ABSTRACT Background In patients with chronic kidney disease (CKD), vascular calcification (VC) is common and is associated with a higher risk of all-cause mortality. Shh, one ligand for Hedgehog (Hh) signaling, participates in osteogenesis and several cardiovascular diseases. However, it remains unclear whether Shh is implicated in the development of VC. Methods Inorganic phosphorus 2.6 mM was used to induce vascular smooth muscle cells (VSMCs) calcification. Mice were fed with adenine diet supplement with 1.2% phosphorus to induce VC. Results Shh was decreased in VSMCs exposed to inorganic phosphorus, calcified arteries in mice fed with an adenine diet, as well as radial arteries from patients with CKD presenting VC. Overexpression of Shh inhibited VSMCs ostosteoblastic differentiation and calcification, whereas its silencing accelerated these processes. Likewise, mice treated with smoothened agonist (SAG; Hh signaling agonist) showed alleviated VC, and mice treated with cyclopamine (CPN; Hh signaling antagonist) exhibited severe VC. Additionally, overexpression of Gli2 significantly reversed the pro-calcification effect of Shh silencing on VSMCs, suggesting that Shh inhibited VC via Gli2. Mechanistically, Gli2 interacted with Runx2 and promoted its ubiquitin proteasomal degradation, therefore protecting against VC. Of interest, the pro-degradation effect of Gli2 on Runx2 was independent of Smurf1 and Cullin4B. Conclusions Our study provided deeper insight to the pathogenesis of VC, and Shh might be a novel potential target for VC treatment.

Abstract Background Laparoscopic surgery has been endorsed by clinical guidelines for colon cancer, but not for rectal cancer on account of unapproved oncologic equivalence with open surgery. Aims We started this largest‐to‐date meta‐analysis to comprehensively evaluate the safety and efficacy of laparoscopy in the treatment of rectal cancer compared with open surgery. Materials & Methods Both randomized and nonrandomized controlled trials comparing laparoscopic proctectomy and open surgery between January 1990 and March 2020 were searched in PubMed, Cochrane Library and Embase Databases (PROSPERO registration number CRD42020211718). The data of intraoperative, pathological, postoperative and survival outcomes were compared between two groups. Results Twenty RCTs and 93 NRCTs including 216,615 patients fulfilled the inclusion criteria, with 48,888 patients received laparoscopic surgery and 167,727 patients underwent open surgery. Compared with open surgery, laparoscopic surgery group showed faster recovery, less complications and decreased mortality within 30 days. The positive rate of circumferential margin (RR = 0.79, 95% CI: 0.72 to 0.85, p < 0.0001) and distal margin (RR = 0.75, 95% CI: 0.66 to 0.85 p < 0.0001) was significantly reduced in the laparoscopic surgery group, but the completeness of total mesorectal excision showed no significant difference. The 3‐year and 5‐year local recurrence, disease‐free survival and overall survival were all improved in the laparoscopic surgery group, while the distal recurrence did not differ significantly between the two approaches. Conclusion Laparoscopy is non‐inferior to open surgery for rectal cancer with respect to oncological outcomes and long‐term survival. Moreover, laparoscopic surgery provides short‐term advantages, including faster recovery and less complications.

Vascular malformations are due to abnormal development of blood and/or lymphatic vessels during embryonic life without endothelial cell proliferation. Most of the previous treatments were symptomatic methods as surgery and sclerotherapy because the pathogenic mechanism was not clearly understood. With advances in molecular biology, the pathogenesis of vascular malformations is thought to be related to inherited and/or somatic mutations that eventually activate the PI3K/ATK/mTOR, Ras/Raf/MEK/ERK pathways. Also, related studies have promoted the use of targeted inhibitors. This article provides a review of current causative genes and targeted drugs for pediatric vascular malformations, aiming to provide a basis for promoting accurate molecular diagnosis and precision targeted therapy for these diseases.

BACKGROUND:Patients with chronic kidney disease (CKD) suffered from vascular calcification (VC), one major contributor for their increased mortality rate. Hedgehog (Hh) signaling plays a crucial role in physiological bone mineralization and is associated with several cardiovascular diseases. However, the molecular changes underlying VC is ill defined and it remains unclear whether Hh signaling intervention affects VC.METHODS:We constructed human primary vascular smooth muscle cell (VSMC) calcification model and performed RNA sequencing. Alizarin red staining and calcium content assay were conducted to identify the occurrence of VC. Three different R packages were applied to determine differentially expressed genes (DEGs). Enrichment analysis and protein-protein interaction (PPI) network analysis were carried out to explore the biological roles of DEGs. qRT-PCR assay was then applied to validate the expression of key genes. By using Connectivity Map (CMAP) analysis, several small molecular drugs targeting these key genes were obtained, including SAG (Hedgehog signaling activator) and cyclopamine (CPN) (Hedgehog signaling inhibitor), which were subsequently used to treat VSMC.RESULTS:Obvious Alizarin red staining and increased calcium content identified the occurrence of VC. By integrating results from three R packages, we totally obtained 166 DEGs (86 up-regulated and 80 down-regulated), which were significantly enriched in ossification, osteoblast differentiation, and Hh signaling. PPI network analysis identified 10 key genes and CMAP analysis predicted several small molecular drugs targeting these key genes including chlorphenamine, isoeugenol, CPN and phenazopyridine. Notably, our in vitro experiment showed that SAG markedly alleviated VSMC calcification, whereas CPN significantly exacerbated VC.CONCLUSIONS:Our research provided deeper insight to the pathogenesis of VC and indicated that targeting Hh signaling pathway may represent a potential and effective therapy for VC.

Cytogenetic aberrations (CAs) are vital markers for risk stratification of multiple myeloma (MM). The prognostic significance of the aberration, t(11;14)(q13;q32), in MM has remained controversial over recent years. In addition, studies on the heterogeneity of t(11;14) MM and the impact of additional CAs are rare.[1] We therefore conducted a retrospective study on relevant data collected at our center in order to further analyze the characteristics of Chinese patients with t(11;14) MM and elaborate on heterogeneity in their genetic profile. All newly-diagnosed patients with MM (NDMM) treated at Peking University People's Hospital from January 2009 to December 2019 with fluorescence in-situ hybridization (FISH) proven t(11;14)(q13;q32) were enrolled in the study group. Patients were excluded if they had been diagnosed with primary plasma cell (PC) leukemia or had been followed-up for < 1 year. All interphase FISH before 2015 were performed without CD138 sorting. From January 2015, the specimens were purified using CD138 microbeads magnetic cell sorting (Miltenyi Biotec, Bergisch Gladbach, Germany). High risk (HR) CA included t(4;14)(p16;q32), t(14;16)(q32;q23), deletion (del) (17p13), and gain/amplification (amp) of 1q21. Standard risk (SR) CA was based on FISH without any of the above HR aberrations. The study group consisted of 109 t(11;14) positive NDMM patients while the control group included 109 control cases who were selected randomly from 1046 non-t(11;14) NDMM patients at a ratio of 1:1 using the time of diagnosis as the matching variable. The case-control matching was based on the year of diagnosis. The median follow-up period was 5.18 years. All the statistical analyses were performed using SPSS 23.0 (SPSS Inc., Chicago, IL, USA). The study was approved by the Peking University People's Hospital Institutional Review Board (ID: 2021PHB299–001). A total of 109 patients in the t(11;14) group, the median age was 59.4 years (range 38–81 years), with 75 being male. Twenty cases (18.3%) had renal impairment (serum creatinine >2.0 mg/dL). The number of patients classified as international staging system (ISS) stage I, II, and III were 25, 44, and 40, respectively. As shown in Supplementary Table 1, https://links.lww.com/CM9/B69, there were no statistical differences in median age and sex distribution at diagnosis between the t(11;14) and non-t(11;14) groups. The distribution of ISS stage was also similar in the two groups. In the t(11;14) group, the free light chain subtype of M protein was present in 33.9% (37/109) of patients compared to 20.2% (22/109) in the non-t(11;14) group (P = 0.019). Fewer gain/amp of 1q21 was found in the t(11;14) group than that in the non-t(11;14) group (45.9% [50/109] vs. 60.6% [66/109], respectively, P = 0.026). The positive rate of CD20 in the t(11;14) group which was significantly higher than that in the non-t(11;14) group (31.7% [33/104] vs. 13.9% [14/101], respectively, P = 0.002). There was no statistical difference in treatment patterns between the two groups. In the study group, the patients received different induction regimens: 67 (61.5%) a proteasome inhibitor (PI)-based regimen; 16 (14.7%) an immunomodulator (IMiD)-based regimen; 25 (22.9%) bortezomib combined with thalidomide or lenalidomide; and one patient who received conventional chemotherapy. After induction therapy, 24 (22.0%) patients received first-line autologous stem cell transplantation (ASCT) as consolidation. In the non-t (11;14) control group, the treatments included a PI-based regimen in 78 patients (71.6%), an IMiD-based regimen in 15 (13.8%), a PI+IMiD-based regimen in 13 (11.9%), and conventional therapy in 3 (2.8%). The treatment response for myeloma was based on the International Myeloma Working Group response criteria. As shown in Supplementary Table 1, https://links.lww.com/CM9/B69, after induction therapy the overall and very good partial response (VGPR) + complete response responses were similar in the t(11;14) and non-t(11;14) groups. Median progression free survival (PFS) was 2.48 (95% confidence interval [CI], 1.99–2.97) years and 1.87 (95% CI, 1.17–2.57) years for patients in the t(11;14) and non-t(11;14) groups, respectively (P = 0.342). There was a trend towards a longer median overall survival (OS) in the t(11;14) group in comparison with that observed in the non-t(11;14) group (7.25 years [no CI] vs. 4.75 [95%CI,3.62–5.89], respectively, P = 0.074). All 218 patients were subdivided into four groups: t(11;14) without HR CA, t(11;14) with at least one HR CA, non-t(11;14) with at least one HR CA, and non-t(11;14) without HR CA. As shown in Figure 1, we compared the PFS and OS in these four groups, with the results showing that patients with t (11;14) +non-HR CA had comparable outcomes to that of the non-t(11;14) + non-HR CA patients, whereas patients with HR CA had inferior outcomes independent of whether or not they possessed t(11;14). These findings suggested that the outcome of patients relied mainly on whether HR CA existed and that t(11;14) did not confer any benefits or inflict any harm on clinical outcomes.Figure 1: Kaplan-Meier curves for PFS and OS. PFS (A) and OS (B) of patients with t(11;14) and different CA. PFS (C) and OS (D) of patients with/without gain/amp of (1q21) in the subgroup of t(11;14). Amp: Amplification; CA: Cytogenetic aberrations; HR: High risk; NDMM: Newly diagnosed multiple myeloma; OS: Overall survival; PFS: Progression-free survival.We next analyzed the t(11;14) positive study group separately by subdividing the t(11;14)+ group into gain/ amp of 1q21 positive and negative groups. There was no significant difference in gender, age, ISS stage, renal function damage, lactate dehydrogenase (LDH) level, platelet count, free light chain M-protein ratio, the proportion of PCs, G-banding abnormalities in the BM samples, and the incidence of extramedullary infiltration (P > 0.050) between the 1q21 positive and negative groups [Supplementary Tables 2, https://links.lww.com/CM9/B69 and 3, https://links.lww.com/CM9/B69]. Compared with the 1q21 negative group, the positive group had a lower lymphocyte-monocyte ratio (LMR) (median, 3.48 vs. 4.61; P = 0.022) and higher neutrophil-lympho-cyte ratio (NLR) (median, 3.14 vs. 2.14; P = 0.002). There were no significant differences between the two groups in the patterns of different treatments. There was also no difference in overall response (ORR) and ≥VGPR between the gain/amp of 1q21 positive and negative groups. The median PFS was 3.49 years in the 1q21 negative group and 1.65 years in the 1q21 positive group (P = 0.003). However, there was a trend towards a shorter median OS in the 1q21 positive group compared to that observed in the 1q21-group (5.41 years vs. not reached; P = 0.091). Multivariate analysis showed that the gain/amp of 1q21 was an independent factor for PFS (P = 0.030, HR = 2.350, 95% CI: 1.343–4.112) and OS (P = 0.004, HR = 5.660, 95% CI: 1.725–18.575) in the t(11;14) positive NDMM. In the gain/amp of 1q21 positive patients, no further significant differentiation was observed for the various gain/amp ratios of 1q21 (5%, 10%, 20%, 30%, 40%, and 50%, respectively). Our study showed that patients harboring t(11;14) without HR CA had comparable survival to that of t(11;14) negative patients without any HR CA. Similar conclusions have been reported in the literature. Saini et al,[2] using the same 1:1 propensity score matching method as used in our study, compared outcomes and showed no significant differences between PFS and OS in the t(11;14) and control SR groups. Gao et al[3] analyzed one ASCT cohort and showed that patients with t(11;14) alone had outcomes similar to those of patients with a SR. However, Lakshman et al[1] from the Mayo Clinic investigated 365 patients with t(11;14) and 730 matched control NDMM patients, and found that both PFS and OS in the t(11;14) patients were significantly shorter than those in the patients with no translocation. One possible explanation for this discrepancy was the FISH examination spectrum and the question as to whether cytoplasmic immunoglobulin FISH (cIg FISH) or CD138 magnetic bead sorting FISH was used. For instance, FISH detection carried out at the Mayo Clinic used cIg FISH with the spectrum including trisomy (ie, chromosomes 3, 7, 9, and 15), and the partner chromosome of 14q32 including t (4;14), t(8;14), t(6;14), t(14;20), and t(14;16), which was considerably more complex than those used in other studies and had the potential to improve identification of more "high risk" indicators. Our study showed that gain/amp of 1q21 was an independent prognostic risk factor for PFS and OS in t (11;14) NDMM. Only a small number of studies have analyzed 1q21 in the t(11;14) population alone. Pawlyn et al[4] analyzed 847 patients in a clinical trial in which all patients received thalidomide-based or traditional chemotherapy. In the 127 patients with t(11;14), it was found that the concurrent del (17p) or gain/amp of 1q21 was an independent risk factor for OS (38.1 months vs. 51.2 months, P = 0.050) and that there was a trend towards a difference in PFS (24.2 months vs. 19.7months, P = 0.108). In contrast to these findings on the gain/amp of 1q21, Gao et al[3] analyzed 455 MM patients who all received ASCT, including 55 patients with t(11;14). Their results showed that in the t(11;14) MM subgroup, gain/amp of 1q21 accounted for 38.9% and had no impact on median PFS or OS. In our study, we were able to observe the prognostic significance of the gain/amp of 1q21 in the patient group treated with either a PI or IMiD, whereas in patients receiving ASCT, the adverse effect of gain/amp of 1q21 was offset. This result indicated that the inconsistency probably resulted from a different spectrum of treatment. Although the number of patients receiving transplantation was small, our study showed that in the 1q21+ group, the patients who received ASCT had a trend towards a better OS (P = 0.076, data not shown) compared with those who did not receive ASCT. This suggests that ASCT was very important for this MM subtype. The above results raise the question as to why additional gain/amp of 1q21 confers inferior significance in NDMM with t(11;14)(q13;q32). Analysis of clinical and laboratory indices showed no significant difference in ISS stage, LDH level, extramedullary plasmacytoma, or proportion of peripheral PCs between the 1q21 positive and negative patients. There was also no significant difference in the effect on ORR or at least VGPR. On the other hand, there is evidence that co-occurrence of 1q21+ is likely to be associated with a worse prognosis in not only t(11;14) MM but also other subgroups of NDMM.[5] Our results showed that the adverse effect of 1q21+ on prognosis may not occur by reducing the induced remission rate, but rather through an increase in the early recurrence rate. A similar viewpoint was reported by Schmidt TM.[5] It is therefore very important to closely monitor disease status after treatment, especially during the consolidation/maintenance phase. We observed a lower LMR and higher NLR in the 1q21+ group, and this finding may reflect a possible immune dysfunction mechanism for the adverse significance of 1q21. Our study had several limitations including its retrospective design, heterogeneous treatment population, and a relatively small number of patients. However, our study was based on data pertaining to a Chinese population, and using this data we explored the impact of additional CA in t(11;14) MM. In conclusion, this single-center, retrospective study showed that patients harboring t(11;14) had comparable survival to patients without any high-risk cytogenetics. Gain/amp of 1q21 was an adverse prognostic risk factor for patients with t(11;14) myeloma, a finding that provides a better understanding of this particular type of myeloma. Funding This research was supported partly by Capital's Funds for Health Improvement and Research (No. 2020–2–4082), Peking University People's Hospital Scientific Research Development Funds (No. RDY2019–33), and National Natural Science Foundation of China (No. 82170196).

Abstract. Background:. Cell competition is an important feature in pancreatic cancer (PC) progression, but the underlying mechanism remains elusive. This study aims to explore the role of exosomes derived from normal pancreatic ductal epithelial cells involved in PC progression. Methods:. PC cells and pancreatic stellate cells (PSCs) were treated with exosomes isolated from pancreatic ductal epithelial cells. Cell proliferation was assessed by CCK8 assays. Cell migration and invasion were assessed by Transwell assays. PC and matched adjacent non-tumor tissue specimens were obtained from 46 patients pathologically diagnosed with PC at Peking University First Hospital from 2013 to 2017. Tissue miR-485-3p and p21-activated kinase-1 (PAK1) expression was examined by real-time polymerase chain reaction (RT-PCR), and the relationship of the two was analyzed using Pearman's product-moment correlation. The clinical significance of miR-485-3p was analyzed using the Chi-square test, Wilcoxon rank-sum test, and Fisher exact probability, respectively. The binding of miR-485-3p to PAK1 5′-untranslated region (5′-UTR) was examined by luciferase assay. PC cells were xenografted into nude mice as a PC metastasis model. Results:. Exosomes from pancreatic ductal epithelial cells suppressed PC cell migration and invasion as well as the secretion and migration of PSCs. MiR-485-3p was enriched in the exosomes of pancreatic ductal epithelial cells but deficient in those of PC cells and PSCs, in accordance with the lower level in PSCs and PC cells than that in pancreatic ductal cells. And the mature miR-485-3p could be delivered into these cells by the exosomes secreted by normal pancreatic duct cells, to inhibit PC cell migration and invasion. Clinical data analysis showed that miR-485-3p was significantly decreased in PC tissues (P < 0.05) and was negatively associated with lymphovascular invasion (P = 0.044). As a direct target of miR-485-3p, PAK1 was found to exert an inhibitory effect on PC cells, and there was a significantly negative correlation between the expression levels of miR-485-3p and PAK1 (r = −0.6525, P < 0.0001) in PC tissues. Moreover, miR-485-3p could suppress PC metastasis in vivo by targeting p21-activated kinase-1. Conclusions:. Exosomal miR-485-3p delivered by normal pancreatic ductal epithelial cells into PC cells inhibits PC metastasis by directly targeting PAK1. The restoration of miR-485-3p by exosomes or some other vehicle might be a novel approach for PC treatment.

目的 观察中性粒细胞淋巴细胞比值(NLR)、血小板淋巴细胞比值(PLR)对结肠癌根治术后手术部位感染(SSI)的预测价值.方法 选取2018年1月至2021年1月首都医科大学附属北京世纪坛医院收治的96例结肠癌根治术患者,将术后发生SSI的19例患者纳入感染组,余77例纳入未感染组,观察两组患者术前基线实验室检查资料,比较两组患者NLR、PLR水平,采用logistics回归分析影响患者发生SSI的危险因素,采用ROC曲线分析术前NLR、PLR对结肠癌根治术后SSI的预测价值.结果 感染组患者NLR、PLR水平高于未感染组,差异有统计学意义(P<0.05).两组患者中性粒细胞计数(NEUT)、淋巴细胞计数(TLC)、血小板计数(PLT)、血红蛋白(HB)水平比较差异无统计学意义(P>0.05).logistics回归分析显示,NLR、PLR水平均是影响结肠癌术后SSI发生的影响因素(P<0.05).ROC曲线分析显示,术前NLR、PLR水平用于评估结肠癌根治术后SSI患者诊断价值的AUC分别为0.722、0.681.结论 NLR、PLR水平与结肠癌根治术后SSI发生密切相关,术前重视其水平对结肠癌根治术后SSI的发生具有一定的预测价值.

Introduction. Colorectal cancer (CRC) is one of the most common cancers worldwide. Multiple risk factors are involved in CRC development, including age, genetics, lifestyle, diet and environment. Of these, the role of the gut microbiota in cancer biology is increasingly recognized.Hypothesis/Gap Statement. Micro-organisms have been widely detected in stool samples, but few mucosal samples have been detected and sequenced in depth.Aim. Analysis of cultured mucosal bacteria from colorectal cancer and adjacent normal mucosal tissues with metagenomics sequencing.Methodology. Twenty-eight paired tumour and non-tumour tissues from 14 patients undergoing surgery for CRC were analysed. We removed the influence of eukaryotic cells via culture. The composition of mucosal microbiota in intestinal mucosa were detected and analysed with metagenomic sequencing.Results. Compared with non-cultured mucosal sample, 80 % bacteria species could be detected after culture. Moreover, after culture, additional 30 % bacteria could be detected, compared with non-cultured samples. Since after culture it was difficult to estimate the original abundance of microbiome, we focused on the identification of the CRC tissue-specific species. There were 298 bacterial species, which could only be cultured and detected in CRC tissues. Myroides odoratimimus and Cellulophaga baltica could be isolated from all the tumour samples of 14 CRC patients, suggesting that these species may be related to tumour occurrence and development. Further functional analysis indicated that bacteria from CRC tissues showed more active functions, including basic metabolism, signal transduction and survival activities.Conclusion. We used a new method based on culture to implement information on prokaryotic taxa, and related functions, which samples were from colorectal tissues. This method is suitable for removing eukaryotic contamination and detecting micro-organisms from other tissues.

近20年来,恶性肿瘤发病率呈上升趋势.恶性肿瘤导致的死亡已经成为重大公共卫生问题,防治形势严峻.恶性肿瘤防治措施主要包括:开展科普宣传教育,提高全社会癌症防控意识,普及科学防癌理念,引导公众远离不良生活习惯,践行健康生活方式,降低肿瘤发病率;通过基础研究、转化研究、临床研究,提高恶性肿瘤早诊率和治愈率,改善晚期肿瘤患者的生活质量.而上述措施的施行,需要肿瘤学科发展,培养大量肿瘤专科人才.

To investigate the clinical characteristics, survival, prognostic factors, and treatment of brain metastasis (BM) from colorectal cancer (CRC). Twenty-one patients with BM from CRC were retrospectively reviewed. Predictive factors for BM and prognostic factors after the diagnosis of BM were examined by univariate and multivariate COX analysis. The time from the development of extracranial metastases, including lung, bone, and liver, to the occurrence of BM was recorded separately. The median overall survival time was 7 months. In univariate prognostic analysis, median survival with multimodal therapy was better than that with unimodal therapy (10 months vs 3 months, P = .000). In addition, median survival with Karnofsky performance status (KPS) < 70, 1 BM lesion, primary tumor stage of II-III, extracranial lesions < 2, and no extracranial metastasis were much better than the other groups (P < .05 of all). Although there was not a significant difference in median survival between patients receiving combination treatment with bevacizumab and those who did not, treatment with bevacizumab was associated with better survival (10 months vs 5 months, P = .436). The time intervals from bone, liver, and lung metastases to BM were 3, 6.5, and 11 months, respectively. Based on multivariate Cox analysis, KPS and treatment modalities were independent prognosis factors (P = .039 and P = .000, respectively). CRC patients with a high KPS and multimodal treatment have improved survival.

目的 探讨腹腔镜腹股沟疝无张力修补术后并发缺血性睾丸炎的危险因素并建立风险预测模型.方法 选取2015年1月至2019年12月在首都医科大学附属北京世纪坛医院行腹腔镜腹股沟疝无张力修补术的患者180例,其中术后并发缺血性睾丸炎的90例患者作为观察组,未发生缺血性睾丸炎的90例患者作为对照组.回顾性分析两组患者的临床资料,通过单因素分析和多因素logistic回归分析确定术后缺血性睾丸炎的独立危险因素,构建列线图风险模型,并对该模型的预测效能进行评价.结果 单因素分析显示观察组患者中年龄<18岁、腹股沟疝病程≥24个月、嵌顿性疝、疝内容物进入阴囊、复发性疝及采用前入路手术方式的比例明显高于对照组,差异有显著性(P<0.05).Logistic回归分析显示,患者年龄<18岁(OR=2.941,95％CI 1.465～5.903)、腹股沟疝病程≥24个月(OR=3.302,95％CI 1.648～6.614)、嵌顿性疝(OR=3.601,95％CI 1.619～8.010)、复发性疝(OR=2.295,95％CI 1.065～4.944)及前入路手术方式(OR=3.479,95％CI 1.519～7.967)是术后发生缺血性睾丸炎的独立危险因素(P<0.05).基于以上危险因素建立列线图风险模型,验证结果显示,初始模型一致性指数为0.869,与内部验证的一致性指数0.872较为接近,校正曲线显示该列线图模型具有良好的区分度及一致性.结论 年龄<18岁、腹股沟疝病程≥24个月、嵌顿性疝、复发性疝及前入路手术是腹腔镜腹股沟疝无张力修补术后发生缺血性睾丸炎的独立危险因素,据此建立的列线图模型具有较高的预测效能,可为临床提供有针对性的指导.

目的 探索主要促进因子超家族蛋白2A(major facilitator superfamily domain containing 2A,MFSD2A)对肝癌细胞增殖、凋亡和侵袭的影响.方法 使用慢病毒载体构建差异表达MFSD2A的肝癌细胞株HepG2和SMMC-7721,由qPCR及Western blotting法评估其转染效率;CCK-8法分析差异表达MFSD2A对细胞增殖的影响,流式细胞术测定转染后细胞的基础凋亡率的变化,Transwell小室细胞侵袭实验明确MFSD2A对细胞侵袭能力的影响.结果 在肝癌细胞中上调MFSD2A表达可以显著抑制细胞增殖、促进基础凋亡,同时还可降低细胞的侵袭能力;而下调MFSD2A则可导致相反的效应.结论 MFSD2A在肝癌的肿瘤进程中发挥抑癌基因的功能,这种功能主要是通过抑制细胞增殖并诱导凋亡实现的.

Circulating tumour cells (CTCs) have potential utility in various clinical applications for cancer management. The present study focused on evaluating the diagnostic role of CTCs in colorectal cancer (CRC). A total of 89 blood samples from 59 patients diagnosed with CRC and 30 healthy individuals were collected for CTC detection. The Cyttel method is an improved CTC detection strategy, which combines negative enrichment with immunofluorescence and fluorescencein situhybridization. This method effectively detected a significant increase in total CTCs in patients with CRC (49/59) compared with those in healthy controls (3/30). A cut-off value of 2 CTCs/3.2 ml blood yielded a sensitivity of 83.05% and a specificity of 100%. Additionally, three traditional serum tumour markers, namely carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and CA72-4, were examined by immunoassays. The diagnostic sensitivity of CTCs was much higher than that of CEA, CA19-9 and CA72-4 alone or in combination, particularly in patients with early stage CRC. The combined sensitivity of CTCs and CEA reached 91.53%, which was only slightly lower than the sensitivity of all four markers combined (CTCs + CEA + CA19-9 + CA72-4). CTCs with aneuploidy of chromosome 7 or 8 were carefully distinguished, and the associations among different types of CTCs, clinicopathological characteristics and overall survival were statistically analysed. Total CTCs were revealed to be significantly associated with tumour differentiation and nerve invasion. CTCs were more likely to be detected in poorly differentiated CRC tumours than in well- and moderately-differentiated tumours (P=0.026). Furthermore, to the best of our knowledge, the present study was the first to report that CTCs with multiploidy of chromosome 7 were significantly associated with TNM stage. These CTCs exhibited a high chance of being identified in the peripheral blood of patients with late-stage CRC (stage III-IV; P=0.031). The present study suggests that the combination of CTCs and CEA may serve as an effective potential diagnostic and prognostic indicator in patients with CRC. Detection of CTCs with aneuploidy may have increased specificity in predicting highly malignant and invasive tumours in CRC management.

Colorectal cancer (CRC) remains a major cause of carcinoma-related deaths worldwide. MicroRNA-498 (miR-498) modulates the development of a variety of biological events, including tumorigenesis. Nevertheless, it is unclear whether miR-498 plays a role in CRC. This study was designed to elucidate the underlying mechanism and role of miR-498 in modulation of the viability and invasiveness of CRC cells. We report that CRC tissues and cells exhibited decreased expression of miR-498, and that overexpression of miR-498 resulted in reduced proliferation of CRC cells, concomitant with increased apoptosis. Furthermore, bioinformatic prediction and dual-luciferase reporter assay revealed that miR-498 targeted the 3'-UTR of Bcl-2 for silencing. However, Bcl-2 overexpression suppressed the proapoptosis of miR-498 on CRC cells. In summary, we describe a possible role of miR-498 in CRC, which may lead to the identification of new targets for treatment of this malignancy.

Objective: The functional role and mechanism of the long noncoding RNA (lncRNA) H19 in regulating human pancreatic cancer (PC) cell stemness and invasion have not been completely elucidated. This study aimed to evaluate the role of H19 in regulating the stemness, epithelial-mesenchymal transition (EMT), invasion and chemosensitivity of PC cells. Methods: The sphere-forming ability was assessed using serum-free floating-culture systems. Chemosensitivity was evaluated via CCK-8 and flow cytometry assays in vitro. Migration and invasion were evaluated by transwell assays. The expression of stemness and EMT markers was detected by flow cytometry, qRT-PCR and western blot analyses. Xenograft initiation, growth and sensitivity were examined; Ki-67 nuclear staining intensity was evaluated by immunohistochemistry; and in situ apoptosis was evaluated by a TUNEL assay. Results: H19 played an important role in maintaining PC cell stemness. Upregulated H19 expression in CAPAN-1 cells promoted tumor cell migration, invasion, EMT and chemoresistance. In contrast, downregulated H19 expression in PANC-1 cells yielded the opposite results. These effects were mediated by positively modulating the STAT3 pathway. Furthermore, SOCS5, an endogenous inhibitor of the STAT3 pathway, was a direct target of miR-675-3p, which was positively regulated by H19 in PC cells. Conclusions: The H19/miR-675-3p signaling axis plays a critical role in maintaining the EMT process and stemness of PC cells by directly targeting SOCS5 to activate the STAT3 pathway. These data provide new insights into the oncogenic function of H19 in human PC and reveal potential targets for the development of optimal treatment approaches for this disease.

目的 探索抗生素锁技术在预防婴幼儿肿瘤患者出现植入式静脉输液港相关感染并发症中的效果.方法 选取首都医科大学附属北京世纪坛医院60例确诊神经系统恶性肿瘤并接受手术放置植入式静脉输液港的婴幼儿患者,进行随机对照研究,实验组30例患儿在术后预防性使用抗生素锁技术封管,对照组30例患儿单纯使用肝素盐水封管,按严格随访计划观察所有患儿在术后1个月中是否出现感染并发症,比较两组间的差异并寻找导致感染并发症的危险因素.结果 两组患儿一般情况的组间比较差异无统计学意义(P<0.05),预防性使用抗生素锁技术组的患儿术后感染率为3.33％,而对照组患儿的术后感染率为13.33％,两组比较差异无统计学意义(P=0.353);分析后未发现导致感染并发症出现的独立危险因素.结论 预防性应用抗生素锁技术可能会在一定程度上减少婴幼儿肿瘤患者植入式静脉输液港相关感染并发症的发生率,但需要后续扩大样本量深入研究来证实其临床效果.

Background The effectiveness in surveillance colonoscopy largely depends on the quality of bowel preparation. We aimed to investigate the quality of bowel preparation segmentally and its effect on Adenoma Detection Rate (ADR) and Advanced Adenoma Detection Rate (AADR) at corresponding bowel segments. Methods This is a single-centered and cross-sectional study. A consecutive of 5798 patients who underwent colonoscopy examination were included. Bowel preparation was evaluated based on Bowel Bubble Scale (BBS) in general and Boston Bowel Preparation Scale (BBPS) in each segment (right side, transverse and left side of colon) and total BBPS scores. The quality of bowel preparation was correlated with ADR and AADR. Results Four thousand nine hundred forty colonoscopies (14,820 bowel segments) were included in the final analysis. In which 30.9% scored 3, 57.5% scored 2, 11.2% scored 1 and 0.4% scored 0 on basis of BBPS. For each score, ADR were 10.8, 7.7, 4.9 and 3.2%, respectively; whereas AADR were 4.5, 2.8,1.8 and 1.6% ( P < 0.05). 36.9% of the colonoscopies showed presence of minimal bubbles and 34.3% with no bubble. For bowels without bubbles and with a large amount of bubbles, ADR were 28.3 and 20.0% respectively; and AADR were 13.3 and 7.1% respectively. Conclusions Segmental bowels’ cleanliness and the amount of bubbles in bowels significantly affect ADR and AADR. The better the bowel preparation at each segment is and the less bubbles in the bowel there are, the higher ADR and AADR we got. We suggest repeating colonoscopy if any segment of the bowel preparation is poor, or if there is more bubbles, even if the total score of BBPS indicates good or fair bowel preparation.

目的 探讨小鼠骨髓间充质干细胞来源的外泌体(bone marrow mesenchymal stem cell-derived exosomes,BMSCs-exo)对紫外线辐射后的鼠真皮成纤维细胞(Fibroblasts,FBs)的保护作用.方法 用流式细胞术鉴定小鼠骨髓间充质干细胞(BMSCs),提取并鉴定其上清液来源的外泌体(exosome).用紫外线照射FBs建立细胞光老化模型,采用不同浓度的BMSCs-exo处理照射后的FBs.采用β-半乳糖苷酶染色法进行FBs衰老检测.通过Western blot检测处理后FBs的Ⅰ型胶原蛋白,基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)和弹性蛋白的蛋白质水平.结果 β-半乳糖苷酶染色法显示BMSCs-exo浓度越高细胞衰老数目越少.Western blot检测显示BMSCs-exo浓度越高MMP-1表达越低,Ⅰ型胶原蛋白和弹性蛋白表达越高.结论 BMSCs-exo可以缓解紫外线诱导的鼠真皮成纤维细胞光老化进展.

目的:探讨中医西结合治疗脑梗死的疗效及对患者侧支循环建立的影响.方法:选取2017年6月至2019年1月北京市第二医院收治的脑梗死患者128例作为研究对象,按照随机数字表法分为对照组和观察组,每组64例.对照组患者应用常规西医治疗(依达拉奉注射液),观察组在对照组的基础上联合中医治疗(疏血通注射液),比较2组患者的治疗效果,及治疗前后神经功能缺损情况(NIHSS评分)、日常生活能力(Bathel评分)、血脂血液流变学及缺血区脑血流量.结果:观察组患者治疗总有效率为90.6％(58/64),高于对照组的75％(48/64),2组比较差异有统计学意义(P<0.05);治疗前,2组NIHSS评分、Bathel评分、血脂水平及血液流变学指标、缺血区脑血流量比较,差异均无统计学意义(P>0.05);治疗后,观察组NIHSS评分低于对照组、Bathel评分明显高于对照组(P<0.05);治疗后观察组各项血脂水平及血液流变学指标均优于对照组,观察组缺血区脑血流量高于对照组(均P<0.05).结论:中西医结合治疗能有效提高脑梗死患者治疗效果,有利于提高患者神经功能及日常生活能力,改善患者血脂及血液流变学指标,有利于患者侧支循环的建立.

目的 分析腹膜恶性间皮瘤(malignant peritoneal mesothelioma,MPM)中肿瘤浸润性淋巴细胞(tumor infiltrating lympho-cytes,TILs)和Ki-67增殖指数与临床病理特征及预后关系,探讨TILs和Ki-67对MPM预后的影响.方法 光镜下观察并计数MPM中TILs数量,应用免疫组化EnVision法检测28例MPM中Ki-67增殖指数.Kaplan-Meier法构建生存曲线,Cox回归模型单因素和多因素分析影响MPM的预后因素.结果 TILs和Ki-67增殖指数与MPM患者性别、年龄、组织学亚型均无关(P>0.05).Log-rank生存分析显示,TILs中密度、高密度患者的总生存期高于低密度患者,差异有统计学意义(40.4个月vs 11.1个月,P=0.012);肿瘤细胞Ki-67高增殖指数患者总生存期低于Ki-67低增殖指数患者,差异有统计学意义(30.2个月vs 11.1个月,P=0.049).多因素分析显示,TILs是MPM的独立预后因素(OR=3.666,95％CI=1.1～11.8,P=0.024).结论 MPM中Ki-67增殖指数水平和TILs密度与患者总生存期显著相关.TILs是MPM的独立预后因素之一.