Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

[摘 要] 无义介导的mRNA降解（NMD）作为一种质量控制机制，可降解含有过早终止密码子（PTC）的异常mRNA，参与生长发育、调节免疫功能，且与肿瘤微环境密切相关。NMD对肿瘤有抑制或促进的双重作用：一方面，NMD通过下调促癌蛋白表达、抑制促癌信号通路和应激微环境等途径抑制肿瘤进展；另一方面，NMD通过抑制抑癌基因的表达、癌细胞凋亡和肿瘤新抗原的产生促进肿瘤进展。此外，NMD并非降解所有携带PTC的mRNA，PTC出现的位置可能决定NMD触发或逃逸，由于各基因的高频突变区域各不相同，因此不同基因发生PTC突变后是否触发NMD则具有不同的倾向性。随着二代测序技术的成熟与普及，基因突变筛查已成为临床诊疗常规手段，这使得从多基因层面探究NMD的规律与意义成为可能。因此，在进一步了解NMD的功能及其机制的基础上，通过高通量测序与计算机算法评估NMD水平，有望在临床工作中扬长避短地发挥NMD潜在的临床价值，助力个性化临床诊治与精准医疗的发展。

Objective:To investigate the correlation between RYR1 gene and the development of gastric cancer,as well as the mechanism of RYR1 in promoting the progression of gastric cancer.Methods:We analyzed gastric cancer data from TCGA and conducted high-throughput targeted sequencing and transcriptome sequencing on 81 gastric cancer tissue samples at Tianjin Medical University Cancer Institute&Hos-pital(TJMUCH)from December 2010 to December 2012.We collected clinicopathological data,compared the correlation between RYR1 mutations and expression levels,and analyzed the impact of RYR1 on the prognosis of patients with gastric cancer.Additionally,we explored the underlying molecular mechanism to study its role in promoting the development of gastric cancer by generating stable cell lines overex-pressing RYR1.Results:In TCGA gastric cancer patients,the mutation rate of RYR1 in Asian population was higher than that in others popula-tion(12.68%vs.8.13%).In gastric cancer patients from TJMUCH,RYR1 mutations ranked ninth in frequency,with a mutation rate of 33.33%.Mutations in RYR1 were negatively correlated with RYR1 expression(P=0.006 9,P<0.000 1).Patients with high RYR1 expression had significantly worse overall survival than those with low RYR1 expression(P=0.009 0,P=0.042 0).Overexpression of RYR1 promoted prolifera-tion,migration,invasion and reduced apoptosis of gastric cancer cell lines.Moreover,RYR1 overexpression was associated with decreased sensitivity to chemotherapeutic drugs in gastric cancer cells.Inhibiting RYR1-mediated calcium over-release could suppress malignant beha-viors and reverse chemoresistance.Conclusions:RYR1 had a high mutation rate in Asian gastric cancer patients and a significantly negative correlation with RYR1 mRNA levels.High RYR1 expression serves as a novel prognostic predictive marker for gastric cancer.RYR1 overex-pression promoted malignant progression of gastric cancer and chemoresistance by increasing the release of calcium ions from the endo-plasmic reticulum.Thus,RYR1 inhibition can reduce the proliferation,migration,and invasion of gastric cancer cells and reverse chemores-istance,which highlights potential combination therapies for gastric cancer.

Objective: To evaluate the application of self-made-dispensing-ampoule car in the medicine dispensing for venous transfusion. Methods: The self-made-dispensing-ampoule car made based on the ergonomics is a temporary carrier device for medical waste in the need of the whole process of dispensing process. The overall exterior is made of 304 stainless steel, separated into 2 layers. The Upper layer has a frame with integral medicine glass hole made of stainless steel, which can be dismantled from the upper layer. The medicine glasses are small empty medicine bottles used to hold the dispensed medicine; while the lower layer is a slide platform which can put on 3 medical waste classification boxes. The bottom has universal wheels with brakes to help the car move and stop. To focus on 42 emergency department nurses using the device, to analyze their error rate of medicine dispensing, the dispensing time for the same batch of patients with same dosages and shuttle time from dispensing car to buffer room to pour medical waste and compare the data the year before and the year using the device. Results: After using it, the dispensing error occurrence rate and nurses dispensing time and shuttle times of pouring waste were 0.31 ‱ (3/97 785), (70.08±3.28) min/time, two times, which were all obviously lower than 1.95‱ (18/92 095), (110.04±6.91) min/time, 30 times without using it (χ²=11.64, 204.16, t=71.70, all P<0.01). Conclusion Using the dispensing ampoule car can optimize the dispensing process in dispensing of venous transfusion, ensure patients with safe venous transfusion, raise the efficiency of nurses saving time and efforts.

With the advancement of high-throughput sequencing technology, improvements in big data processing and analysis have been witnessed. Evaluation of anti-tumor effects of targeted therapy and immunotherapy using various molecular markers based on high-throughput sequencing and big data are moving towards clinical application. Panel detection of different genetic markers pro-vides the basis for cancer diagnosis and treatment. In this article, the classification of high-throughput sequencing panel, application of large panel in cancer diagnosis, targeted therapy, immunotherapy, and the problems encountered in the clinical application of large panels are reviewed in order to provide a reference for their clinical application and promote the advancement of precision medicine.

Objective: To investigate the application of single-molecule PCR (SM-PCR) in the detection of plasma ctDNA for the treat-ment of patients with advanced lung adenocarcinoma. Methods: In total, 30 patients diagnosed with advanced lung adenocarcinoma were enrolled between June 2017 and May 2018. ctDNA fragments of the target genes (EGFR, KRAS, BRAF, ALK, HER2, and TP53) from the blood samples were enriched by SM-PCR, and DNA libraries were prepared. Finally, a high-throughput sequencing was performed. The EGFR detection of tumor tissue samples was performed using real-time fluorescence PCR based on the amplification refractory mutation system (ARMS) and consistency in the results of EGFR mutation detection in the plasma and tissue was compared. Results:The results of both the methods were consistent (Kappa=0.867, P<0.001). The McNemar's test also indicated that the results are not statistically different (P=0.500). Conclusions: SM-PCR can be used for the detection of plasma EGFR mutations. The target detection sites are more comprehensive and multiple mutations can be detected at the same time. Results of the analysis are more precise and can be absolutely quantified.

Breast cancer is the most common cancer for Chinese women. Early screening is the best way to improve the rates of early diagnosis and early treatment of breast cancer. The peak ages of breast cancer in Chinese women are obviously different from those in the European and American countries. It is imperative to develop a guideline for breast cancer screening that is suitable for Chinese women. Based on the analysis and summary of breast cancer screening data in China, and the latest guidelines and consensus on breast cancer screening in Europe, the United States and East Asia, China Anti-Cancer Association and National Clinical Research Center for Cancer (Tianjin Medical University Cancer Institute and Hospital) has developed a population-based guideline for breast cancer screening in Chinese women. This guideline has provided detailed recommendations on the screening starting age, screening modalities, and screening interval in Chinese women with average risk and high risk of breast cancer, respectively. This article aims to interpret the above guideline, providing references for professionals in breast cancer screening.

免疫治疗是继传统的手术、化疗、放疗和靶向治疗后的一种新兴的肿瘤治疗手段。以免疫检查点抑制剂（ICP）疗法为 代表的免疫治疗在肿瘤临床治疗中取得了突破性进展。随着ICP在临床的应用，用于肿瘤诊断、疗效及预后的生物标志物的探 索也成为肿瘤免疫治疗研究的热点。在当前精准医疗的背景下，多项临床研究证实程序性死亡蛋白配体-1（PD-L1）表达、肿瘤突 变负荷、微卫星不稳定以及肿瘤微环境相关的生物标志物与免疫治疗的疗效密切相关。然而，许多患者并不能从这些疗法中受 益，缺乏有效的疗效和预后生物标志物在很大程度上限制了其临床应用。本文总结了有关免疫治疗生物标志物的相关研究文 献，重点关注免疫治疗疗效和预后生物标志物在临床应用的相关研究进展，阐述可能有助于指导临床决策及治疗方案选择的潜 在生物标志物。

Objective:To study the effects of IL-8 on the polarization of monocytes and the effects of IL-8-induced tumor-associated macrophages(TAMs)on the invasion and metastasis of hepatocellular carcinoma(HCC).Methods:After exogenous IL-8 stimulation of THP-1 cells for 72h,the percentages of M1 and M2 TAMs were examined.RT-PCR and Western blot assays were used to study epitheli-al-mesenchymal transition(EMT),and wound-healing and transwell assays were preformed to study the invasion potential of HCC cells after co-culturing with TAMs and HCC cell lines in vitro.Lastly,100 cases of HCC tissue samples were used to validate the correlation among TAM numbers,IL-8,and EMT features of HCC cells via immunohistochemistry(IHC)staining methods.Results:Exogenous IL-8 induced significant M2 polarization of TAMs in THP-1 cells.TAMs further promoted EMT in HCC and enhanced the invasion potential of HCC in vitro.Finally,significant positive correlations among the numbers of TAMs,IL-8 expression,and N-cadherin expression were identified in primary HCC tissue samples(r=0.22,r=0.20,P<0.05).Conclusions:IL-8 locally attracted and activated TAMs,and promot-ed M2 polarization of TAMs,which further promoted the EMT and invasion potential of HCC cells both in vitro and in vivo.

Objective: To detect eight highly related driver genes in non-small cell lung cancer (NSCLC), and to analyze the relationship between gene variations and clinical-pathological features. Methods: We collected 212 NSCLC samples from Tianjin Medical University Cancer Institute and Hospital, and sequenced eight genes which are EGFR, KRAS, BRAF, ALK, MET, ERBB2, ROS1 and RET. Results: EGFR gene variation rate was as high as 52.8%, followed by KRAS (8.5%), ALK (8.0%), ERBB2 (6.1%), MET (3.8%), BRAF (1.4%), RET (0.9%) and ROS1 (0.9%) in eight detecting genes, at least one driver gene variant was detected in 75% samples, and driver gene variant showed strong mutual exclusion. The most common EGFR mutations were 19 exon deletion and L858R mutation, and the mutation of EGFR T790M was accompanied by the above two mutations. The proportion of non-EGFR T790M mutations in patients with exon 19 dele-tion was lower than that of L858R mutations (P=0.04). There were 15.2% patients with EGFR mutation accompanied by EGFR amplifica-tion, and the proportion of patients with EGFR mutation frequency greater than 40% with EGFR amplification was higher than that without EGFR amplification (P<0.01). Women, non-smoking, patients with adenocarcinoma were prone to carry EGFR especially EGFR sensitive mutations (P<0.01). Patients with lung adenocarcinoma (P=0.013), late clinical stage (P=0.048), and lymph node metastasis (P=0.027) had a higher proportion of EGFR amplification. The incidence of KRAS mutation was higher in men, left lung cancer and smoking patients (P=0.009, P=0.048, P=0.037). Patients with non-KRAS mutations, ALK fusions were younger (P=0.005, P=0.031), and with KRAS mutations were older (P=0.055). Conclusions: Next-generation sequencing (NGS) can simultaneously detect eight highly re-lated driver genes in NSCLC patients to provide evidence for clinicians. NGS based on detection of multiple genes provides more possi- bilities for individualized diagnosis and treatment of NSCLC.