ABSTRACT Objective This study aimed to explore the potential association between neuroticism and lung cancer. Methods We conducted analyses on publicly accessible aggregated data from genome‐wide association studies (GWAS) that included individuals of European descent. The objective was to identify single nucleotide polymorphisms (SNPs) significantly associated with neuroticism and utilize them as instrumental variables in a two‐sample Mendelian randomization framework to evaluate the gender‐specific causal link between neuroticism and lung cancer risk. We applied four statistical methods: Inverse variance weighting (IVW), weighted median, MR‐Egger regression, and weighted mode. Our analysis also considered the mediating effect of educational attainment on this relationship. Results We selected 67 SNPs associated with neuroticism at genome‐wide significance levels from GWAS datasets. Our primary findings using IVW suggest a notable increase in lung cancer risk associated with neuroticism across the general population (odds ratio [OR] = 1.175; 95% confidence interval [CI] 1.020–1.354, p = 0.026). Gender‐specific analysis revealed that neuroticism posed a slight but significant risk increase in men (OR = 1.006; 95% CI 1.000–1.012, p = 0.045) and women (OR = 1.005; 95% CI 1.002–1.009, p = 0.002), with findings corroborated by the additional statistical methods. Further, evidence from both observational and Mendelian randomization analyses suggests that genetically predicted neuroticism is causally associated with a modestly increased risk of incident lung cancer, with ∼17% of this effect mediated by educational attainment. Conclusions The results from this Mendelian randomization study provide robust evidence supporting a potential association between neuroticism and an increased risk of lung cancer. This association appears more pronounced in men than women. Additionally, educational level serves as a mediator in the nexus between these conditions, suggesting that interventions aimed at increasing educational attainment might mitigate some of the risk neuroticism poses for developing lung cancer.

396 Background: PD-1 inhibitor combined with chemotherapy is one of the standard regimens for first line gastric. The addition of anti-vascularization agents has been reported to help improve the overall survival (OS) in GC/GEJC patients (pts) through vascular-normalization in the microenvironment. In this phase I/IIa study, we aim to explore the safety and efficacy of tislelizumab combined with anlotinib and XELOX (TAXE regimen) as first line treatment for advanced GC/GEJC. Methods: This prospective, multicenter, phase I/IIa study planned to enroll 9 patients in phase I and 57 patients in Phase IIa. The aim of this Phase 1 study was to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and safety of 8 mg, 10 mg or 12 mg anlotinib in combination with XELOX and tislelizumab. The maximum tolerable dosage (MTD) would be administered to all pts in phase II. The primary and objective response rate(ORR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), OS, and safety. The exploring endpoint was to evaluate the association between the efficacy and the expression of biomarkers including PD-L1, microsatellite instability profile, and genome stability (GS). Results: From march 2021 to August 2022, 38 pts were enrolled (9 pts in phase 1). Phase 1 was completed without dosage limiting toxicities (DLTs). 12mg anlotinib was recommended for phase 2. Thirty two (84.21%) pts had at least one treatment-related adverse events (TRAEs), and 7 patients (18.42%) had at least one grade 3/4 TRAEs. Anemia (15 pts, 39.47%), leukopenia (12 pts, 31.58%) and fatigue (10 pts, 26.32%) were the most common TRAEs. Two pts achieved complete response (CR), 20 pts achieved partial response (PR), and 7 pts achieved stable disease (SD). The ORR was 75.86% (95% CI: 57.89%-87.78%), and the DCR was 100%. Conclusions: The preliminary results of this Phase I/IIa trial by using tislelizumab combined with anlotinib and XELOX had shown great potential in improving the response rate in advanced GC/GEJC patients with manageable toxicity. Clinical trial information: NCT04963088 .

目的:总结儿童及青少年急性早幼粒细胞白血病诊治中的主要并发症,分析其发生的危险因素.方法:回顾性分析2010年1月-2021年5月南京医科大学第一附属医院收治的43例初诊急性早幼粒细胞白血病儿童及青少年病例,总结分析各类并发症的发病率,根据分化综合征临床诊断标准分为分化综合征组和非分化综合征组,采用多因素Logistic回归分析分化综合征发生的危险因素,采用Kaplan-Meier生存分析评估患者的累积无事件生存率和总生存期.结果:43例急性早幼粒细胞白血病患者中,与非分化综合征组比较,分化综合征组的维甲酸诱导后血清铁蛋白、乳酸脱氢酶(lactate dehydrogenase,LDH)、白细胞介素6(interleukin-6,IL-6)、白蛋白都高于非分化综合征组,差异有统计学意义(P＜0.01).多因素Logistic逐步回归分析显示,外周血白细胞数(white blood cell,WBC)最高值(WBCmax)、血清铁蛋白、LDH和lL-6显著升高是诱导治疗期间发生分化综合征的独立危险因素(P＜0.01).高危组和低危组累积总生存率和无事件生存率相比,差异无统计学意义.结论:儿童及青少年急性早幼粒细胞白血病诊治过程中可出现出血和分化综合征等多种并发症.维甲酸诱导治疗后的WBC、LDH、血清铁蛋白和IL-6等炎症因子过度升高是发生分化综合征的危险因素.

目的:探讨胎盘绒毛膜血管瘤对胎儿及新生儿的影响.方法:回顾性分析2015-2021年经病理确诊为胎盘绒毛膜血管瘤的25例孕妇及其新生儿的临床资料,总结其临床特征,并根据胎盘绒毛膜血管瘤直径将患儿分为巨大血管瘤组(直径≥5 cm)和普通血管瘤组(直径＜5 cm),比较两组患儿临床特点及结局.结果:19例胎盘绒毛膜血管瘤合并有围产期并发症,胎儿期发生羊水过多7例(28％),胎儿生长受限7例(28％),胎儿宫内窘迫5例(20％),胎儿水肿2例(8％),胎儿贫血3例(12％),胎儿心胸比增大3例(12％),早产9例(36％),新生儿期合并有新生儿贫血6例、凝血功能异常3例、新生儿血小板减少1例、先天性心脏病9例、新生儿心律失常1例、新生儿坏死性小肠结肠炎1例、先天性肺囊腺瘤畸形1例、尿道下裂1例.2例患儿因胎儿期羊水过多、胎儿心胸比增大、重度贫血及生后重度窒息而死亡.其余新生儿目前随访均存活良好,无生长发育迟缓者.巨大血管瘤组羊水增多比例高于普通血管瘤组(P＜0.05).结论:胎盘绒毛膜血管瘤可导致胎儿及新生儿多种并发症,并且肿瘤大小对胎儿及新生儿并发症的发生有一定预测价值,加强围产期监测,及时采取干预措施,可能有助于改善胎儿及新生儿结局.

目的:以经皮内镜经椎间孔入路腰椎间盘切除术(PETD)作为对照,探讨经皮内镜经椎板间入路腰椎间盘切除术(PEID)治疗下腰椎椎间盘突出症(LDH)患者的临床应用价值.方法:回顾性分析2018年1月至2021年5月收治的136例下腰椎LDH患者,包括L4/5 LDH患者75例,其中39例采用PETD,36例采用PEID;L5/S1 LDH患者61例,其中36例采用PETD,25例采用PEID.记录并比较患者术中透视次数、手术时间、术后住院时间,及术前和术后1 d、1个月及6个月疼痛视觉模拟量表评分(VAS)、Oswestry功能障碍指数(ODI),以及并发症发生情况.结果:所有患者均顺利完成手术.无论L4/5还是L5/S1 LDH患者,PEID组患者术中透视次数少于PETD组患者,且差异有统计学意义(P<0.001),而两组患者手术时间、术后住院时间差异均无统计学意义(P均>0.05).无论L4/5还是L5/S1 LDH患者,无论采用PEID还是PETD,患者术后1 d、1个月及6个月VAS评分、ODI均低于术前,且差异均有统计学意义(P均<0.05).无论L4/5还是L5/S1 LDH患者,术前、术后1 d、1个月及6个月PEID组与PETD组患者VAS评分、ODI差异均无统计学意义(P均>0.05).PETD组1例患者术后出现椎间隙感染.无一例患者复发.结论:与PETD比较,PEID治疗下腰椎(L4/5,L5/S1)LDH患者同样有效,且术中辐射明显更少.应依据具体情况选择合适的手术入路.

Acute myeloid leukemia (AML) is the most prevalent form of acute leukemia. Patients with AML often have poor clinical prognoses. Hypoxia can activate a series of immunosuppressive processes in tumors, resulting in diseases and poor clinical prognoses. However, how to evaluate the severity of hypoxia in tumor immune microenvironment remains unknown. In this study, we downloaded the profiles of RNA sequence and clinicopathological data of pediatric AML patients from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, as well as those of AML patients from Gene Expression Omnibus (GEO). In order to explore the immune microenvironment in AML, we established a risk signature to predict clinical prognosis. Our data showed that patients with high hypoxia risk score had shorter overall survival, indicating that higher hypoxia risk scores was significantly linked to immunosuppressive microenvironment in AML. Further analysis showed that the hypoxia could be used to serve as an independent prognostic indicator for AML patients. Moreover, we found gene sets enriched in high-risk AML group participated in the carcinogenesis. In summary, the established hypoxia-related risk model could act as an independent predictor for the clinical prognosis of AML, and also reflect the response intensity of the immune microenvironment in AML.

Objective: A retrospective study was carried out to explore the detection rate and drug resistance of Haemophilus influenzae (H. influenzae) in children with respiratory tract infections in Nanjing and Wuhan, so as to provide guidance for clinicians in rational drug use. Methods: The fresh sputum of 1,000 children with acute respiratory infections (ARI) hospitalized in Nanjing and Wuhan from January 2017 to December 2018 were collected using aseptic negative pressure suction, and H. influenzae was cultured and isolated from the samples. The detection rate and drug resistance to antibiotics of H. influenzae were retrospectively studied. Results: In Nanjing and Wuhan, H. influenzae infections occur mostly in children younger than 3 years old, and H. influenzae was detected in the sputum samples of more than 95.00% of these children. The detection rate of H. influenzae was high in winter and spring, reaching 56.80% in winter. The sensitivity of H. influenzae to ampicillin, amoxicillin, and cefuroxime decreased significantly in 2018 compared to 2017, while its sensitivity to beta-lactamase and the compound sulfamethoxazole increased (all P <= 0.001). Conclusion: H. influenzae infections in the respiratory tract are seasonal and occur mostly in winter. Antibiotics should be used reasonably according to the drug-susceptibility testing (DST) results in the clinic to avoid drug resistance.

The discovery of long noncoding RNAs (lncRNAs) has increased our understanding of the development and progression of many cancers, but their contributions to non-small cell lung cancer (NSCLC) remain poorly understood. Here, we profiled lncRNA expression in NSCLC and investigated in detail the molecular function of one upregulated lncRNA, LINC01234. LINC01234 was overexpressed in NSCLC compared with normal lung tissue and correlated positively with poor prognosis. Downregulation of LINC01234 impaired cell proliferation in vitro and tumor growth in vivo. RNA pull-down/mass spectrometry experiments showed that LINC01234 interacted with the RNA-binding protein heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), which, in turn, led to the recruitment of DiGeorge syndrome critical region gene 8 (DGCR8), a subunit of the microRNA (miRNA) microprocessor complex. Accordingly, depletion of either LINC01234 or HNRNPA2B1 reduced the processing of several miRNA precursors, including primary microRNA (pri-miR)-106b. miR-106b-5p enhanced NSCLC cell growth by downregulating cryptochrome 2 (CRY2), thereby increasing c-Myc expression. Finally, we found that activated c-Myc binds to the LINC01234 promoter to increase its transcription, creating a c-Myc-LINC01234-HNRNPA2B1-miR-106b-5p-CRY2-c-Myc positive-feedback loop. We identified numerous lncRNAs with dysregulated expression in NSCLC and demonstrated a novel oncogenic axis involving LINC01234, HNRNPA2B1, miR-106b-5p, CRY2, and c-Myc. Components of this axis may be potential novel targets for NSCLC.

Lung cancer is the leading cause of cancer-related death worldwide. Owing to the difficulty in early diagnosis and the lack of effective treatment strategies, the 5-year survival rates for lung cancer remain very low. With the development of whole genome and transcriptome sequencing technology, long non-coding RNA (lncRNA) has attracted increasing attention. LncRNAs regulate gene expression at the epigenetic, transcriptional and post-transcriptional levels and are widely involved in a variety of diseases, including tumorigenesis. In lung cancer studies, multiple differentially expressed lncRNAs have been identified; several lncRNAs were identified as oncogenic lncRNAs with tumor-driving effects, while other lncRNAs play a role in tumor inhibition and are called tumor-suppressive lncRNAs. These tumor-suppressive lncRNAs are involved in multiple physiological processes such as cell proliferation, apoptosis, and metastasis and thus participate in tumor progression. In this review, we discussed the oncogenic and tumor-suppressive lncRNAs in lung cancer, as well as their biological functions and regulatory mechanisms. Furthermore, we found the potential significance of lncRNAs in clinical diagnosis and treatment.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib, have been established as first-line treatments for non-small cell lung cancer (NSCLC) patients and have exhibited notable clinical efficacy. However, resistance to TKIs has become one of the major obstacles in improving the therapeutic efficacy of patients with NSCLC. This study aims to investigate the role of the long non-coding RNA (IncRNA) LINC01116 in gefitinib resistance of NSCLC and explore its underlying mechanism. In this study, we found that LINC01116 is upregulated in the gefitinib-resistant NSCLC cells and tissues. Loss- and gain-of-function assays uncovered that LINC01116 downregulation sensitized gefitinib resistance, whereas the overexpression of LINC01116 conferred PC9/R cells to gefitinib resistance. Moreover, LINC01116 silencing increased IFI44 expression. Overexpression of IFI44 reversed the resistance to gefitinib in PC9/R cells, and rescue experiments confirmed that LINC01116 affects the gefitinib resistance of PC9/R cells partly dependent on regulating IFI44 expression.Moreover, downregulation of LINC01116 increased the sensitivity of PC9/R cells to gefitinib in vivo. Our study demonstrates that LINC01116 plays a critical role in gefitinib resistance of NSCLC cells by affecting IFI44 expression, providing a novel therapeutic target to overcome TKI resistance in NSCLC.

Objective:To observe the clinical efficacy, surgical techniques, and complications of percutaneous endoscopic lumbar discectomy (PELD) in the treatment of lumbar disc herniation with single-segment prolapse.Methods:The clinical data of 40 patients (including 22 males and 18 females, aged 18-52 years old, with an average age of 32 years) with single-segment prolapse and free lumbar disc herniation from January 2018 to March 2019 in Wuxi People's Hospital affiliated to Nanjing Medical University were retrospectively analyzed. The diseased segment included L 3/4 (4 cases), L 4/5 (29 cases), and L 5/S 1 (7 cases). According to the Lee classification criteria, the severity of lumbar disc herniation was type Ⅰ in 3 cases, type Ⅱ in 7 cases, type Ⅲ in 21 cases, and type Ⅳ in 9 cases. All 40 patients were treated with PELD, 34 and 6 of which underwent the foraminal approach and interlaminar approach, respectively. The patients' postoperative recovery and complications were observed, and patients' visual analogue scale (VAS) and Oswestry disability index (ODI) were compared before operation and 1 day, 1 month, and 6 months after operation. At 6 months after the operation, the MRI was reviewed to determine whether the nucleus pulposus relapsed. The MacNab standard was used to evaluate the efficacy at 6 months after surgery. Results:The operation was successfully conducted in all patients. The operation time was 45.9-72.0 (59.8±12.5) min. The intraoperative blood loss of all patients was less than 18 mL. One case of intervertebral space infection occurred in a postoperative patient with the foraminal approach, and one patient had residual symptoms after an interlaminar approach. All 40 patients were followed up after surgery. The follow-up time was 6-12 (8.2±2.7) months. The VAS scores were (2.3±0.7), (0.8±0.3), and (0.3±0.1) 1 day, 1 month, and 6 months after surgery, and the ODI was 21.3%±3.4%, 11.9%±2.9%, and 3.1%±1.5%, respectively, which were all lower than the preoperative values (7.2±1.3) and (62.8%±5.5%). The difference was statistically significant ( F=10.812, 8.750, all P values<0.05). MRI was re-examined 6 months after the operation. One patient that underwent the interlaminar approach had residual prolapsed nucleus pulposus, and none of the remaining patients showed residual nucleus pulposus or recurrence. According to the MacNab standard, the curative effect was evaluated at 6 months after operation. Thirty-six cases were rated as excellent, two cases were good, and two cases were fair. The rating of excellent and good curative effect was 95.0%. Conclusions:PELD has satisfactory clinical effects in the treatment of single-segment prolapsed lumbar intervertebral disc herniation; however, treating patients with high prolapse and tail displacement is still challenging for surgeons.

Objective The aim of this study was to compare the clinical efficacy of percutaneous endoscopic interlaminar discectomy (PEID) and percutaneous endoscopic transforaminal discectomy (PETD) in treating L5/S1 disc herniation. Methods A retrospective analysis of 76 patients with L5/S1 intervertebral disc herniation was performed. There were two surgical treatment groups: one with patients receiving PEID and the other with patients receiving PETD. The two groups were compared by length of surgery, times of intraoperative X‐ray exposure, postoperative time in bed, length of hospital stay, operative complications, patient's assessment of pain using a visual analogue scale (VAS), and disability using the Oswestry disability index (ODI) before and after surgery. Results Subjects in the PEID group were in surgery for 60.90 ± 13.11 min and needed intraoperative X‐ray exposure 4.10 ± 1.09 times. Patients in this group were ambulatory by 7.52 ± 1.08 h after surgery and were hospitalized for 5.05 ± 0.92 days. In contrast, patients in the PETD group were in surgery for 84.06 ± 15.58 min and needed intraoperative X ray exposure 12.81 ± 8.46 times. These patients were ambulatory by 7.06 ± 0.91 h after surgery and remained in the hospital for 4.94 ± 0.80 days. Based on these data, operation time and fluoroscopy time were significantly less (P < 0.002 and P < 0.001, respectively) for subjects in the PEID group. However, ambulatory time and hospitalization were similar for both in terms of pain relief and decreased disability, and subjects in both groups responded well to the surgery and showed a significant decrease in both VAS and ODI scores at their 1‐year follow‐up (P < 0.01). Furthermore, there were no statistically significant differences between the two surgeries in terms of pain relief and decrease in disability. Conclusion For L5/S1 disc herniation, PEID and PETD provide similar results for patients. However, PEID has the advantage over PETD in that it is a shorter procedure and exposes the patient to less radiation. Keywords

目的:探讨新生儿肺动脉高压的相关高危因素.方法:收集近3年南京医科大学第一附属医院儿科收治的肺动脉高压新生儿41例,分为足月儿组和早产儿组,回顾性分析了两组的临床资料与新生儿肺动脉高压的关系.结果:早产儿组23例,足月儿组18例.早产儿组胎膜早破、胎盘早剥、绒毛膜羊膜炎、子痫的发生率高于足月儿组,差异有统计学意义(P＜0.05).足月儿组的孕母妊娠期糖尿病5例(占27.8％),早产儿组孕母妊娠期糖尿病共1例(占4.3％),与足月儿组比较,差异有统计学意义(x2=4.437,P=0.035).与足月儿组相比,早产儿组的原发病以呼吸窘迫综合征为主(x2=19.158,P＜0.001),容易合并肺出血(x2=4.433,P=0.035)、颅内出血(x2=8.715,P=0.003).足月儿组原发疾病主要为先天性心脏病(室间隔缺损)(x2=10.786,P=0.001).新生儿肺炎在两组均有较高发生率,但差异无统计学意义(x2=0.327,P＞0.05).两组之间并发代谢性酸中毒、新生儿低血糖、气胸、败血症等统计比较,差异无统计学意义(P＞0.05).早产儿组治愈21例,死亡2例,足月儿组治愈15例,死亡3例,治疗效果两组比较差异无统计学意义(P＞0.05).结论:早产儿肺动脉高压的高危原发疾病是呼吸窘迫综合征、重症肺炎、肺出血以及孕母有胎膜早破、胎盘早剥等并发症;患有先天性心脏病如室间隔缺损的足月儿,要重视可能伴有的肺动脉高压并及时诊治.

BACKGROUND:Long noncoding RNAs (lncRNAs) are known to regulate tumorigenesis and cancer progression, but their contributions to non-small-cell lung cancer (NSCLC) metastasis remain poorly understood. Our previous and other studies have revealed the involvement of upregulated LINC01234 in regulating gastric cancer and colon cancer cells proliferation, and we aimed to investigate whether LINC01234 overexpression also contribute to cancer cells metastasis in this study.METHODS:We collect the NSCLC tissues and adjacent non-tumor tissues and analyzed expression levels of LINC01234 by quantitative reverse-transcription PCR. LINC01234 were knocked down by using siRNAs or shRNAs, and overexpressed by transfection with overexpression vector; RNA levels of miRNA were downregulated or upregulated with inhibitors or mimics. Transwell assays were used to evaluate cell migration and invasive ability; in vivo metastasis experiments were performed to investigate the effect of LINC01234 on NSCLC cells metastasis. Luciferase reporter, RIP, and ChIP assays were used to determine the regulation of LINC01234 on its targets.RESULTS:LINC01234 expression is increased in NSCLC tissues, and its upregulation is associated with metastasis and shorter survival in NSCLC. Downregulation of LINC01234 impairs cell migration and invasion in vitro, and inhibits cells metastasis in vivo by acting as a competing endogenous RNA for the miR-340-5p and miR-27b-3p. LINC01234 also interacts with the RNA-binding proteins LSD1 and EZH2, leading to histone modification and transcriptional repression of the anti-proliferative genes BTG2.CONCLUSIONS:Taken together, our findings identify two oncogenic regulatory axes in NSCLC centering on LINC01234: one involving miR-340-5p/miR-27b-3p in the cytoplasm and the second involving EZH2, LSD1, and BTG2 in the nucleus. Our study indicates that these genes may be targeted to reduce or prevent NSCLC metastasis.

Lung cancer is the most common cancer all around the world, with high morbidity and mortality. Long noncoding RNA (lncRNA) has been reported to have a critical role in non-small-cell lung cancer (NSCLC) proliferation and migration. In the present study, we analyzed The Cancer Genome Atlas (TCGA) data, and we found that lncRNA Small Nucleolar RNA Host Gene 17 (SNHG17) was upregulated in NSCLC driven by the amplification of copy number, indicating the special role of SNHG17 in NSCLC. The full exact length of SNHG17 was determined by rapid amplification of cDNA ends (RACE). We modulated SNHG17 expression by RNAi and a series of functional assays were performed. Flow cytometry was used to explore the involvement of SNHG17 in NSCLC cell apoptosis. Results showed that the knockdown of SNHG17 inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. We acquired the global gene expression profile regulated by SNHG17 in A549 through RNA sequencing (RNA-seq) assays. We found 637 genes were upregulated while 581 genes were downregulated. We selected three genes (FOXA1, XAF1, and BIK) that were closely related to proliferation and apoptosis, and we confirmed their altered expression in A549 and PC-9 cells treated with small interfering RNA si-SNHG17. Our findings indicated gene amplification-driven lncRNA SNHG17 promotes cell proliferation and migration in NSCLC, suggesting its potential value as a biomarker in NSCLC.

目的 回顾性分析71例恶性腹腔积液的治疗效果. 方法 选取2012年1月～2018年12月我院收治的71例给于腔内药物灌注治疗的恶性腹腔积液患者为研究对象,采用回顾性队列分析,按治疗药物分为顺铂组和顺铂联合恩度组及氟尿嘧啶组;按治疗次数分为初治组和复发组. 结果 顺铂组治疗胃癌12例, ORR为50%,顺铂联合恩度组治疗胃癌14例,ORR为57.1%,两者比较差异有统计学意义(P＜0.05);顺铂组治疗卵巢癌8例,ORR为 62.5%,顺铂联合恩度组治疗卵巢癌5例,ORR为60%,差异无统计学意义(P＞0.05);顺铂组治疗肺癌3例,ORR为0,顺铂联合恩度组治疗肺癌6例,ORR为16.7%,差异无统计学意义(P＞0.05);氟尿嘧啶组治疗结直肠癌13例,ORR为15.3%,胰胆系统癌7例,ORR为0.初治组中,给予顺铂治疗9例,ORR为66.7%,顺铂联合恩度治疗12例,ORR为66.7%,差异无统计学意义(P＞0.05);复治组中,给与顺铂治疗14例,ORR为35.7%,顺铂联合恩度治疗16例,ORR为31.2%,差异无统计学意义(P＞0.05);在顺铂组中,初治的ORR为66.7%,复治组的ORR为35.7%,差异有统计学意义(P＜0.05);在顺铂联合恩度组中,初治的ORR为66.7%,复治组的ORR为31.2%,差异无统计学意义(P＞0.05).顺铂组和顺铂联合恩度组在药物毒副反应上无统计学差异,氟尿嘧啶组药物毒副反应轻. 结论 顺铂依然是恶性腹腔积液腔内治疗的有效药物,尤其是对于胃癌和卵巢癌.

Background: Long non-coding RNA with a length of more than 200 nucleotides, called long non-coding RNA (LncRNAs), lncRNAs can regulate its activity or change its location by interfering with the activity of mRNA and directly binding to proteins. It can also affect the expression of downstream genes by inhibiting RNA polymerase, And as a competitive endogenous RNAs to regulate gene expression, thus playing an important role in the biological process. Colorectal cancer is a malignant lesion of colorectal mucosa caused by environmental, genetic and epigenetic factors. The occurrence of colorectal cancer is a multi-stage, multi-gene process, but its pathogenesis is not fully understood. With the discovery of new molecular and epigenetic mechanisms in CRC, lncRNA has become a biological target for diagnostic, prognostic and therapeutic applications.Methods: Therefore, by screening the GEO database, we found that the expression of Linc01003 in cancer tissues was significantly different from that in paracancerous tissues, and then the expression was detected in 60 pairs of colorectal cancer tissues, five colorectal cancer cell lines and normal intestinal epithelial cell lines. In order to verify the phenotype of linc01003 by knockdown and overexpression experiments, and to explore the mechanism of linc01003 regulating mechanism of proliferation and apoptosis, the upstream transcription factors were predicted by database and verified by related experiments. The related downstream targets were screened by high throughput sequencing and verified by qRT-PCR, Western blot, RIP, ChIP, RNA-FISH and other experiments.Results: Highly expressed linc01003 is closely related to more advanced pathological stages and shorter life cycles.The results showed that the expression of LncRNA Linc01003 induced by transcription factor FOXP1 was significantly increased in colorectal cancer tissues and cells. Knockdown of Linc01003 in colorectal cells could significantly inhibit cell proliferation and induce apoptosis, while overexpression could promote cell proliferation. This can also be proved in animal experiments. After high throughput sequencing, it was found that the expression of crude oncogene HKDC1 was up-regulated and the expression of tumor suppressor gene DIC was down-regulated. Then through bioinformatics prediction and RIP experiments, it was proved that linc01003 binds to EZH2 and AGO2 proteins. CHIP experiments showed that Linc01003 could bind EZH2 to participate in the transcriptional regulation of HKDC1. Luciferase reporter gene confirmed that linc01003 competitive adsorption of miR-106b-5p promoted SLC25A10( DIC) expression. Therefore, we conclude that long non-coding RNA Linc01003 with high expression is associated with later stage and worse prognosis, and transcription factor FOXP1 can induce high expression of long non-coding RNA Linc01003. The high expression of linc01003 promotes the proliferation and inhibits the apoptosis of colorectal cancer cells. Lin01003 promotes the proliferation of colorectal cancer cells through EZH2/HKDC1 and miR-106b-5p/DIC regulatory axes.Conclusions: Therefore, we conclude that the transcription factor FOXP1 induced linc01003 promotes proliferation and inhibits apoptosis of colorectal cancer cells through EZH2/HKDC1 and miR-106b-5p/DIC regulatory axis . It is expected to be a diagnostic marker for CRC and a potential biotherapeutic target.Funding Statement: This study was supported by grants from the National Natural Sciences Foundation of China (grant no. 81772603), Key talents of young medicine in Jiangsu Province(grant no.QNRC2016662), Nanjing Health Science and Technology Development Medical Key Technology Development Project (grant no.YKK18190).Declaration of Interests: The authors declare no competing financial interests.Ethics Approval Statement: All patients provided written informed consent, and all the experiments were approved by the Research Ethics Committee of Nanjing Medical University. This study was conducted in strict accordance with the guidelines of the National Institutes of Health (NIH) on the use of laboratory animals. Our plan has been approved by the Animal Experimental Ethics Committee of Nanjing Medical University.

目的 观察重组人甲状旁腺素 1-34 ( recombinant human parathyroid hormone 1-34 )应用于绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)患者的临床疗效.方法 筛选出68例绝经后骨质疏松症患者,所有患者入组后均口服元素钙500 mg/d和维生素D 200 U/d,连续服用26周后加用皮下注射重组人甲状旁腺素1-34(特立帕肽)20 μg /d,再连续治疗26周,于应用特立帕肽治疗前及治疗后的13 和26 周测定腰椎(L1-4)和股骨近端骨密度(BMD),采静脉血测定血清骨钙素(OC)、碱性磷酸酶(AKP)水平,应用疼痛视觉模拟评分法(VAS 评分)评价患者的疼痛程度,并记录不良反应情况.结果 68位患者均完成全疗程治疗.应用特立帕肽治疗13周时,腰椎L1-4、股骨颈、大粗隆和股骨干骨密度改善不明显( P＞0. 05),血清骨钙素和碱性磷酸酶较治疗前升高(P＜0. 05),疼痛缓解明显(P＜0. 05);治疗26周时,腰椎L1-4和股骨颈骨密度较治疗前明显增高(P ＜0. 05),而大粗隆和股骨干骨密度改善不明显(P＞0. 05),血清骨钙素和碱性磷酸酶呈持续升高趋势(P＜0. 05),疼痛明显减轻(P＜0. 05).治疗期间不良反应的情况均较轻微,没有给予特殊处理即自行缓解.结论 连续26周使用重组人甲状旁腺素1-34能有效地促进患者骨形成,缓解骨质疏松症患者疼痛症状,提高患者腰椎、股骨骨密度.

BACKGROUND:To evaluate the clinical efficacy and toxicity of single pemetrexed treatment compared with platinum-based pemetrexed doublet pemetrexed-based as first-line treatment for advanced nonsquamous nonsmall cell lung cancer (NS-NSCLC) in elderly Chinese patients.METHODS:The study retrospectively reviewed 175 elderly Chinese patients with NS-NSCLC from June 2010 to September 2013: 90 patients received single pemetrexed treatment, 45 received pemetrexed plus oxaliplatin, and 40 received pemetrexed plus carboplatin. Clinical efficacy was assessed using disease control rate (DCR), overall survival (OS), and progression-free survival (PFS).RESULTS:DCR, OS, and PFS did not significantly differ between single pemetrexed treatment (OS: 14.9 months; DCR: 62.2%; PFS: 3.3 months), pemetrexed plus oxaliplatin (OS: 16.5 months; DCR: 71.1%; PFS: 4.5 months), and pemetrexed plus carboplatin (OS: 15.5 months; DCR: 70.0%; PFS: 4.6 months) groups. Pemetrexed treatment caused significantly lower incidences of adverse events, such as hepatotoxicity and peripheral nerve injury. Performance status (PS), TNM stage, and Thymidylate synthase (TS) expression were predictive factors of DCR. Pemetrexed chemotherapy cycles, PS, and TNM stage were independent prognostic factors.CONCLUSIONS:Single pemetrexed was noninferior to platinum-based pemetrexed doublet for clinical efficacy and safety in elderly Chinese patients with advanced NS-NSCLC. Chemotherapy cycles, performance status, and TNM stage were independent prognostic factors.

Wilms’ tumor is associated with a high treatment success rate, but there is still a risk of recurrence. Cisplatin, which is one of the chemotherapeutic agents used for its treatment, is associated with a very high rate of resistance. Par-4 (prostate apoptosis response 4) is a tumor suppressor, which is capable of sensitizing tumor cells to chemotherapy. Therefore, the aim of this study was to determine whether combined treatment with Par-4 and cisplatin is effective for inhibiting growth of Wilms’ tumor. Wilms’ tumor and control cell samples were collected and analyzed by immunofluorescence assay and immunohistochemistry. Total proteins extracted from cultured cells were analyzed using western blotting and flow cytometry. In addition, a mouse xenograft model was established. We discovered significantly low expression of Par-4 in the tumor tissue, which was positively correlated with high expression of GRP78 (glucose-regulated protein 78). In addition, we found that ectopic Par-4 co-localized with cell surface GRP78 and induced high expression of the endoplasmic reticulum proteins ATF4 and BAX, which activated the endoplasmic reticulum apoptosis pathway. Moreover, treatment with ectopic Par-4 and cisplatin suppressed xenograft growth in nude mice. In conclusion, our results showed that Par-4 overexpression and cisplatin had a synergistic effect on SK-NEP-1 cells, as a result of which cell growth was inhibited and cellular apoptosis was induced. Thus, in vitro and in vivo upregulation of Par-4 expression is indispensable for the trafficking of GRP78 to the cell membrane and subsequent apoptosis of cancer cells.