The endophytic fungus named FSN006 was isolated from the inner bark of Juglans mandshurica. It grew quickly and formed circular colony on PDA plate. The upper side of the colony was white, while the lower side of the colony and the conditioned medium were light yellow as a result of significant yellow pigment substances were produced and secreted by the fungi. Green elliptic conidia appeared when cultured on CMX plate. Based on the morphology identification and ITS sequence, it was clear that this fungus belonged to the Deuteromycotina, HyPhomycetes, Moniliales, Trichoderma longibrachiatum. The conditioned medium of FSN006 showed a high anti-tumor ability against liver cancer cell-HepG2, and reached its IC50 concentration after being diluted 20 times, while the IC50 concentration of curcumine was(11.49 +/- 0.12) mg x L(-1). In addition, there was preeminent selective inhibiting effect against the normal liver cell strain HL-7702 and its caner counter strain HepG2. The inhibiting effect against strain HL-7702 was only one quarter of that against HepG2 at the concentration of IC50. Therefore, the fermentation of FSN006 may provide a possible way to produce anticancer drug with higher efficiency and lower toxicity.
Antineoplastic Agents ; chemistry ; isolation & purification ; metabolism ; pharmacology ; Biological Factors ; chemistry ; isolation & purification ; metabolism ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Juglans ; microbiology ; Plant Bark ; microbiology ; Trichoderma ; chemistry ; genetics ; isolation & purification ; metabolism

Objective:To investigate the influencing factors for lymph node metastasis and prognosis in stage T1 and T2 esophageal squamous cell carcinoma after radical surgery and construct nomogram prediction models.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 672 patients with T1 and T2 esophageal squamous cell carcinoma who were admitted to the Affiliated Hospital of North Sichuan Medical College from January 2014 to December 2019 were collected. There were 464 males and 208 females, aged (65±8)years. All patients under-went radical esophagectomy+2 or 3 field lymph node dissection. Observation indicators: (1) lymph node dissection, metastasis and follow-up. (2) risk factors for lymph node metastasis of esophageal cancer after radical resection. (3) prognostic factors of esophageal cancer after radical resection. (4) construction and evaluation of the prediction models of lymph node metastasis and prognosis of esophageal cancer after radical resection. Follow-up was conducted using outpatient examination, telephone and internet consultations to detect survival of patients up to April 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to calculate survival rate and draw survival curve. Log-Rank test was used for survival analysis. Logistic regression model was used for univariate and multivariate analyses of risk for lymph node metastasis, and COX regression model was used for univariate and multivariate analyses of prognosis. Based on the results of multi-variate analysis, the nomogram prediction models for lymph node metastasis and prognosis predic-tion were constructed. The prediction discrimination of the nomogram models were evaluated using the area under curve (AUC) of the receiver operating characteristic curve (ROC). The calibration curve was used to evaluate the prediction consistency of the models. Results:(1) Lymph node dissection, metastasis and follow-up. The number of lymph node dissected was 14±8 and the number of lymph node metastasis was 2(range, 1?19) in 672 patients. Of the 672 patients, there were 182 cases had lymph node metastasis, including 58 cases in T1 stage and 124 cases in T2 stage. All 672 patients were followed up for 38 (range, 1?85)months. The average overall survival time of 672 patients was 65 months, with the 1-, 3-, 5-year overall survival rate as 89.0%, 74.3%, 66.0%, respectively. The average overall survival time of 325 patients in T1 stage and 347 patients in T2 stage were 70 months and 61 months. The 1-, 3-, 5-year overall survival rate of 325 patients in T1 stage and 347 patients in T2 stage were 95.0%, 83.5%, 73.4% and 87.4%, 69.9%, 59.2%, respectively, showing a significant difference in survival between them ( χ2=14.51, P<0.05). (2) Risk factors for lymph node metastasis of esophageal cancer after radical resection. Results of univariate analysis showed that tumor location, tumor histological grade, tumor T staging were related factors affecting lymph node metastasis of esophageal cancer after radical resection ( odds ratio=1.40, 1.54, 2.56, 95% confidence interval as 1.07?1.85, 1.20?1.99, 1.79-3.67, P<0.05). Results of multivariate analysis showed that tumor location, tumor histological grade, tumor T staging were independent factors affecting lymph node metastasis ( odds ratio=1.42, 1.61, 2.63, 95% confidence interval as 1.07?1.89, 1.25?2.09, 1.82?3.78, P<0.05). (3) Prognostic factors of esophageal cancer after radical resection. Results of univariate analysis showed that preoperative comorbidities, postoperative complications, tumor histological grade (G3), tumor T staging, tumor N staging (N1 stage, N2 stage, N3 stage), tumor TNM staging (Ⅲ stage, Ⅳ stage) were related factors affecting prognosis of esophageal cancer after radical resection ( hazard ratio= 1.48, 1.64, 2.23, 1.85, 2.09, 4.48, 4.97, 3.54, 5.53, 95% confidence interval as 1.08?2.03, 1.20?2.23, 1.47?3.39, 1.34?2.54, 1.44?3.04, 2.89?6.95, 1.57?15.73, 2.48?5.05, 1.73?17.68, P<0.05). Results of multivariate analysis showed that preoperative comorbidities, G3 of tumor histological grade, T2 stage of tumor T staging, N1 stage, N2 stage, N3 stage of tumor N staging were independent risk factors affecting prognosis of esophageal cancer after radical resection ( hazard ratio=1.57, 1.89, 1.63, 1.71, 3.72, 3.90, 95% confidence interval as 1.14?2.16, 1.23?2.91, 1.17?2.26, 1.16?2.51, 2.37?5.83, 1.22?12.45, P<0.05). (4) Construction and evaluation of the prediction models of lymph node metastasis and prognosis of esophageal cancer after radical resection. Based on the results of multivariate analysis, tumor location, tumor histological grade, tumor T staging were applied to construct a nomo-gram model for lymph node metastasis prediction of esophageal cancer after radical resection, the score of tumor location, tumor histological grade, tumor T staging were 82, 100, 100, respectively, and the sum of the scores corresponding to the lymph node metastasis rate. Preoperative comor-bidity, tumor histological grade, tumor T staging, tumor N staging were applied to construct a nomo-gram model for 1-, 3-, 5-year overall survival rate prediction of esophageal cancer after radical resection, the score of preoperative comorbidity, tumor histological grade, tumor T staging, tumor N staging were 23, 38, 27, 100, respectively, and the sum of the scores corres-ponding to the 1-, 3-, 5-year overall survival rate. Results of ROC showed that the AUC of nomogram model for lymph node metastasis prediction after radical esophagectomy was 0.66 (95% confidence interval as 0.62?0.71, P<0.05). The AUC of nomogram model for 1-, 3-, 5-year overall survival rate prediction after radical esophagectomy were 0.73, 0.74, 0.71 (95% confidence intervals as 0.66?0.80, 0.68?0.79, 0.65?0.78, P<0.05). Results of calibration curve showed that the predicted lymph node metastasis rate and the predicted 1-, 3-, 5-year overall survival rate by nomogram models were consistent with the actual lymph node metastasis rate and 1-, 3-, 5-year overall survival rate. Conclusions:Tumor location, tumor histological grade, tumor T staging are independent factors affecting lymph node metastasis in T1 and T2 esophageal squamous cell carcinoma after radical surgery and nomogram model constructed by these indicators can predict the lymph node metas-tasis rate. Preoperative comor-bidities, G3 of tumor histological grade, T2 stage of tumor T staging, N1 stage, N2 stage, N3 stage of tumor N staging are independent risk factors affecting prognosis and nomogram model constructed by these indicators can predict the overall survival rate of patients after surgery.

The Regulations on Donation and Transplantation of Human Organs were issued on December 14， 2023. It was interpreted in terms of improving the human organ donation system and clarifying the responsibilities of the Red Cross Society； adding a new system for the acquisition and distribution of human organs， emphasizing the independence of the organ acquisition department， and implementing the priority right of organ distribution； strengthening the management of human organ transplantation， strictly limiting the scope of recipients of living organ transplantation； and regulating the operation of the ethics committee for human organ transplantation and stepping up the crackdown on violations of the regulations. This paper then considered how to implement and improve incentives for human organ donation， including the implementation of the priority rights of organ donors and their close relatives， the improvement of the organ donation compensation system， and the establishment of a humanitarian assistance system； the implementation of a system for the acquisition and distribution of organ donation organization； the acceleration of the construction of the personnel team of the organ acquisition organization； the increase of efforts to advocate and mobilise； and the enhancement of the construction of the ethics committee for human organ transplantation. The Regulations on Donation and Transplantation of Human Organs help to give fuller play to the enthusiasm and creativity in the field of organ transplantation， and all departments should revise the systems and administrative rules relating to human organ donation and transplantation in time， so as to facilitate the work of donation and transplantation of human organ.

Decentralized clinical trials （DCT） are bringing new changes to clinical trials， the core concept of “patient-centered” must be adhered， and the safety and rights of research participants must be adequately safeguarded. Although DCTs have similarities with traditional clinical trials， they are not suitable for all clinical trials， and are more suitable for oral administration， stable condition of study participants， and longer duration of treatment in clinical trials. DCT， elements must be selected based on the characteristics of clinical trials， and strike a balance between improving the sense of gain， safety， and rights and dignity of research participants， as well as the quality of data collected. Currently， DCT in China face many challenges. To actively promote DCTs in China， regulatory regulations and guiding principles should be improved. Based on patient-centered design principles， the first discussion requires real-time online communication. Researchers should provide more clinical trial services， improve risk control and accessibility of medical assistance， use third-party convenient payments， ensure fair recruitment of research participants， consider compliance， validate digital health technology， remote monitoring and electronic informed consent compliance， ensure the security of data collection， transmission， and analysis， as well as strengthen multi-party training. Ethical review is one of the important means to protect the safety and rights of research participants. Ethics committees should focus on appropriate DCTs elements that are patient-centered， compliance and effectiveness of electronic informed consent， processing and reporting of security information， privacy protection of data collection， compliance of remote monitoring， family health follow-up， management of biological samples and experimental medical products， and training programs. The author believed that the complementarity and combination with traditional clinical trials will make DCTs elements implemented more easily and smoothly. By leveraging the power of scientific and technological advances， DCTs will boost the speed of China’s drug and medical device research and development， enhance international competitiveness， and benefit more patients.