Mitophagy is the selective degradation of damaged mitochondria, and it is of great significance to maintain the normal quantity and quality of mitochondria to ensure cell homeostasis and survival. Necroptosis is a type of programmed cell necrosis that can be induced by excessive mitophagy. Reactive oxygen species (ROS) are produced mainly by mitochondria and can damage mitochondria. Hyperoxic acute lung injury (HALI) is a serious complication of clinical oxygen therapy, and its pathogenesis is not clear. Existing studies have shown that mitophagy and necroptosis are involved in the occurrence of HALI. There are many mechanisms regulating mitophagy and necroptosis, including tumor necrosis factor-α (TNF-α), E3 ubiquitin protein ligase (PINK1/Parkin) protein pathway encoded by PTEN-induced kinase 1/PARK2 gene, phosphoglycerate mutase 5 (PGAM5), etc. PGAM5 has been proved to be a key factor linking mitophagy and necroptosis. Previous studies of our team found that the mechanism of microRNA-21-5p (miR-21-5p) alleviating HALI was related to its pGAM5-mediated inhibition of mitophagy, but the mechanism of PGAM5-mediated mitophagy and necroptosis remains unclear. Therefore, this paper reviews the targets of PGAM5-mediated mitophagy and necroptosis, in order to find clues of lung protection of pGAM5-mediated mitophagy and necroptosis in HALI, and provide theoretical basis for subsequent basic research.

Endodontic microsurgery is a vital treatment modality for teeth with persistent periradicular pathoses that have not responded to nonsurgical retreatment. The principle is to determine the reason for failure, completely eliminate the infection and promote periapical healing. Within recent years, endodontic microsurgery has evolved to become standardized and presents with a high success rate. However, its outcome is still influenced by many factors, including anatomy, periodontal condition, crown-to-root ratio, occlusion, the type of periradicular lesion, and prosthesis. Moreover, endodontists always concentrate on “the apex”, paying little attention to the general preoperative evaluation, accurate diagnosis, and comprehensive treatment plan. This article reviews the latest literature on these issues and the clinical experience of our research group and discusses the correlation between endodontic microsurgery and other oral disciplines, including periodontology, prosthodontics, oral implantology, oral and maxillofacial surgery and orthodontics. The oral interdisciplinary assessment should be made with comprehensive consideration of the root canal system, periradicular lesion, adjacent anatomical relationships, periodontal condition, occlusion, and esthetic rehabilitation. Based on these findings, the continuity of treatment will be optimized, and the best treatment plan will be proposed to provide clinical strategies for the diagnosis and treatment of complex periradicular diseases.

Objective:In this study, we compared the funding rates of applicants who participated in the expert preliminary counseling with those who did not, to explore the role of the expert preliminary counseling in improving the funding rate of the National Natural Science Fund, so as to provide further reference for the management of scientific research.Methods:Statistical methods was used to analyze relevant data from 2012 to 2019 to compare the approval and funding rate of the applicants that participated in and did not participate in the expert preliminary counseling using.Results:From 2012 to 2019, the proportion of funded applicants in the expert preliminary counselling group was 30.45%, and the overall funding rate was 18.51%. Under the same research basis, the funding rate of the group was 29.91%, which was significantly higher than the group did not participate in the expert preliminary counselling (funding rare: 13.59%, P<0.001). Conclusions:We should pay more attention to and participate actively in the expert preliminary counselling, which can increase the quality of the projects and improve their funding rate significantly.

Public hospitals play an important role in independent innovation of basic medicine and clinical medicine. As key players in translation of medical research achievements, they play a pivotal role in promoting the development of medical sciences. At present, these hospitals however, are faced with challenges in the translation, namely system defects, unclear property rights ownership, misleading research project goals, defective assessment mechanism, insufficient funding, and lack of translation channels. In such considerations, the authors suggested based on their experiences to improve the translation system of scientific research achievements, set up special departments for translation, clarify the rights to use and dispose of scientific research achievements and that to yields. They also proposed to actively guide the establishment of clinical application projects, improve the evaluation mechanism, and broaden channels of funding. These measures are expected to accelerate the translation of scientific research achievements.

Objective: A label-free electrochemical immunosensor was developed for the detection of nuclear matrix protein-22 (NMP22) as a biomarker of bladder cancer. Methods: The study was based on the establishment and validation of the methodology. Urine samples were collected from 20 patients with bladder cancer and 20 controls in the affiliated Hongqi hospital of Mudanjiang medical university from September in 2017 to July in 2019 to validate the developed method. A screen-printed electrode (SPE) was modified with a film of a composite made from the reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) immobilized Zn-based-Metal-organic frameworks deposited with Au nanoparticles (rGO-TEPA@Au-ZIF8). Primary antibody against NMP22 was immobilized on the Au nanoparticles on the surface of the modified SPE, which then was blocked with bovine serum albumin to elimiate nonspecific binding sites. The process of the construction of the proposed sensorwas characterized by cyclic voltammetry and electrochemical impedance spectroscopy. Differential pulse voltammetry was used to evaluate the linear range, recovery, precision, selectivity and stability. The data were analyzed by Mann-Whitney U test. Results: Under optimal conditions, the immunosensor exhibited a linear range of 0.01-1000 ng/mlwith a detection limit of 3.33 pg/ml (S/N=3) and a standard recovery of 97.65%-107.05%. The levels of NMP22 in urine samples from patients with bladder cancer [66.03 (4.34, 91.74)]ng/ml determined by the proposed sensor were significantly higher than those of controls 0.54(0.06, 8.84) ng/ml(P=0.001). Conclusion The immunosensor can achieve sensitive, rapid and acucurate detection of NMP22, and has potential application prospects in monitoring tumor markers.

OBJECTIVETo evaluate the efficacy of self-made gasbag double-cannula stool drainage device for prevention of anastomotic leakage following anterior resection.

METHODSClinical data of 169 rectal cancer patients in the 8th Affiliated Hospital of Sun Yat-sen University between October 2010 and October 2016 were retrospectively analyzed. Among them, a self-made gasbag double-cannula stool drainage device was placed in 71 patients(stool drainage group), and the remaining 98 patients were taken as control. After an anastomosis, the drainage device was transanally placed by the assistant and the distal tube of drainage device was stretched more than 15 cm from anastomosis. The gasbag was inflated to fully expand the intestine. The main tube was fixed on perianal skin with 7-0 suture, kept more than 3-5 cm outside the anus, and connected to the drainage bag. The incidence of anastomotic leakage was compared between the two groups.

RESULTSThe baseline data were similar between the two groups (all P>0.05). The differences in operative time, intraoperative blood loss, and time to bowel function recovery were not statistically significant (all P>0.05), however, time to oral intake and postoperative stay were shorter in stool drainage group as compared to the control group (both P<0.05). There was no perioperative death in both groups. In stool drainage group, there were 6 cases whose drainage device was pulled out within 48 hours due to intolerance. The ruptured gasbag was replaced 5 times and the tube was clogged by fecal material 21 times. After flushing, the tube did not recanalized and was pulled out in 3 cases. The incidence of anastomotic leakage in stool drainage group was significantly lower than that in the control group (2.8% vs. 11.2%, P=0.043). As for the low anastomosis (the distance to anal verge less than 5 cm), the incidence of anastomotic leakage in stool drainage group was also significantly lower than that in the control group (2.3% vs. 15.4%, P=0.028), while as for the high anastomosis, the difference was not statistically significant (3.6% vs. 3.0%, P=0.906). Logistic regression analysis revealed that the presence of a stool drainage device was an independent protective factor for anastomotic leakage (OR=0.316, 95%CI:0.114 ~ 0.769, P=0.003).

CONCLUSIONSThe self-made gasbag double-cannula stool drainage device effectively prevents anastomotic leakage after anterior resection of rectal cancer. However it is not suitable for those patients with high anastomosis.

Objective:To investigate the reasons of anastomotic leakage following learning curve by laparoscopic anterior resection of rectal cancer.Methods:From December,2011 to March,2015,the clinical information of 179 patients in our hospital who underwent dixon of rectal cancer were collected.The patients were divided into a laparoscopic learning group,a laparotomy group and a laparoscopic group,The reasons of anastomotic leakage for each group were comparatively analyzed.Repeated cutting of anastomotic stoma was compared between the laparoscopic learning group and the laparoscopic group.The male,age,obesity,nutrition complications and the position of anastomotic stoma were compared among the 3 groups.Results:The rate of anastomotic leakage in the laparoscopic learning group was significantly higher than that in the laparotomy group and the laparoscopic group (P＜0.05).Repeated cutting was a significant risk factor in the laparoscopic learning group (P＜0.05),but not in the laparoscopic group.Except obesity,the four factors were significant risk factors in the laparoscopic learning group (P＜0.05).All of the five factors were not the significant risk factors in the laparotomy group and the laparoscopic group (P＞0.05).Conclusion:The operation technical shortcoming is the major factor in the learning of the laparoscopic anterior resection of rectal cancer.In order to reduce the rate of anastomotic leakage in the learning curve period,the selection of patients following the laparoscopic anterior resection of rectal cancer should avoid the following factors:male,older age,the low position of the tumor and the nutrition complications.

Objective: To observe the therapeutic response of radiosynovectomy with p-32 colloid on hemophilic arthropathy, and to assess the effects of radiosynovectomy with Denver Score on hemophilic arthritis staging. Methods: Radiosynovectomy with p-32 colloid was performed on 326 hemophilic arthritis patients (405 joints) , and recorded bleeding before and after treatment. The MRI performance of 102 joints was evaluated by using Denver scoring system, then was divided into 0-6 and 7-10 groups. Finally, the differences between 2 groups were analyzed. Results: Average pain score of all hemophilic arthritis patients at 6 months, 1, 2 and 3 years post treatment decreased from 3.2±2.4 (n=326) to 1.2±0.6 (n=285, P=0.021) , 1.7±0.5 (n=242, P=0.032) , 2.1±1.1 (n=212, P=0.030) and 2.2±1.6 (n=176, P=0.037) , respectively. The frequency of bleeding in 405 joints at 1, 2 and 3 years post treatment decreased from 15.1±3.6 to 2.1±0.7, 4.3±0.6, and 4.8±0.8 times per year (P<0.01) , respectively; Meanwhile, the proportions of significantly ameliorated joints’ activities were observed as of 68.50% (248/362) , 58.39% (181/310) , 55.67% (162/239) and 42.61% (75/176) , respectively. The frequencies of haemarthrosis at 1 and 2 years post treatment in patients with 0-6 Denver Score (45 target joints) reduced from 13.0±1.9 to 1.3±0.6 (P=0.002) and 3.1±0.9 (P=0.009) times per year, respectively, which also decreased in 7-10 group (57 target joints) from 16.6±2.1 to 3.1±0.9 (P=0.008) and 5.7±1.1 (P=0.004) times per year, respectively. There was no statistical difference between 0-6 and 7-10 groups before treatment in the terms of haemarthrosis frequency (P=0.773) . However, 7-10 group had higher haemarthrosis frequency at 1 and 2 years post treatment compare with 0-6 group (P=0.028 and 0.042, respectively) . Synovial volumes in 29 joints reduced after 6 month when compared with baseline [ (2 362.15±32.41) mm³ vs (3 012.40±39.78) mm³, t=7.621, P<0.001]. Conclusion Radiosynovectomy with p-32 colloid on haemophilic synovitis was a safe and effective procedure. The patients with Denver Score of 0-7 had lower frequency of haemarthrosis.

Objective: To investigate the association between expression of phosphoglycerate kinase 1 (PGK1) in liver cancer tissue and prognosis, as well as its influence on metastasis and invasion of hepatocellular carcinoma (HCC) cells. Methods: Overexpression and downregulated expression of PGK1 in HCC cells were mediated by lentivirus to establish hepatoma cell lines with different expression levels of PGK1. The Transwell chamber invasion assay, wound healing assay, and colony-forming assay were used to investigate the influence of PGK1 on metastasis, invasion, and proliferation of HCC cells. Immunohistochemistry was used to measure the expression of PGK1 in liver cancer tissue samples from 116 patients with hepatocellular carcinoma who underwent radical surgery, and the Kaplan-Meier method and the log-rank test were used to determine the association between PGK1 expression and prognosis of patients with liver cancer. Results: HCCLM3 and MHCC97H HCC cells with high metastatic potential had significantly higher expression of PGK1 than Hep3B and Huh7 HCC cells with low metastatic potential. Downregulation of PGK1 expression significantly inhibited the migration (31.2% ± 2.4% vs 12.0% ± 1.3%, t = 21.57, P < 0.01), invasion (58 ± 11 vs 21 ± 8, t = 4.687, P < 0.05), and colony-forming ability (168.6 ± 15.1 vs 118.4 ± 8.1, t = 6.650, P < 0.05) of MHCC97H cells, while overexpression of PGK1 enhanced the migration (62.8% ± 4.4% vs 83.6% ± 6.1%, t = 20.56, P < 0.01), invasion (80 ± 12 vs 121 ± 15, t = 4.603, P < 0.05), and colony-forming ability (52.3 ± 8.6 vs 84.7 ± 9.0, t = 27.18, P < 0.01) of Hep3B cells. The high PGK1 expression group had significantly shorter median disease-free survival time and mean survival time than the low PGK1 expression group (22.00 ± 8.51 vs not reached, P < 0.05; 46.00 ± 16.87 vs not reached, P < 0.01). Conclusions PGK1 is involved in the regulation of metastasis and invasion of HCC cells and can promote the migration and invasion of HCC cells. Therefore, PGK1 may be an important predictor of prognosis and postoperative recurrence in patients with liver cancer.

Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. vaccae Bacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between M. vaccae and M. vaccae BCG revealed that M. vaccae was more malignant than M. vaccae in mice. We also demonstrated that serum from the M. vaccae-infected mice contained a higher expression level of gamma-interferon (IFN-γ), tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especially after week 4. Furthermore, when the numbers of CD3⁺CD4⁺IFN-γ⁺ and CD3⁺CD4⁺IL4⁺ cells in the infected mice were observed by flow cytometry, we found that a powerful T helper 1 (Th1) response was induced by M. vaccae infection, which was associated with the emergence of CD3⁺CD4⁺IFN-γ⁺ cells. However, the Th1 response declined over time, which was associated with appearance of the CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD25⁺CD152⁺Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that M. vaccae infection increased the production of type I IFNs, which was associated with a reduced Th1 response.
Animals ; Bacillus ; Bacteria ; Chemokine CCL2 ; Flow Cytometry ; Injections, Intraperitoneal ; Interferon-gamma ; Interleukin-10 ; Interleukin-12 ; Interleukins ; Lymph Nodes ; Mice* ; Mycobacterium bovis ; Mycobacterium* ; Pathology ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha