基于网络药理学和临床试验探讨前列消汤对ⅢA型前列腺炎IL-17与Foxp3表达影响研究＊

目的 基于网络药理学进行前列消汤治疗慢性前列腺炎的预测，同时采用临床试验进行验证，证明前列消汤对ⅢA型前列腺炎患者的临床疗效及对前列腺液（Expressed Prostatic Secretion， EPS）中白细胞介素17（interleukin 17， IL-17）及双头叉转录因子p3（Forkhead box p3， Foxp3）表达的影响。方法 采用网络信息学分析方法，筛选出前列消汤在ⅢA型前列腺炎治疗中发挥疗效的主要作用靶点，采用临床随机非盲法，将符合纳入标准的80例ⅢA型前列腺炎湿热下注证患者随机分为观察组和对照组各40例，观察组口服自拟前列消汤，对照组口服银花泌炎灵片。观察治疗前后两组的症状及证候评分情况、前列腺按摩液以及其IL17、Foxp3表达的差异。取40例正常男性前列腺液为正常对照。结果 网络药理学分析结果提示IL17信号通路为前列消汤治疗慢性前列腺炎的重要通路之一，临床试验结果提示经治疗后观察组有效率达89.19%，较对照组的73.68%为优（P < 0.05）。两组患者服药后的临床表现、前列腺按摩液WBC、症状及证候评分均存在明显改善。观察组和对照组IL-17水平较治疗前下降，Foxp3表达较治疗前升高（P < 0.05）。观察组对降低IL-17表达和提升Foxp3表达上较对照组差异更大（P < 0.05）。观察组治疗后与正常组IL-17和Foxp3水平比较差异较小（P > 0.05）。结论 网络药理学能一定程度上预测中药作用于疾病的相应靶点，前列消汤对ⅢA型前列腺炎湿热下注证患者的临床症状有明显改善作用，并能降低IL-17表达，对Foxp3表达有提升作用，在总有效率和对细胞因子的影响上较银花泌炎灵片组明显。     

LEOPARD综合征一家系PTPN11基因突变分析

【摘要】 目的 明确1个LEOPARD综合征家系的PTPN11基因突变。方法 对中国科学院大学宁波华美医院确诊的1例LEOPARD综合征先证者的家系进行现场调查。提取家系内4例患者、2例健康成员及与该家系无关的100例健康对照外周血标本。PCR扩增PTPN11基因所有外显子，使用Sanger测序法进行突变位点分析。结果 该家系3代14人，其中6人患病（男3例，女3例），符合常染色体显性遗传。患者皮损主要分布于面部、躯干和四肢，具有特殊面容及心血管系统异常。4例患者存在PTPN11基因的错义突变c.1632G＞T（p.R558L），导致第558位由精氨酸变为亮氨酸，该突变既往未曾报道。该家系2例健康成员及100例健康对照未发现PTPN11基因突变。结论 该LEOPARD综合征家系患者PTPN11基因13号外显子发生c.1632G＞T错义突变，可能是该家系患者发病的分子基础。     

小细胞肺癌CT影像学特征及其组织病理特征相关性分析

小细胞肺癌(small cell lung cancer,SCLC)是一种恶性程度高,具有高度侵袭性神经内分泌功能的肿瘤[1-2]。SCLC病情进展快,预后效果较差,研究报道局限期SCLC治愈机率为20%~25%,而广泛期SCLC采用的治疗以放化疗为主[3-4]。由于SCLC发病时具有隐匿特点,早期诊断与鉴别诊断难度较高。但随着临床病理研究的深入,影像学技术水平不断成熟,采用低剂量CT进行肺癌筛查可提高肺癌的早期检出率,并且联合手术、CT引导下穿刺活检、气管镜以及胸水细胞学等辅助检查可进一步增强早期SCLC诊断准确率,临床中尽早了解SCLC CT影像学特征与组织病理特征对于治疗具有临床价值。     

Diagnosis of intrahepatic cholangiocarcinoma by Raman spectroscopy provides high efficiency: A protocol for systematic review and meta-analysis

Background:We aim to evaluate the efficiency of Raman spectroscopy (RS) in diagnosing suspected patients with intrahepatic cholangiocarcinoma (ICC), manifested by diagnostic sensitivity, specificity, and accuracy.Methods:We will research widely the articles concerning the use of RS in ICC through authenticated database including PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, Cochrane Library, and CNKI between January 2012 and November 2020, retrieving at least 1500 spectra with strict criteria. This study will be carried out in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We are going to summarize the test performance using random effects models.Results:Based on the pooled sensitivity, specificity, and diagnostic accuracy, we intend to provide the relative diagnostic efficiency in ICC through RS.Conclusion:Through this systematic review and meta-analysis, we intend to provide the pooled sensitivity, specificity and diagnostic accuracy of RS in the diagnosis of suspected ICC. Other parameters like positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), and area under curve (AUC) of the summary receiver operating characteristics (SROC) curve will also be calculated and related figures will be drawn to help illustrate the efficacy of RS in the diagnosis of ICC.     

Collimating micro-lens fiber array for noncontact near-infrared diffuse correlation tomography

Near-infrared diffuse correlation spectroscopy/tomography (DCS/DCT) has recently emerged as a noninvasive measurement/imaging technology for tissue blood flow. In DCT studies, the high-dense collection of light temporal autocorrelation curves (g₂(τ)) via fiber array are critical for image reconstruction of blood flow. Previously, the camera-based fiber array limits the field of view (FOV), precluding its applications on large-size human tissues. The line-shape fiber probe based on lens combination, which is predominantly used in current DCT studies, requires rotated-scanning over the surface of target tissue, substantially prolonging the measurement time and increasing the system instability. In this study, we design a noncontact optical probe for DCT based on collimating micro-lens fiber array, termed as FA-nc-DCT system. For each source/detector fiber, a single optical path was collimated by coupling with one micro-lens in the fiber array that is integrated in a square-shape base. Additionally, an 8×8 optical switch is used to share the hardware laser and detectors without spatial scanning. The FA-nc approach for the precise collection of g₂(τ) curves was validated through a speed-varied phantom experiment and the human experiments of cuff occlusion, from which the expected value of the blood flow index (BFI) was obtained. Furthermore, the flow anomaly in the phantom and the ischemic muscle in human were accurately reconstructed from the FA-nc-DCT system, which is combined with the imaging framework based on the Nth-order linear algorithm that we recently created. Those outcomes demonstrated the great potential of FA-nc-DCT technology for fast and robust imaging of various diseases such as human breast cancers.     

A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

Comparison between tension band and cerclage with X-Plate and lag screws in treatment of comminuted patellar fractures

BackgroundComminuted patellar fractures are not rare, and the ideal treatment method remains controversial. The present study was conducted to evaluate effects and compare complications of two different methods used to treat comminuted patellar fractures.MethodsFrom March 2010 to August 2016, 102 cases of 34-C2 or 34-C3 comminuted patellar fractures were treated at our hospital, wherein patients received two different treatments: titanium cable tension band with cerclage method (group A) and intrafragmentary screws with X-shaped plating technique (group B). At follow-ups, articular step-off, range of motion (ROM), Lysholm scores, time of union, and complications were recorded and analyzed. Radiographic and clinical data as well as rate of complications were statistically analyzed.ResultsIn total, 87 patients were included in the final analysis (n = 47 in group A and n = 40 in group B). No significant differences were noted in terms of cost of implant, age, gender, rate of 34-C3 fractures, rate of layered inferior pole fractures, postoperative articular step-off and union time. At 2-year follow-up, average Lysholm scores, ROM and rate of complications were (89.0 ± 4.5), (122°±12°) and (27.7%) in group A and (90.2 ± 3.9), (124°±11°) and (17.5%) in group B, respectively, with no significant differences (p > 0.05). The mean time of surgery in group B was shorter than that in group A with significant difference (p < 0.05).ConclusionsTreatment using the intrafragmentary screws and plate method for amenable comminuted patellar fractures achieved similar complication rate and favorable functional outcomes at the 2-year follow-up, which was comparable to the titanium cable tension band with cerclage method. Thus, the intrafragmentary screws and plate method is effective, safe and convenient for 34-C2/C3 comminuted patellar fractures, especially appropriate for patients with layered fragments.     

High expression of HVEM is associated with improved prognosis in intrahepatic cholangiocarcinoma

Herpesvirus entry mediator (HVEM) displays dual signals in T-cell activation according to the ligands and intracytoplasmic effectors it interacts with. High HVEM expression may play an immunosuppressive role in several malignancies. The present study investigated the clinical impact of HVEM on intrahepatic cholangiocarcinoma (ICC), including its prognostic value, and association with clinicopathological features and immune status. The clinical data of 102 consecutive patients with ICC who underwent surgical treatment from January 2012 to December 2017 were collected. The expression of HVEM and different types of tumor-infiltrating lymphocytes (TILs) were investigated in ICC tissue samples by immunohistochemical staining. HVEM expression was detected in the tumor tissues of 92 (90.2%) patients with ICC. Patients with high HVEM expression were more likely to have increased peripheral blood lymphocyte (PBL) concentrations (P=0.031), decreased CEA (P=0.036), low TNM stage (P=0.043) and high frequencies of small-duct histological type (P=0.021) and BAP1 retained expression (P=0.010). Survival analysis showed that high HVEM expression was a favorable independent predictor of overall postoperative survival (P=0.034, hazard ratio=0.486, 95% confidence interval=0.249–0.945). In addition, no significant association of HVEM expression with CD4⁺ (P=0.512), CD8⁺ (P=0.750) or CD45RO⁺ (P=0.078) TILs was identified in the ICC tissues. These results indicate that HVEM may serve as a favorable prognostic marker for ICC. Furthermore, co-stimulatory signals from HVEM may play a dominant role in the progression of ICCs, which can be explained by an increase in the number of PBLs rather than a change in the number of TILs. However, the function of the HVEM network in ICC progression is complex and requires further study.     

经桡动脉途径行外周血管介入的临床研究

目的评价经桡动脉途径(TRA)行外周血管介入的安全性和可行性。方法回顾性收集2017年9月至2019年3月于中国医学科学院肿瘤医院TRA行外周血管介入治疗的106例肿瘤患者的临床资料,分析患者的桡动脉穿刺率、穿刺完成后续操作的手术成功率以及术后30 d内相关并发症。结果106例患者中,TRA外周血管介入操作112例次,其中行经导管肝动脉化疗栓塞术83例次,支气管动脉灌注术4例次,盆腔肿瘤栓塞术11例次,其他手术14例次。所有介入操作穿刺成功率为97.3%(109/112),手术成功率为98.2%(107/109)。5例患者TRA失败,转为股动脉穿刺,并顺利完成操作。手术严重并发症为主动脉夹层2例次;轻微并发症中,桡动脉闭塞2例次,桡动脉痉挛1例次,手臂疼痛1例次,穿刺点血肿1例次。严重并发症和轻微并发症发生率分别为1.8%(2/112)和4.5%(5/112)。急诊操作16例次,均顺利完成操作,无并发症发生。结论TRA行外周血管介入治疗是安全、可行的。