Objective:To explore the patterns of failure after postoperative intensity-modulated radiotherapy for gastric cancer.Methods:Clinical data of patients diagnosed with gastric cancer or gastroesophageal junction carcinoma with pathological stages T 3-4N 0 or T xN 1-3 admitted to Cancer Hospital of Chinese Academy of Medical Sciences from May 2009 to December 2018 were retrospectively analyzed. All patients received postoperative radiotherapy. During the follow-up, tumor recurrence was confirmed by imaging or endoscopic or pathological data, etc. According to the location of tumor recurrence, recurrence patterns were divided into local, regional and distant recurrence. Differences in recurrence patterns among different groups were compared using t-test and Chi-square test. Patient survival was assessed through Kaplan-Meier method. Results:A total of 76 patients were enrolled, with a median age of 49 years old (27-67 years old), 34 cases (45%) were classified as T 3 stage, 40 cases (53%) of T 4 stage, and 75 cases (99%) of N 1-3 stage, respectively. Seventy-three patients (92%) were classified as stage Ⅲ, and 38 patients (50%) underwent D2 dissection. The median follow-up time was 32.8 months (7.1-138.5 months). The median time of recurrence was 17.6 months (2.9-113.6 months). The median survival time after recurrence was 8.19 months (0.6-91.9 months). There were 13 cases (17%) of local recurrence, 6 cases (8%) of regional recurrence, and 72 cases (95%) of distant metastasis in patients. Peritoneal metastasis (33 cases, 43%) and distant lymph node metastasis (12 cases, 16%) were the main patterns of distant recurrence. Conclusions:By intensity-modulated radiotherapy technology, adjuvant radiotherapy yields favorable local and regional control for gastric cancer. Distant metastasis is still the main pattern of recurrence.

Objective:To analyze clinical efficacy of intensity-modulated chemoradiotherapy for patients with anal squamous cell carcinoma and identify prognostic factors.Methods:Clinical data of patients with anal squamous cell carcinoma who received intensity-modulated chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1, 2010 to January 1, 2022 were retrospectively analyzed. Regular follow-up was carried out. The main indexes included disease-free survival (DFS), locoregional failure-free survival (LRFFS) and overall survival (OS), and adverse reactions were recorded. The survival curve was delineated by Kaplan-Meier method and the influencing factors of survival were analyzed by Cox regression models.Results:A total of 65 patients were enrolled with 19 (29%) males and 46 (71%) females. According to the American Joint Committee on Cancer (AJCC) 7 th edition staging, there were 7 (11%), 28 (43%), 10 (15%), and 20 (31%) patients with stage I, II, IIIa, and IIIb, respectively. Before the chemoradiotherapy, 2 (3%) patients received chemotherapy and 12 (18%) patients received local resection. The median dose of radiotherapy was 54 Gy (range: 45-64 Gy) and the main concurrent chemotherapy regimen was capecitabine combined with cisplatin ( n=34, 52%). The completion rate of radiotherapy during concurrent chemoradiotherapy was 100%, and the chemotherapy completion rate was 88%. During the therapy, 5 patients (8%) were interrupted but completed concurrent chemoradiotherapy in full dose, and 8 patients (12%) reduced the dose of concurrent chemotherapy due to the toxicities. During the chemoradiotherapy, 15 cases (23%) experienced grade 3-4 leukopenia, and 17 cases (26%) experienced grade 3-4 radiation dermatitis. No treatment-related death occurred during the treatment. The median follow-up time was 50.4 months (range: 4.4-142.2 months), local recurrence occurred in 7 cases (11%), distant metastasis occurred in 3 cases (5%), and the 5-year DFS, LRFFS and OS rates were 78.8%, 86.5% and 85.1%, respectively. Cox univariate analysis indicated that T stage was significantly associated with DFS ( P=0.006), and tended to be associated with OS ( P=0.054). Conclusions:Intensity-modulated radiotherapy combined with concurrent chemotherapy is an effective treatment for anal squamous cell carcinoma, with tolerable acute toxicities. T stage is an influencing factor of DFS in anal squamous cell carcinoma patients.

Objective: To conduct a systematic review and meta-analysis of studies evaluating the oncological and fertility outcomes of early-stage endometrial cancer (EC) treated with the levonorgestrel-releasing intrauterine system (LIUS)-based regimens. Methods: The Meta-analyses Of Observational Studies in Epidemiology statement for meta-analyses was followed. Searches were conducted on MEDLINE, Embase, PubMed, Preprints, and the Cochrane Central Register of Controlled Trials from January 1990 to August 4, 2022. The Joanna Briggs Institute Critical Appraisal Checklist was used for quality assessment. The primary endpoint was the complete response (CR) rate and the secondary endpoints were relapse, pregnancy, and live birth rate. Results: A total of 25 studies (821 women) were included. The CR rate of LIUS-based regimens was 63.4% (95% confidence interval [CI]=52.3%–73.2%), with 29.6% (95% CI=23.3%–36.8%) of cases experiencing recurrence during follow-up. In sensitivity analyses, patients younger than 45 years of age with a body mass index <30 kg/m2 who were treated with LIUS-based regimens achieved a high CR rate of 84.6% (95% CI=80.3%–88.1%) over a median follow-up of more than 24 months. Overall pregnancy and live birth rates were 37.9% (95% CI=24.1%–53.9%) and 39.3% (95% CI=24.0%–57.0%), respectively. No statistical differences were apparent in CR or relapse rates among the LIUS+GnRH agonist, LIUS+oral progesterone, or hysteroscopic resection followed by LIUS subgroups. Conclusion LIUS-based therapies are viable for the conservative management of early-stage endometrioid EC on CR and fertility outcome.

The seventh article of Measures for the Ethical Review of Biomedical Research Involving Humans (2016) stipulated that medical and health institutions without an ethics committee shall not carry out biomedical research involving Humans. The Opinions on Strengthening the Governance of Ethics in Science and Technology, issued in March 2022, clearly stated that the institutions that do not meet the conditions for establishing a scientific and technological ethics (review) committee should entrust other institutions to conduct the review. The fourteenth article of Measures for Ethical Review of Life Science and Medical Research Involving Humans (2023) proposes that if an institution, which carries out life science and medical research involving humans, has not established an ethics committee or its ethics committee is not competent for ethics review, it can entrust a competent ethics committee or regional ethics committee in writing to carry out ethical review. Most medical institutions at or above the second level in China have set up ethics committees. While most universities and colleges, scientific research institutions, enterprises and grass-roots medical and health institutions have not set up ethics committees, which lack a working system to protect the safety and interests of the participants, and is difficult to conduct life sciences and medical research involving humans. At present, there is a need for some research institutions that do not have the conditions to establish ethics committees to entrust their projects of life science and medical research involving humans to other institutions for ethical review. The entrusted review is still in the exploratory stage, and there is no relevant specification. The hasty implementation of entrusted review may not achieve the goal of effectively protecting the safety and interests of the participants, and even cause legal disputes. Based on the thematic discussion, with reference to the relevant laws and regulations, departmental rules, ethical standards, and the experience of the ethics committees of some domestic institutions in implementing the entrusted review, the guideline was formulated for the reference of the current entrusted review to ensure the safety and interests of the participants.

AIM: To evaluate the effect of inhibiting ubiquitin-specific protease 14 (USPl4) activity on oxidative stress induced by H2O2 of H9c2 cells.METHODS: The H9c2 cells were incubated with H2O2 at 25 μmol/L for 2 h to establish the oxidative stress injury model.The cells were divided into control group, H2O2 group, IU1 group (25 μmol/L or 50 μmol/L) and IU1+ H2O2 group.The H9c2 cells activity was measured by MTS assay.The level of intracellular reactive oxygen species (ROS) and cell survival rate were analyzed by flow cytometry assay.The changes of the mitogen-activated protein kinase (MAPK) family related proteins were detected by Western blot.RESULTS: Compared with control group, the cell activity and the viability rate in H2O2 group were decreased (P<0.05), while the intracellular ROS, the protein levels of Bax/Bcl-2, P53, p-ERK1/2, p-JNK and p-P38 were increased (P<0.05).Compared with H2O2 group, the cell activity and the viability rate of the H9c2 cells in IU1+H2O2 group were increased (P<0.05), while the intracellular ROS, the protein levels of Bax/Bcl-2, P53, p-ERK1/2, p-JNK and p-P38 were decreased (P<0.05).CONCLUSION: Inhibition of USPl4 activity reduces the oxidative stress injury of the H9c2 cells.The mechanism may be related to inhibition of the MAPK signaling and down-regulation of apoptosis related proteins.

The use of human biological specimen has great significance to the development of biomedicine. Meanwhile, the powerful electronic data set with sophisticated analytic techniques creates challenge to the protec-tion of private information. As for the research with human biological specimen, how to facilitate the research con-duct on the basis of ethical principles is one of the key considerations when the US Department of Health and Hu-man Service initiated the revision of Code of Federal Regulations ( CFR) -theCommon Rule for subject protec-tion. The Notice of Proposed Rulemaking ( NPRM) proposed:Respect for autonomy will be enforced by broad con-sent to enforce and waiver of consent intend to be rare;If the research risks only involve privacy protection, review process will be simplified under the premise of ensuring the implementation of privacy laws and other protective measures. The paper introduced the revisions related to the researches using human biological specimen in NPRM, analyzed the terms of broad consent, exemption and exclusion, and explored the elicitation to ethical review prac-tice in China.

[ ABSTRACT] AIM:To investigate the effects of microRNA-378*( miR-378*) on the survival and apoptosis of human mesenchymal stem cells ( hMSCs ) .METHODS: The expression of miR-378* was determined by microRNA arrays and quantitative real-time PCR ( qRT-PCR) .H2 O2 was used to induce hMSCs apoptosis.By transfection of miR-378*mimic or inhibitor, we up-regulated or down-regulated miR-378* expression in hMSCs.The effect of miR-378*and connective tissue growth factor ( CTGF) on hMSC survival and apoptosis were detected by MTT, LDH, caspase-3/7 and TUNEL assays.RESULTS:The expression of miR-378*was up-regulated in the old hMSCs compared with the young hMSCs.H2 O2 increased the expression of miR-378*, decreased the expression of CTGF.Up-regulation of miR-378*re-sulted in increasing apoptosis and decreasing survival of hMSCs.Conversely, down-regulation of miR-378*resulted in de-creasing cell apoptosis and increasing survival.The regulation of miR-378*on hMSC apoptosis and survival was attenuated by inhibiting the expression of miR-378* and CTGF together.Direct repression of CTGF expression inhibited the hMSC survival and increased apoptosis.CONCLUSION:miR-378*enhances apoptosis of hMSCs by repressing the expression of CTGF.

From the point of view of ethics review work situation of our country, the existing capacity of our review of ethical problems in development are analyzed, a preliminary summary of the Chinese medicine ethics review ca-pacity development, systematically analyzes the Assessment Human Research Protection System of TCM and Chinese medicine clinical research ethics review platform evaluation work, and to improve the ethical review system to perfect supervision system, improve the medical ethics review standards and guidelines, carrying out the innovation and con-struction of ethical review professional knowledge training, to promote Chinese medicine ethics review certification and accreditation system construction work and Chinese medical ethics review of the clinical research objective, the practice of ethical review management of Chinese medicine are discussed.

In September 2012, the Assessment for Ethics Review of Traditional Chinese Medicine (TCM) Re-search with Human Participants (named CAP, Chinese medicine assessment human research protection system) was officially commissioned to the World Federation of Chinese Medicine Societies to organize by the State Ad-ministration of TCM. Through the assessment of 20 medical institutions, a comprehensive analysis on ethical re-view platform was conducted. Combined with current regulatory system of ethics in the U.S., this article discussed independent assessment on important CAP features of local brands, the practice and benefit of construction pro-motion based on assessment and continuous improvement, as well as the importance of vigorously promote CAP assessment .

Objective To summarize the experience of establishing the stable rat model of chronic allograft nephropathy. Methods We used Fisher rats as donors and Lewis rats as recipients.After the left kidney of the donor perfused in situ under hypothermic condition, the left renal vein,abdominal aorta and bladder flap of the donor was anastomosed with the left renal vein, renal artery and bladder of the recipient, respectively. The recipients were given cyclosporin oral solution 10 mg/kg every day by gavage for 10 days after transplantation. The blood and urine samples were collected 1 month, 2 months and 4 months after transplantation and renal function and total urine protein were examined. The pathological changes of the renal allograft were observed 2 and 4 months after transplantation. Results Forty-five rats received operation and achievement ratio was 85%. The renal transplantations were finished in 120 ± 20 min. The Scr, BUN, Cycs and total urine protein demonstrated a significant increase one month after transplantation. On the second and fourth month,with the exception of urine protein continued to increase, the other indicators did not change significantly. Two months after transplantation renal pathology demonstrated light to moderate interstitial fibrosis, infiltration of lymphocytes and plasma cells. At 4th month the renal allografts showed extensive interstitial fibrosis, a large number of infiltrating interstitial cells, thickening,hardening, occlusion of glomerular basement membrane, and renal tubular atrophy that were consistent with pathological changes of chronic allograft nephropathy. Conclusion Through adequate surgical training and improvement, and specification for rat nephrectomy, transplantation surgery,and postoperative management in every detail, the model with high success rate and stability can be achieved.