果酸联合调q激光治疗中波紫外线诱导黄褐斑鼠模型的实验研究

目的 研究果酸联合调q激光治疗中波紫外线诱导的黄褐斑鼠模型的疗效及可能机制。方法 选取健康雌性豚鼠30只,分为正常组（6只）和实验组（24只）。实验组予中波紫外线联合黄体酮注射液复制黄褐斑鼠模型,从中随机选取6只与正常组豚鼠一起处死,观察血清超氧化物歧化酶（SOD）和丙二醛(MDA)的表达水平,局部皮损行HE及免疫组织化学染色。实验组余18只为模型组,随机分为A、B、C组,每组6只。A组予以果酸联合调q激光治疗,B组予以氢醌治疗,C组不做任何处理。4个月后分别检测各组豚鼠血清、肝脏、皮肤SOD活力、MDA表达水平及皮肤组织病理改变。结果 模型组黄褐斑鼠模型复制区可见深褐色斑形成;模型组与正常组比较,血清SOD水平下降,MDA水平上升（P?<0.05）;模型组皮损HE及免疫组织化学染色显示病理表现符合黄褐斑病理改变;A、B组与C组比较,A组、B组皮损肉眼观及组织病理表现明显改善;治疗后血清、肝脏、皮肤中SOD水平上升,MDA水平下降（P?<0.05）,A组与B组比较,差异无统计学意义（P?>0.05）。结论 果酸联合调q激光治疗黄褐斑鼠疗效显著,可能与果酸的剥脱作用、抗氧化作用,以及调q激光选择性破坏黑素细胞、减少黑色素生成有关。     

颅内外血栓在系统性红斑狼疮患儿中的发生情况比较*

目的 通过回顾性比较儿童系统性红斑狼疮（SLE）患者发生颅内、外血栓的情况,旨在发现SLE合并不同部位血栓的危险因素。方法 选取2006年1月—2019年12月首都医科大学附属北京儿童医院收治的SLE患儿,收集患儿人口学资料、临床表现、活动度评估及治疗、病程及随访资料等,并收集实验室检查数据及血栓相关数据等,根据血栓部位将患儿分为颅内血栓组及颅外血栓组,对两组资料进行比较。结果 27例SLE合并血栓患儿中,6例（22.22%）发生颅内血栓,21例（77.78%）患儿发生颅外血栓。颅内血栓以颅内静脉窦血栓形成（CVST）更为多见,横窦是CVST最常见的受累部位。颅外血栓常见受累部位依次为股总静脉、髂外静脉及股深浅静脉。颅外血栓组合并肾脏受累比例较颅内血栓组高（P?<0.05）,颅内血栓组合并神经系统受累比例较颅外血栓组高（P?<0.05）。颅外血栓组的Hb、C3、C4水平较颅内血栓组低,尿蛋白水平较颅内血栓组高（P?<0.05）。治疗后两组血栓均有一定程度的好转,其中颅内血栓组1例（16.7%）患儿血栓消失再通,颅外血栓组11例（52.4%）患儿血栓消失再通。结论 SLE合并颅内、外血栓形成有不同的特点,神经系统症状是颅内血栓最常见的症状,肾脏受累的患儿更易发生颅外血栓。早期诊断,积极治疗可明显改善SLE合并血栓患儿的预后。     

Silencing of CXCR4 Inhibits Tumor Cell Proliferation and Neural Invasion in Human Hilar Cholangiocarcinoma

Background/Aims

To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing.

Methods

An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay.

Results

The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation.

Conclusions

CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.     

Video-assisted mediastinoscopic resection compared with video-assisted thoracoscopic surgery in patients with esophageal cancer

Objective

The purpose of this study was to explore the indications of radical vedio-assisted mediastinoscopic resection for esophageal cancer.

Methods

The data of 109 patients with T1 esophageal cancer who underwent video-assisted mediastinoscopic resection (VAMS group) in Third Affiliated Hospital of Soochow University Hospital from December 2005 to December 2011 were collected in the study for comparison with the 58 patients with T1 esophageal cancer who underwent video-assisted thoracoscopic surgery (VATS group) in Zhongshan Hospital, Fudan University. The perioperative safety and survival were compared between the two groups.

Results

All operations were successful in both groups. One perioperative death was noted in the VATS group. The incidences of post-operative complications were not significantly different between these two groups, whereas the VAMS group was favorable in terms of operative time (P<0.001) and blood loss (P<0.001), and a significantly larger number of chest lymph nodes were dissected in the VATS group compared with the VAMS group (P<0.001). Long-term follow-up showed that the overall survival was not significantly different between these two groups (P=0.876).

Conclusions

T1N0M0 esophageal cancer can be as the indication of VAMS radical resection. VAMS radical resection can be considered as the preferred option for patients with poor pulmonary and cardiac function or a history of pleural disease.     

Diagnostic delay of pulmonary nontuberculous mycobacterial infection in China

Background

Nontuberculous mycobacteria (NTM) infection is an emerging, but neglected public health concern in China.

Findings

To investigate diagnostic delay of NTM diseases in China, we analyzed 91 patients with pulmonary NTM infection in ShandongProvince. The median diagnostic delay time of the analyzed patients was 84 days, which was significantly associated with rural inhabitance (135 days vs. 73 days of urban inhabitance, p?<?0.01) and lower level of first visiting hospitals/clinics (70 and 82 days of tertiary and secondary hospitals/clinics respectively vs. 120 days of primary hospitals/clinics, p?<?0.05). M. farcinogenes was isolated from a 79-year-old male patient, which is the first report of pulmonary infection in humans.

Conclusions

Our results indicate a significant diagnostic delay of NTM diseases in China, especially for rural patients with limited access to higher-level healthcare services.

     

Infrequent ERBB2 mutations in Chinese patients with non-small cell lung cancer

ERBB2 mutations have been reported to occur in a subset of patients with lung adenocarcinomas or lung squamous cell carcinomas for some ethnicities, but it is unclear for Chinese patients with lung squamous cell carcinomas up to now. We retrospectively evaluated the status of ERBB2 mutations in a large cross-sectional cohort of 212 Chinese patients with non-small cell lung cancer (NSCLC) diagnosed in several hospitals from southern China during a time period of 1.5 years by polymerase chain reaction (PCR)-based direct sequencing and PCR-single strand conformation polymorphism (PCR-SSCP) analysis. ERBB2 mutation was found in 1 of 49 lung adenocarcinomas (2.0%) and none in lung squamous cell carcinomas and lung adenosquamous carcinomas. It implies the occurrence of ERBB2 mutations is infrequent in Chinese patients with NSCLC, especially in lung squamous cell carcinomas.     

Identification and characterization of alphavirus M1 as a selective oncolytic virus targeting ZAP-defective human cancers

Oncolytic virotherapy is a growing treatment modality that uses replicating viruses as selective antineoplastic agents. Safety and efficacy considerations dictate that an ideal oncolytic agent would discriminate between normal and cancer cells on the basis of common genetic abnormalities in human cancers. Here, we identify a naturally occurring alphavirus (M1) as a novel selective killer targeting zinc-finger antiviral protein (ZAP)-deficient cancer cells. In vitro, in vivo, and ex vivo studies showed potent oncolytic efficacy and high tumor tropism of M1. We showed that the selectivity depends on ZAP deficiency by systematic identification. A large-scale multicenter pathology study using tissue microarrays reveals that ZAP is commonly deficient in human cancers, suggesting extensive application prospects for M1. Additionally, M1 killed cancer cells by inducing endoplasmic reticulum stress-mediated apoptosis. Our report provides novel insights into potentially personalized cancer therapy using oncolytic viruses.Despite advances in cancer therapy over the past few decades, cancer is still a major health problem all over the world (1). One innovative class of targeted anticancer strategies is the use of replicating oncolytic viruses with selective tropism for cancerous cells and tissues (2, 3). The tumor selectivity of oncolytic virus is primarily based on the genetic abnormalities of malignant cells, including innate immune defects, aberrant oncogenic signaling, and tumor-specific receptors (4–6). The thriving viruses in tumor cells may lead to direct cell lysis, anticancer immune response, or modulation of tumor vasculature (3, 7). Moreover, some of the cancer-targeted multimechanistic oncolytic viruses have been proven to be well-tolerated in clinical trials, with patients exhibiting only mild flu-like symptoms, offering great potential for increasing efficacy while eliminating the side effects (8). To date, several oncolytic viruses have been tested in preclinical and clinical trials, of which the milestone is a pivotal phase III trial using talimogene laherparepvec for unresected melanoma (2, 3, 9). Although a few therapeutic viruses are performing well in clinical trials, not all patients showed good response. Novel oncolytic viruses that grow better in some cancer cells in a predictable manner remain to be discovered for potentially personalized cancer therapy.M1 is a strain of Getah-like alphavirus that was isolated from culicine mosquitoes collected on Hainan Island of China (10, 11). Getah virus is transmitted mainly among horses and pigs, and it has not been linked to human illness (12–14). Also, M1 does not cause apparent disease symptoms in mice or rats, even on administration of doses up to 3 × 10⁷ pfu per mouse or 3 × 10⁸ pfu per rat. Earlier, we reported that M1 induces apoptosis in glioma cells (10). Thus, we hypothesized that an apathogenic cancer cell-killing virus could be a candidate for systemic oncolytic therapy.In this study, we sought to investigate the anticancer effectiveness and tumor tropism of M1 and uncover the mechanisms, aiming to identify a candidate for personalized oncolytic virotherapy.     

人源类器官的研究进展及在口腔医学的展望

类器官是指在体外三维培养构建的,依赖于人造细胞外基质的多细胞团,具有自我更新、自我组织能力,并维持了其来源组织的生理结构和功能。类器官作为一种新兴的研究模型,兼具细胞系和动物模型两者的优点。其构建材料简单、培养效率高、耗时短,在疾病研究模型构建、临床药敏试验和再生医学中有良好的应用前景。类器官模型主要分为三种细胞来源类型：胚胎干细胞/诱导多能干细胞、成体干细胞、肿瘤细胞。本文将重点介绍三种细胞来源类器官最新的研究进展,并展望其在口腔医学中的应用。     

牙周牙髓联合病变的综合治疗效果观察

目的研究牙周牙髓综合治疗对下前牙牙周牙髓联合病变的疗效,以期为临床治疗提供依据。 方法收集2017年1月至2018年2月至广州市海珠区口腔医院就诊的31例下颌重度牙周炎伴牙髓病变前牙,给予牙周治疗（龈上洁治、龈下刮治及根面平整术）,根管治疗和松牙固定的综合治疗。记录患者基线、治疗后3个月、6个月、12个月的牙石指数（CI）、龈沟出血指数（SBI）、探诊深度（PD）、附着水平（AL）值,采用单因素重复测量资料方差分析统计数据（检验水准α = 0.05）,比较患牙治疗前、后差异,评价临床疗效。 结果31例患牙中,牙周牙髓联合治疗有效率为96.8%。患牙在术后3、6、12个月较基线相比,其CI、SBI、PD、AL值均显著下降,差异均有统计学意义（P<0.001）。术后6个月与3个月相比,PD、AL值继续下降,差异有统计学意义（F_PD = 112.51,P_PD<0.001;F_AL = 117.64,P_AL<0.001）;术后12个月较6个月仍持续降低,但差异无统计学意义（F_PD = 0.04,P_PD = 0.815;F_AL = 0.09,P_AL = 0.786）。 结论对于下前牙牙周牙髓联合病变,综合治疗效果显著。