Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in tongue squamous cell carcinoma (TSCC) tumorigenesis. However, the comprehensive regulation of lncRNAs-transcription factors (TFs)-messenger RNAs (mRNAs) in TSCC remains largely unknown. The purpose of this study was to identify aberrantly expressed lncRNAs and the associated TF-mRNA network in TSCC. To explore lncRNA and mRNA expression profiles and their biological functions in TSCC, we surveyed the lncRNA and mRNA expression profiles of TSCC and adjacent tissues using next-generation RNA sequencing in six patients. Thousands of significantly differentially expressed lncRNAs (DELs) and mRNAs (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to demonstrate the principal functions of the significantly dysregulated lncRNAs and genes. A total of 40 DELs were screened between TSCC and adjacent non-cancerous tissues. Results obtained from GEPIA and StarBase confirmed the expression levels of nine pivotal DELs obtained in our study. Three of the nine deregulated DELs were identified to have a significant impact on the overall survival of TSCC patients, which were evaluated with GEPIA and StarBase. LncMAP was used to predict the lncRNA-TF-mRNA triplets in TSCC. Furthermore, based on these results, we established lncRNA-TF-mRNA coexpression networks for the up- and downregulated lncRNAs using Cytoscape. We also found that among the nine pivotal lncRNAs, there is limited research on the abnormally expressed lncRNAs, including RP11-54H7.4, CTD-2545M3.8, RP11-760H22.2, RP4-791M13.3, and LINC01405, in TSCC pathogenesis. This is the first study to show that RP11-54H7.4, LINC00152, and LINC01405 can be acted as a prognostic target for TSCC. Our findings provide a novel perspective and lay the foundation for future research on the potential roles of lncRNAs, TFs, and mRNAs in TSCC. Verification of the potential lncRNA-TF-mRNA regulatory networks will provide a more comprehensive understanding of the pathogenesis of TSCC.
Objective: To compare the long-term outcomes of intersphincteric (trans-internal and external) sphincter resection (ISR) and abdominoperineal proctocolectomy (APR) for low-grade rectal cancer. Methods: We used a meta-analytic approach to compare these procedures . Published reports comparing ISR and APR for low rectal cancer in Pubmed, Medline, EMBASE and Cochrane, China Knowledge Network (CNKI), China Biomedical Literature Database, and Vipers databases between January 2005 and January 2023 were searched and those meeting the eligibility criteria were selected for extraction of data for analysis. Inclusion criteria were as follows: (1) all reports comparing ISR and APR for low rectal cancer before January 2023; and (2) prospective randomized controlled studies or well-designed cohort studies. Exclusion criteria were as follows: (1) full text not available; (2) duplicate publications, missing primary outcome indicators, and unknown data; and (3) invalid statistical analysis. Results: Sixteen studies with 2498 patients were included in this study. Compared with the APR group, patients in the ISR group were relatively younger (weighted mean difference [WMD]=-1.82, 95%CI=-2.94 to -0.70, P=0.01), had tumors farther from the anal verge (WMD=0.43, 95%CI=0.18 to 0.67, P<0.01), and lower pathological T-stage (T3-4 stage: OR=0.54, 95%CI=0.36 to 0.81, P<0.01). In contrast, there were no statistically significant differences between the two groups in gender (P=0.78), body mass index (P=0.77), or pathological N stage (P=0.09). Compared with the APR group, patients in the ISR group had a lower rate of postoperative complications (OR=0.77, 95%CI=0.60 to 0.99, P=0.04), shorter hospital stay (WMD=-4.30, 95%CI=-7.07 to -1.53, P<0.01), higher 5-year overall survival (HR=0.54, 95%CI=0.33 to 0.88, P=0.01), and higher 5-year disease-free survival (HR=0.65, 95%CI=0.47 to 0.90, P<0.01). Five-year locoregional failure (HR=0.66, 95%CI=0.40 to 1.10, P=0.11) and time to surgery (WMD=-9.71, 95%CI=-41.89 to 22.47, P=0.55) did not differ significantly between the two groups. Conclusion: ISR is a safe and effective alternative to APR for early-stage low-grade rectal cancer.目的： 比较经括约肌间切除术（ISR）与经腹会阴联合切除术（APR）治疗低位直肠癌的长期疗效。 方法： 采取Meta分析方法检索2005年1月至2023年1月期间Pubmed、Medline、EMBASE和Cochrane、中国知网（CNKI）、中国生物医学文献数据库、维普数据库中，比较ISR与APR治疗低位直肠癌的文献，选择符合准入标准的文献提取数据进行分析。纳入标准：（1）2023年1月之前所有比较ISR和APR治疗低位直肠癌的文献；（2）文献类型为前瞻性随机对照研究或设计良好的队列研究；排除无法获得全文的、重复发表或缺少主要结局指标、数据不详以及违反统计学计算原则的文献。主要结局指标包括：术后并发症发生率、5年总生存率（OS）、5年无病生存率（DFS）、5年无局部复发率（LRF）。术后并发症定义为术后30 d内发生的Clavien-Dindo 2级以上的并发症。次要指标包括：手术时间和住院时间。 结果： 总计16篇文献、2 498例患者被纳入本研究。与APR组相比，ISR组的患者相对较年轻（WMD=-1.82，95%CI=-2.94~-0.70，P=0.01），肿瘤距肛缘距离较远（WMD=0.43，95%CI=0.18~0.67，P<0.01），病理T分期较低（T3~4期：OR=0.54，95%CI=0.36~0.81，P<0.01）。而两组在性别（P=0.78）、体质指数（P=0.77）、病理N分期（P=0.09）上，差异没有统计学意义。与APR组相比，ISR组患者术后并发症发生率较低（OR=0.77，95%CI=0.60~0.99，P=0.04），住院时间较短（WMD=-4.30，95%CI=-7.07~-1.53，P<0.01），5年OS（HR=0.54，95%CI=0.33~0.88，P=0.01）和5年DFS（HR=0.65，95%CI=0.47~0.90，P<0.01）均较高。两组5年LRF（HR=0.66，95%CI=0.40~1.10，P=0.11）以及手术时间（WMD=-9.71，95%CI=-41.89~22.47，P=0.55）的差异均无统计学意义。 结论： 对于分期较早的低位直肠癌，ISR可以作为APR安全有效的替代。.
The conserved TOR (target of rapamycin) kinase is part of a TORC1 complex that regulates cellular responses to environmental stress, such as amino acid starvation and hypoxia. Dysregulation of Akt-TOR signaling has also been linked to the genesis of cancer, and thus, this pathway presents potential targets for cancer chemotherapeutics. Here we report that rapamycin-sensitive TORC1 signaling is required for the S-phase progression and viability of yeast cells in response to genotoxic stress. In the presence of the DNA-damaging agent methyl methanesulfonate (MMS), TOR-dependent cell survival required a functional S-phase checkpoint. Rapamycin inhibition of TORC1 signaling suppressed the Rad53 checkpoint-mediated induction of ribonucleotide reductase subunits Rnr1 and Rnr3, thereby abrogating MMS-induced mutagenesis and enhancing cell lethality. Moreover, cells deleted for RNR3 were hypersensitive to rapamycin plus MMS, providing the first demonstration that Rnr3 contributes to the survival of cells exposed to DNA damage. Our findings support a model whereby TORC1 acts as a survival pathway in response to genotoxic stress by maintaining the deoxynucleoside triphosphate pools necessary for error-prone translesion DNA polymerases. Thus, TOR-dependent cell survival in response to DNA-damaging agents coincides with increased mutation rates, which may contribute to the acquisition of chemotherapeutic drug resistance.
Background: The diagnosis, staging, and therapeutic strategy for synchronous multiple primary nonsmall cell lung cancer (SMP-NSCLC) remain unclear.Distinguishing SMP-NSCLC from intrapulmonary metastasis is difficult but of great importance for selecting the surgical procedure and prognoses.Methods: Fifty-two patients diagnosed with SMP-NSCLC according to the modified Martini-Melamed criteria in the thoracic surgery department of the China-Japan Friendship Hospital from November 2004 to December 2015 were enrolled in this retrospective study.A total of 106 tumors were subjected to pathological examination.Close follow-up and survival analysis were performed. Results:The perioperative morbidity rate was 5.8%, with no cases of perioperative death.The overall 5-year survival rate was 40.6%, the cancer-specific 5-year survival rate was 54.5%, and the median survival time was 52 months.Older age (P=0.553),sex (P=0.600),smoking history (P=0.496),tumor distribution (P=0.461),video-assisted thoracoscopic surgery (VATS) (P=0.398), and adjuvant chemotherapy (P=0.078) did not affect survival.Preoperative percentage of forced expiratory volume in the first second (P=0.022),Charlson comorbidity index (P=0.034),surgical procedure (P=0.040), and highest pT stage (P=0.022)were independent risk factors in the multivariate analysis.Different pathological subtypes were identified in 13 of 18 cases of multiple adenocarcinomas.Different gene mutation types and correlations between tumors were identified through NGS in those with the same pathological subtype.Conclusions: Postoperative survival rates in SMP-NSCLC were satisfactory.Non-radical resection might improve the prognosis for patients with a tolerable general condition and pulmonary function.Higher pT stage might result in poorer survival rates.Larger sample size and future study are still needed to identify the prognostic factors.Comprehensive histologic assessment and next generation sequencing (NGS) could be effective methods for screening SMP-NSCLC.
Lung cancer and chronic obstructive pulmonary disease (COPD) are both common diseases in respiratory system and the leading causes of deaths worldwide. The purpose of this study was to determine whether the severity of COPD affects long-term survival in non-small cell lung cancer (NSCLC) patients after surgical resection.A retrospective research was performed on 421 consecutive patients who had undergone lobectomy for NSCLC. Classification of COPD severity was based on guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Characteristics among the three subgroups were compared and recurrence-free survivals were analyzed.A total of 172 patients were diagnosed with COPD, 124 as mild (GOLD-1), 46 as moderate(GOLD-2), and 2 as severe (GOLD-3). The frequencies of recurrence were significantly higher in higher COPD grades group (P<0.001). Recurrence-free survival at five years were 78.1%, 70.4%, and 46.4% in Non-COPD, GOLD-1 COPD, and GOLD-2/3 COPD groups, respectively (P<0.001). In univariate analysis, age, gender, smoking history, COPD severity, tumor size, histology and pathological stage were associated with recurrence-free survival. Multivariate analyses showed that older age, male, GOLD-2/3 COPD, and advanced stage were independent risk factors associated with recurrence-free survival.NSCLC patients with COPD are at higher risk for postoperative recurrence, and moderate/severe COPD is an independent unfavorable prognostic factor. The severity of COPD based on pulmonary function test can be a useful indicator to identify patients at high risk for recurrence. Therefore, it can contribute to adequate selection of the appropriate individualized treatment.背景与目的 肺癌和慢性阻塞性肺病（chronic obstructive pulmonary disease, COPD）和非小细胞肺癌（non-small cell lung cancer, NSCLC）均是呼吸系统的常见病和多发病，在世界范围内均是高发病率和高死亡率的疾病。本研究旨在探讨COPD的严重程度是否影响NSCLC切除术后的远期生存。方法 回顾性分析421例肺叶切除术的NSCLC患者资料，根据慢性阻塞性肺疾病全球倡议（Global Initiative for Chronic Obstructive Lung Disease, GOLD）指南对COPD患者严重程度进行分级，将入组患者分为3组，比较临床病理特征和无复发生存（recurrence-free survival, RFS）的差异。结果 合并COPD者共172例，其中轻度124例，中度46例，重度2例。随着COPD严重程度增加，术后复发率增加（P<0.001）。无COPD组、轻度COPD组（GOLD-1）和中重度COPD组（GOLD-2/3）的5年无复发生存率分别为78.1%，70.4%和46.4%，差异有统计学意义（P<0.001）。单因素分析结果显示，年龄、性别、吸烟史、COPD严重程度、肿瘤直径、组织学类型和病理分期是影响患者无复发生存的危险因素。Cox多因素回归分析结果显示，年龄、性别、中重度COPD和病理分期是影响患者预后的独立危险因素。结论 合并中重度COPD是影响NSCLC患者术后无复发生存的独立危险因素，可结合患者术前肺功能来判断预后，更准确地预测复发风险，为高危患者制定合理的个体化治疗方案。 .
The aim of this study was to determine whether cirrhosis could be reversed after treated with hepatocyte nuclear factor 4α (HNF4α), a key transcriptional regulator of hepatocyte differentiation and function.Early and advanced stages of liver cirrhosis were induced by thioacetamide (TAA) administration. The adenovirus carrying HNF4α gene was injected into cirrhotic rats via the tail vein. The effect of HNF4α on cirrhosis was evaluated by histological and immunohistochemical examination.Early stage of cirrhosis was remarkably resolved by HNF4α to a nearly-normal extent and advanced cirrhosis was partially ameliorated in vivo. The enforced expression of HNF4α downregulated profibrogenic factors remarkably including α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1, fibroblast-specific protein (FSP)-1, collagen I and III. In vivo and in vitro studies revealed that HNF4α administration inhibited extracellular signal-regulated kinase (ERK) signaling pathway through the downregulation of phosphorated ERK and phosphorated JunD. In addition, HNF4α readjusted the balance between extracellular matrix deposition and degradation through the upregulation of matrix metalloproteinase and downregulation of its inhibitors. Moreover, HNF4α treatment inhibited angiogenesis as determined by CD31 and CD34 immunostaining.Our findings broaden the knowledge on the reversibility of different stages of cirrhosis as HNF4α could present a promising alternative for the treatment of liver cirrhosis.
Abstract Objective To identify factors associated with T1 slope (T1S). Methods A total of 215 patients over 18 years old who underwent whole-spine X-rays to evaluate lower back pain were enrolled in this study. T1S, pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), cervical lordosis (CL), thoracolumbar kyphosis (TLK), and sagittal vertical axis (SVA) were measured. Patients were divided into balance, compensatory balance, thoracic compensation, and thoracic decompensation groups. Results TK (p < 0.001), SVA (p < 0.001), and CL (p = 0.020) were significantly related to high T1S. The balance group had the smallest PT, largest SS and largest LL of the four groups (p < 0.001). The thoracic compensation group had the smallest TK of all groups (p < 0.001). There was no significant difference in T1S between the balance and thoracic compensation groups (p = 0.099). The thoracic decompensation group had a larger T1S than the balance group (p = 0.023). Conclusions Caudal spine segments had a sequential effect on cranial spine segments. T1S reflected the compensation ability of the spine. The absence of balance tended to increase the T1S. Pelvic posterior rotation and thoracic compensation were two crucial factors protecting against increased T1S in patients with ASD.
To investigate the effect of repeated lower +Gz exposure on liver injury induced by high +Gz exposure in rats.Sixty male Wister rats were randomly divided into a blank control group, a low G preconditioning group (LG) (exposed to +4 Gz/5 min per day for 3 d before +10 Gz/5 min exposure), and a +10 Gz/5 min group (10G) (n = 20 in each group). Blood specimens and liver tissue were harvested at 0 h and 6 h after +10 Gz/5 min exposure. Liver function was analyzed by measuring serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, and liver injury was further assessed by histopathological observation. Malondialdehyde (MDA), superoxide dismutase (SOD) and Na(+)-K(+)-ATPase were determined in hepatic tissue.The group LG had lower ALT, AST, and MDA values at 0 h after exposure than those in group 10G. SOD values and Na(+)-K(+)-ATPase activity in the LG group were higher than in group 10G 0 h post-exposure. Hepatocyte injury was significantly less in group LG than in group 10G on histopathological evaluation.It is suggested that repeated low +Gz exposure shows a protective effect on liver injury induced by high +Gz exposure in rats.
Abstract Purpose Cervical laminoplasty (CLP) is a developed surgical procedure for the treatment of cervical spondylotic myelopathy (CSM), but only a few of those studies focus on preoperative dynamic cervical sagittal alignment and the study of different degrees of loss of cervical lordosis (LCL) is lacking. This study aimed to analyze patients who underwent CLP to investigate the effect of cervical extension and flexion function on different degrees of LCL. Methods In this retrospective case–control study, we analyzed 79 patients who underwent CLP for CSM between January 2019 and December 2020. We measured the cervical sagittal alignment parameters on lateral radiographs (neutral, flexion, and extension positions) and used Japanese Orthopedic Association (JOA) score to assess clinical outcomes. We defined the extension ratio (EXR) as 100 × Ext ROM (cervical range of extension)/ROM (cervical range of motion). We observed the relationships between collected variables (demographic and radiological variables) and LCL. Patients were classified into the following three groups according to the LCL: stability group: (LCL ≤ 5°); mild loss group (5° < LCL ≤ 10°); and severe loss group (LCL > 10°). We compared the differences of collected variables (demographic, surgical and radiological variables) among the three groups. Results Seventy-nine patients were enrolled (mean age 62.92 years; 51 men, 28 women) in the study. Among the three groups, cervical Ext ROM was the best in the stability group ( p < 0.01). Compared with the stability group, range of flexion (Flex ROM) was significantly higher ( p < 0.05) and EXR was significantly lower ( p < 0.01) in the severe loss group. Compared with the severe loss group, JOA recovery rates were better ( p < 0.01) in the stability group. Receiver-operating characteristic curve (ROC) analysis to predict LCL > 10° (area under the curve = 0.808, p < 0.001). The cutoff value for EXR was 16.80%, with sensitivity and specificity of 72.5% and 82.4%, respectively. Conclusion CLP should be carefully considered for patients with a preoperative low Ext ROM and high Flex ROM, as a significant kyphotic change is likely to develop after surgery. EXR is a useful and simple index to predict significant kyphotic changes.
Video-assisted thoracic surgery (VATS) lobectomy has been proved to have shorter hospital stay, less perioperative complications and less pain compared with lobectomy by thoracotomy, but severe intraoperative complications during VATS lobectomy is rare reported. We compared intraoperative safety between VATS lobectomy and lobectomy by thoracotomy.659 patients with postoperative stage I and IIa non-small cell lung cancer (NSCLC) who underwent lobectomy in China-Japan Friendship Hospital from February 2008 to June 2012 were analyzed retrospectively, in which 277 were performed by thoracotomy, 357 performed by VATS, and 25 performed by VATS converted to open. Outcomes were analyzed to compare the incidence of significant bleeding, with conversion cases were included into VATS group.Ten severe intraoperative complications were identified in 10 patients (6 in VATS, 4 in open), with no intraoperative deaths. The incidence of severe intraoperative complications was similar between VATS group and thoracotomy group [1.57% (6/382) vs. 1.44% (4/277), P=1.0]. Most severe intraoperative complications were related to the injury of major pulmonary vessels (9/10), and most of these complications occurred during upper lobectomy (8/10). There was no statistically significant difference in blood loss (242.85±220.47 vs. 240.43±144.36, P=0.865), and operative time (198.00±75.24 vs. 208.05±61.97, P=0.061) between the open and VATS groups, respectively, but blood loss and operative time are significant different after elimination of conversion cases (214.34±151.85 vs. 240.43±144.36, P<0.01; 193.24±72.64 vs. 208.05±61.97, P<0.01).Our preliminary study demonstrated that the incidence of severe intraoperative complication during VATS lobectomy was low and similar to open lobectomy. The severe intraoperative complications during VATS lobectomy are manageable and the surgeons need to take proper caution in performing VATS lobectomy.
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