Synergistic monitoring of PM2.5 and CO2 based on active and passive remote sensing fusion during the 2022 Beijing Winter Olympics.

Green and low-carbon are the keywords of the 2022 Beijing Winter Olympic Games (WOG) and the core of sustainable development. Beijing's P M 2.5 and C O 2 emissions attracted worldwide attention during WOG. However, the complex emission sources and frequently changing weather patterns make it impossible for a single monitoring approach to meet the high-resolution, full-coverage monitoring requirements. Therefore, we proposed an active-passive remote sensing fusion method to address this issue. The haze layer height (HLH) was first retrieved from vertical aerosol profiles measured by our high-spectral-resolution lidar located near Olympic venues, which provides new insights into the nonuniform boundary layer and the residual aerosol aloft above it. Second, we developed a bootstrap aggregating (bagging) method that assimilates the lidar-based HLH, satellite-based AOD, and meteorological data to estimate the hourly P M 2.5 with 1 km resolution. The P M 2.5 at Beijing region, Bird's Nest, and Yanqing venues during WOG was 23.00±18.33, 22.91±19.48, and 16.33±10.49µg/m 3, respectively. Third, we also derived the C O 2 enhancements, C O 2 spatial gradients resulting from human activities, and annual growth rate (AGR) to estimate the performance of carbon emission management in Beijing. Based on the top-down method, the results showed an average C O 2 enhancement of 1.62 ppm with an annual decline rate of 2.92 ppm. Finally, we compared the monitoring data with six other international cities. The results demonstrated that Beijing has the largest P M 2.5 annual decline rate of 7.43µg/m 3, while the C O 2 AGR is 1.46 ppm and keeps rising, indicating Beijing is still on its way to carbon peaking and needs to strive for carbon neutrality.

Risk and prognosis of secondary thoracic cancers after radiation therapy for esophageal cancer.

BACKGROUND AND AIM: Radiation therapy (RT) is a crucial modality for the local control of esophageal cancer (EC), but the effect of RT on the development of secondary thoracic malignancies is still unclear. This study aims to identify the association between RT for the treatment of primary EC and subsequent secondary thoracic cancer (STC). METHODS: The primary EC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Fine-Gray competing risk regression and standardized incidence ratio (SIR) were used to evaluate the radiotherapy-associated cancer risk. Overall survival (OS) was compared by Kaplan-Meier analysis. RESULTS: A total of 40 255 EC patients from the SEER database were identified, of which 17 055 patients (42.37%) did not receive radiotherapy (NRT) and 23 200 patients (57.63%) had been treated with RT. After 12 months of latency, 162 patients (0.95%) in the NRT group and 272 patients (1.17%) in the RT group developed STC. The incidences of the RT group were significantly higher than the NRT group. Patients who have primary EC were at an increased risk of developing STC (SIR = 1.79, 95% CI: 1.63-1.96). The SIR of STC was 1.37 (95% CI: 1.16-1.60) in the NRT group and 2.10 (95% CI: 1.87-2.34) in the RT group. The OS of STC patients in the RT group was significantly lower than the NRT group (P = 0.006). CONCLUSION: The RT for primary EC was associated with higher risks of developing STC than patients unexposed to radiotherapy. The EC patients treated with RT, especially young patients, require long-term monitoring of the risk of STC.

A novel nomogram predicting the risk of postoperative pneumonia for esophageal cancer patients after minimally invasive esophagectomy.

BACKGROUND: Pneumonia is a common complication after minimally invasive esophagectomy (MIE), which prolongs hospital stay, adding to the cost and increasing the risk to patients' lives. This study aimed to identify risk factors and establish a predictive nomogram for postoperative pneumonia (PP). METHODS: This case control study included 609 patients with esophageal cancer who underwent MIE between March 2015 and August 2019 in Cancer Hospital, Chinese Academy of Medical Sciences. We randomly divided the data into training and validation sets in the ratio of 7:3 and performed univariate and multivariate logistic regression analyses to acquire independent risk factors of the training set. We constructed a nomogram based on the independent risk factors. The concordance index (C-index), receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) plots were used to evaluate the discrimination of the nomogram. Validation set was applied to confirm the predictive value of the nomogram. RESULTS: In the univariate analysis, age, gender, abdominal procedure method, thoracic operative time, duration of chest tube placement, anastomotic leakage, and recurrent laryngeal nerve palsy were found to be correlated with the incidence of PP. In multivariate analysis, all variables except thoracic operative time were found to be independent risk factors for PP. A nomogram was constructed based on these independent risk factors. The C-index of the training and validation sets was 0.769 and 0.734, respectively, and the areas under the curve (AUC) of ROC curves of the training and validation sets were 0.769 and 0.686, respectively. The calibration plots and DCA plots of the training and validation sets showed the accuracy and predictive value of the nomogram. CONCLUSION: The nomogram could accurately identify the risk factors for PP. We could predict the occurrence of PP based on this nomogram and take corresponding measures to reduce the incidence of PP.

Oncologic outcomes of segmentectomy vs lobectomy in pathologic stage IA (≤2 cm) invasive lung adenocarcinoma: A population-based study.

BACKGROUND AND OBJECTIVES: For early-stage invasive lung adenocarcinoma, it remains unclear whether segmentectomy can yield outcomes equivalent to those of lobectomy. This study aimed to compare survival outcomes after segmentectomy and lobectomy among patients with stage IA invasive lung adenocarcinoma. METHODS: We identified patients with stage IA (≤2 cm) invasive lung adenocarcinoma who underwent segmentectomy or lobectomy from the Surveillance, Epidemiology, and End Results database (2004-2015). Propensity score matching (PSM) was used to balance the baseline characteristics. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: A total of 5474 patients were included. Before PSM, the 5-year OS was 78.3% for patients undergoing lobectomy vs 76.5% for patients undergoing segmentectomy (P = .166) while LCSS were 86.8% vs 83.0% (P = .015). After PSM, survival analyses showed that segmentectomy had OS (75.8% vs 76.4%; P = .694) and LCSS (82.7% vs 82.9%; P = .604) equivalent to those of lobectomy. Cox regression demonstrated that segmentectomy was equivalent to lobectomy in terms of OS and LCSS before and after PSM. CONCLUSION: For stage IA (≤2 cm) invasive lung adenocarcinoma, segmentectomy may have oncologic outcomes equivalent to those of lobectomy.

Performance estimation of space-borne high-spectral-resolution lidar for cloud and aerosol optical properties at 532 nm.

Cloud and aerosol contribute with great uncertainty in Earth's radiative budget. There is an urgent need for global 3-D observation of these atmospheric constituents. High-spectral-resolution Lidar (HSRL) can obtain vertical atmosphere profile with high accuracy, hence several space-borne HSRLs are planned to launch in few years. However, as far as we know, the performance evaluation of space-borne HSRL has not been reported yet. In this paper, we present the characteristics of a new designed space-borne HSRL for aerosol and cloud optical property profiling (ACHSRL), which is part of the Aerosol & Carbon Detection Lidar (ACDL) developed in China. The ACHSRL is essentially similar to the famous Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP), which is on board the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO). Moreover, the ACHSRL employs an iodine absorption filter as the spectral discriminator. The atmospheric optical properties data observed by CALIOP is used to estimate the performance of ACHSRL. We chose the level 2 profile data (version 4.10) in South Japan in June 2015 to compare the detection uncertainty of ACHSRL and CALIOP. The simulation calculates the uncertainties of ACHSRL and makes a statistic analysis. The analysis result demonstrates that 73.63% of the backscatter coefficient uncertainties are below 40% for ACHSRL. By contrast, the number is 30.72% for CALIOP. As for absolute extinction coefficient errors, the statistics shows that 76.01% of the extinction coefficient uncertainties are lower than 0.2 km-1 for ACHSRL, while that for CALIOP are 56.97%. The assessment shows that ACHSRL could measure the particulate optical properties with better accuracy and compared with CALIOP. The estimation in this study reveals that the next generation space-borne HSRLs have a promising future.

STAT3 Regulates the Type I IFN-Mediated Antiviral Response by Interfering with the Nuclear Entry of STAT1.

Signal transducer and activator of transcription 3 (STAT3) is a multifunctional factor that regulates inflammation and immunity. Knowledge of its regulatory mechanisms is very limited. Here, we showed that enterovirus 71 (EV71) infection induced the phosphorylation of STAT3 and the expression of its downstream inflammatory regulators. Knockdown of STAT3 with siRNAs significantly restricted viral RNA and protein levels, and also reduced viral titers. With further investigation, we found that importin α family member Karyopherin-α1 (KPNA1) was employed by both STAT1 and STAT3 for their nuclear import. The phosphorylated and un-phosphorylated STAT3 competed with STAT1 for binding to the decreased KPNA1 post infection and repressed downstream ISG expression. STAT3 knockdown alleviated the repressed type I IFN-mediated antiviral response upon infection and led to decreased viral replication. Taken together, our data suggested the role of STAT3 in maintaining the balance of inflammation and antiviral responses in the central nervous system (CNS) upon infection.

A dose-response meta-analysis reveals an association between vitamin B12 and colorectal cancer risk.

OBJECTIVE: The current meta-analysis evaluated the association between vitamin B12 intake and blood vitamin B12 level and colorectal cancer (CRC) risk. DESIGN: The PubMed and EMBASE databases were searched. A dose-response analysis was performed with generalized least squares regression, with the relative risk (RR) and 95 % CI as effect values. SETTING: The meta-analysis included seventeen studies. SUBJECTS: A total of 10 601 patients. RESULTS: The non-linear dose-response relationship between total vitamin B12 intake and CRC risk was insignificant (P=0·690), but the relationship between dietary vitamin B12 intake and CRC risk was significant (P<0·001). Every 4·5 µg/d increment in total and dietary vitamin B12 intake was inversely associated with CRC risk (total intake: RR=0·963; 95 % CI 0·928, 0·999; dietary intake: RR=0·914; 95 % CI 0·856, 0·977). The inverse association between vitamin B12 intake and CRC risk was also significant when vitamin B12 intake was over a dosage threshold, enhancing the non-linear relationship. The non-linear dose-response relationship between blood vitamin B12 level and CRC risk was insignificant (P=0·219). There was an insignificant association between every 150 pmol/l increment in blood vitamin B12 level and CRC risk (RR=1·023; 95 % CI 0·881, 1·187). CONCLUSIONS: Our meta-analysis indicates that evidence supports the use of vitamin B12 for cancer prevention, especially among populations with high-dose vitamin B12 intake, and that the association between CRC risk and total vitamin B12 intake is stronger than between CRC risk and dietary vitamin B12 intake only.

Pathological response and tumor stroma immunogenic features predict long-term survival in non-small cell lung cancer after neoadjuvant chemotherapy.

PURPOSE: Major pathological response (MPR) has become a surrogate endpoint for overall survival (OS) in non-small cell lung cancer (NSCLC) after neoadjuvant therapy, however, the prognostic histologic features and optimal N descriptor after neoadjuvant therapy are poorly defined. METHODS: We retrospectively analyzed data from 368 NSCLC patients who underwent surgery after neoadjuvant chemotherapy (NAC) from January 2010 to December 2020. The percentage of residual viable tumors in the primary tumor, lymph nodes (LN), and inflammation components within the tumor stroma were comprehensively reviewed. The primary endpoint was OS. RESULTS: Of the 368 enrolled patients, 12.0% (44/368) achieved MPR in the primary tumor, which was associated with significantly better OS (HR, 0.36 0.17-0.77, p = 0.008) and DFS (HR = 0.59, 0.36-0.92, p = 0.038). In patients who did not have an MPR, we identified an immune-activated phenotype in primary tumors, characterized by intense tumor-infiltrating lymphocyte or multinucleated giant cell infiltration, that was associated with similar OS and DFS as patients who had MPR. Neoadjuvant pathologic grade (NPG), consisting of MPR and immune-activated phenotype, identified 30.7% (113/368) patients that derived significant OS (HR 0.28, 0.17-0.46, p < 0.001) and DFS (HR 0.44, 0.31-0.61, p < 0.001) benefit from NAC. Moreover, the combination of NPG and the number of positive LN stations (nS) in the multivariate analysis had a higher C-index (0.711 vs. 0.663, p < 0.001) than the ypTNM Stage when examining OS. CONCLUSION: NPG integrated with nS can provide a simple, practical, and robust approach that may allow for better stratification of patients when evaluating neoadjuvant chemotherapy in clinical practice.

Filling the gaps in icosahedral superatomic metal clusters.

Chemically modified superatoms have emerged as promising candidates in the new periodic table, in which Au13 and its doped M n Au13- n have been widely studied. However, their important counterpart, Ag13 artificial element, has not yet been synthesized. In this work, we report the synthesis of Ag13 nanoclusters using strong chelating ability and rigid ligands, that fills the gaps in the icosahedral superatomic metal clusters. After further doping Ag13 template with different degrees of Au atoms, we gained insight into the evolution of their optical properties. Theoretical calculations show that the kernel metal doping can modulate the transition of the excited-state electronic structure, and the electron transfer process changes from local excitation (LE) to charge transfer (CT) to LE. This study not only enriches the families of artificial superatoms, but also contributes to the understanding of the electronic states of superatomic clusters.

Proposed novel grading system for stage I invasive lung adenocarcinoma and a comparison with the 2020 IASLC grading system.

BACKGROUND: Several studies have proposed grading systems for risk stratification of early-stage lung adenocarcinoma based on histological patterns. However, the reproducibility of these systems is poor in clinical practice, indicating the need to develop a new grading system which is easy to apply and has high accuracy in prognostic stratification of patients. METHODS: Patients with stage I invasive nonmucinous lung adenocarcinoma were retrospectively collected from pathology archives between 2009 and 2016. The patients were divided into a training and validation set at a 6:4 ratio. Histological features associated with patient outcomes (overall survival [OS] and progression-free survival [PFS]) identified in the training set were used to construct a new grading system. The newly proposed system was validated using the validation set. Survival differences between subgroups were assessed using the log-rank test. The prognostic performance of the novel grading system was compared with two previously proposed systems using the concordance index. RESULTS: A total of 539 patients were included in this study. Using a multioutcome decision tree model, four pathological factors, including the presence of tumor spread through air space (STAS) and the percentage of lepidic, micropapillary and solid subtype components, were selected for the proposed grading system. Patients were accordingly classified into three groups: low, medium, and high risk. The high-risk group showed a 5-year OS of 52.4% compared to 89.9% and 97.5% in the medium and low-risk groups, respectively. The 5-year PFS of patients in the high-risk group was 38.1% compared to 61.7% and 90.9% in the medium and low-risk groups, respectively. Similar results were observed in the subgroup analysis. Additionally, our proposed grading system provided superior prognostic stratification compared to the other two systems with a higher concordance index. CONCLUSION: The newly proposed grading system based on four pathological factors (presence of STAS, and percentage of lepidic, micropapillary, and solid subtypes) exhibits high accuracy and good reproducibility in the prognostic stratification of stage I lung adenocarcinoma patients.

Genomic characteristics and immune landscape of super multiple primary lung cancer.

BACKGROUND: In recent years, a growing number of patients with multiple primary lung cancer (MPLC) are being diagnosed, and a subset of these patients is found to have a large number of lesions at the time of diagnosis, which are referred to as 'super MPLC'. METHODS: Here, we perform whole exome sequencing (WES) and immunohistochemistry (IHC) analysis of PD-L1 and CD8 on 212 tumor samples from 42 patients with super MPLC. FINDINGS: We report the genomic alteration landscape of super MPLC. EGFR, RBM10 and TP53 mutation and TERT amplification are important molecular events in the evolution of super MPLC. We propose the conception of early intrapulmonary metastasis, which exhibits different clinical features from conventional metastasis. The IHC analyses of PD-L1 and CD8 reveal a less inflamed microenvironment of super MPLC than that of traditional non-small cell lung cancer (NSCLC). We identify the potentially susceptible germline mutations for super MPLC. INTERPRETATION: Our study depicts the genomic characteristics and immune landscape, providing insights into the pathogenesis and possible therapeutic guidance of super MPLC. FUNDING: A full list of funding bodies that supported this study can be found in the Acknowledgements section.

Treatment patterns and clinical outcomes of patients with resectable non-small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World).

BACKGROUND: Neoadjuvant immunotherapy has ushered in a new era of perioperative treatment for resectable non-small cell lung cancer (NSCLC). However, large-scale data for verifying the efficacy and optimizing the therapeutic strategies of neoadjuvant immunochemotherapy in routine clinical practice are scarce. METHODS: NeoR-World (NCT05974007) was a multicenter, retrospective cohort study involving patients who received neoadjuvant immunotherapy plus chemotherapy or chemotherapy alone in routine clinical practice from 11 medical centers in China between January 2010 and March 2022. Propensity score matching was performed to address indication bias. RESULTS: A total of 408 patients receiving neoadjuvant immunochemotherapy and 684 patients receiving neoadjuvant chemotherapy were included. The pathologic complete response (pCR) and major pathologic response (MPR) rates of the real-world neoadjuvant immunochemotherapy cohort were 32.8% and 58.1%, respectively. Notably, patients with squamous cell carcinoma exhibited significantly higher pCR and MPR rates than those with adenocarcinoma (pCR, 39.2% vs 16.5% [P < .001]; MPR, 66.6% vs 36.5% [P < .001]), whereas pCR and MPR rates were comparable among patients receiving different neoadjuvant cycles. In addition, the 2-year rates of disease-free survival (DFS) and overall survival (OS) rate were 82.0% and 93.1%, respectively. Multivariate analyses identified adjuvant therapy as an independent prognostic factor for DFS (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.89; P = .018) and OS (HR, 0.28; 95% CI, 0.13-0.58; P < .001). A significantly longer DFS with adjuvant therapy was observed in patients with non-pCR or 2 neoadjuvant cycles. We observed significant benefits in pCR rate (32.4% vs 6.4%; P < .001), DFS (HR, 0.50; 95% CI, 0.38-0.68; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.94; P = .024) with immunotherapy plus chemotherapy compared to chemotherapy alone both in the primary propensity-matched cohort and across most key subgroups. CONCLUSIONS: The study validates the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy alone for NSCLC. Adjuvant therapy could prolong DFS in patients receiving neoadjuvant immunochemotherapy, and patients with non-pCR or those who underwent 2 neoadjuvant cycles were identified as potential beneficiaries of adjuvant therapy.

Atomically precise chiral silver clusters based on non-chiral ligands for acid/base stimulated luminescence response.

Chiral metal nanoclusters synthesized by non-chiral ligands are usually in the form of racemates. Thus, resolving racemic compounds continues to be a great challenge. Herein, we report a case of the racemic compound hexanuclear silver cluster (Ag6-Rac) protected by the non-chiral sulfhydryl ligand sodium 1H-1,2,3-triazole-5-thiolate (SHTT) and 2,6-bis(diphenylphosphino)pyridine (dpppy). The homochiral clusters in Ag6-Rac are able to spontaneously crystallize and undergo chiral resolution to obtain a racemic conglomerate (Ag6-S/Ag6-R) by solvent-induced crystallization. Interestingly, the Ag6-Rac clusters exhibit strong luminescence in solid and solution, which can respond to trifluoroacetic acid (TFA) and reversible cycling over five times using diethylamine (DEA). This work provides a new research model for resolving racemic clusters and constructing stimulus-responsive clusters.

Multi-omics analysis unravels the underlying mechanisms of poor prognosis and differential therapeutic responses of solid predominant lung adenocarcinoma.

Background: Solid predominant adenocarcinoma (SPA) has been reported to be a subtype with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma (LUAD). However, the underlying mechanisms remain largely unknown and the suitability of immunotherapy for SPA has not been investigated. Methods: We conducted a multi-omics analysis of 1078 untreated LUAD patients with clinicopathologic, genomic, transcriptomic, and proteomic data from both public and internal cohorts to determine the underlying mechanisms of poor prognosis and differential therapeutic responses of SPA and to investigate the potential of immunotherapy for SPA. The suitability of immunotherapy for SPA was further confirmed in a cohort of LUAD patients who received neoadjuvant immunotherapy in our center. Results: Along with its aggressive clinicopathologic behaviors, SPA had significantly higher tumor mutation burden (TMB) and number of pathways altered, lower TTF-1 and Napsin-A expression, higher proliferation score and a more immunoresistant microenvironment than non-solid predominant adenocarcinoma (Non-SPA), accounting for its worse prognosis. Additionally, SPA had significantly lower frequency of therapeutically targetable driver mutations and higher frequency of EGFR/TP53 co-mutation which was related to resistance to EGFR tyrosine kinase inhibitors, indicating a lower potential for targeted therapy. Meanwhile, SPA was enriched for molecular features associated with poor response to chemotherapy (higher chemoresistence signature score, lower chemotherapy response signature score, hypoxic microenvironment, and higher frequency of TP53 mutation). Instead, muti-omics profiling revealed that SPA had stronger immunogenicity and was enriched for positive biomarkers for immunotherapy (higher TMB and T cell receptor diversity; higher PD-L1 expression and more immune cell infiltration; higher frequency of gene mutations predicting efficacious immunotherapy, and elevated expression of immunotherapy-related gene signatures). Furthermore, in the cohort of LUAD patients who received neoadjuvant immunotherapy, SPA had higher pathological regression rates than Non-SPA and patients with major pathological response were enriched in SPA, confirming that SPA was more prone to respond to immunotherapy. Conclusions: Compared with Non-SPA, SPA was enriched for molecular features associated with poor prognosis, unsatisfactory response to chemotherapy and targeted therapy, and good response to immunotherapy, indicating more suitability for immunotherapy while less suitability for chemotherapy and targeted therapy.

Mesenchymal cystic hamartoma of the lung: A case report.

RATIONALE: Mesenchymal cystic pulmonary hamartoma is a rare type of hamartoma that has been reported in all cases in the literature. Most patients were reported to have spontaneous pneumothorax and were treated by surgery, and finally confirmed to be caused by rupture of the cystic hamartoma. Here, we report a case of mesenchymal cystic pulmonary hamartoma detected using computed tomography (CT) during a health check-up without obvious symptoms. PATIENT CONCERNS: A 60-year-old woman was detected using CT during her health check-up. She was a non-smoker and had no symptoms or history of specific diseases. DIAGNOSIS: The final pathological examination confirmed that the lesion was a mesenchymal cystic hamartoma of the lung. INTERVENTIONS: A uniportal video-assisted thoracic surgery wedge resection was performed for biopsy. OUTCOMES: The patient recovered smoothly and was discharged on postoperative day 3. LESSONS: For cystic pulmonary hamartoma, it is usually difficult to make a correct diagnosis using CT imaging. A chest magnetic resonance imaging examination may be helpful for differentiation diagnosis before video-assisted thoracic surgery biopsy.

GINS4 might be a novel prognostic immune-related biomarker of not only esophageal squamous cell carcinoma and other cancers.

BACKGROUND: Immunotherapy using immune checkpoint inhibitors (ICIs), such as antibody of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) has showed as a promising treatment for esophageal squamous cell carcinoma (ESCC), but resistance is unavoidable. This study aimed to find more immune-related genes to promote the efficiency of immunotherapy. MATERIALS AND METHODS: Three datasets were downloaded from Gene Expression Omnibus (GEO) database. Gene differential analysis was performed to identify differentially expressed genes (DEGs), then ceRNA network was constructed based on differentially expressed lncRNAs and mRNAs. Next, Functional enrichment analysis and protein-protein interaction (PPI) network were built to reveal the potential function of mRNAs in ceRNA network. Survival analysis and immune cell infiltration level analysis were utilized to identify prognostic immune-related genes. Finally, pan-cancer analysis was performed to show the role of immune-related genes in other cancers. RESULTS: The data of 215 samples in total were obtained from GEO database (98 normal tissues and 117 tumor tissues), and 1685 differentially expressed mRNAs (176 downregulated and 1509 upregulated) and 3 upregulated lncRNAs (MCM3AP-AS1, HCP5 and GUSBP11, all upregulated) were found. ceRNA network was constructed to reveal some special correlation. Function enrichment showed some potential functions of mRNAs in ceRNA network such as mitotic cell cycle process, negative regulation of DNA-binding transcription factor activity, ossification, VEGFA-VEGFR2 signaling pathway, epithelial to mesenchymal transition, embryonic morphogenesis and so on. PPI network showed the physical interactions between each mRNA in ceRNA network. Through survival analysis and immune cell infiltration level analysis, GINS4 was confirmed as an immune-related prognostic gene in ESCC. GSEA showed some potential functions such as negative regulation of monocyte chemotaxis, antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, positive regulation of antigen processing and presentation, dendritic cell antigen processing and presentation and so on. Finally, pan-cancer analysis revealed that GINS4 might be a novel immune-related prognostic gene in ESCC and other cancers. CONCLUSION: Our study suggested that GINS4 was correlated with prognosis and immune cell infiltration level of ESCC and other cancers. It may deserve further investigation as a potential immune-related prognostic biomarker of ESCC and other cancers.

Effect of histology on the efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer: A systematic review and meta-analysis.

Background: Little is known about the effect of histology on the efficacy of immune checkpoint inhibitors (ICI) in non-small-cell lung cancer (NSCLC). We conducted a systematic review and meta-analysis to assess the potential differences in the efficacy of ICIs between squamous NSCLC (SQ-NSCLC) and non-squamous NSCLC (non-SQ-NSCLC). Methods: Systematic searches of PubMed, Embase, Scopus, and Cochrane Library databases were conducted. All randomized clinical trials of ICIs with available hazard ratios (HR) for progression-free survival (PFS) or overall survival (OS) according to histology were included. The primary endpoint was to assess the difference in the efficacy of ICIs between SQ-NSCLC and non-SQ-NSCLC, measured by the ratio of the HR in SQ-NSCLC to the HR in non-SQ-NSCLC (RHR). Results: A total of 40 trials were included in the meta-analysis. ICI monotherapy could improve OS in both SQ-NSCLC (OS-HR 0.71, 95% CI 0.65-0.77) and non-SQ-NSCLC (OS-HR 0.80, 95% CI 0.73-0.87) while OS benefit was larger in SQ-NSCLC (OS-RHR 0.89, 95% CI 0.80-0.99). In terms of PFS, ICI monotherapy could reduce the risk of progression by 35% (PFS-HR 0.65, 95% CI 0.56-0.77) in SQ-NSCLC while the PFS benefit was smaller (10%) and not statistically significant in non-SQ-NSCLC (PFS-HR 0.90, 95% CI 0.76-1.07). Similarly, ICI-based combination treatments could reduce the risk of both progression and death in SQ-NSCLC (OS-HR 0.70, 95% CI 0.61-0.80; PFS-HR 0.56, 95% CI 0.48-0.65) and non-SQ-NSCLC (OS-HR 0.78, 95% CI 0.74-0.83; PFS-HR 0.63, 95% CI 0.57-0.69) while the survival benefits were larger in SQ-NSCLC (OS-RHR 0.83, 95% CI 0.70-0.99; PFS-RHR 0.82, 95% CI 0.70-0.96). Conclusions: ICIs could deliver survival benefits in both SQ-NSCLC and non-SQ-NSCLC while the magnitude of survival benefits was histology-dependent. Future researches should consider the effect of histology on the efficacy of ICIs. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42022299603].

Time-dependent expression and distribution of monoacylglycerol lipase during the skin-incised wound healing in mice.

The study investigated the expression of monoacylglycerol lipase (MGL) during the skin-incised wound healing in mice and applicability of the time-dependent expression of MGL to wound age determination by immunofluorescent staining, Western blotting, and real-time PCR. Furthermore, cell types were identified by double immunofluorescence. A total of 45 BALB/c male mice were used in this study. After a 1.5-cm-long incision in the central dorsum skin, mice were killed at intervals ranging from 6 h to 14 days, followed by the sampling of wound margin. In the control, there was a low-level expression of MGL in the epidermis, hair follicles, and glandulae sebaceae. In the injured skin, MGL immunoreactivity was mainly detected in the neutrophils, macrophages, and myofibroblasts. Morphometrically, the average ratios of MGL-positive cells were more than 50% at 5 and 7 days post-wounding, whereas it was <50% at the other posttraumatic intervals. By Western blotting analysis, the average ratio of MGL protein expression was highest at 5 days after injury, which had a ratio of >2.30. Similarly, the relative quantity of MGL mRNA expression maximized at posttraumatic 5 days in comparison with control as detected by real-time PCR, with an average ratio of >2.54. In conclusion, MGL expression is detected in neutrophils, macrophages, and myofibroblasts and significantly up-regulated, suggesting that it may play roles in response to inflammation during skin-incised wound healing. From the viewpoint of forensic pathology, MGL detection is applicable to skin wound age determination.

Comparison of Two Proposed Changes to the Current Nodal Classification for Non--small Cell Lung Cancer Based on the Number and Ratio of Metastatic Lymph Nodes.

BACKGROUND: The current nodal classification is unsatisfactory in distinguishing the prognostically heterogeneous N1 or N2 non-small cell lung cancer (NSCLC). RESEARCH QUESTION: Is the combination of the current N category and the number of metastatic lymph nodes (N-#number) or the combination of the current N category and the ratio of the number of positive to resected lymph nodes (N-#ratio) better than the current N category alone? STUDY DESIGN AND METHODS: We identified 2,162 patients with N1 or N2 NSCLC from the Surveillance, Epidemiology, and End Results database (2004-2016). We classified these patients into three N-#number categories (N-#number-1, N-#number-2a, N-#number-2b) and three N-#ratio categories (N-#ratio-1, N-#ratio-2a, N-#ratio-2b). Lung cancer-specific survival (LCSS) were compared using the Kaplan-Meier method. The prognostic significance of the new nodal classifications was validated across each tumor size category (≤3 cm, 3-5 cm, 5-7cm, >7 cm). Cox proportional hazards regression was used to evaluate the association between each nodal classification and LCSS. RESULTS: The survival curves showed clear differences between each pair of N-#number and N-#ratio categories. A significant tendency toward the deterioration of LCSS from N-#number-1 to N-#number-2b was observed in all tumor size categories. However, the differences between each pair of N-#ratio categories were significant only in tumors from 3 to 7 cm. Although all three nodal classifications were independent prognostic indicators, the N-#number classification provided more accurate prognostic stratifications compared with the N-#ratio classification and the current nodal classification. INTERPRETATION: The N-#number classification followed by the N-#ratio classification might be better prognostic determinants than the current nodal classification in prognostically heterogeneous N1 or N2 NSCLC.

Identification of Tumor Microenvironment-Related Prognostic lncRNAs in Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is a severe threat to human health. Although many therapies have been applied to LUAD, the long-term survival rate of patients remains unsatisfactory. We aim to find reliable immune microenvironment-related lncRNA biomarkers to improve LUAD prognosis. METHODS: ESTIMATE analysis was performed to evaluate the degree of immune infiltration of each patient in TAGA LUAD cohort. Correlation analysis was used to identify the immune microenvironment-related lncRNAs. Univariate cox regression analysis, LASSO analysis, and Kaplan Meier analysis were used to construct and validate the prognostic model based on microenvironment-related lncRNAs. RESULTS: We obtained 1,178 immune microenvironment-related lncRNAs after correlation analysis. One hundred and eighty of them are independent prognostic lncRNAs. Sixteen key lncRNAs were selected by LASSO method. This lncRNA-based model successfully predicted patients' prognosis in validation cohort, and the risk score was related to pathological stage. Besides, we also found that TP53 had the highest frequency mutation in LUAD, and the mutation of TP53 in the high-risk group, which was identified by our survival model, has a poor prognosis. lncRNA-mRNA co-expression network further suggested that these lncRNAs play a vital role in the prognosis of LUAD. CONCLUSION: Here, we filtered 16 key lncRNAs, which could predict the survival of LUAD and may be potential biomarkers and therapeutic targets.