目的：探讨穿心莲内酯（Andro）调节脂肪酸合成酶（Fas）/脂肪酸合成酶配体（FasL）信号轴对子宫内膜癌Ishikawa细胞顺铂（DDP）耐药性的影响。方法：采用0、5、10、20 μg/mL DDP分别处理Ishikawa细胞和顺铂耐药的Ishikawa/DPP细胞，0、5、10、25、50 μmol/L Andro处理Ishikawa/DDP细胞，MTT法检测细胞增殖情况并为后续实验选择合适的给药剂量。将Ishikawa/DDP细胞随机分为对照组、DDP组（DDP干预）、Andro组（DDP、Andro干预）、pcDNA3.1-NC组（转染pcDNA3.1+DDP、Andro干预）、pcDNA3.1-Fas/FasL组（转染pcDNA3.1-Fas/FasL+DDP、Andro干预），24 h后，采用qPCR法检测Fas、FasL mRNA的表达，平板克隆形成实验、Transwell实验和流式细胞术分别检测细胞克隆能力、细胞迁移与侵袭和细胞凋亡，WB法检测增殖细胞核抗原（PCNA）、BAX、Bcl-2、MMP-2、PD-L1、多药耐药蛋白-1（MDR-1）及Fas、FasL蛋白表达。结果：DDP以剂量依赖的方式抑制Ishikawa和Ishikawa/DPP细胞增殖，并且与Ishikawa细胞比较，Ishikawa/DPP细胞对DDP的敏感性更低（均P<0.05）；Andro以剂量依赖性的方式抑制Ishikawa/DPP细胞的增殖（均P<0.05）。Ishikawa/DPP细胞中Fas、FasL的表达水平均高于Ishikawa细胞（均P<0.05）。选取20 μg/mL DDP和25 μmol/L Andro为干预剂量，干预时间24 h。与对照组比较，DDP组Ishikawa/DPP细胞中PD-L1、MDR-1、Fas、FasL mRNA及蛋白表达水平显著升高（P<0.05），而克隆形成率、迁移与侵袭细胞数、凋亡率差异均无统计学意义（均P>0.05）；与DDP组比较，Andro组Ishikawa/DPP细胞中Fas、FasL mRNA表达水平、细胞克隆形成率、迁移与侵袭细胞数、PCNA、Bcl-2、MMP-2、PD-L1、MDR-1、Fas、FasL蛋白表达水平显著降低，BAX蛋白表达水平及凋亡率显著升高（P<0.05或P<0.01），pcDNA3.1-NC组与Andro组类似；与pcDNA3.1-NC组比较，pcDNA3.1-Fas/FasL组Ishikawa/DPP细胞上述指标变化均被逆转（P<0.05）。结论：Andro可能通过抑制Fas/FasL信号轴来抑制Ishikawa/DPP细胞增殖、迁移与侵袭，促进凋亡，从而降低细胞对DDP的耐药性。

OBJECTIVE To systematically review the efficacy and safety of ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with mild ischemic stroke or transient ischemic attack(TIA). METHODS Databases such as PubMed, Embase, the Cochrane Library, CNKI, and Wanfang were systematically searched, and the search period was from database establishment to June 2022. Two reviewers independently screened literature, extracted data, and evaluated the methodological quality of the included studies. Meta-analysis was performed using RevMan 5.3 software. RESULTS A total of 2 studies with 7 087 patients were included. Compared with clopidogrel, ticagrelor reduced the incidence of stroke[RR=0.78, 95%CI(0.66−0.93), I2=0%, P=0.007] and vascular event[RR=0.78, 95%CI(0.66−0.91), I2=0%, P=0.002] in patients with mild ischemic stroke or TIA carrying the CYP2C19 loss-of-function allele. The incidence of any bleeding[HR=2.18, 95%CI(1.66−2.85)] and minor bleeding[HR=2.41, 95%CI (1.81−3.20)] in the ticagrelor-aspirin group was higher than that in the clopidogrel-aspirin group, and dyspnea (1.2% vs 0.2%, P<0.001) and arrhythmias(1.7% vs 0.8%, P=0.001) were more common in the ticagrelor-aspirin group than in the clopidogrel-aspirin group. There was no significant difference in the incidence of severe bleeding between the two groups. CONCLUSION Compared with clopidogrel, ticagrelor reduces the incidence of stroke and vascular events in patients with mild ischemic stroke or TIA carrying the CYP2C19 loss-of-function allele, and did not increase the risk of severe bleeding. However, the ticagrelor group had a higher incidence of minor bleeding, dyspnea and arrhythmias.

The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.

Objective To investigate the HPV vaccination status of children aged 9-14 years, parents’ vaccine-related cognition, willingness to vaccinate children and their influencing factors. Methods From January to April 2021, the convenience sampling method was used to collect data based on the online platform and the Department of Pediatrics and Adolescent Gynecology of the Children&#39;s Hospital of Zhejiang University School of Medicine. The data were analyzed by descriptive analysis, Chi-square test, and logistic regression. Results A total of 864 questionnaires were collected, and 846 valid questionnaires were obtained after screening, with an effective rate of 97.9%. 13.57% of mothers and 3.09% of girls were vaccinated, and the vaccine awareness rate was 68.43%. 87.22% of parents were willing to bring their children for vaccination. Risk perception (OR=4.79, 95% CI: 2.22-10.35), willingness to vaccinate themselves (OR =29.01, 95% CI: 12.62-66.69), awareness of sex education (OR =3.73, 95% CI: 1.08-12.83) and whether the vaccines were free (P<0.001) were related to whether parents were willing to vaccinate their children. Conclusion Parents of children aged 9-14 have high awareness of HPV and HPV vaccine and are willing to vaccinate their children with HPV vaccine , but the vaccination rate in children is low. Disease perception, willingness to vaccinate, awareness of sex education, and whether vaccines are free are all the factors influencing parents&#39; willingness to vaccinate children.

Objective     To investigate the risk factors for postoperative complications Clavien-Dindo classification≥grade Ⅱ after lung cancer surgery. Methods     The patients who underwent lung cancer surgery in a multicenter observational study from November 2017 to January 2020 were included. The Clavien-Dindo classification of postoperative complications was analyzed. Logistic regression was used to identify the risk factors for complications≥ gradeⅡ. Results     A total of 388 patients were enrolled, including 203 males and 185 females with a mean age of 56.14±10.36 years. The incidence of postoperative complications was 25.52% (99/388) after lung cancer surgery and the incidence of complications≥gradeⅡ was 20.10% (78/388). The five most common postoperative complications were pneumonia (6.96%), prolonged pulmonary air leak (>7 days, 5.67%), incision dehiscence (4.64%), arrhythmia (3.87%), and postoperative pleural effusion (3.35%). Multivariate analysis showed that open surgery [reference: uniportal thoracoscopic surgery, OR=2.18, 95%CI (1.01, 4.70), P=0.047], extended resection [reference: sublobar resection, OR=2.86, 95%CI (1.11, 7.19), P=0.030; reference: lobectomy, OR=2.20, 95%CI (1.10, 4.40), P=0.026] and operative time≥3 h [OR=2.07, 95%CI (1.12, 3.85), P=0.021] were independent risk factors for postoperative complications≥gradeⅡ after lung cancer surgery. Conclusion     Surgical approach, extent of resection and operative time are independent influencing factors for postoperative complications≥gradeⅡ after lung cancer surgery.

Telephone follow-up is one of the important ways to follow up patients. High-quality follow-up can benefit both doctors and patients. However, clinical research-related follow-up is often faced with problems such as time-consuming, laborious and poor patient compliance. The authors belong to a team that has been committed to the study of patient-reported outcomes for a long time. The team has carried out long-term follow-up of symptoms, daily function and postoperative complications of more than 1 000 patients after lung cancer surgery, and accumulated certain experience. In this paper, the experience of telephone follow-up was summarized and discussed with relevant literatures from the aspects of clarifying the purpose of clinical research follow-up, understanding the needs of patients in follow-up, and using follow-up skills.

[摘 要] 目的：探讨吴茱萸碱（Evo）是否通过调控lncRNA LINC00858表达调控神经母细胞瘤SK-N-SH细胞的增殖、迁移及侵袭。方法：在体外以3、6、12 μmol/L Evo处理人神经母细胞瘤SK-N-SH细胞，利用RNA干扰技术分别将si-NC、si-LINC00858转染至SK-N-SH细胞，将pcDNA、pcDNA-LINC00858转染至SK-N-SH细胞并经12 μmol/L Evo处理，实验分为对照组、Evo低剂量组、Evo中剂量组、Evo高剂量组、si-NC组、si-LINC00858组、Evo+pcDNA组、Evo+pcDNA-LINC00858组。采用qPCR法检测各组细胞LINC00858的表达量，MTT、Transwell实验分别检测细胞的增殖、迁移、侵袭能力，WB法检测细胞中cyclinD1、MMP-2、MMP-9和p21蛋白的表达。结果：与对照组相比，Evo低、中、高剂量组SK-N-SH细胞中LINC00858表达均显著降低（均P<0.05），细胞增殖抑制率显著升高、迁移及侵袭细胞数显著减少（均P<0.01），cyclinD1、MMP-2、MMP-9蛋白表达降低、p21蛋白表达升高（均P<0.01）。与si-NC组相比，si-LINC00858组细胞的增殖抑制率、迁移和侵袭细胞数及相关蛋白表达变化同Evo低、中、高剂量组。与Evo+pcDNA组相比，Evo+pcDNA-LINC00858组细胞的增殖抑制率显著降低、迁移及侵袭细胞数均显著增多（均P<0.01），cyclinD1、MMP-2、MMP-9蛋白表达升高、p21蛋白表达降低（均P<0.05）。结论：Evo通过下调LINC00858表达抑制神经母细胞瘤SK-N-SH细胞的增殖、迁移及侵袭。

Objective: To explore the effect of C1q / tumor necrosis factor-related protein 9 ( CTRP9 ) on the expression of genes and proteins related to lipid metabolism of brown adipose tissue (BAT) in mice after cold stimulation． Methods : C57BL /6J male mice were injected with adenovirus Ad-GFP (control group) or Ad-CTRP9 ( experience group) into the scapular region and kept for 7 days．After cold stimulation at 4 ℃ for 10 hours，the expression levels of BAT marker genes and proteins were detected by real time PCR and Western blot. Results: Overexpression of CTRP9 induced by cold stimulation significantly increased the mRNA level of iodothyronine deiodinase 2 (Dio2) in BAT (P＜0. 01) ．Additionally，there was no significant difference in the expression of BAT marker genes ( UCP-1，PGC-1 α , PRDM16 and ARβ3) ，and liposynthesis and lipolysis related genes (PPARγ , HSL and ATGL) ．Uncoupling protein 1 (UCP-1) protein expression was upregualted in Ad-CTRP9 compared to the Ad-GFP control group ，while the expression of lipolysis related protein adipose triglyceride lipase ( ATGL) decreased significantly (P＜0. 05) ． Conclusion In cold environment，overexpression of CTRP9 promotes the accumulation of UCP-1 protein in BAT，upregulates the expression of thyroid hormone signal related gene Dio2，and inhibits triglyceride hydrolysis to maintain a constant body temperature.

OBJECTIVE To explore how to shorten the time from approval to start-up of drug clinical trial project. METHODS Twenty-two phase Ⅱ-Ⅲ multi-center drug clinical trial projects start up in The First People&#39;s Hospital of Nanning from 2020 to 2021 were selected. The time-consuming of each link before the launch was analyzed, and the time- consuming of project approval, ethical review and contract review between the sponsor and research institution was compared, as well as the influence of using the contract template of each party on the time-consuming of contract review was compared. RESULTS Contract review took the longest time. There was no significant difference in the time-consuming between the sponsor and the research institutions in the three links of project approval, ethical review and contract review. Used the contract template of the research institutions, the time spent by the sponsor and the research institution in the review process, as well as the contract signing time of the project were shorter. CONCLUSION Using the clinical trial management system, conduct differentiated ethical review methods, advance drug delivery and commitment letter submission, use the contract template of research institutions or sign a framework contracts, establish a effective communication methods are all effective ways to reduce the time taken before start-up.

Objective    To investigate the use of opioid analgesics during the postoperative hospitalization in patients undergoing lung resection and analyse its influencing factors. Methods    The clinical data of 450 patients undergoing lung resection in Sichuan Cancer Hospital among a multicenter symptom research database (CN-PRO-Lung 1) between November 2017 and January 2020 were analyzed. There were 248 males and 202 females with an average age of 54.7±10.3 years. Results    A total of 448 (99.6%) patients used opioid analgesics. The average daily morphine equivalent dose during the postoperative hospitalization was 48.9 mg. There were statistical differences in postoperative morphine equivalent dose across patients with different sex, age, highest level of education, Charlson Comorbidity Index score, surgical approach, surgical type, operative time, postoperative hospital stay and grade of postoperative complications (all P<0.05). Multivariate analysis showed that sex, surgical approach and postoperative hospital stay were independent influencing factors for morphine use during the postoperative hospitalization in patients undergoing lung resection (all P<0.05). Conclusion    In clinical practice, attention should be paid to postoperative pain for male patients, as well as to promote the application of minimally invasive surgery, and to shorten the length of postoperative hospital stay, in order to ultimately reduce the use of opioids.