Dual-Region Computed Tomography Radiomics-Based Machine Learning Predicts Subcarinal Lymph Node Metastasis in Patients with Non-small Cell Lung Cancer.

BACKGROUND: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC. METHODS: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation. RESULTS: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727. CONCLUSIONS: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models.

Hydrogen-Bonding-Assisted Substituent Engineering for Modulating Magnetic Spin Couplings and Switching in m-Phenylene Nitroxide Diradicals.

Rational modification of the coupler for the theoretical design of molecular magnets has attracted extensive interest. Substituent insertion is a widely used strategy for adjusting molecular properties, but its effect and modulation on magnetic spin couplings have been less investigated. In this work, we predict the magnetic properties of the design m-phenylene nitroxide (NO) diradicals regulated by introducing substituents. The calculated results for those two pairs of diradicals indicate that the signs of their magnetic coupling constants J do not change, but the magnitudes remarkably change after substituent regulation in the range from 253 to 730 cm-1. Such noticeable magnetic changes induced by introducing subsituents are mainly attributed to different electronic effects of substituents, assisted by the proximity of two NO groups, good planarity, conjugation, and an intramolecular hydrogen bond. In particular, the insertion of intramolecular H-bonds not only indicates an electronic effect but also has greatly changed the spin density distribution. Further aromaticity of the coupler ring, spin densities, and molecular orbitals and energetics was evaluated to gain a better understanding of magnetic regulation. Interestingly, further protonation of some substituents (e.g., -NO2 and -CO2) can noticeably turn the spin coupling from ferromagnetic to antiferromagnetic, showing manipulable magnetic switching. This work provides a promising strategy based on substituent engineering for magnetic spin coupling modulation, not only turning the coupling magnitude but also enabling the magnetic switching, thus providing insights into molecular magnetic manipulation for spintronics applications.

Metformin attenuates chronic lung allograft dysfunction: evidence in rat models.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) directly causes an abysmal long-term prognosis after lung transplantation (LTx), but effective and safe drugs are not available. Metformin exhibits high therapeutic potential due to its antifibrotic and immunomodulatory effects; however, it is unclear whether metformin exerts a therapeutic effect in CLAD. We sought to investigate the effect of metformin on CLAD based on rat models. METHODS: Allogeneic LTx rats were treated with Cyclosporin A (CsA) in the first week, followed by metformin, CsA, or vehicle treatment. Syngeneic LTx rats received only vehicles. All rats were sacrificed on post-transplant week 4. Pathology of lung graft, spleen, and thymus, extent of lung fibrosis, activity of profibrotic cytokines and signaling pathway, adaptive immunity, and AMPK activity were then studied. RESULTS: Allogeneic recipients without maintenance CsA treatment manifested CLAD pathological characteristics, but these changes were not observed in rats treated with metformin. For the antifibrotic effect, metformin suppressed the fibrosis extent and profibrotic cytokine expression in lung grafts. Regarding immunomodulatory effect, metformin reduced T- and B-cell infiltration in lung grafts, spleen and thymus weights, the T- and B-cell zone areas in the spleen, and the thymic medullary area. In addition, metformin activated AMPK in lung allografts and in α-SMA+ cells and T cells in the lung grafts. CONCLUSIONS: Metformin attenuates CLAD in rat models, which could be attributed to the antifibrotic and immunomodulatory effects. AMPK activation suggests the potential molecular mechanism. Our study provides an experimental rationale for further clinical trials.

The application of radiomics in esophageal cancer: Predicting the response after neoadjuvant therapy.

Esophageal cancer (EC) is one of the fatal malignant neoplasms worldwide. Neoadjuvant therapy (NAT) combined with surgery has become the standard treatment for locally advanced EC. However, the treatment efficacy for patients with EC who received NAT varies from patient to patient. Currently, the evaluation of efficacy after NAT for EC lacks accurate and uniform criteria. Radiomics is a multi-parameter quantitative approach for developing medical imaging in the era of precision medicine and has provided a novel view of medical images. As a non-invasive image analysis method, radiomics is an inevitable trend in NAT efficacy prediction and prognosis classification of EC by analyzing the high-throughput imaging features of lesions extracted from medical images. In this literature review, we discuss the definition and workflow of radiomics, the advances in efficacy prediction after NAT, and the current application of radiomics for predicting efficacy after NAT.

Double-lung versus heart-lung transplantation for end-stage cardiopulmonary disease: a systematic review and meta-analysis.

We compared posttransplant outcomes following double-lung transplantation (DLTx) and heart-lung transplantation (HLTx), based on a search of PubMed, Cochrane Library, and Embase, from inception to March 8, 2022, for studies that report outcomes of these procedures. We then performed a meta-analysis of baseline characteristics and posttransplant outcomes. Subgroup analyses were implemented according to indication, publication year, and center. This study was registered on PROSPERO (number CRD42020223493). Ten studies were included in this meta-analysis, involving 1230 DLTx patients and 1022 HLTx patients. The DLTx group was characterized by older donors (P = 0.04) and a longer allograft ischemia time (P < 0.001) than the HLTx group. The two groups had comparable 1-year, 3-year, 5-year, 10-year survival rates (all P > 0.05), with similar results identified in subgroup analyses. We found no significant differences in 1-year, 5-year, and 10-year chronic lung allograft dysfunction (CLAD)-free survival, length of intensive care unit stay and hospital stay, length of postoperative ventilation, in-hospital mortality, or surgical complications between the groups (all P > 0.05). Thus, DLTx provides similar posttransplant survival to HLTx for end-stage cardiopulmonary disease. These two procedures have a comparable risk of CLAD and other posttransplant outcomes.

Long-term outcomes of laparoscopic Extralevator Abdominoperineal excision with modified position change for low rectal Cancer treatment.

BACKGROUND: Extralevator abdominoperineal excision (ELAPE) has been recommended for treating low rectal cancer due to its potential advantages in improving surgical safety and oncologic outcomes as compared to conventional abdominoperineal excision (APE). In ELAPE, however, whether the benefits of intraoperative position change to a prone jackknife position outweighs the associated risks remains controversial. This study is to introduce a modified position change in laparoscopic ELAPE and evaluate its feasibility, safety and the long-term therapeutic outcomes. METHODS: Medical records of 56 consecutive patients with low rectal cancer underwent laparoscopic ELAPE from November 2013 to September 2016 were retrospectively studied. In the operation, a perineal dissection in prone jackknife position was firstly performed and the laparoscopic procedure was then conducted in supine position. Patient characteristics, intraoperative and postoperative outcomes, pathologic and 5-year oncologic outcomes were analyzed. RESULTS: The mean operation time was 213.5 ± 29.4 min and the mean intraoperative blood loss was 152.7 ± 125.2 ml. All the tumors were totally resected, without intraoperative perforation, conversion to open surgery, postoperative 30-day death, and perioperative complications. All the patients achieved pelvic peritoneum reconstruction without the usage of biological mesh. During the follow-up period, perineal hernia was observed in 1 patient, impaired sexual function in 1 patient, and parastomal hernias in 3 patients. The local recurrence rate was 1.9% and distant metastasis was noted in 12 patients. The 5-year overall survival rate was 76.4% and the 5-year disease-free survival rate was 70.9%. CONCLUSIONS: Laparoscopic ELAPE with modified position change is a simplified, safe and feasible procedure with favorable outcomes. The pelvic peritoneum can be directly closed by the laparoscopic approach without the application of biological mesh.

Right lung transplantation with a left-to-right inverted anastomosis in a rat model.

Objective: Right lung transplantation in rats has been attempted occasionally, but the technical complexity makes it challenging to apply routinely. Additionally, basic research on inverted lobar lung transplantation is scarce because of the lack of a cost-effective experimental model. We first reported right lung transplantation in a rat model using left-to-right inverted anastomosis to imitate the principle of clinically inverted lung transplantation. Methods: Right lung transplantation was performed in 10 consecutive rats. By using a 3-cuff technique, the left lung of the donor rat was implanted into the right thoracic cavity of the recipient rat. The rat lung graft was rotated 180° along the vertical axis to achieve anatomic matching of right hilar structures. Another 10 consecutive rats had received orthotopic left lung transplantation as a control. Results: All lung transplantation procedures were technically successful without intraoperative failure. One rat (10%) died of full pulmonary atelectasis after right lung transplantation, whereas all rats survived after left lung transplantation. No significant difference was observed in heart-lung block retrieval (8.6 ± 0.8 vs 8.4 ± 0.9 minutes), cuff preparation (8.3 ± 0.9 vs 8.7 ± 0.9 minutes), or total procedure time (58.2 ± 2.6 vs 56.6 ± 2.1 minutes) between the right lung transplantation and standard left lung transplantation groups (P > .05), although the cold ischemia time (14.2 ± 0.9 vs 25.5 ± 1.7 minutes) and warm ischemia time (19.8 ± 1.5 vs 13.7 ± 1.8 minutes) were different (P < .001). Conclusions: Right lung transplantation with a left-to-right inverted anastomosis in a rat model is technically easy to master, expeditious, and reproducible. It can potentially imitate the principle of clinically inverted lung transplantation and become an alternative to standard left lung transplantation.

Hepatic portal venous gas associated with rapid infusion of postoperative early enteral nutrition after radical total gastrectomy.

Hepatic portal venous gas (HPVG) is a rare and severe imaging manifestation for surgeons, and it may require emergency surgery. We report an unusual case of HPVG in association with the drip rate of enteral nutrition (EN) after laparoscopic-assisted radical total gastrectomy with Roux-en-Y reconstruction. A 66-year-old woman with gastric cancer was admitted to our hospital. She was diagnosed with cirrhosis of unknown cause and underwent radical total gastrectomy. The rapid infusion of postoperative early EN caused the intestine to expand quickly and injured intestinal mucosa. Hepatic portal venous gas and pneumatosis intestinalis (PI) were discovered subsequently. Early detection and timely effective intervention eventually and completely cured the patient; meanwhile, we avoided unnecessary exploratory laparotomy. Hepatic portal venous gas and PI after radical total gastrectomy can be cured with careful conservative management; the drip rate of EN should be tightly controlled and monitored during treatment after radical total gastrectomy.

Photoinduced Three-Component Difluoroamidosulfonylation/Bicyclization: A Route to Dihydrobenzofuran Derivatives.

A visible-light-induced photocatalyst-free three-component radical cascade bicyclization has been achieved to obtain diverse difluoroamidosulfonylated dihydrobenzofurans in moderate to good yields. This protocol avoids potential toxicity and the tedious removal procedure for photocatalysts and also features mild reaction conditions and a good functional group tolerance. Moreover, mechanistic investigations reveal the formation of a charge-transfer complex and the involvement of an intramolecular 1,5-hydrogen atom transfer process in this transformation.

Genetic effect of ischemia-reperfusion injury upon primary graft dysfunction and chronic lung allograft dysfunction in lung transplantation: evidence based on transcriptome data.

The unclear mechanism that ischemia-reperfusion injury (IRI) contributes to the development of primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) remains a major issue in lung transplantation. Differentially expressed PGD-related genes and CLAD-related genes during IRI (IRI-PGD common genes and IRI-CLAD common genes) were identified using GEO datasets (GSE127003, GSE8021, GSE9102) and GeneCards datasets. Enrichment analysis and four network analyses, namely, protein-protein interaction, microRNA (miRNA)-gene, transcription factor (TF)-gene, and drug-gene networks, were then performed. Moreover, GSE161520 was analyzed to identify the differentially expressed core miRNAs during IRI in rats. Finally, Pearson correlation analysis and ROC analysis were performed. Eight IRI-PGD common genes (IL6, TNF, IL1A, IL1B, CSF3, CXCL8, SERPINE1, and PADI4) and 10 IRI-CLAD common genes (IL1A, ICAM1, CCL20, CCL2, IL1B, TNF, PADI4, CXCL8, GZMB, and IL6) were identified. Enrichment analysis showed that both IRI-PGD and IRI-CLAD common genes were significantly enriched in "AGE-RAGE signaling pathway in diabetic complication" and "IL-17 signaling pathway". Among the core miRNAs, miR-1-3p and miR-335 were differentially expressed in IRI rats. Among core TFs, CEBPB expression had a significant negative correlation with P/F ratio (r = -0.33, P = 0.021). In the reperfused lung allografts, the strongest positive correlation was exhibited between PADI4 expression and neutrophil proportion (r = 0.76, P < 0.001), and the strongest negative correlation was between PADI4 expression and M2 macrophage proportion (r = -0.74, P < 0.001). In lung allografts of PGD recipients, IL6 expression correlated with activated dendritic cells proportion (r = 0.86, P < 0.01), and IL1B expression correlated with the neutrophils proportion(r = 0.84, P < 0.01). In whole blood of CLAD recipients, GZMB expression correlated with activated CD4+ memory T cells proportion (r = 0.76, P < 0.001).Our study provides the novel insights into the molecular mechanisms by which IRI contributes to PGD and CLAD and potential targets for therapeutic intervention.

Direct synthesis of indazole derivatives via Rh(III)-catalyzed C-H activation of phthalazinones and allenes.

A novel Rh(III)-catalyzed annulation of phthalazinones or pyridazinones with various allenes was developed, leading to the formation of indazole derivatives bearing a quaternary carbon in moderate to good yields. The targeted products were synthesized via sequential C-H activation and olefin insertion, followed by ß-hydride elimination and intramolecular cyclization. The synthetic protocol proceeded efficiently with broad functional group tolerance, high atom efficiency and high Z-selectivity. The practicability of this method was proved by synthetic transformation.

Copper-Catalyzed Phosphorylation of 2,3-Allenoic Acids and Phosphine Oxide: Access to Phosphorylated Butenolides.

We investigated a novel Cu-catalyzed annulation of 2,3-allenoic acids with diphenylphosphine oxide, leading to the formation of 4-phosphate butenolides in up to 88% yield. The formation of the C-P bond provides new avenues for the functionalization of different furan-2(5H)-ones, with favorable features such as suitable functional group tolerance and mild synthesis conditions.

Risk factors for lymph node metastasis in T1 esophageal squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Lymph node metastasis (LNM) affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma (ESCC). However, reports of the risk factors for LNM have been controversial. AIM: To evaluate risk factors for LNM in T1 ESCC. METHODS: We searched Embase, PubMed and Cochrane Library to select studies related to LNM in patients with T1 ESCC. Included studies were divided into LNM and non-LNM groups. We performed a meta-analysis to examine the relationship between LNM and clinicopathologic features. Odds ratio (OR), mean differences and 95% confidence interval (CI) were assessed using a fixed-effects or random-effects model. RESULTS: Seventeen studies involving a total of 3775 patients with T1 ESCC met the inclusion criteria. After excluding studies with heterogeneity based on influence analysis, tumor size (OR = 1.93, 95%CI = 1.49-2.50, P < 0.001), tumor location (OR = 1.46, 95%CI = 1.17-1.82, P < 0.001), macroscopic type (OR = 3.17, 95%CI = 2.33-4.31, P < 0.001), T1 substage (OR = 6.28, 95%CI = 4.93-8.00, P < 0.001), differentiation (OR = 2.11, 95%CI = 1.64-2.72, P < 0.001) and lymphovascular invasion (OR = 5.86, 95%CI = 4.60-7.48, P < 0.001) were found to be significantly associated with LNM. Conversely, sex, age and infiltrative growth pattern were not identified as risk factors for LNM. CONCLUSION: A tumor size > 2 cm, lower location, nonflat macroscopic type, T1b stage, poor differentiation and lymphovascular invasion were associated with LNM in patients with T1 ESCC.

Palladium-Catalyzed [2 + 2 + 1] Annulation of Alkyne-Tethered Aryl Iodides with Diaziridinone: Synthesis of 3,4-Fused Tricyclic Indoles.

A novel palladium-catalyzed [2 + 2 + 1] annulation of alkyne-tethered aryl iodides with diaziridinone was developed, leading to the formation of 3,4-fused tricyclic indoles. From a mechanistic standpoint, the formation of fused tricyclic indole scaffolds involved C,C-palladacycles, which were synthesized through the intramolecular reaction of aryl halides and alkynes. The cascade reaction described herein could be carried out with a broad range of substrates and provided various 3,4-fused tricyclic indoles with yields up to 98%.

Rh(iii)-catalyzed, hydrazine-directed C-H functionalization with 1-alkynylcyclobutanols: a new strategy for 1H-indazoles.

Rh(iii)-catalyzed coupling of phenylhydrazines with 1-alkynylcyclobutanols was realized through a hydrazine-directed C-H functionalization pathway. This [4+1] annulation, based on the cleavage of a Csp-Csp triple bond in alkynylcyclobutanol, provides a new pathway to prepare diverse 1H-indazoles under mild reaction conditions.

Effect of coffee consumption on the risk of gastric cancer: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND AND OBJECTIVES: Results from observational epidemiologic studies on the relationship between coffee consumption and gastric cancer are inconsistent and inconclusive. To assess the association between coffee consumption and the risk of gastric cancer, we summarized evidence from prospective cohort studies. METHODS: Relevant studies were retrieved through computer searches (PubMed, EmBase and the Cochrane Library) and a review of references up to December 2014. The quality of the included studies was evaluated by Newcastle-Ottawa quality assessment scale. We used a meta-analytic approach to estimate overall hazard ratios (HRs) and 95% confidence intervals (CIs) for regular coffee drinkers versus individuals who seldom drank coffee. Sensitivity analysis and subgroup analysis were performed to assess the reliability of our results. A dose-response analysis was performed to assess the risk of gastric cancer based on the level of coffee consumption. RESULTS: Nine prospective cohort studies involving 1,250,825 participants and 3027 gastric cancer cases were included in this meta-analysis. The pooled HR of gastric cancer for the study-specific regularly versus seldom coffee drinking categories was 1.05 (95% CI, 0.88 to 1.25) with significant heterogeneity across studies (I(2) = 74.0%, P = 0.000). After the sensitivity analysis, three studies were deleted; however the association remained insignificant (HR, 0.99; 95% CI, 0.91 to 1.08). Subgroup analysis by anatomic location showed a risk for coffee consumption associated with cardia cancer (HR, 1.23; 95% CI, 1.04 to 1.45; heterogeneity, I(2) = 36.4, P = 0.207). In the dose-response analysis, there was no significant association between coffee intake (in cups) and the risk of gastric cancer (P for linearity trend and non-linearity > 0.05). CONCLUSION: Our meta-analysis demonstrated that coffee consumption was not associated with overall gastric cancer risk; however, coffee consumption may be a risk factor for gastric cardia cancer.