Oxidative stress is an important pathophysiological pathway for the development and progression of ferroptosis. Under pathological conditions, the production of a large amount of reactive oxygen species （ROS） exceeds the buffering capacity of the antioxidant defense system, resulting in lipid peroxidation and cell ferroptosis in the state of oxidative stress. Cellular lipid peroxidation can generate toxic aldehydes, which interact with important biological macromolecules and break the normal function of cells. At present, it has been found that aldehyde dehydrogenase 2 （ALDH2） can eliminate these aldehydes and regulate the cycle of toxic aldehydes-ROS-oxidative stress-lipid peroxidation, thereby improving the prognosis of diseases associated with iron death. Ferroptosis and ALDH2 were introduced, and the current researches on ALDH2 were summarized to improve diseases associated with iron death, which can open up new directions for the subsequent research on the treatment of diseases associated with iron death.

Accurate prediction of drug responses in cancer cell lines(CCLs)and transferable prediction of clinical drug responses using CCLs are two major tasks in personalized medicine.Despite the rapid advancements in existing computational methods for preclinical and clinical cancer drug response(CDR)prediction,chal-lenges remain regarding the generalization of new drugs that are unseen in the training set.Herein,we propose a multimodal fusion deep learning(DL)model called drug-target and single-cell language based CDR(DTLCDR)to predict preclinical and clinical CDRs.The model integrates chemical descriptors,mo-lecular graph representations,predicted protein target profiles of drugs,and cell line expression profiles with general knowledge from single cells.Among these features,a well-trained drug-target interaction(DTI)prediction model is used to generate target profiles of drugs,and a pretrained single-cell language model is integrated to provide general genomic knowledge.Comparison experiments on the cell line drug sensitivity dataset demonstrated that DTLCDR exhibited improved generalizability and robustness in predicting unseen drugs compared with previous state-of-the-art baseline methods.Further ablation studies verified the effectiveness of each component of our model,highlighting the significant contribution of target information to generalizability.Subsequently,the ability of DTLCDR to predict novel molecules was validated through in vitro cell experiments,demonstrating its potential for real-world applications.Moreover,DTLCDR was transferred to the clinical datasets,demonstrating satisfactory performance in the clinical data,regardless of whether the drugs were included in the cell line dataset.Overall,our results suggest that the DTLCDR is a promising tool for personalized drug discovery.

Accurate prediction of drug responses in cancer cell lines (CCLs) and transferable prediction of clinical drug responses using CCLs are two major tasks in personalized medicine. Despite the rapid advancements in existing computational methods for preclinical and clinical cancer drug response (CDR) prediction, challenges remain regarding the generalization of new drugs that are unseen in the training set. Herein, we propose a multimodal fusion deep learning (DL) model called drug-target and single-cell language based CDR (DTLCDR) to predict preclinical and clinical CDRs. The model integrates chemical descriptors, molecular graph representations, predicted protein target profiles of drugs, and cell line expression profiles with general knowledge from single cells. Among these features, a well-trained drug-target interaction (DTI) prediction model is used to generate target profiles of drugs, and a pretrained single-cell language model is integrated to provide general genomic knowledge. Comparison experiments on the cell line drug sensitivity dataset demonstrated that DTLCDR exhibited improved generalizability and robustness in predicting unseen drugs compared with previous state-of-the-art baseline methods. Further ablation studies verified the effectiveness of each component of our model, highlighting the significant contribution of target information to generalizability. Subsequently, the ability of DTLCDR to predict novel molecules was validated through in vitro cell experiments, demonstrating its potential for real-world applications. Moreover, DTLCDR was transferred to the clinical datasets, demonstrating satisfactory performance in the clinical data, regardless of whether the drugs were included in the cell line dataset. Overall, our results suggest that the DTLCDR is a promising tool for personalized drug discovery.

Objective To observe the value of the ratio of cerebral hyperdensities(PCHD)/venous sinus maximum density for predicting hemorrhagic transformation(HT)after endovascular treatment(EVT)in patients with acute ischemic stroke(AIS).Methods Data of 79 AIS patients with PCHD immediately after EVT were retrospectively analyzed.The patients were divided into HT group(n=41)or non-HT group(n=38)based on the presence of HT or not.Clinical data and CT parameters were compared between groups.The value of the ratio of PCHD/venous sinus maximum density for predicting HT was evaluated.Results The maximum density of PCHD and the ratio of PCHD/venous sinus maximum density in HT group were both higher than those in non-HT group(both P＜0.001).Taken 87 HU as the best cut-off value of the maximum density of PCHD,the sensitivity,specificity and area under the curve(AUC)for predicting HT after EVT in AIS patients was 90.24%,71.05%and 0.79,respectively.Taken 0.94 as the best cut-off value of the ratio of PCHD/venous sinus maximum density,the sensitivity,specificity and AUC was 97.56%,71.05%and 0.81,respectively.No significant difference of AUC was found between the former and the latter(P＞0.05).Conclusion The ratio of PCHD/venous sinus maximum density immediately after EVT could be used to predict HT in AIS patients.

AIM:To explore the expression level of vitamin D receptor(VDR)in lung adenocarcinoma and its impact on the biological function of lung adenocarcinoma cells.METHODS:The mRNA expression level of VDR in lung adenocarcinoma and its relationship with prognosis were analyzed through 6 lung adenocarcinoma datasets(compris-ing a total of 792 lung adenocarcinoma tissues and 230 adjacent non-tumor tissues).Immunohistochemistry was used to de-tect VDR protein expression in 30 lung cancer patients.Lung adenocarcinoma cell lines A549 and H1650 were studied,with transfection of negative control(NC)or two VDR short hairpin RNAs(VDR-shRNAs).CCK-8 assay compared the cell viability of cells in each experimental group.Transwell and wound-healing assays compared the invasion and migra-tion capabilities.Gene set enrichment analysis identified pathways enriched in lung adenocarcinoma tissues with high VDR expression.RESULTS:The mRNA expression level of VDR was significantly increased in lung adenocarcinoma tissues(P<0.01).Immunohistochemistry further confirmed the high expression of VDR in lung adenocarcinoma(P<0.01).The survival analysis showed that the expression of VDR had no significant effect on the overall survival of lung ad-enocarcinoma patients(P>0.05).Knockdown of VDR significantly inhibited the cell viability,invasion,and migration ca-pacity of lung adenocarcinoma cells(P<0.05).Gene set enrichment analysis showed that lung adenocarcinoma tissues with high VDR expression were enriched in signaling pathways such as epithelial-mesenchymal transition(P<0.05).CONCLUSION:VDR is highly expressed in lung adenocarcinoma,and VDR knockdown can inhibit the cell viability,in-vasion,and migration capacity of lung adenocarcinoma cells.

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection(ESD) for early hypopharyngeal carcinoma and precancerous lesions.Methods:Data of 23 patients with early hypopharyngeal carcinoma and precancerous lesions who underwent ESD in Sichuan Cancer Hospital from December 2015 to May 2019 were analyzed.Results:A total of 23 patients with 30 lesions were enrolled in the study. All patients were male, with mean age of 60.3 years (ranged 47-72). Of the 23 patients, 13 had synchronous esophageal cancer, 3 had metachronous esophageal cancer, and 7 high-grade intraepithelial neoplasia(HGIN) of the esophagus. The mean procedure time was 74 minutes. The en bloc resection rate was 100%. Pathological results revealed that 21 lesions were HGIN, 8 lesions were intramucosal carcinoma and 1 lesion had tumor invasion of the submucosa. Two patients had positive horizontal margin and 1 patient had positive vertical margin. The curative resection rate was 90%. No bleeding, perforation or dyspnea occurred during or after ESD.Conclusions:ESD is safe and effective for early hypopharyngeal cancer and precancerous lesions.

Objective: To evaluate the feasibility, safety and clinical value of endonasopharyngeal ultrasound-guided transnasopharyngeal needle aspiration (ENUS-TNNA) in the diagnosis of submucosal nasopharyngeal carcinoma. Methods: Clinical data of 9 patients from Sichuan Cancer Hospital with submucosal nasopharyngeal carcinoma undergoing ENUS-TNNA between December 2013 and January 2018 were retrospectively analyzed. The feasibility and safety were analyed. All 9 patients were all males with a mean age of (49.2±10.9) years. Results: Needle puncture biopsies were successfully performed in all cases, and sufficient tissue sample for histopathological examination was obtained from each of the 9 patients. No major bleeding or persistent bleeding occurred during and after puncture procedures. There were 5 patients with undifferentiated nonkeratinizing carcinoma and 4 patients poorly differentiated carcinoma. Conclusion ENUS-TNNA is a safe, feasible and effective technique to provide a diagnosis of submucosal growth type of nasopharyngeal neoplasms, which has some clinical value.

OBJECTIVETo explore the role of TNFα induced protein 3 interacting protein 1 (TNIP1) in the pathogenesis of myasthenia gravis (MG) among patients with thymoma.

METHODSFrom December 2014 to March 2015, 11 patients with MG associated thymoma (MGT) and 11 non-MG thymoma (NMGT) patients receiving thymectomy were selected. Thymus specimens were obtained during surgery, and peripheral venous blood samples were obtained before the surgery. For the MGT cohorts, peripheral venous blood samples were also collected at 3-6 months after the surgery. TNIP1 mRNA was determined with quantitative real-time PCR (qPCR), and its protein expression was evaluated by Western blotting.

RESULTSFor both thymus specimen and peripheral blood samples, the levels of TNIP1 mRNA and protein in the MGT group were both significantly lower than those of the NMGT patients (P<0.05). For the MGT group, the levels of TNIP1 mRNA and protein of the peripheral blood samples have increased following thymus resection compared with before the surgery.

CONCLUSIONReduced TNIP1 expression may have a role in the pathogenesis of MG for patients with thymoma. Thymectomy may help to recover the expression of TNIP1 among such patients.

Blotting, Western ; DNA-Binding Proteins ; genetics ; metabolism ; Female ; Gene Expression ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Myasthenia Gravis ; complications ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Thymectomy ; Thymoma ; complications ; surgery ; Thymus Neoplasms ; complications ; surgery

OBJECTIVETo investigate the clinical efficacy and learning curve of thoracoscopic and laparoscopic esophagectomy(TLE) in the treatment of esophageal carcinoma.

METHODSClinical data of 350 consecutive patients with esophageal carcinoma undergoing TLE in the West China Hospital between February 2008 and October 2013 were retrospectively analyzed. Patients in the early stage(n=150) were chronologically and evenly divided into three groups, and perioperative outcomes were compared between the three groups in order to evaluate the learning curve.

RESULTSThere were no intraoperative deaths. Intraoperative complications occurred in 29(8.3%) patients. Thirteen(3.7%) cases were converted to open operation including 9 thoracotomy and 4 laparotomy. The mean operative time was 332.5(range 230-780) min and the mean blood loss was 160.8(range 15-4000) ml. The tumor free resection margins (R0) were completely in 333(95.1%) cases. The mean lymph nodes harvested was 21.6(range 6-42). The average length of postoperative hospital stay was 11.6(range 7-93) d. Postoperative complications occurred in 75(21.4%) patients, and 3(0.8%) patients died within 30 days after surgery. Compared with TLE 1 group, TLE 2 group presented shorter operative time, less blood loss, shorter postoperative hospital stay, lower postoperative complication rate, and more lymph nodes harvested(all P<0.05). Only blood loss was less in TLE 3 group as compared to TLE 2 group, and other perioperative results were found to be of no statistical differences between the two groups. There was no significant difference in 30-day mortality between the three groups.

CONCLUSIONSTLE is a technically feasible and safe procedure and provides comparable oncological outcomes with open esophagectomy, thus suggesting that TLE is an alternative approach in the treatment of esophageal carcinoma. A plateau of TLE skill can be reached after 50 surgical procedures.

China ; Esophageal Neoplasms ; Esophagectomy ; Humans ; Laparoscopy ; Length of Stay ; Lymph Node Excision ; Lymph Nodes ; Operative Time ; Postoperative Complications ; Retrospective Studies