Right gastroepiploic artery length determined anastomotic leakage after minimally invasive esophagectomy for esophageal cancer- a prospective cohort study.

BACKGROUND: This prospective cohort study, conducted at a high-volume esophageal cancer center from July 2019 to July 2022, aimed to investigate the link between the right gastroepiploic artery (RGEA) length and anastomotic leakage (AL) rates following minimally invasive esophagectomy (MIE). Real-world data on stomach blood supply in the Chinese population were examined. MATERIALS AND METHODS: A total of 516 cases were enrolled, categorized into two groups based on the Youden index-determined optimal cut-off value for the relative length of RGEA (length of RGEA/length of gastric conduit, 64.69%) through ROC analysis: Group SR (short RGEA) and Group LR (long RGEA). The primary observation parameter was the relationship between AL incidence and the ratio of direct blood supply from RGEA. Secondary parameters included the mean length of the right gastroepiploic artery, greater curvature, and the connection type between right and left gastroepiploic vessels. Patient data were prospectively recorded in electronic case report forms. RESULTS: The study revealed median lengths of 43.60 cm for greater curvature, 43.16 cm for the gastric conduit, and 26.75 cm for RGEA. AL, the most common postoperative complication, showed a significant difference between groups (16.88% vs. 8.84%, P=0.01). Multivariable binary logistic regression identified Group SR and LR (Odds ratio: 2.651, 95% CI: 1.124-6.250, P=0.03) and Neoadjuvant therapy (Odds ratio: 2.479, 95% CI: 1.374-4.473, P=0.00) as independent predictors of AL. CONCLUSIONS: The study emphasizes the crucial role of RGEA length in determining AL incidence in MIE for esophageal cancer. Preserving RGEA and fostering capillary arches between RGEA and LGEA are recommended strategies to mitigate AL risk.

A review of mitigation technologies and management strategies for greenhouse gas and air pollutant emissions in livestock production.

One of the key issues in manure management of livestock production is to reduce greenhouse gas (GHG) and air pollutant emissions, which lead to significant environmental footprint and human/animal health threats. This study provides a review of potentially efficacious technologies and management strategies that reduce GHG and air pollutant emissions during the three key stages of manure management in livestock production, i.e., animal housing, manure storage and treatment, and manure application. Several effective mitigation technologies and practices for each manure management stage are identified and analyzed in detail, including feeding formulation adjustment, frequent manure removal and air scrubber during animal housing stage; solid-liquid separation, manure covers for storage, acidification, anaerobic digestion and composting during manure storage and treatment stage; land application techniques at appropriate timing during manure application stage. The results indicated several promising approaches to reduce multiple gas emissions from the entire manure management. Removing manure 2-3 times per week or every day during animal housing stage is an effective and simple way to reduce GHG and air pollutant emissions. Acidification during manure storage and treatment stage can reduce ammonia and methane emissions by 33%-93% and 67%-87%, respectively and proper acid, such as lactic acid can also reduce nitrous oxide emission by about 90%. Shallow injection of manure for field application has the best performance in reducing ammonia emission by 62%-70% but increase nitrous oxide emission. The possible trade-off brings insight to the prioritization of targeted gas emissions for the researchers, stakeholders and policymakers, and also highlights the importance of assessing the mitigation technologies across the entire manure management chain. Implementing a combination of the management strategies needs comprehensive considerations about mitigation efficiency, technical feasibility, local regulations, climate condition, scalability and cost-effectiveness.

Itraconazole inhibits tumor growth via CEBPB-mediated glycolysis in colorectal cancer.

Advanced colorectal cancer (CRC) is characterized by a high recurrence and metastasis rate, which is the primary cause of patient mortality. Unfortunately, effective anti-cancer drugs for CRC are still lacking in clinical practice. We screened FDA-approved drugs by utilizing targeted organoid sequencing data and found that the antifungal drug itraconazole had a potential therapeutic effect on CRC tumors. However, the effect and mechanism of itraconazole on CRC tumors have not been investigated. A cell line-derived xenograft model in tumor-bearing mice was established and single-cell RNA sequencing was performed on tumor samples from four mice with or without itraconazole treatment. The proportion of cell populations and gene expression profiles was significantly different between the two groups. We found that itraconazole could inhibit tumor growth and glycolysis. We revealed that CEBPB was a new target for itraconazole, and that silencing CEBPB could repress CRC glycolysis and tumor growth by inhibiting ENO1 expression. Clinical analysis showed that CEBPB expression was obviously elevated in CRC patients, and was associated with poor survival. In summary, itraconazole treatment remodeled cell composition and gene expression profiles. Itraconazole inhibited cell glycolysis and tumor growth via the CEBPB-ENO1 axis. In this study, we illustrate a new energy metabolism mechanism for itraconazole on tumor growth in CRC that will provide a theoretical basis for CRC targeting/combination therapy.

Erianin Impedes the Proliferation and Metastatic Migration Through Suppression of STAT-3 Phosphorylation in Human Esophageal Cancer Cells.

In this study, we have investigated erianin, a natural phenolic drug that impedes proliferation and metastatic migration through suppression of STAT-3 phosphorylation in human esophageal cancer cells. Eca-109 cells were treated with different concentrations of erianin (4, 8, 12 µM) for 24 h, and then cell proliferation, apoptosis, and metastatic markers were evaluated. Erianin-induced cytotoxicity and cell proliferation were examined using MTT and crystal violet staining techniques. The measurement of reactive oxygen species (ROS) and the study of apoptotic changes were conducted through flow cytometry. Furthermore, protein expression analyses via western blotting included an evaluation of JAK-STAT3, cell survival, cell cycle, proliferation, and apoptosis-related proteins. Moreover, erianin treatment-associated MMP expressions were studied by RT-PCR. In this study, erianin treatment induces substantial cytotoxicity and ROS production based on the concentrations in Eca-109 cells. Moreover, erianin inhibits the MAPK phosphorylation, proliferation, and metastatic protein in Eca-109 cells. STAT-3 is a crucial transcriptional factor that regulates numerous downstream proteins, such as proliferation, anti-apoptosis, and metastatic proteins. In this study, erianin treatment inhibited the protein expression of IL-6, IL-10, JAK-1, and p-STAT-3 expressions leading to induce apoptosis in Eca-109 cells. Moreover, erianin inhibited the expression of proliferation, metastatic, and anti-apoptotic markers in Eca-109 cells. Hence, erianin suppressed the JAK/STAT-3 signaling pathway and demonstrates potential as a chemotherapeutic agent for the treatment of esophageal cancer.

Learning curve in relation to health-related quality of life in long-term, disease free survivors after McKeown minimally invasive esophagectomy.

BACKGROUND: The potential impact of learning curve on long-term health-related quality of life (QoL) after esophagectomy for cancer has not been investigated. The aim of this article is to investigate the relationship between learning curve for McKeown minimally invasive esophagectomy (MIE) and health-related quality of life (QoL) in long-term, disease free survivors up to 10 years after esophageal cancer resection. METHODS: Esophageal cancer patients who underwent McKeown MIE between 2009 and 2019 were identified in which 280 who were free of disease at the time of survey and completed health-related QoL and symptom questionnaires, including EORTC QLQ-C30, EORTC QLQ-OES18, and Digestive Symptom Questionnaire. Patients were assessed in 3 cohorts according to the learning phases of expertise reported by our previous study: initial phase; plateau phase, and; experienced phase. RESULTS: Median time from operation to survey was 5.8 years (interquartile range 4.6-8.2). The QLQ-C30 mean scores of functional scales, and symptom scales of respiratory and digestive systems including dyspnea (P = 0.006), shortness of breath (P = 0.003), and dysphagia (P = 0.031) were significantly better in experienced phase group. Furthermore, in the subgroup analyses for patients without postoperative major complications, patients in the initial learning phase remained suffering from more symptoms of dyspnea (P = 0.040) and shortness of breath (P = 0.001). CONCLUSION: Esophageal cancer patients undergoing McKeown MIE in initial learning phase tend to suffer from a deterioration in long-term health-related QoL and higher symptomatic burden as compared to experienced learning phase, which did not improved over time and warranted more attention.

K+ and pH homeostasis in plant cells is controlled by a synchronized K+ /H+ antiport at the plasma and vacuolar membrane.

Stomatal movement involves ion transport across the plasma membrane (PM) and vacuolar membrane (VM) of guard cells. However, the coupling mechanisms of ion transporters in both membranes and their interplay with Ca2+ and pH changes are largely unclear. Here, we investigated transporter networks in tobacco guard cells and mesophyll cells using multiparametric live-cell ion imaging and computational simulations. K+ and anion fluxes at both, PM and VM, affected H+ and Ca2+ , as changes in extracellular KCl or KNO3 concentrations were accompanied by cytosolic and vacuolar pH shifts and changes in [Ca2+ ]cyt and the membrane potential. At both membranes, the K+ transporter networks mediated an antiport of K+ and H+ . By contrast, net transport of anions was accompanied by parallel H+ transport, with differences in transport capacity for chloride and nitrate. Guard and mesophyll cells exhibited similarities in K+ /H+ transport but cell type-specific differences in [H+ ]cyt and pH-dependent [Ca2+ ]cyt signals. Computational cell biology models explained mechanistically the properties of transporter networks and the coupling of transport across the PM and VM. Our integrated approach indicates fundamental principles of coupled ion transport at membrane sandwiches to control H+ /K+ homeostasis and points to transceptor-like Ca2+ /H+ -based ion signaling in plant cells.

Comparison of two different methods for lymphadenectomy along the left recurrent laryngeal nerve by minimally invasive esophagectomy in patients with esophageal squamous cell carcinoma: a prospective randomized trial.

BACKGROUND: Lymph nodes along the left recurrent laryngeal nerve (LRLN) is thought to be highly involved in esophageal cancer. Given the unique anatomical positioning of the nerve, performing lymphadenectomy in this region requires advanced techniques within limited working space. Meanwhile, high incidence of morbidity and mortality is associated with lymphadenectomy. Although several methods have been applied to reduce the technical requirement and the incidence of postoperative complication, the optimal method remains controversial. METHODS: This study was a single-center, prospective, randomized trial to investigate the utility of lymphadenectomy along the LRLN during the minimally invasive esophagectomy in esophageal squamous cell carcinoma patients by comparing the surgical outcome, postoperative complication, survival rate, and quality of life (QoL) between the retraction method (RM) and the suspension method (SM) in patients with esophageal cancer from June 2018 to November 2020. QoL was assessed according to questionnaire: EQ-5D-5L. RESULTS: Of 94 patients were enrolled and randomized allocated to RM and SM group equally. Characteristics did not differ between groups. The duration of lymph node dissection along LRLN was significant longer in SM group ( P <0.001). No difference was observed about postoperative complications. One of in-hospital death was occurred in each group ( P >0.999). Patients in neither of groups exhibiting difference about 3-year disease-free survival rate ( P =0.180) and overall survival rate ( P =0.430). No difference was observed in postoperative QoL between groups at different time points (all, P >0.05). CONCLUSION: Both methods of lymph node dissection along the LRLN during minimally invasive esophagectomy in esophageal squamous cell carcinoma patients are technically feasible and safe. The RM appears more favorable in terms of reducing surgical duration compared to the SM.

Impact of perioperative decreased serum albumin level on anastomotic leakage in esophageal squamous cell carcinoma patients treated with neoadjuvant chemotherapy followed by minimally invasive esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a severe complication following esophagectomy with high mortality. Perioperative decreased serum albumin level is considered a predictive of AL, however, its impact on AL incidence in patients treated with neoadjuvant chemotherapy (NCT) followed by minimally invasive esophagectomy (MIE) is not well defined. METHODS: The data of 318 consecutive esophageal cancer patients who underwent MIE were collected retrospectively from January 2021 to December 2021. The perioperative level of albumin was detected and the baseline of altering levels for albumin was established. The incidence of postoperative complications and survival rate were analyzed between groups. RESULTS: After exclusion, 137 patients were enrolled and assigned to more decreased albumin (MA) and less decreased albumin (LA) groups. The levels of albumin descended significantly after MIE (p < 0.0001). There was no significant difference in the clinicopathologic characteristics or surgical outcomes between groups. The incidence of postoperative AL was 10.2% in MA group and 1.4% in LA group (p = 0.033). Three patients died due to AL in MA group, while no mortality was observed in LA group (p = 0.120). The rate of other postoperative complications was similar between groups. Progression-free survival (PFS) in LA group was a little higher than that in MA group, but it was no significant difference (p = 0.853). Similarly, no difference was observed in overall survival (OS) between groups (p = 0.277). CONCLUSIONS: Severely deficient serum albumin after MIE was an indicator of AL in esophageal cancer patients treated with NCT. TRIAL REGISTRATION: Chinese clinical trial registry: ChiCTR2200066694, registered December14th,2022. https://www.chictr.org.cn/edit.aspx?pid=185067&htm=4 .

Concurrent radiotherapy cannot provide superiority of surgical oncological outcome and long-term survival rate in locally advanced esophageal squamous cell carcinoma patients receiving neoadjuvant chemotherapy followed by minimally invasive esophagectomy.

BACKGROUND: To evaluate effectiveness of concurrent radiotherapy in esophageal cancer patient treated with neoadjuvant therapy. METHODS: The data of 1026 consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent minimally invasive esophagectomy (MIE) were retrospectively collected. The main inclusion criteria were patients with locally advanced (cT2-4N0-3M0) ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) followed by MIE, and divided into two groups according to different neoadjuvant strategies. Propensity score matching was performed to improve the comparability between the two groups. RESULTS: After exclusion and matching, 141 patients were enrolled retrospectively: 92 received NCT, and 49 received NCRT. No difference in clinicopathologic characteristics or incidence of adverse events between groups. A shorter operation time (215.7 ± 35.5 min) (p < 0.001), less blood loss (111.2 ± 67.7 ml) (p = 0.0007) and a greater number of lymph nodes retrieved (33.8 ± 11.7) (p = 0.002) were observed in NCT group than in NCRT group. The incidence of postoperative complications was similar between groups. Although patients in NCRT group had better pathological complete response (16, 32.7%) (p = 0.0026) and ypT0N0 (10, 20.4%) (p = 0.0002) rates, there was no significant difference in 5-year progression-free survival (p = 0.1378) or disease-specific survival (p = 0.1258) between groups. CONCLUSIONS: Compared with NCRT, NCT has certain advantages in that it can simplify the surgical procedure and decrease the surgical technique required without compromising the surgical oncological outcomes and long-term survival of patients.

Safety and feasibility of three-dimensional McKeown minimally invasive esophagectomy.

BACKGROUND: To compare the perioperative outcomes from McKeown minimally invasive esophagectomy (MIE) when performed in three-dimensional versus two-dimensional visualization system, and investigate the learning curve of a single surgeon who implemented three-dimensional McKeown MIE. METHODS: A total of 335 consecutive cases (three-dimensional or two-dimensional) were identified. Perioperative clinical parameters were compared and cumulative sum learning curve was plotted. Propensity score matching was used to reduce selection bias from confounding factors. RESULTS: Patients in three-dimensional group were associated with more chronic obstructive pulmonary disease (23.9% vs 3.0%, p < 0.01). After propensity score matching (108 matched patients in each groups), this finding was no longer statistically significant. Comparing to two-dimensional group, significant improvement in total retrieved lymph nodes (28 vs 33, p = 0.003) was observed in three-dimensional group. In addition, more lymph nodes around the right recurrent laryngeal nerve were harvested in three-dimensional group than that in two-dimensional group (p = 0.045). However, there were no significantly differences were found between the two groups in terms of other intraoperative parameters (e.g., operative time) and postoperative relevant outcomes (e.g., lung infection). Furthermore, the change point in the cumulative sum learning curves for intraoperative blood loss and thoracic procedure time was 33 procedures, respectively. CONCLUSION: Three-dimensional visualization system appears to be superior in performing lymphadenectomy during McKeown MIE to that of a two-dimensional technique. For surgeons proficient in performing two-dimensional McKeown MIE, the learning curve for a three-dimensional procedure appears to begin near proficiency after more than 33 cases.

Systematic pan-cancer analysis identifies cuproptosis-related gene DLAT as an immunological and prognostic biomarker.

Lipoylated dihydrolipoamide S-acetyltransferase (DLAT), the component E2 of the multi-enzyme pyruvate dehydrogenase complex, is one of the key molecules of cuproptosis. However, the prognostic value and immunological role of DLAT in pan-cancer are still unclear. Using a series of bioinformatics approaches, we studied combined data from different databases, including the Cancer Genome Atlas, Genotype Tissue-Expression, the Cancer Cell Line Encyclopedia, Human Protein Atlas, and cBioPortal to investigate the role of DLAT expression in prognosis and tumor immunity response. We also reveal the potential correlations between DLAT expression and gene alterations, DNA methylation, copy number variation (CNV), tumor mutational burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), immune infiltration levels, and various immune-related genes across different cancers. The results show that DLAT displays abnormal expression within most malignant tumors. Through gene set enrichment analysis (GSEA), we found that DLAT was significantly associated with immune-related pathways. Further, the expression of DLAT was also confirmed to be correlated with the tumor microenvironment and diverse infiltration of immune cells, especially tumor-associated macrophages (TAMs). In addition, we found that DLAT is co-expressed with genes encoding major histocompatibility complex (MHC), immunostimulators, immune inhibitors, chemokines, and chemokine receptors. Meanwhile, we demonstrate that DLAT expression is correlated with TMB in 10 cancers and MSI in 11 cancers. Our study reveals that DLAT plays an essential role in tumorigenesis and cancer immunity, which may be used to function as a prognostic biomarker and potential target for cancer immunotherapy.

Improving bowel preparation for colonoscopy with a smartphone application driven by artificial intelligence.

Optimal bowel preparation is a prerequisite for a successful colonoscopy; however, the rate of inadequate bowel preparation remains relatively high. In this study, we establish a smartphone app that assesses patient bowel preparation using an artificial intelligence (AI)-based prediction system trained on labeled photographs of feces in the toilet and evaluate its impact on bowel preparation quality in colonoscopy outpatients. We conduct a prospective, single-masked, multicenter randomized clinical trial, enrolling outpatients who own a smartphone and are scheduled for a colonoscopy. We screen 578 eligible patients and randomize 524 in a 1:1 ratio to the control or AI-driven app group for bowel preparation. The study endpoints are the percentage of patients with adequate bowel preparation and the total BBPS score, compliance with dietary restrictions and purgative instructions, polyp detection rate, and adenoma detection rate (secondary). The prediction system has an accuracy of 95.15%, a specificity of 97.25%, and an area under the curve of 0.98 in the test dataset. In the full analysis set (n = 500), adequate preparation is significantly higher in the AI-driven app group (88.54 vs. 65.59%; P < 0.001). The mean BBPS score is 6.74 ± 1.25 in the AI-driven app group and 5.97 ± 1.81 in the control group (P < 0.001). The rates of compliance with dietary restrictions (93.68 vs. 83.81%, P = 0.001) and purgative instructions (96.05 vs. 84.62%, P < 0.001) are significantly higher in the AI-driven app group, as is the rate of additional purgative intake (26.88 vs. 17.41%, P = 0.011). Thus, our AI-driven smartphone app significantly improves the quality of bowel preparation and patient compliance.

Effect of pleural adhesions on short- and long-term outcomes after minimally invasive esophagectomy: a propensity score matching analysis.

BACKGROUND: The extent to which the presence of pleural adhesions affects the surgical and oncological outcomes of patients undergoing McKeown minimally invasive esophagectomy (MIE) for esophageal cancer (EC) has not previously been studied. METHODS: Data of consecutive EC patients undergoing McKeown MIE by a single surgeon in the Department of Thoracic Surgery at Daping Hospital from November 2015 to December 2020 were collected. Patients were grouped according to the presence or absence of pleural adhesions when entering the chest cavity. Propensity score matching (PSM) was used to reduce selection bias from confounding factors. Kaplan-Meier was used to assess the survival differences. RESULTS: A total of 617 consecutive EC patients underwent McKeown MIE were enrolled. There were 116 patients with pleural adhesions (Group A) and 501 patients without pleural adhesions (Group B). Patients in Group A were more likely to be older than those of patients in Group B: (66.26 vs. 63.27, P = 0.001). In addition, Group A had more patients with chronic obstructive pulmonary disease (COPD) (24.1% vs. 16.8%, P = 0.04). After propensity score matching (102 matched patients in Group A and 185 matched patients in Group B), these findings were no longer statistically significant. Postoperative pulmonary infection occurred in 57 patients in Group A and in 15 patients in Group B (53.9% vs. 13.0%, P < 0.001). In addition, the presence of pleural adhesions was significantly associated with the prolonged operation time (232 min vs. 210 min, P < .001), length of stay (12 days vs. 10 days, P = 0.001), and hydrothorax requiring drainage (12.7% vs. 5.4%, P = 0.04). However, the disease-specific survival and disease-free survival rates were comparable between the two groups (P = 0.40 and 0.13, respectively). CONCLUSIONS: The presence of pleural adhesions predicted an increased operation time, length of stay, postoperative pneumonia, and hydrothorax requiring drainage of EC patients undergoing McKeown MIE, but did not exert unfavourable effect on long-term survival.

Tobacco leaf tissue rapidly detoxifies direct salt loads without activation of calcium and SOS signaling.

Salt stress is a major abiotic stress, responsible for declining agricultural productivity. Roots are regarded as hubs for salt detoxification, however, leaf salt concentrations may exceed those of roots. How mature leaves manage acute sodium chloride (NaCl) stress is mostly unknown. To analyze the mechanisms for NaCl redistribution in leaves, salt was infiltrated into intact tobacco leaves. It initiated pronounced osmotically-driven leaf movements. Leaf downward movement caused by hydro-passive turgor loss reached a maximum within 2 h. Salt-driven cellular water release was accompanied by a transient change in membrane depolarization but not an increase in cytosolic calcium ion (Ca2+ ) level. Nonetheless, only half an hour later, the leaves had completely regained turgor. This recovery phase was characterized by an increase in mesophyll cell plasma membrane hydrogen ion (H+ ) pumping, a salt uptake-dependent cytosolic alkalization, and a return of the apoplast osmolality to pre-stress levels. Although, transcript numbers of abscisic acid- and Salt Overly Sensitive pathway elements remained unchanged, salt adaptation depended on the vacuolar H+ /Na+ -exchanger NHX1. Altogether, tobacco leaves can detoxify sodium ions (Na+ ) rapidly even under massive salt loads, based on pre-established posttranslational settings and NHX1 cation/H+ antiport activity. Unlike roots, signaling and processing of salt stress in tobacco leaves does not depend on Ca2+ signaling.

Up-Regulation of SH3TC2 Induced by YTHDF1 Predicts Poor Outcome and Facilitates Cell-Cycle Progress in Colorectal Cancer.

N6-methyladenosine (m6A) modification plays a crucial role in determining the fate and function of RNA transcripts in tumor cells. Nevertheless, how m6A regulates the expression of key molecules and coordinates its involvement in the development of colorectal cancer (CRC) remains largely unclear. Here, we report that the m6A reading protein YTHDF1-mediated up-regulation of SH3TC2 promotes CRC growth both in vitro and in vivo. In a pan-cancer analysis across more than thirty types of cancer, we found that SH3TC2 was dysregulated in nine cancers, including BLCA, CHOL, COAD, LAML, PAAD, READ, SKCM, BRCA, and TGCT, and was closely associated with patient prognosis in four cancers, including COAD, MESO, PAAD, and READ. In particular, SH3TC2 was overexpressed in CRC as confirmed by six independent study cohorts. Clinically, high expression of SH3TC2 predicted worse disease-free survival (DFS) in CRC patients. SH3TC2 showed fascinating diagnostic value and was correlated with immunosuppression in CRC. Functionally, RNA-sequencing combined with experiments revealed that knockdown of SH3TC3 significantly inhibited cell-cycle progress of CRC, impairing cell growth. Mechanistically, YTHDF1 protein directly binds with SH3TC2 mRNA and promotes its elevation in an m6A-dependent manner. Thus, our findings provide a mechanism to target the YTHDF1/SH3TC2 axis for CRC therapy.

The tumor microenvironment in gastrointestinal adenocarcinomas revealed a prognostic and immunotherapeutic biomarker.

Accumulated evidence has elucidated that the tumor microenvironment (TME) is great of clinical significance in predicting survival outcomes and therapeutic efficacy. Nonetheless, few studies have investigated the prognostic and immunotherapeutic signature correlated with TME phenotypes in gastrointestinal adenocarcinomas (GIAC). Here, by estimating the TME pattern of immune infiltration and expression in over 1,000 GIAC patients, we revealed three TME subgroups and identified six key differential genes. To predict the TME phenotypes, TMEscore was established and validated to be an independent prognostic factor, where the high TMEscore was characterized by immune activation and response to immunotherapy and accompanied with favorable prognosis in GIAC. Furthermore, TMEscore was confirmed to predict prognosis and immunotherapeutic response in six datasets. In summary, depicting TME landscape of GIAC patients may be beneficial for interpreting survival and immunotherapeutic response, and provide new strategies for clinical treatment of GIAC.

Neoadjuvant immunotherapy combined with chemotherapy significantly improved patients' overall survival when compared with neoadjuvant chemotherapy in non-small cell lung cancer: A cohort study.

Background: Programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors displayed considerable advantages in neoadjuvant therapy of non-small cell lung cancer (NSCLC), but the specific application of neoadjuvant immunotherapy has not been well determined, and the long-term prognostic data of neoadjuvant immunochemotherapy combined with surgical resection of NSCLC remains limited. In this study, we intended to assess the efficacy of the neoadjuvant therapy of the PD-1 inhibitor and long-term prognosis in patients with resectable NSCLC. Methods: We retrospectively analyzed NSCLC surgical patients treated with neoadjuvant therapy in our hospital, and divided them into a neoadjuvant chemotherapy group and a neoadjuvant immunotherapy combined with chemotherapy group. The propensity score matching method was used to evaluate the effectiveness of immunotherapy combined with chemotherapy in the treatment of resectable lung cancer, and the long-term prognosis of these two groups was compared. Results: A total of 62 cases were enrolled, including 20 patients (20/62, 32.26%) in the immunotherapy group and 42 patients (42/62, 67.74%) in the chemotherapy group. The clinical baseline data of these two groups were balanced. In the immunotherapy group, all patients had tumor regression in imaging finding (tumor regression ratio: 11.88% - 75.00%). In the chemotherapy group, 30 patients had tumor regression (tumor regression ratio: 2.70% - 58.97%). The R0 removal rates of cancers were comparable between the immunotherapy group and chemotherapy group (19/20, 95.00% vs. 39/42, 92.86%, P=1.000). The two groups were balanced in complete minimally invasive surgery, pneumonectomy, operative duration, blood loss, postoperative complications, and hospital stay. The immunotherapy group had more sleeve resection (36.84% vs. 10.26%, p=0.039) including bronchial sleeve and vascular sleeve, higher pathological complete response (pCR) rate (57.89% vs. 5.13%, P<0.001) and major pathologic response (MPR) rate (78.95% vs. 10.26%, P<0.001). There were no differences in survival curves for: smoker and non-smoker, squamous cell carcinoma and adenocarcinoma, or right lung cancer and left lung cancer. Moreover, patients who achieved MPR (including pCR) had significantly better overall survival (OS) and disease-free survival (DFS). Patients in immunotherapy group had significantly better OS and longer DFS than those in chemotherapy group. Conclusions: In conclusion, neoadjuvant immunotherapy combined with chemotherapy can provide better OS and DFS and improving pCR and MPR rates by shrinking tumors.This study has been registered in the Chinese Clinical Trial Registry, number ChiCTR2200060433. http://www.chictr.org.cn/edit.aspx?pid=170157&htm=4.

Mask-wearing behavior during COVID-19 in China and its correlation with e-health literacy.

Background: During the Coronavirus (COVID-19) pandemic, wearing masks became crucial for preventing infection risk and maintaining basic health. Therefore, it is necessary to understand the behavioral characteristics of the mask-wearing public to provide theoretical reference for the prevention and control of COVID-19. Methods: We conducted a nationwide survey on the mask-wearing behavior of the public and their health literacy levels by distributing electronic questionnaires. Univariate and logistic regression analyses were performed to determine the factors influencing mask-wearing behavior. Pearson's correlation was used to analyze the correlation between mask-wearing behaviors and e-health literacy. Results: A total of 1,972 valid questionnaires were collected; 99.8% of the public wore masks when going out and 59.2% showed good mask-wearing behavior. Most people choose to wear disposable medical masks (61.3%), followed by medical surgical masks (52.9%). All participants indicated that they had understood the information on how to use masks, and most obtained it through social media (61.8%). The average of the e-health literacy scores of those with good mask-wearing behavior was significantly higher than those with poor mask-wearing behavior (P < 0.05), and each item score of the former's e-health literacy was significantly higher than the latter (P < 0.05). Further, there was a positive correlation between mask-wearing behavior and e-health literacy (R = 0.550, P < 0.05). Logistic regression analysis showed that seven factors are related to mask-wearing behavior, including gender, place of residence, educational level, work or living environment, marital status, flu symptoms, and whether living with people in home quarantine (P < 0.01). Conclusion: The overall compliance of the public's mask-wearing behavior in China during COVID-19 is good. However, there are shortcomings regarding the selection, use, and precautions. The differences in mask-wearing behavior are related to factors including gender, place of residence, educational level, work or living environment, marital status, presence of flu symptoms, and whether living with people in home quarantine. Higher levels of e-health literacy indicated better mask-wearing behavior. Therefore, it is necessary to strengthen the public's popularization and education regarding the prevention and control of COVID-19.

Identification and Validation of an m6A-Related LncRNA Signature to Predict Progression-Free Survival in Colorectal Cancer.

The RNA methylation of N6 adenosine (m6A) plays a crucial role in various biological processes. Strong evidence reveals that the dysregulation of long non-coding RNAs (lncRNA) brings about the abnormality of downstream signaling in multiple ways, thus influencing tumor initiation and progression. Currently, it is essential to discover effective and succinct molecular biomarkers for predicting colorectal cancer (CRC) prognosis. However, the prognostic value of m6A-related lncRNAs for CRC remains unclear, especially for progression-free survival (PFS). Here, we screened 24 m6A-related lncRNAs in 622 CRC patients and identified five lncRNAs (SLCO4A1-AS1, MELTF-AS1, SH3PXD2A-AS1, H19 and PCAT6) associated with patient PFS. Compared to normal samples, their expression was up-regulated in CRC tumors from TCGA dataset, which was validated in 55 CRC patients from our in-house cohort. We established an m6A-Lnc signature for predicting patient PFS, which was an independent prognostic factor by classification analysis of clinicopathologic features. Moreover, the signature was validated in 1,077 patients from six independent datasets (GSE17538, GSE39582, GSE33113, GSE31595, GSE29621, and GSE17536), and it showed better performance than three known lncRNA signatures for predicting PFS. In summary, our study demonstrates that the m6A-Lnc signature is a promising biomarker for forecasting patient PFS in CRC.

Neoadjuvant Anlotinib and chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced esophageal squamous cell carcinoma: Short-term results of an open-label, randomized, phase II trial.

Background: Clinical benefits of neoadjuvant Anlotinib for locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear. This study evaluated the efficacy and safety of neoadjuvant Anlotinib plus chemotherapy followed by minimally invasive esophagectomy (MIE) for the treatment of patients with locally advanced ESCC. Methods: Patients with locally advanced ESCC were randomly assigned to neoadjuvant Anlotinib combined with chemotherapy (Anlotinib group) or neoadjuvant chemoradiotherapy alone (nCRT group) with an allocation ratio of 1:1. The primary endpoint was the R0 surgical resection rate. Secondary endpoints included postoperative pathologic stage, complete response (CR) rate, and safety. Safety was assessed by adverse events (AEs) and postoperative complications. Results: From August 2019 to August 2021, 93 patients were assigned to the nCRT or Anlotinib group. Of the 93 patients, 79 underwent MIE and were finally included in the per-protocol set (nCRT group: n=39; Anlotinib group: n=40). The R0 resection rate was 97.4% for nCRT versus 100.0% for Anlotinib group (p>0.05). Compared with the nCRT group, patients in the Anlotinib group had shorter total operation duration (262.2 ± 39.0 vs. 200.7 ± 25.5 min, p=0.010) and less blood loss (161.3 ± 126.7 vs. 52.4 ± 39.3 mL, p<0.001). No significant differences were found in the postoperative pathologic stage between the Anlotinib group and nCRT group (all p>0.05). Besides, the incidences of AEs (80.0% vs. 92.3%) and postoperative complications (22.5% vs. 30.8%) were similar between the two groups (all p>0.05). Conclusions: Neoadjuvant Anlotinib plus chemotherapy had a similar safety profile and pathologic response, but better surgical outcomes than nCRT for locally advanced ESCC.