼吸频率快、手术方式为三切口、伴发有多器官功能障碍综合征(MODS)。观察组患者经护理干预后入住ICU的时间与使用呼吸机的时间显著少于对照组，术后并发症的发生率也显著小于对照组，差异均有统计学意义(均 P<0.05)。 结论:根据食管癌术后吸入性肺炎合并ARDS的预后高危因素在常规护理的基础上实施早期集束化护理可有效减少患者入住ICU的时间与使用呼吸机的时间，降低术后并发症发生率。

Background Oxaliplatin (L-OHP) and 5-fluorouracil (5-FU) resistance in colorectal cancer (CRC) is a major medical problem. Therefore, detailed mechanisms and predictive markers are urgently needed. The aim of this study was to identify key pathways, a robust prognostic gene signature and potential drug-repurposing. Methods In order to confirm the predictive markers and detailed molecular mechanisms of L-OHP and 5-Fu chemoresistant CRC, we performed weighted correlation network analysis (WGCNA), an unsupervised analysis method, to identify the chemoresistant CRC significantly related genes. Then, the gene prognostic model was conducted by Univariate Cox regression and Lasso penalized Cox regression analysis. Subsequently, the time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curve were performed to assess the prognostic capacity of the model. Simultaneously, pathway enrichment was done to identify the key pathways involved in chemoresistant CRC. Moreover, we explored how the hub genes interacted with key pathways and transcription factors. Then, we found the potential drug target by the subcellular location fo hub genes. Finally, we identified the potential drug-repurposing by virtual screening for chemoresistant CRC according to ZINC 15 database. Results We identified the key pathways using KEGG over-representation test and Gene Set Enrichment Analysis (GSEA): Ribosome KEGG pathway. Moreover, six hub-genes prognostic model was conducted by Univariate Cox regression and Lasso penalized Cox regression analysis. Additionally, the detailed interactions among the pathway and hub genes (RBM6, PNN, LEF1, ANO1, PAFAH1B3 and BHLHE41) were examined by protein-protein interaction (PPI) network and shortest-pathway analysis. Furthermore, ANO1 was considered the potential drug target based on the subcellular location and ZINC000018043251 was verified the potential drug by virtual screening. Conclusions Our study identified a novel six-gene resistant signature for CRC prognosis prediction and the molecular details of these interactions between hub genes (RBM6, PNN, LEF1, ANO1, PAFAH1B3 and BHLHE41) and Ribosome key pathways. Furthermore, ZINC000018043251 was verified the potential drug for ANO1 by virtual screening, which might help to improve the outcome of CRC patients.

[目的]探讨系统性红斑狼疮(SLE)合并妊娠孕妇孕期病情变化以及对妊娠结局的影响,分析不良妊娠结局的相关危险因素.[方法]回顾性分析2013年1月1日至2018年12月31日在中山大学附属第三医院产检并分娩,且病例资料完整的合并SLE孕妇,共89例孕妇,95次妊娠,分析孕期SLE病情活动情况及妊娠结局,找出不良妊娠结局的相关危险因素.[结果]①根据SLE疾病活动指数(SLEDAI)评价病情变化,将其分为疾病活动组及稳定组,其中孕期出现病情活动39例(活动组,A组),病情稳定56例(稳定组,B组),狼疮活动率为41.05％,其中妊娠期初发病例和孕前病情不清非计划妊娠的患者中为100％(17/17),在孕前病情稳定计划妊娠的患者中为28.21％(22/78),差异有统计学意义(P<0.05);②不良妊娠结局:其中胎儿丢失、早产、胎儿宫内生长受限(IUGR)、子痫前期、活动性狼疮肾炎在活动组发生率分别为20.51％、35.90％、43.59％、17.95％、41.02％,稳定组分别为1.8％、14.29％、17.86％、3.57％、0,两组相比差异有统计学意义(P<0.05),胎儿窘迫、新生儿窒息、新生儿狼疮在活动组发生率分别为10.26％、7.69％、2.56％,稳定组分别为1.79％、1.79％、0,两组相比差异无统计学意义(P>0.05);③孕前SLE病情不清非计划妊娠、此次妊娠发生活动性狼疮肾炎、aPL阳性、抗SSA阳性均为不良妊娠结局的危险因素(P<0.05).[结论]SLE患者妊娠时机的选择对孕期疾病活动情况至关重要,孕期SLE病情活动增加胎儿丢失、早产、IUGR、子痫前期、活动性狼疮肾炎的发生率;孕前SLE病情不清非计划妊娠、此次妊娠发生活动性狼疮肾炎、aPL阳性、抗SSA阳性与不良妊娠结局密切相关.