Single-cell profiling of response to neoadjuvant chemo-immunotherapy in surgically resectable esophageal squamous cell carcinoma.

BACKGROUND: The efficacy of neoadjuvant chemo-immunotherapy (NAT) in esophageal squamous cell carcinoma (ESCC) is challenged by the intricate interplay within the tumor microenvironment (TME). Unveiling the immune landscape of ESCC in the context of NAT could shed light on heterogeneity and optimize therapeutic strategies for patients. METHODS: We analyzed single cells from 22 baseline and 24 post-NAT treatment samples of stage II/III ESCC patients to explore the association between the immune landscape and pathological response to neoadjuvant anti-PD-1 combination therapy, including pathological complete response (pCR), major pathological response (MPR), and incomplete pathological response (IPR). RESULTS: Single-cell profiling identified 14 major cell subsets of cancer, immune, and stromal cells. Trajectory analysis unveiled an interesting link between cancer cell differentiation and pathological response to NAT. ESCC tumors enriched with less differentiated cancer cells exhibited a potentially favorable pathological response to NAT, while tumors enriched with clusters of more differentiated cancer cells may resist treatment. Deconvolution of transcriptomes in pre-treatment tumors identified gene signatures in response to NAT contributed by specific immune cell populations. Upregulated genes associated with better pathological responses in CD8 + effector T cells primarily involved interferon-gamma (IFNγ) signaling, neutrophil degranulation, and negative regulation of the T cell apoptotic process, whereas downregulated genes were dominated by those in the immune response-activating cell surface receptor signaling pathway. Natural killer cells in pre-treatment tumors from pCR patients showed a similar upregulation of gene expression in response to IFNγ but a downregulation of genes in the neutrophil-mediated immunity pathways. A decreased cellular contexture of regulatory T cells in ESCC TME indicated a potentially favorable pathological response to NAT. Cell-cell communication analysis revealed extensive interactions between CCL5 and its receptor CCR5 in various immune cells of baseline pCR tumors. Immune checkpoint interaction pairs, including CTLA4-CD86, TIGIT-PVR, LGALS9-HAVCR2, and TNFSF4-TNFRSF4, might serve as additional therapeutic targets for ICI therapy in ESCC. CONCLUSIONS: This pioneering study unveiled an intriguing association between cancer cell differentiation and pathological response in esophageal cancer patients, revealing distinct subgroups of tumors for which neoadjuvant chemo-immunotherapy might be effective. We also delineated the immune landscape of ESCC tumors in the context of clinical response to NAT, which provides clinical insights for better understanding how patients respond to the treatment and further identifying novel therapeutic targets for ESCC patients in the future.

Serum lipid levels, genetic risk, and lung cancer incidence: A large prospective cohort study.

BACKGROUND: Previous studies usually focused on the separate association of metabolism or genetic factors with lung cancer risk and have largely ignored their combined effect. We aimed to examine the associations between serum lipid levels, genetic risk, and lung cancer risk. METHODS: 426,524 participants of the UK Biobank were included. The Cox proportional hazards models and restricted cubic splines were performed to assess the association between serum lipid and lung cancer risk. Polygenic risk score (PRS) was constructed to assess its joint effect and interaction with serum lipid on lung cancer risk. RESULTS: Higher level of apolipoprotein A were significantly correlated with lower lung cancer risk. A inverse-J-shaped relationship between HDL and incident lung cancer was found. Individuals with low total cholesterol, HDL, LDL, apolipoprotein A, and apolipoprotein B, combined with high PRS, showed significantly elevated lung cancer risks. Compared to those with low PRS and low triglycerides, participants with high PRS and elevated triglyceride levels had a notably higher risk. The interaction effect of high PRS and low LDL (RERI:0.25, 95%CI: 0.04-0.46), as well as the interaction effect of high PRS and low apolipoprotein B (RERI:0.28, 95%CI: 0.07-0.48), were both greater than the sum of their individual effects on lung cancer risk. CONCLUSIONS: Serum lipids were associated with lung cancer risk. LDL or apolipoprotein B interacting with genetic risk may affect lung cancer risk. IMPACT: Our findings emphasize the need for individuals with heightened genetic risk should pay more attention to their lipid levels to reduce lung cancer risk.

Pd-catalyzed divergent regioselective annulation of phosphinyl allenes accessing polyarylfurans and 2H-chromenes.

A novel and efficient regioselective annulation of phosphinyl allenes with 2-bromophenol or 1-bromo-2-naphthol is achieved by palladium catalysis. The divergent pathway delivers structurally diverse polyarylfurans and 2H-chromene skeletons via two different Heck-type annulations. This protocol represents regioselectivity-tunable transformation of allenes into functionalized O-containing heterocycles with excellent group compatibility.

Statins as a risk factor for diabetic retinopathy: a Mendelian randomization and cross-sectional observational study.

BACKGROUND: Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. METHODS: The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. RESULTS: Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). CONCLUSIONS: This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.

Outcomes following the excision of sarcoma and chest wall reconstruction using 3D printed implant.

The survival outcomes of patients with chest wall sarcomas (CWS) were evaluated after receiving wide excision and chest wall reconstruction by using three-dimensional printed (3DP) implants. The survival outcomes evaluating the effect of 3DP implants for chest wall reconstruction is lacking. Here, forty-nine patients with CWS underwent radical wide excision and chest wall reconstruction using 3DP implants. The surgical data and long-term survival outcomes were collected and analyzed. With a median follow-up of 36 months, the disease-free survival (DFS) and overall survival (OS) were 31.7% and 58.5%, respectively. In addition, the 3-year DFS and OS can be significantly differentiated using the classification criteria of tumor grade, tumor size tumor area. Hence, wide excision and chest wall reconstruction using three-dimensional printed implants are a safe and effective treatment for chest wall sarcoma. The novel classification criteria of tumor size and area have the potential to predict the prognosis of CWS.

Molecular subgroup establishment and signature creation of lncRNAs associated with acetylation in lung adenocarcinoma.

BACKGROUND: The significance of long non-coding RNAs (lncRNAs) as pivotal mediators of histone acetylation and their influential role in predicting the prognosis of lung adenocarcinoma (LUAD) has been increasingly recognized. However, there remains uncertainty regarding the potential utility of acetylation-related lncRNAs (ARLs) in prognosticating the overall survival (OS) of LUAD specimens. METHODS: The RNA-Seq and clinical information were downloaded from The Cancer Genome Atlas (TCGA). Through the differential analysis, weighted correlation network analysis (WGCNA), Pearson correlation test and univariate Cox regression, we found out the prognosis associated ARLs and divided LUAD specimens into two molecular subclasses. The ARLs were employed to construct a unique signature through the implementation of the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. Subsequently, the predictive performance was evaluated using ROC analysis and Kaplan-Meier survival curve analysis. Finally, ARL expression in LUAD was confirmed by quantitative real-time PCR (qRT-PCR). RESULTS: We triumphantly built a ARLs prognostic model with excellent predictive accuracy for LUAD. Univariate and multivariate Cox analysis illustrated that risk model served as an independent predictor for influencing the overall survival OS of LUAD. Furthermore, a nomogram exhibited strong prognostic validity. Additionally, variations were observed among subgroups in the field of immunity, biological functions, drug sensitivity and gene mutations within the field. CONCLUSIONS: Nine ARLs were identified as promising indicators of personalized prognosis and drug selection for people suffering with LUAD.

How long can pulmonary resection surgery be performed after SARS-CoV-2 infection? A multicenter retrospective study.

BACKGROUND: No studies to date have focused on the timing of pulmonary resection in patients with previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present study, the authors analyzed the surgical outcomes and evaluated the optimal time point of pulmonary resection surgery following SARS-CoV-2 infection. MATERIALS AND METHODS: In this multicenter retrospective cohort study, patients were divided into different groups according to the time interval between SARS-CoV-2 diagnosis and pulmonary resection. The primary outcome measure was postoperative complications within 30 days after surgery, which was investigated to determine the optimal time point of pulmonary resection. Logistic regression models were used to calculate the risk factors for postoperative complications. RESULTS: In total, 400 patients were enrolled, and the postoperative pathologic examination of 322 (80.5%) patients showed lung cancer. As the interval between SARS-CoV-2 infection and pulmonary resection increased, the incidence of complications gradually decreased in each group. The incidence of grade ≥II complications was higher in the ≤2-week and 2-week to 4-week groups than in the 4-week to 6-week, 6-week to 8-week and >8-week groups [3 (21.4%), 17 (20.2%), 10 (10.6%), 13 (7.9%), and 3 (6.5%), respectively] ( P <0.05). Multiclassification regression analysis showed that the risk of grade ≥II complications in the ≤2-week and 2-week to 4-week groups was significantly higher than that in the >8-week group [odds ratio (95% CI), 3.937 (1.072-14.459), P =0.039 and 3.069 (1.232-6.863), P =0.015]. The logistic regression analysis suggested that underlying disease, persistent SARS-CoV-2 symptoms, and surgical timing (≤4 weeks) were independent risk factors for complications of pulmonary resection after SARS-CoV-2 infection. CONCLUSION: Pulmonary resection should be delayed for at least 4 weeks following SARS-CoV-2 infection to reduce the risk of postoperative complications.

Smyd3 negatively regulates the anti-viral pathway by promoting TAK1 degradation in teleost fish.

IMPORTANCE: In this study, we have found that the existence of Smyd3 promoted the replication of SCRV. Additionally, we report that Smyd3 negatively regulates the NF-κB and IRF3 signaling pathway by facilitating the degradation of TAK1 in fish. Our findings suggest that Smyd3 interacts with TAK1. Further investigations have revealed that Smyd3 specifically mediates K48-linked ubiquitination of TAK1 and enhances TAK1 degradation, resulting in a significant inhibition of the NF-κB and IRF3 signaling pathway. These results not only contribute to the advancement of fish anti-viral immunity but also provide new evidence for understanding the mechanism of TAK1 in mammals.

Exploration of a novel prognostic model based on nomogram in non-small cell lung cancer patients with distant organ metastasis: implications for immunotherapy.

Background: Evidence for the effects of immunotherapy in non-small cell lung cancer (NSCLC) patients with distant organ metastasis is insufficient, and the predictive efficacy of established markers in tissue and blood is elusive. Our study aimed to determine the prognostic factors and develop a survival prognosis model for these patients. Methods: A total of 100 advanced NSCLC patients with distant organ metastases, who received single or combination immune checkpoint inhibitors (ICIs) in Xijing Hospital between June 2018 and June 2021, were enrolled for retrospective analysis. The major clinicopathological parameters were collected, and associated survival outcomes were followed up by telephone or inpatient follow-up for nearly 3 years to assess prognoses. The survival prognosis model was established based on univariate and multivariate Cox regression analyses to determine the candidate prognostic factors. Results: From the start of immunotherapy to the last follow-up, 77 patients progressed and 42 patients died, with a median follow-up of 18 months [95% confidence interval (CI): 15-19.9]. The median progression-free survival (PFS) and overall survival (OS) were 8 months (95% CI: 5.6-10.4) and 21 months (95% CI: 8.9-33.1), respectively. Multivariate Cox proportional hazards analysis showed Eastern Cooperative Oncology Group performance status (ECOG PS), body mass index (BMI), age-adjusted Charlson comorbidity index (ACCI), lactate dehydrogenase (LDH), and absolute neutrophil count (ANC) were correlated significantly with OS. Based on these five predictive factors, a nomogram and corresponding dynamic web page were constructed with a concordance index (C-index) of 0.81 and a 95% CI of 0.778-0.842. Additionally, the calibration plot and time-receiver operating characteristic (ROC) curve validated the precision of the model at 6-, 12-, and 18-month area under the curves (AUCs) reached 0.934, 0.829, and 0.846, respectively. According to the critical point of the model, patients were further divided into a high-risk total point score (TPS) >258, middle-risk (204< TPS ≤258), and low-risk group (TPS ≤204), and significant OS differences were observed among the three subgroups (median OS: 4.8 vs. 13.0 vs. 32.9 months). Conclusions: A feasible and practical model based on clinical characteristics has been developed to predict the prognosis of NSCLC patients with distant organ metastasis undergoing immunotherapy.

A novel protein encoded by circVPS13D attenuates antiviral innate immunity by targeting MAVS in teleost fish.

IMPORTANCE: The expression of circVPS13D was upregulated with SCRV invasion, which proved that circVPS13D was involved in the regulation of the antiviral immune response. Our study revealed that the existence of circVPS13D promoted the replication of SCRV. Functionally, circVPS13D negatively regulates the antiviral responses of fish. Mechanistically, we confirmed that circVPS13D inhibited RLRs antiviral signaling pathway via the encoded protein VPS13D-170aa by targeting MAVS. Our study provided novel insights into the roles of protein-coding circRNAs and supported VPS13D-170aa as a negative regulator in the antiviral immune responses of teleost fish.

Anti-VEGF combined with ocular corticosteroids therapy versus anti-VEGF monotherapy for diabetic macular edema focusing on drugs injection times and confounding factors of pseudophakic eyes: A systematic review and meta-analysis.

PURPOSE: To assess the effectiveness and safety of combining intravitreal endothelial growth factor inhibitor (anti-VEGF) and ocular corticosteroids for diabetic macular edema (DME). METHODS: Articles concentrating on the efficacy and safety of combining anti-VEGF and ocular corticosteroids therapy for DME versus anti-VEGF monotherapy was screened systematically. Meta-analysis was conducted on the basis of a protocol registered in the PROSPERO (CRD42023408338) and performed on the extracted continuous variables and dichotomous variables. The outcome was expressed as weighted mean difference (MD) and risk ratio (RR). RESULTS: Add up to 21 studies including 1468 eyes were enrolled in this study. The MD for best-corrected visual acuity (BCVA) improvement at 1/3/6/12-month between the combination therapy group and monotherapy group were 2.56 (95% CI [0.43, 4.70]), 2.46 (95% CI [-0.40, 5.32]), - 1.76 (95% CI [-3.18, -0.34]), - 1.94 (95% CI [-3.87, 0.00]), respectively. The MD for central retinal thickness (CMT) reduction at 1/3/6/12-month between two groups were - 66.27 (95% CI [-101.08, -31.47]), - 33.62 (95% CI [-57.55, -9.70]), - 4.54 (95% CI [-16.84, 7.76]), - 26.67 (95% CI [-41.52, -11.82]), respectively. Additionally, the combination group had higher relative risk of high intraocular pressure and cataract progression events. CONCLUSIONS: Anti-VEGF combined with ocular corticosteroids had a significant advantage over anti-VEGF monotherapy within 3 months of DME treatment, which reached the maximum with increasing anti-VEGF injection times to 3. However, with the prolongation of the treatment cycle, the effect of combined therapy after 6 months was no better than monotherapy, and the side effects of combined therapy were more severe.

Targeting METTL3 reprograms the tumor microenvironment to improve cancer immunotherapy.

The tumor microenvironment (TME) is a heterogeneous ecosystem containing cancer cells, immune cells, stromal cells, cytokines, and chemokines which together govern tumor progression and response to immunotherapies. Methyltransferase-like 3 (METTL3), a core catalytic subunit for RNA N6-methyladenosine (m6A) modification, plays a crucial role in regulating various physiological and pathological processes. Whether and how METTL3 regulates the TME and anti-tumor immunity in non-small-cell lung cancer (NSCLC) remain poorly understood. Here, we report that METTL3 elevates expression of pro-tumorigenic chemokines including CXCL1, CXCL5, and CCL20, and destabilizes PD-L1 mRNA in an m6A-dependent manner, thereby shaping a non-inflamed TME. Thus, inhibiting METTL3 reprograms a more inflamed TME that renders anti-PD-1 therapy more effective in several murine lung tumor models. Clinically, NSCLC patients who exhibit low-METTL3 expression have a better prognosis when receiving anti-PD-1 therapy. Collectively, our study highlights targeting METTL3 as a promising strategy to improve immunotherapy in NSCLC patients.

Prevalence and associated outcomes of coinfection between SARS-CoV-2 and influenza: a systematic review and meta-analysis.

OBJECTIVES: To estimate the prevalence of influenza coinfection in COVID-19 patients and investigate its association with severe clinical outcomes. METHODS: We systematically searched the Web of Science, PubMed, Scopus, Embase, The Cochrane Library, and CNKI for studies published between January 01, 2020, and May 31, 2023. Meta-analysis was performed to estimate the pooled prevalence of coinfection and the impact on clinical outcomes. Systematic review registered in PROSPERO (CRD42023423113). RESULTS: A total of 95 studies involving 62,107 COVID-19 patients were included. The pooled prevalence of coinfection with influenza virus was 2.45% (95% confidence interval [CI]: 1.67-3.58%), with a high proportion of influenza A. Compared with mono-infected patients (COVID-19 only), the odds ratio (OR) for severe outcomes (including intensive care unit admission [OR = 2.20, 95% CI: 1.68-2.87, P < 0.001], mechanical ventilation support [OR = 2.73, 95% CI: 1.46-5.10, P = 0.002], and mortality [OR = 2.92, 95% CI: 1.16-7.30, P = 0.022]) was significantly higher among patients coinfected influenza A. CONCLUSION: Although the prevalence of coinfection is low, coinfected patients are at higher risk of severe outcomes. Enhanced identification of both viruses, as well as individualized treatment protocols for coinfection, are recommended to reduce the occurrence of serious disease outcomes in the future.

Neoadjuvant Camrelizumab Plus Platinum-Based Chemotherapy vs Chemotherapy Alone for Chinese Patients With Resectable Stage IIIA or IIIB (T3N2) Non-Small Cell Lung Cancer: The TD-FOREKNOW Randomized Clinical Trial.

Importance: The benefit of neoadjuvant camrelizumab plus chemotherapy for resectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) remains unknown. Objective: To assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy vs chemotherapy alone for patients with resectable stage IIIA or IIIB NSCLC. Design, Setting, and Participants: In this randomized phase 2 clinical trial conducted at 2 hospitals in China, patients aged 18 to 70 years with resectable stage IIIA or IIIB (T3N2) NSCLC were enrolled between April 7, 2020, and January 12, 2022. Interventions: Patients were randomly assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m2, and platinum [cisplatin, 75 mg/m2; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m2]) or chemotherapy alone, followed by surgery after 4 to 6 weeks. Main Outcomes and Measures: The primary end point was the pathologic complete response (pCR) rate. Secondary end points included the major pathologic response (MPR) rate, objective response rate (ORR), event-free survival (EFS), and safety. Disease-free survival (DFS, defined as the time from surgery to disease recurrence or death from any cause) was analyzed post hoc. Efficacy was assessed on a modified intention-to-treat basis. Results: Ninety-four Chinese patients were randomized, and 88 (93.6%; median age, 61 years [IQR, 54-65 years]; 74 men [84.1%]) received allocated neoadjuvant treatment (43 received camrelizumab plus chemotherapy, and 45 received chemotherapy alone). Among these 88 patients, the pCR rate was 32.6% (14 of 43; 95% CI, 19.1%-48.5%) with camrelizumab plus chemotherapy vs 8.9% (4 of 45; 95% CI, 2.5%-21.2%) with chemotherapy alone (odds ratio, 4.95; 95% CI, 1.35-22.37; P = .008). The MPR rates were 65.1% (95% CI, 49.1%-79.0%) with camrelizumab plus chemotherapy and 15.6% (95% CI, 6.5%-29.5%) with chemotherapy alone. The radiographic ORRs were 72.1% (95% CI, 56.3%-84.7%) with camrelizumab plus chemotherapy and 53.3% (95% CI, 37.9%-68.3%) with chemotherapy alone. With a median follow-up of 14.1 months (IQR, 9.2-20.9 months), the median EFS and DFS were not reached in either group. The most common neoadjuvant treatment-related adverse events of grade 3 or higher were decreased white blood cell count (6 of 43 [14.0%] in the camrelizumab plus chemotherapy group vs 2 of 45 [4.4%] in the chemotherapy group) and decreased neutrophil count (3 of 43 [7.0%] in the camrelizumab plus chemotherapy group vs 5 of 45 [11.1%] in the chemotherapy group). No treatment-related deaths were reported. Conclusions and Relevance: This randomized clinical trial found that among patients with resectable stage IIIA or IIIB (T3N2) NSCLC, camrelizumab plus chemotherapy, compared with chemotherapy alone, significantly improved the pCR rate with manageable toxic effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04338620.

Emerging role of ubiquitination/deubiquitination modification of PD-1/PD-L1 in cancer immunotherapy.

As members of the immune checkpoint family, PD-1 and its ligand PD-L1 play critical roles in maintaining the balance between autoimmunity and tolerance. The interaction of PD-1/PD-L1 is also involved in tumor evasion inside the tumor microenvironment, caused by reduced T cell activation, proliferation, cytotoxic secretion, and survival. Previous research has shown that the expression level of PD-1/PD-L1 may be regulated by ubiquitin-mediated proteasome degradation, which is an important mode of post-translational modification (PTM). PD-1/PD-L1 ubiquitin modification research in tumor immunotherapy is the subject of the present review, which aims to assess the most recent developments in this area. We offer a short explanation of PD-1/PD-L1 as well as some basic background information on the UPS system and discuss many routes that target E3s and DUBs, respectively, in the regulation of PD-1/PD-L1 in tumor immunotherapy. In addition, we offer numerous innovative prospective research areas for the future, as well as novel immunotherapy concepts and ideas. Taken together, the information compiled herein should serve as a comprehensive repository of information about tumor immunotherapy that is currently available, and it should be useful in the design of future studies, as well as the development of potential targets and strategies for future tumor immunotherapy.

JMJD6 functions as an oncogene and is associated with poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a high prevalence and poor prognosis. It is an urgent problem to deeply understand the molecular mechanism of ESCC and develop effective diagnostic and prognostic methods. METHODS: Using tumor tissue and corresponding paracancerous samples from 141 resected ESCC patients, we assessed Jumonji domain-containing protein 6 (JMJD6) expression using Immunohistochemical (IHC) staining. Kaplan-Meier survival analysis and univariate or multivariate analysis were used to investigate the relationship between JMJD6 expression and clinicopathological features. The expression status and prognostic value of JMJD6 were analyzed by bioinformatics and enrichment analysis. RESULTS: The expression of JMJD6 in ESCC samples was higher than that in the corresponding paracancerous samples, and high expression of JMJD6 was positively associated with poor prognosis of ESCC patients. In addition, bioinformatics analysis of the expression and prognosis of JMJD6 in a variety of tumors showed that high expression of JMJD6 was significantly associated with poor overall survival (OS) in ESCC patients. Enrichment analysis indicated that the high expression of genes similar to JMJD6, such as Conserved oligomeric Golgi 1(COG1), Major facilitator superfamily domain 11 (MFSD11) and Death Effector Domain Containing 2 (DEDD2), was associated with poor prognosis of ESCC, suggesting that JMJD6 might be involved in the occurrence and prognosis of ESCC. CONCLUSION: Our study found that JMJD6 expression was significantly increased in ESCC patients and positively correlated with prognosis, indicating that targeting JMJD6 might be an attractive prognostic biomarker and provides a potential treatment strategy for ESCC. TRIAL REGISTRATION: The study was approved by Tangdu Hospital ethics committee (No. TDLL-202110-02).

A multicenter, single-arm, open study of neoadjuvant or conversion atezolizumab in combination with chemotherapy in resectable small cell lung cancer (Cohort Study).

BACKGROUND: This study aimed to investigate the prospects of using chemotherapy in combination with atezolizumab in the neoadjuvant or conversion treatment of small cell lung cancer (SCLC). METHODS: Prior to surgery, untreated patients with limited-stage SCLC received three cycles of neoadjuvant or conversion atezolizumab combined with chemotherapy of etoposide and platinum. The primary endpoint of the trial was pathological complete response (pCR) in the per-protocol (PP) cohort. In addition, safety was assessed based on treatment-related adverse events (AEs) and postoperative complications. RESULTS: Overall, 13 of 17 patients (including 14 males and 3 females) underwent surgery. In the PP cohort, pCR and major pathological response were observed in 8 (8/13, 61.5%) and 12 (12/13, 92.3%) patients, respectively. According to the intention-to-treat (ITT) analysis, the pCR and major pathological response in the ITT cohort were 47.1% (8/17) and 70.6% (12/17), respectively. In addition, an overall response rate of 100% was recorded in the PP cohort. Moreover, 15 (15/17, 88.2%) patients and 1 (1/17, 5.9%) in the ITT cohort attained partial remission (PR), and complete remission, respectively, with an overall response rate of 94.1%. The median overall survival of the patients of pCR and the median event-free survival of the patients on surgery had not achieved. However, the median overall survival of the patients of non-pCR was 18.2 months and the median event-free survival of the nonsurgical patients was 9.5 months. During the neoadjuvant treatment, the incidence of grade 3 or higher AEs was 58.8% (10/17). Additionally, three patients (17.6%) developed immune-related adverse event (grades 1-2). CONCLUSION: In patients with SCLC, neoadjuvant or conversion atezolizumab combined with chemotherapy significantly improved pCR with manageable AEs. Therefore, this regimen may be considered a safe and effective treatment for SCLC.

Pharmacological roles of lncRNAs in diabetic retinopathy with a focus on oxidative stress and inflammation.

Diabetic retinopathy (DR) is a complication caused by abnormal glucose metabolism, which affects the vision and quality of life of patients and severely impacts the society at large.DR has a complex pathogenic process. Evidence from multiple studies have shown that oxidative stress and inflammation play pivotal roles in DR.Additionally, with the rapid development of various genetic detection methods, the abnormal expression of long non-coding RNAs (lncRNAs) have been confirmed to promote the development of DR.Research has demonstrated the potential of lncRNAs as ideal biomarkers and theranostic targets in DR. In this narrative review, we will focus on the research results on mechanisms underlying DR, list lncRNAs confirmed to be closely related to these mechanisms, and discuss their potential clinical application value and limitations.

Visible-Light-Induced Palladium-Catalyzed Construction of Polyarylfuran Skeletons via Cascade Aryl Radical Cyclization and C(sp3)-P(V) Bond Cleavage.

Herein, a novel and expedient method was established for the synthesis of polyarylfuran derivatives. The coupling of allenylphosphine oxide and bromophenol or bromonaphthol enabled by visible light and palladium catalysis directly furnishes polyarylfuran skeletons, which involves a radical tandem cyclization and cascade C(sp3)-P(V) bond cleavage. This protocol features easy operation, a broad substrate scope, and a high step economy, affording polyarylfurans in moderate to good yields.