Neoadjuvant aumolertinib monotherapy for EGFR-mutant lung squamous cell carcinoma: a case report.

Background: Lung cancer is the malignant tumor with high incidence and mortality in China, and more than 30% of non-small cell lung cancer (NSCLC) patients are in the locally advanced stage at the first-time diagnosis. Currently, neoadjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) combined with radical surgery is effective in the treatment of unresectable stage III EGFR-mutated NSCLC (NSCLCm), and related studies are gradually increasing. But the feasibility of neoadjuvant EGFR-TKI combined with radical surgery for unresectable stage III EGFR-mutant lung squamous cell carcinoma (LUSQm) remains controversial. Case Description: This report presented a successful case of neoadjuvant target-therapy with aumolertinib, the third-generation EGFR-TKI, combined with radical surgery for a stage IIIA LUSQm female patient. After four cycles (28 days/cycle) of neoadjuvant target-therapy, the tumor had a partial response on imaging evaluation and pathological evaluation after surgery showed complete tumor response. The neoadjuvant target-therapy was well tolerated. All adverse events (AEs) that occurred during the treatment were grade I, including decreased platelets, impaired liver function, and diarrhea. The patient was instructed to continue taking Aumolertinib for 3 years after surgery. At the cut-off date of April 1, 2024, the patient had no recurrence after 20 months of treatment. Conclusions: The result of patient treatment demonstrated the potential feasibility of neoadjuvant Aumolertinib monotherapy for locally advanced LUSQm. The report provides some support for neoadjuvant target-therapy for LUSQm.

Enhanced expression of miR-20a driven by nanog exacerbated the degradation of extracellular matrix in thoracic aortic dissection.

Thoracic aortic dissection (TAD) is a life-threatening vascular disease manifested as intramural bleeding in the medial layers of the thoracic aorta. The key histopathologic feature of TAD is medial degeneration, characterized by depletion of vascular smooth muscle cells (VSMCs) and degradation of extracellular matrix (ECM). MicroRNA, as essential epigenetic regulators, can inhibit the protein expression of target genes without modifying the sequences. This study aimed to elucidate the role and underlying mechanism of miR-20a, a member of the miR-17-92 cluster, in regulating ECM degradation during the pathogenesis of TAD. The expression of the miR-17-92 cluster was significantly increased in synthetic VSMCs derived from TAD lesions compared to contractile VSMCs isolated from normal thoracic aortas. Notably, the expression of miR-20a was increased in VSMCs in response to serum exposure and various stimuli. In TAD lesions, the expression of miR-20a was significantly negatively correlated with that of elastin. Elevated expression of miR-20a was also observed in thoracic aortas of TAD mice induced by ß-aminopropionitrile fumarate and angiotensin II. Overexpression of miR-20a via mimic transfection enhanced the growth and invasive capabilities of VSMCs, with no significant impact on their migratory activity or the expression of phenotypic markers (α-SMA, SM22, and OPN). Silencing of miR-20a with inhibitor transfection mitigated the hyperactivation of MMP2 in VSMCs stimulated by PDGF-bb, as evidenced by reduced levels of active-MMP2 and increased levels of pro-MMP2. Subsequently, TIMP2 was identified as a novel target gene of miR-20a. The role of miR-20a in promoting the activation of MMP2 was mediated by the suppression of TIMP2 expression in VSMCs. In addition, the elevated expression of miR-20a was found to be directly driven by Nanog in VSMCs. Collectively, these findings indicate that miR-20a plays a crucial role in maintaining the homeostasis of the thoracic aortic wall during TAD pathogenesis and may represent a potential therapeutic target for TAD.

Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II-III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study.

This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3-48.1) in arm A and were 55.6% (95% CI 21.2-86.3) and 11.1% (95% CI 0.3-48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8-61.6) and 55.6% (95% CI 21.2-86.3). With a median follow-up of 22.4 months (95% CI 19.0-26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II-III NSCLC.

Limited resection is comparable to lobectomy for tumor size ≤ 2 cm pulmonary invasive mucinous adenocarcinoma.

OBJECTIVES: Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. METHODS: Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer-specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. RESULTS: In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157-5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). CONCLUSIONS: Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Construction land reduction projects as a pathway to sustainability: an empirical analysis of risks factors in China.

Construction land reduction (CLR) is an effective instrument to improve intensive land use, restrict the expansion of construction land, safeguard the requisition-compensation balance of construction land in China, and realize sustainable development. But multiple risks arise from the process of construction land reduction. In that case, identifying and analyzing the key risks of CLR is the prerequisite for formulating practical policy guidelines. This study is conducted to identify the risk factors of CLR and analyze these risks based on expert opinion. Initially, the original risk factors are sourced from existing literature. In order to tailor them to China's specific context, the Delphi method is employed to systematically refine risk definitions, consolidate similar risk elements, and identify any previously unrecognized risks in the literature. Following an in-depth review of the literature, we create a contextual relationship-based model employing an integrated technique of interpretive structural modeling (ISM) and Cross-Impact Matrix Multiplication Applied to Classification (MICMAC) analysis. Based on the ISM and MICMAC analysis, five key risks were identified, and the prevention strategies and policy recommendations for CLR project risks are put forward.

Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies.

We performed comprehensive proteogenomic characterization of small cell lung cancer (SCLC) using paired tumors and adjacent lung tissues from 112 treatment-naive patients who underwent surgical resection. Integrated multi-omics analysis illustrated cancer biology downstream of genetic aberrations and highlighted oncogenic roles of FAT1 mutation, RB1 deletion, and chromosome 5q loss. Two prognostic biomarkers, HMGB3 and CASP10, were identified. Overexpression of HMGB3 promoted SCLC cell migration via transcriptional regulation of cell junction-related genes. Immune landscape characterization revealed an association between ZFHX3 mutation and high immune infiltration and underscored a potential immunosuppressive role of elevated DNA damage response activity via inhibition of the cGAS-STING pathway. Multi-omics clustering identified four subtypes with subtype-specific therapeutic vulnerabilities. Cell line and patient-derived xenograft-based drug tests validated the specific therapeutic responses predicted by multi-omics subtyping. This study provides a valuable resource as well as insights to better understand SCLC biology and improve clinical practice.

Overexpression of VEGFA mediated by HIF-1 is associated with higher rate of spread through air spaces in resected lung adenocarcinomas.

BACKGROUND: Spread through air spaces (STAS), a newly identified pattern of invasion in lung adenocarcinomas (LACs), is an unfavorable prognostic factor for patients with LAC, but the molecular characteristics and mechanisms underlying STAS have not been adequately explored. METHODS: In total, 650 pathologically confirmed invasive LAC patients who underwent curative resection between December 2019 and April 2020 were reviewed. Disease-free survival (DFS) and overall survival (OS) were analyzed using the log-rank test and the Cox proportional hazards model. A comparative deep sequencing analysis was conducted to explore the molecular characteristics underlying STAS. Vascular endothelial growth factor A (VEGFA) expression was evaluated by immunoblotting and immunohistochemical analysis using fresh tumor tissue and tissue microarray. RESULTS: STAS was more prevalent in patients with a smoking history (p < 0.001), high pathological TNM stage (p < 0.001), lymphovascular invasion (p < 0.001), visceral pleural invasion (p < 0.001) and micropapillary/solid histological subtypes (p < 0.001). STAS-negative patients had better DFS (p < 0.001) and OS (p = 0.003) compared to STAS-positive patients with invasive LACs, especially in the lymph node-negative population (p < 0.001). After RNA-sequencing analysis, hypoxia-inducible factor-1 (HIF-1) signaling was enriched and appeared to be strongly correlated with STAS, and more STAS-positive individuals were detected in the higher VEGFA-expressing group (p = 0.042). CONCLUSIONS: We demonstrated that STAS was an independent prognostic marker of poor clinical outcome, especially in lymph node-negative patients, and that higher VEGFA expression mediated by HIF-1 signaling was associated with an increased STAS rate.

Perioperative outcomes comparison of robotic and video-assisted thoracoscopic thymectomy for thymic epithelial tumor: a single-center experience.

BACKGROUND: The advent of robot-assisted thoracoscopic surgery (RATS) has completely revolutionized the modality of thymectomy, which could reportedly achieve equivalent efficacy compared with a minimally invasive approach. This study was conducted to further compare the perioperative outcomes between these two modalities. METHODS: A retrospective single-center study that included patients receiving either a robotic or video-assisted thoracoscopic (VAT) thymectomy between February 2021 and January 2023 was conducted. All the patients were pathologically confirmed with thymic epithelial tumors. Clinical and pathological characteristics and perioperative outcomes were collected and compared between these two cohorts. RESULTS: A total of 190 patients were included in this study, with 61 (32.1%) and 129 (67.9%) receiving robotic and video-assisted thymectomy, respectively. The clinicopathological characteristics were not significantly different between these 2 groups. The size of the resected specimens in the RATS cohort was larger than the VATS cohort [median (IQR), 13.0 (8.0-16.0) vs. 9.0 (6.7-12.0) cm, p < 0.001], while the procedural duration was longer for the RATS group than its counterpart [median (IQR), 105 (85-143) vs. 85 (69-115) min, p = 0.001]. Moreover, no other significant difference was observed between these two groups. Since more than half of the robotic thymectomy was performed using a subxiphoid approach, a subgroup analysis was further conducted. Similarly, the robotic group through a subxiphoid approach harbored a longer procedural duration, and the size of the specimens obtained was larger than the VATS group [median (IQR), 14.0 (11.0-16.5) vs. 12.5 (8.5-15.0) cm, p = 0.061]. CONCLUSIONS: The early clinical efficacy of robotic thymectomy was proven comparable to the established VATS approach, and such a modality might have strength when obtaining larger specimens, which could contribute to improving long-term efficacy. Despite the longer procedural duration recorded in the early stage of conducting robotic thymectomy, further accumulation would help decrease the time.

Prognostic Significance of the Proposed Residual Tumor Classification in Patients With NSCLC After Sleeve Lobectomy.

Introduction: To validate the residual tumor (R) classification proposed by the International Association for the Study of Lung Cancer (IASLC) in NSCLC after sleeve lobectomy. Methods: A total of 682 patients were analyzed. The R status, on the basis of the Union for International Cancer Control (UICC) criteria, was recategorized according to the IASLC descriptors. Recurrence-free survival (RFS) and overall survival (OS) among different R classifications were assessed for the entire cohort and pathologic node (pN) subgroups. Results: All in all, 631 (92.5%), 48 (7.1%), and three patients (0.4%) were classified as R0, R1, and R2, respectively, by the UICC criteria, whereas 489 (71.7%), 110 (16.1%), and 83 patients (12.2%), received R0, uncertain resection (R[un]), and R1/2 resection, respectively, according to the IASLC criteria. There were 96 patients (15.2%) with UICC R0 who were reclassified as R(un), mainly because of the positive highest mediastinal node station (82 of 96, 85.4%). A total of 46 patients (7.3%) were reassigned from UICC R0 to IASLC R1/2 owing to extracapsular extension. For the entire cohort, patients with R(un) and R1/2 exhibited worse RFS (R[un], adjusted p = 0.023; R1/2, adjusted p = 0.001) and OS (R[un], adjusted p = 0.040; R1/2, adjusted p = 0.051) compared with R0. No significant differences were observed between R(un) and R1/2 (RFS, adjusted p = 0.586; OS, adjusted p = 0.781). Furthermore, subgroup analysis revealed a distinct prognostic impact of the IASLC R status-with prognostic significances in the pN1 and pN2 subgroups, but not in the pN0 subgroup. Conclusions: The IASLC R descriptors helped to stratify the prognosis of NSCLC after sleeve lobectomy, with its prognostic impact varied among pN stages.

Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study.

Afatinib, an irreversible ErbB-family blocker, could improve the survival of advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patients (NSCLCm+). This phase II trial (NCT04201756) aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLCm+. Forty-seven patients received neoadjuvant Afatinib treatment (40 mg daily). The primary endpoint was objective response rate (ORR). Secondary endpoints included pathological complete response (pCR) rate, pathological downstaging rate, margin-free resection (R0) rate, event-free survival, disease-free survival, progression-free survival, overall survival, treatment-related adverse events (TRAEs). The ORR was 70.2% (95% CI: 56.5% to 84.0%), meeting the pre-specified endpoint. The major pathological response (MPR), pCR, pathological downstaging, and R0 rates were 9.1%, 3.0%, 57.6%, and 87.9%, respectively. The median survivals were not reached. The most common TRAEs were diarrhea (78.7%) and rash (78.7%). Only three patients experienced grade 3/4 TRAEs. Biomarker analysis and tumor microenvironment dynamics by bulk RNA sequencing were included as predefined exploratory endpoints. CISH expression was a promising marker for Afatinib response (AUC = 0.918). In responders, compared to baseline samples, increasing T-cell- and B-cell-related features were observed in post-treatment tumor and lymph-node samples, respectively. Neoadjuvant Afatinib is feasible for stage III NSCLC+ patients and leads to dynamic changes in the tumor microenvironment.

Prognostic factors and role of postoperative radiotherapy in surgically resected thymomas.

Objective: To investigate the prognostic factors in and role of postoperative radiotherapy (PORT) for surgically resected thymomas. Methods: A total of 1540 patients with pathologically confirmed thymomas undergoing resection between 2000 and 2018 were identified retrospectively from the SEER (Surveillance, Epidemiology, and End Results) database. Tumors were restaged as local (limited to thymus), regional (invasion to mediastinal fat and other neighboring structures), or distant stage. Disease-specific survival (DSS) and overall survival (OS) were estimated by the Kaplan-Meier method and the log-rank test. Adjusted hazard ratios (HRs) with 95% CIs were calculated by Cox proportional hazards modeling. Results: Tumor stage and histology were independent predictors of both DSS (regional: HR, 3.711; 95% CI, 2.006-6.864; distant: HR, 7.920; 95% CI, 4.061-15.446; type B2/B3: HR, 1.435; 95% CI, 1.008-2.044) and OS (regional: HR, 1.461; 95% CI, 1.139-1.875; distant: HR, 2.551; 95% CI, 1.855-3.509; type B2/B3: HR, 1.409; 95% CI, 1.153-1.723). For patients with regional stage and type B2/B3 thymomas, PORT was associated with better DSS after thymectomy/thymomectomy (HR, 0.268; 95% CI, 0.099-0.727), but the association was not significant after extended thymectomy (HR, 1.514; 95% CI, 0.516-4.44). Among patients with lymph node metastases, those who received PORT (HR, 0.372; 95% CI, 0.146-0.949), chemotherapy (HR, 0.843; 95% CI, 0.303-2.346), or both (HR, 0.296, 95% CI, 0.071-1.236) had a better OS. Conclusions: The extent of invasion and tumor histology were independent predictors of worse survival following surgical resection of thymoma. Patients with regional invasion and type B2/B3 thymoma who undergo thymectomy/thymomectomy may benefit from PORT, while patients with nodal metastases may benefit from multimodal therapy, including PORT and chemotherapy.

Identify the Clinicopathological Characteristics of Lung Carcinoma Patients Being False Negative in Folate Receptor Based Circulating Tumor Cell Detection.

In lung cancer diagnosis, folate receptor (FR)-based circulating tumor cell (CTC) has shown its ability to distinguish malignancy from benign disease to some extent. However, there are still some patients that cannot be identified by FR-based CTC detection. And studies comparing the characteristics between true positive (TP) and false negative (FN) patients are few. Thus, the study comprehensively analyzes the clinicopathological characteristics of FN and TP patients in the current study. According to inclusion and exclusion criteria, 3420 patients are enrolled. Combining the pathological diagnosis with CTC results, patients are divided into FN and TP groups, and clinicopathological characteristics are compared between two groups. Compared with TP patients, FN patients have smaller tumor, early T stage, early pathological stage, and without lymph node metastasis. Epidermal growth factor receptor (EGFR) mutation status is different between FN and TP group. And this result is also demonstrated in lung adenocarcinoma subgroup but not in lung squamous cell carcinoma subgroup. Tumor size, T stage, pathological stage, lymph node metastasis, and EGFR mutation status may influence the accuracy of FR-based CTC detection in lung cancer. However, further prospective studies are needed to confirm the findings.

The Prognostic Impact of Epidermal Growth Factor Receptor Mutation in Clinical Stage I Lung Adenocarcinoma.

BACKGROUND: This study investigated the prognostic impact of epidermal growth factor receptor (EGFR) mutation in clinical stage I lung adenocarcinoma patients. METHODS: Data for 952 patients who received surgical resection and underwent detection of oncogenic driver mutations were retrospectively collected. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the log-rank test. The adjusted hazard ratio (aHR) with 95% CI of the prognosticator was calculated by Cox proportional hazards model, and cumulative incidence function was measured by competing risk regression model. RESULTS: EGFR mutation was detected in 581 patients (61.0%) and was more frequent in women (63.9%), nonsmokers (85.5%), and those with ground-glass nodules (GGNs; 56.6%). EGFR mutation was not associated with recurrence and death in the entire cohort or GGN cohort. However, for patients with radiologic pure-solid appearance, EGFR mutation was an independent risk factor for RFS (aHR, 1.623; 95% CI, 1.192-2.210) and distant recurrence (aHR, 1.863; 95% CI, 1.311-2.650), but not OS. Subsequently, subgroup analysis based on EGFR mutation subtypes, including exon 19 deletions (19-Del), exon 21 L858R substitution (L858R), and rare mutations in patients with radiologic pure-solid appearance, revealed that all 3 subtypes have poorer RFS (19-Del: aHR, 1.424; 95% CI, 0.991-2.047; L858R: aHR, 1.708; 95% CI, 1.172-2.490; rare mutations: aHR, 2.500; 95% CI, 1.400-4.465) and higher prevalent distant recurrence (19-Del: aHR, 1.595; 95% CI, 1.061-2.400; L858R: aHR, 2.073; 95% CI, 1.371-3.140; rare mutations: aHR, 2.657; 95% CI, 1.397-5.050) compared with wild-type. CONCLUSIONS: In clinical stage I lung adenocarcinoma, EGFR mutation was associated with worse RFS and higher prevalent distant recurrence in patients with radiologic pure-solid appearance but not in patients with GGN.

Identifying potential targets for lung cancer intervention by analyzing the crosstalk of cancer-associated fibroblasts and immune and metabolism microenvironment.

BACKGROUND: Cancer-associated fibroblasts (CAFs) have been reported to play a crucial role in the tumor microenvironment and progression. METHODS: The data used in this study were obtained from the Cancer Genome Atlas and Gene Expression Omnibus databases, and all analyses were performed using R software. RESULTS: We first quantified the CAFs infiltration through single sample gene set enrichment analysis in the TCGA and combined GEO cohort (GSE30219, GSE37745, and GSE50081). Our result showed that patients with high levels of CAF infiltration were associated with worse clinical features and poor prognosis. Immune microenvironment analysis indicated that high CAF infiltration might result in increased infiltration of immune cells, including aDC, B cells, CD8+ T cells, cytotoxic cells, DC, eosinophils, iDC, macrophages, mast cells, neutrophils, NK CD56dim cells, NK cells, pDC, and T cells. Correlation analysis showed a significant positive correlation between CAFs and M2 macrophages, while a negative correlation was found between CAFs and glycerophospholipid metabolism. Kaplan-Meier survival curves indicated that glycerophospholipid metabolism was a protective factor against lung cancer. Biological enrichment analysis showed that pathways such as allograft rejection, epithelial-mesenchymal transition, KRAS signaling, TNF-α signaling, myogenesis, IL6/JAK/STAT3 signaling, IL2/STAT5 signaling were upregulated in the patients with high CAF infiltration. Moreover, patients with high CAF infiltration had a lower proportion of immunotherapy responders. Genome analysis showed that low CAFs infiltration was associated with high genome instability. We identified FGF5 and CELF3 as key genes involved in the interaction between CAFs, M2 macrophages, and glycerophospholipid metabolism, and further analyzed FGF5. In vitro experiments showed that FGF5 promoted the proliferation, invasion and migration of lung cancer cells and was primarily localized in the nucleoli fibrillar center. CONCLUSIONS: Our study provides novel insights into the roles of CAFs in lung cancer progression and the underlying crosstalk of tumor metabolism and immune microenvironment.

Single- versus multi-port video-assisted thoracic surgery for pulmonary aspergilloma: a propensity-matched study.

OBJECTIVES: The utilization of single-port video-assisted thoracic surgery for pulmonary aspergilloma (PA) has not been well studied. The study was performed to evaluate the safety and feasibility of it for PA compared with multi-port video thoracic-assisted surgery. METHODS: From August 2007 to December 2019, consecutive PA patients receiving surgeries at Shanghai Pulmonary Hospital were enrolled retrospectively. Propensity score matching based on preoperative clinical variables was utilized to compare perioperative and long-term outcomes. RESULTS: In all 358 patients, a total of 63 patients underwent single-port video-assisted thoracic surgery, and 63 out of 145 patients for multi-port surgeries were paired with the single-port video-assisted thoracic surgery recipients. The median follow-up period was 40 months (range, 2-140 months). Patients receiving single-port video-assisted thoracic surgery showed a similar operation time, intraoperative blood loss, drainage duration and drainage volume to those of multi-port video-assisted thoracic surgery recipients (P > 0.05). Patients undergoing lobectomy by single-port approach experienced a shorter postoperative hospital stay {4.9 [standard deviation (SD): 2.0] vs 5.9 (SD: 2.3), P = 0.014}. The average postoperative pain scores [day 0: 2.6 (SD: 0.7) vs 3.1 (SD: 0.8), day 3: 4.0 (SD: 0.9) vs 4.8 (SD: 3.9), day 7: 2.2 (SD: 0.5) vs 3.1 (SD: 0.8), P < 0.001] and the number of days that patients required analgesic agents [3.0 (SD: 2.2) vs 4.8 (SD: 2.1), P < 0.001] were also decreased in the single-port video-assisted thoracic surgery group. CONCLUSIONS: Single-port video-assisted thoracic surgery is a safe and feasible alternative to multi-port video-assisted thoracic surgery for simple PA and selected complex ones, with a potential advantage of reduced postoperative pain.

Short-term outcomes of uniportal robotic-assisted thoracic surgery anatomic pulmonary resections: experience of Shanghai Pulmonary Hospital.

Background: To share our experience of uniportal robotic-assisted thoracic surgery (U-RATS) anatomic pulmonary resection. Methods: A retrospective study was conducted to compare the efficacy of U-RATS and biportal-RATS (B-RATS; 2 ports). From March 2021 to June 2022, 109 patients were enrolled in this study. The perioperative results of U-RATS and B-RATS were compared. Results: Perioperative outcomes were comparable between the two groups, including the length of hospital stay and the rate of post-operative (post-op) complications. The mean duration of surgery of the two groups were 124.1 vs. 103.6 min (P=0.049), mean intraoperative blood loss was 131.7 vs. 143.1 mL, mean post-op hospital stay was 3.83 vs. 3.05 days (P=0.037), and the thoracic drainage of the first day after surgery were 230.9 vs. 207.1 mL. The visual analogue scale (VAS) scores after the first post-op day were 3.83 vs. 4.57 (P=0.018). No perioperative mortality occurred in either group. Conclusions: Both U-RATS and B-RATS are safe and feasible methods for major pulmonary resections. U-RATS achieved similar perioperative outcomes and lower VAS-scores for the patients, which may improve the post-op experience and the quality of patients' lives. Further follow-up investigations are required to evaluate the long-term efficacy of U-RATS.

Cardiac index: A superior parameter of cardiac function than left ventricular ejection fraction in risk stratification of hypertrophic cardiomyopathy.

BACKGROUND: An appropriate indicator of cardiac function in the risk stratification of hypertrophic cardiomyopathy (HCM) patients is urgently needed. Cardiac index that reflects cardiac pumping function may be suitable. OBJECTIVE: The purpose of this study was to investigate the clinical significance of reduced cardiac index in HCM patients. METHODS: A total of 927 HCM patients were enrolled. The primary endpoint was cardiovascular death. The secondary endpoints were sudden cardiac death (SCD) and all-cause death. Combination models were constructed by adding reduced cardiac index and reduced left ventricular ejection fraction (LVEF) to the HCM risk-SCD model. Predictive accuracy was determined by C-statistics. RESULTS: Reduced cardiac index was defined as cardiac index ≤2.42 L/min/m2. During median follow-up of 4.3 years, 51 patients reached the endpoint. Reduced cardiac index independently increased the risk of cardiovascular death (adjusted hazard ratio [aHR] 2.976; P = .007), SCD (aHR 6.385; P = .001), and all-cause death (aHR 2.428; P = .010). By adding reduced cardiac index to the HCM risk-SCD model, the model C-statistic increased from 0.691 to 0.762, with an integrated discrimination improvement of 0.021 (P = .018) and a net reclassification improvement of 0.560 (P = .007). The addition of reduced LVEF failed to improve the original model. Better predictive accuracy for all endpoints was also indicated in reduced cardiac index than in reduced LVEF. CONCLUSION: Reduced cardiac index is an independent predictor of poor prognoses in HCM patients. Combining reduced cardiac index rather than reduced LVEF improved the HCM risk-SCD stratification strategy. The reduced cardiac index showed better predictive accuracy than reduced LVEF for all endpoints.

Relationship between iodine knowledge and dietary iodine intake in pregnant and lactating women: a cross-sectional study.

OBJECTIVE: This study assessed the iodine knowledge of pregnant and lactating women and the relationship to dietary iodine intake and iodine status. The factors influencing iodine intake were analysed. DESIGN: Basic information and iodine knowledge were collected via a questionnaire. A FFQ assessed dietary iodine intake. The urinary iodine concentration (UIC) was measured using the arsenic-cerium catalytic spectrophotometric determination of iodine in urine (WS/T 107 -2016). SETTING: A cross-sectional study involving pregnant and lactating women in Xinjiang, China was conducted. PARTICIPANTS: A total of 1181 pregnant women and 504 lactating women were enrolled in the study. RESULTS: The median UIC for pregnant and lactating women was 179·27 and 192·81 µg/l, respectively, and the dietary iodine intake was 407·16 and 356·89 µg/d, respectively. Of the pregnant and lactating women, 73·4 % and 82·5 % had medium iodine knowledge, respectively. In pregnant women, iodine knowledge and dietary iodine intake were positively correlated. High iodine knowledge and iodine education were shown to be protective factors for excessive iodine intake in pregnant women. CONCLUSION: This study demonstrated that the iodine nutritional status of women in Xinjiang was appropriate, and iodine knowledge was at a medium level, but there was confusion about iodine nutrition. Public education is needed to improve iodine knowledge and active iodine supplementation awareness among these populations of women.

Differentiation-related genes in tumor-associated macrophages as potential prognostic biomarkers in non-small cell lung cancer.

Background: The purpose of this study was to evaluate the role of differentiation-related genes (DRGs) in tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC). Methods: Single cell RNA-seq (scRNA-seq) data from GEO and bulk RNA-seq data from TCGA were analyzed to identify DRGs using trajectory method. Functional gene analysis was carried out by GO/KEGG enrichment analysis. The mRNA and protein expression in human tissue were analyzed by HPA and GEPIA databases. To investigate the prognostic value of these genes, three risk score (RS) models in different pathological types of NSCLC were generated and predicted NSCLC prognosis in datasets from TCGA, UCSC and GEO databases. Results: 1,738 DRGs were identified through trajectory analysis. GO/KEGG analysis showed that these genes were predominantly related to myeloid leukocyte activation and leukocyte migration. 13 DRGs (C1QB, CCL4, CD14, CD84, FGL2, MS4A6A, NLRP3, PLEK, RNASE6, SAMSN1, SPN, TMEM176B, ZEB2) related to prognosis were obtained through univariate Cox analysis and Lasso regression. C1QB, CD84, FGL2, MS4A6A, NLRP3, PLEK, SAMSN1, SPN, and ZEB2 were downregulated in NSCLC compared to non-cancer tissue. The mRNA of 13 genes were significantly expressed in pulmonary macrophages with strong cell specificity. Meanwhile, immunohistochemical staining showed that C1QB, CCL4, SPN, CD14, NLRP3, SAMSN1, MS4A6A, TMEM176B were expressed in different degrees in lung cancer tissues. ZEB2 (HR=1.4, P<0.05) and CD14 (HR=1.6, P<0.05) expression were associated with a worse prognosis in lung squamous cell carcinoma; ZEB2 (HR=0.64, P<0.05), CD84 (HR=0.65, P<0.05), PLEK (HR=0.71, P<0.05) and FGL2 (HR=0.61, P<0.05) expression were associated with a better prognosis in lung adenocarcinoma. Three RS models based on 13 DRGs both showed that the high RS was significantly associated with poor prognosis in different pathological types of NSCLC. Conclusions: This study highlights the prognostic value of DRGs in TAMs in NSCLC patients, providing novel insights for the development of therapeutic and prognostic targets based on TAM functional differences.

Application of the Novel Grading System of Invasive Pulmonary Adenocarcinoma in a Real Diagnostic Scenario: A Brief Report of 9353 Cases.

Introduction: The International Association for the Study of Lung Cancer proposed a novel grading system of invasive pulmonary adenocarcinoma (IPA), but the application of this grading system and its genotypic characterization in the real diagnostic scenario has never been reported. Methods: We prospectively collected and analyzed the clinicopathological and genotypic features of a cohort of 9353 consecutive patients with resected IPA, including 7134 patients with detection of common driver mutation. Results: In the entire cohort, 3 (0.3%) of lepidic, 1207 (19.0%) of acinar, and 126 (23.6%) of papillary predominant IPAs were diagnosed as grade 3. In chronological order, an evident downtrend of the proportion of grade 2 was observed in chronological order. Conversely, the diagnostic ratio of grade 1 (8.0%-14.5%) and grade 3 (27.9%-32.3%) experienced a gradual rise. EGFR mutation was more frequently detected in grade 2 (77.5%) and grade 1 (69.7%) IPA than grade 3 (53.7%, p < 0.001), whereas the mutation rates of KRAS, BRAF, ALK, and ROS1 were higher in grade 3 IPA. More importantly, the rate of EGFR mutation gradually fell as the proportion of high-grade components increased, to 24.3% in IPA with more than 90% high-grade components. Conclusions: The grading system for IPA could be applied to stratify patients with different clinicopathological and genotypic features in a real diagnostic scenario.