Artificial intelligence aided precise detection of local recurrence on MRI for nasopharyngeal carcinoma: a multicenter cohort study.

Background: MRI is the routine examination to surveil the recurrence of nasopharyngeal carcinoma, but it has relatively lower sensitivity than PET/CT. We aimed to find if artificial intelligence (AI) could be competent pre-inspector for MRI radiologists and whether AI-aided MRI could perform better or even equal to PET/CT. Methods: This multicenter study enrolled 6916 patients from five hospitals between September 2009 and October 2020. A 2.5D convolutional neural network diagnostic model and a nnU-Net contouring model were developed in the training and test cohorts and used to independently predict and visualize the recurrence of patients in the internal and external validation cohorts. We evaluated the area under the ROC curve (AUC) of AI and compared AI with MRI and PET/CT in sensitivity and specificity using the McNemar test. The prospective cohort was randomized into the AI and non-AI groups, and their sensitivity and specificity were compared using the Chi-square test. Findings: The AI model achieved AUCs of 0.92 and 0.88 in the internal and external validation cohorts, corresponding to the sensitivity of 79.5% and 74.3% and specificity of 91.0% and 92.8%. It had comparable sensitivity to MRI (e.g., 74.3% vs. 74.7%, P = 0.89) but lower sensitivity than PET/CT (77.9% vs. 92.0%, P < 0.0001) at the same individual-specificities. The AI model achieved moderate precision with a median dice similarity coefficient of 0.67. AI-aided MRI improved specificity (92.5% vs. 85.0%, P = 0.034), equaled PET/CT in the internal validation subcohort, and increased sensitivity (81.9% vs. 70.8%, P = 0.021) in the external validation subcohort. In the prospective cohort of 1248 patients, the AI group had higher sensitivity than the non-AI group (78.6% vs. 67.3%, P = 0.23), albeit nonsignificant. In future randomized controlled trials, a sample size of 3943 patients in each arm would be required to demonstrate the statistically significant difference. Interpretation: The AI model equaled MRI by expert radiologists, and AI-aided MRI by expert radiologists equaled PET/CT. A larger randomized controlled trial is warranted to demonstrate the AI's benefit sufficiently. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), and Guangzhou Science and Technology Program (2023A04J1788).

Deep learning-based precise prediction and early detection of radiation-induced temporal lobe injury for nasopharyngeal carcinoma.

Background: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. Methods: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3-5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. Findings: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P < 0.001). The temporal lobes in all the cohorts were stratified into three groups with discrepant TLI-free survival. Personalized follow-up schedules developed for each risk group could detect TLI 1.9 months earlier than the RTOG recommendation. According to a higher median predicted 3-year TLI-free survival (99.25% vs. 99.15%, P < 0.001), the model identified a better plan than previous models. Interpretation: The deep learning model predicted TLI more precisely. The model-determined risk-based follow-up schedule detected the TLI earlier. The planning evaluation was refined because the model identified a better plan with a lower risk of TLI. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), Medical Scientific Research Foundation of Guangdong Province (A2022367), and Guangzhou Science and Technology Program (2023A04J1788).

[Identification of active components of Dendrobium inhibit growth of gastric cancer cells based on component-activity relationship].

Three cancer cell lines including gastric cancer SGC-7901, HGC-27, and MGC-803 cells were employed to evaluate the bioactivity of seven Dendrobium species. Simultaneously, these Dendrobium species were assessed with UPLC-Q-TOF-MS, and 504 common peaks were found. Based on the hypothesis that biological effects varied with differences in components, multivariate relevance analysis for chemical component-activity relationship of Dendrobium, including grey relation(GRA) and partial least squares(PLS) analysis were performed to evaluate the contribution of each identified component. The target peaks were identified by standards toge-ther with databases of Dendrobium, Nature Chemistry, MassBank, etc. Finally, four active components, including 3,5,9-trihydroxy-23-methylergosta-7,22-dien-6-one, diacylglycerol(14∶1/22∶6/0∶0), pipercitine, and 22-tricosenoic acid, might have negative effect on the growth of gastric cancer cells.

Effect of Induction Chemotherapy in Nasopharyngeal Carcinoma: An Updated Meta-Analysis.

BACKGROUND: Previous meta-analysis had evaluated the effect of induction chemotherapy in nasopharyngeal carcinoma. But two trials with opposite findings were not included and the long-term result of another trial significantly differed from the preliminary report. This updated meta-analysis was thus warranted. METHODS: Literature search was conducted to identify randomized controlled trials focusing on the additional efficacy of induction chemotherapy in nasopharyngeal carcinoma. Trial-level pooled analysis of hazard ratio (HR) for progression free survival and overall survival and risk ratio (RR) for locoregional control rate and distant control rate were performed. RESULTS: Twelve trials were eligible. The addition of induction chemotherapy significantly prolonged both progression free survival (HR=0.68, 95% confidence interval [CI] 0.60-0.76, p<0.001) and overall survival (HR=0.67, 95% CI 0.54-0.80, p<0.001), with 5-year absolute benefit of 11.31% and 8.95%, respectively. Locoregional (RR=0.80, 95% CI 0.70-0.92, p=0.002) and distant control (RR=0.70, 95% CI 0.62-0.80) rates were significantly improved as well. The incidence of grade 3-4 adverse events during the concurrent chemoradiotherapy was higher in leukopenia (p=0.028), thrombocytopenia (p<0.001), and fatigue (p=0.038) in the induction chemotherapy group. CONCLUSIONS: This meta-analysis supported that induction chemotherapy could benefit patients with nasopharyngeal carcinoma in progression free survival, overall survival, locoregional, and distant control rate.

Enhancement of epithelial cell autophagy induced by sinensetin alleviates epithelial barrier dysfunction in colitis.

Intestinal epithelial barrier dysfunction is a key pathology of colitis. Autophagy of epithelial cells maintains homeostasis of the intestinal barrier by inhibiting apoptosis and stimulating degradation of the tight junction protein claudin-2. This study investigated the effects and mechanism of activity of sinensetin, a polymethylated flavonoid isolated from tangerine peel and citrus, on intestinal barrier dysfunction in colitis. Animal model of colitis were established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid and oral treatment with dextran sulfate sodium. Epithelial barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in Caco-2 cells, respectively. Epithelial cell autophagy assayed by autophagosome formation and expression of autophagy-related protein. Sinensetin reversed colitis-associated increase in intestinal permeability, significantly promoted epithelial cell autophagy, and further decreased epithelial cell apoptosis, and reduced mucosal claudin-2. Sinenstetin alleviated colitis symptoms rats and mice with colitis. Knockdown of 5' adenosine monophosphate-activated protein kinase (AMPK) reversed the promotion of epithelial autophagy by sinensetin. In conclusion, sinensetin significantly alleviated intestinal barrier dysfunction in colitis by promoting epithelial cell autophagy, and further inhibiting apoptosis and promoting claudin-2 degradation. The results highlighted novel potential benefits of sinensetin in colitis.

Diversity of culture-independent bacteria and antimicrobial activity of culturable endophytic bacteria isolated from different Dendrobium stems.

Dendrobium is known for its pharmacological actions including anti-cancer effect, anti-fatigue effect, gastric ulcer protective effect, and so on. At present, only studies on endophytic fungi of Dendrobium affecting the metabolites of host plants have been reported, very little research has been done on endophytic bacteria. In this study, we have demonstrated the great diversity of endophytic bacteria in 6 Dendrobium samples from different origins and cultivars. According to the results of the culture-independent method, the endophytic bacterial community in Dendrobium stems showed obvious different in the 6 samples and was influenced by origin and cultivar. Some bacteria including Ralstonia, Comamonas and Lelliottia were first detected in Dendrobium in this study. Based on the culture-dependent method, a total of 165 cultivable endophytic bacteria isolates were isolated from the sterilized Dendrobium stems, and were classified into 43 species according to the 16S rRNA gene sequence analysis. Moreover, 14 of the 43 strains showed antimicrobial activity against phytopathogen using the Kirby-Bauer method. Strain NA-HTong-7 (Bacillus megaterium, 99.12%) showed the highest antimicrobial activity. This study was the first comprehensive study on endophytic bacteria of Dendrobium from different origins and cultivars, which provides new insights into the endophytic bacteria from Dendrobium.

Change of the peripheral blood immune pattern and its correlation with prognosis in patients with liver cancer treated by sorafenib.

OBJECTIVE: To study the change of the peripheral blood immune pattern and its correlation with prognosis in patients with liver cancer after treated by sorafenib. METHODS: Patients with advanced liver cancer admitted in our hospital were enrolled and treated with sorafenib. After two months of the treatment, their peripheral blood was collected. The immune cell subset and cytokines level were determined by flow cytometry and luminex technology. According to the reaction expressed by patients towards sorafenib, patients were divided into the response group and the no response group. The changes of the peripheral blood immune pattern and its correlation with prognosis of patients in the two groups were compared. RESULTS: Before and after treatment of sorafenib, there was no significant difference in the ratios of T cells, NK cells and their subtypes in peripheral blood of patients between the two groups; while after treatment the ratio of B cells and regulatory B cells (Breg) of patients in the response group was significant higher than that of the no response group (P < 0.05), and the prognosis conditions of patients with decreased ratio of Breg cells were better than other patients after undergoing chemotherapy. The levels of plasma cytokines IL-6, IL-10, IL-12, IL17, FIL-3L, IFN-γ, TNF-α, MCP-1 and VEGF showed no significant differences. CONCLUSIONS: After treatment of sorafenib, the prognosis conditions of patients of advanced liver cancer with a reduced Breg ratio are better than patients with an unaltered or increased Breg ratio. The ratio of Breg in peripheral blood may be considered as early biological indicator for the prediction of the curative effects of sorafenib.

Modulation of staurosporine-activated volume-sensitive outwardly rectifying Cl⁻ channel by PI3K/Akt in cardiomyocytes.

Chloride (Cl⁻) channels participate in the regulation of cardiac function in response to stress although the underlying regulatory mechanism remains poorly understood. This study was designed to examine the impact of the pro-apoptotic stimulus staurosporine (STS) on the volume-sensitive outwardly rectifying Cl⁻ current (I(Cl,Vol)) in cardiomyocytes and possible regulatory mechanism involved with a focus on phosphatidylinositol-3 kinase (PI3K)/Akt. Primary cultured rat neonatal cardiomyocytes were subjected to hypotonic and isotonic environment in the presence or absence of STS prior to whole-cell voltage-clamp evaluation of Cl⁻ current. Whole-cell recordings revealed that STS activated an outwardly rectifying Cl⁻ current with phenotypic properties reminiscent of I(Cl,Vol). These currents were outwardly rectifying with a time-dependent inactivation at positive potentials and were sensitive to 4,4'-diisothiocya-natostilbene- 2,2'- disulfonicacid (DIDS), a non-selective Cl⁻ channel blocker, and 4-(2-butyl-6,7-dichlor-2-cyclopentyl-indan-1-on-5-yl)oxybutyric acid (DCPIB), a selective VSOR Cl⁻ channel blocker. DIDS and DCPIB inhibited I(Cl,Vol) by 92.6% ± 7.3% and 78.4% ± 5.5%, respectively. Our data further revealed that the PI3K inhibitor LY294002 facilitated the current with the peak amplitude of 19.54 ± 2.70 pA/pF. To the contrary, insulin partially inhibited the current amplitude with the peak current amplitude of 15.4 ± 2.13 pA/pF. Taken together, our data depicted staurosporine is capable of activating I(Cl,Vol) channel in cardiomyocytes via possibly a PI3K/Akt-dependent mechanism.