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Abstract Background Cancer stem cells (CSCs) are a specific subpopulation of cancer cells with the ability of self‐renewal, infinite proliferation, multidifferentiation and tumorigenicity, and play critical roles in cancer progression and treatment resistance. CSCs are tightly regulated by the tumor microenvironment, such as hypoxia; however, how hypoxia regulates CSCs in non‐small cell lung cancer (NSCLC) remains unclear. Methods The proportion of ALDHhi cells was examined using the Aldefluor assay. Tankyrase inhibitor XAV939 and siRNA were used to inhibit β‐catenin while pcDNA3‐β‐catenin (S33Y) plasmid enhanced the expression of β‐catenin. Western blot was administered for protein detection. The mRNA expression was measured by quantitative real‐time PCR. Results We found that hypoxia led to an increase in the proportion of ALDHhi cells in lung squamous carcinoma (LUSC) H520 cells, while causing a decrease in the ALDHhi cell proportion in lung adenocarcinoma (LUAD) A549 cells. Similarly, β‐catenin expression was upregulated in H520 cells but downregulated in A549 cells upon exposure to hypoxia. Mechanically, the proportion of ALDHhi cells in both cell lines was decreased by β‐catenin inhibitor or siRNA knockdown, whereas increased after β‐catenin overexpression. Furthermore, hypoxia treatment suppressed E‐cadherin expression in H520 cells and enhanced N‐cadherin and β‐catenin expression, while this effect was completely opposite in A549 cells. Conclusion The hypoxia‐EMT‐β‐catenin axis functions as an important regulator for the proportion of CSCs in NSCLC and could potentially be explored as therapeutic targets in the future.

Abstract Background The efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients harboring neurotrophin receptor kinase (NTRK) family mutations remains obscure. Methods The Zehir cohort from cBioPortal was used to analyze the mutations (MT) frequency of NTRK family in patients with NSCLC, and their correlation with clinical characteristics and patient survival. The influence of NTRK MT on ICIs efficacy was evaluated in ICIs-treated patients from Samstein cohort and further validated by use of data from OAK/POPLAR cohort. Results In the Zehir cohort, a significant difference was observed in median overall survival (mOS) between patients with NTRK MT and wild-type (WT) (mOS: 18.97 vs. 21.27 months, HR = 1.34, 95%CI 1.00-1.78; log-rank P = 0.047). In Samstein cohort, the mOS of NTRK mutant patients receiving ICIs has improved compared to WT patients (mOS: 21.00 vs. 11.00 months, log-rank P = 0.103). Notably, in subgroup analysis, ICIs significantly prolonged mOS in patients with NTRK3 MT than in WT patients (mOS: not available vs. 11.00 months, HR = 0.36, 95%CI 0.16–0.81; log-rank P = 0.009). Identical mOS between NTRK MT and WT patients receiving ICIs treatment (mOS: 13.24 vs. 13.50 months, log-rank P = 0.775) was observed in OAK/POPLAR cohort. Moreover, a similar programmed death ligand 1 (PD-L1) expression, but higher tumor mutational burden (TMB), blood TMB (bTMB) and enriched anti-tumor immunity were observed in NTRK MT compared to WT (P

Located at an average elevation of approximately 2000 m, the Minjiang River Basin (MJB), a key tributary of the Upper Yangtze River, straddles the Western Sichuan Plateau and the Sichuan Basin. Vegetation here is crucial for human life, providing oxygen and energy. However, the influence of climatic variables, human activities, and rugged terrain on vegetation vitality is still debated. This study mainly leverages data from the Normalized Difference Vegetation Index (NDVI), meteorological stations data, and land use data. Analytical techniques include trend analysis, partial correlation coefficient analysis (PCC), principal component analysis (PCA), and partial least squares structural equation modeling (PLS-SEM). Results indicate a stable upward trend in vegetation growth with minimal fluctuations, with a growth rate of 0.95 × 10−3/a (p < 0.01). PCC analysis shows a positive correlation between NDVI and key climatic elements in over 60% of the area. The areas with significant vegetation growth had the highest average PCC. PCA and PLS-SEM identify temperature and precipitation as primary growth drivers, while elevation and land use intensity hinder growth. The MJB landscape reveals thresholds and tipping points, with specific temperature and precipitation benchmarks varying by elevation, delineating the boundary between flourishing vegetation and growth inhibition.

Small watersheds are fundamental units for natural processes and social management in Southwestern China. Accurately assessing carbon sinks in small watersheds is crucial for formulating carbon sink management policies. However, there has been a lack of assessment of the dynamics of carbon fluxes in the major ecosystems of small watersheds. Here, we selected the Reshuihe River watershed, which is a typical small watershed in Southwestern China, to measure carbon fluxes using eddy covariance systems for two years (October 2021 to September 2023) from three major ecosystems, namely forest, cropland, and non-timber forest. We compared variations and controlling factors of net ecosystem exchange (NEE), gross primary productivity (GPP), and ecosystem respiration (Re) among different ecosystems, and estimated annual watershed carbon flux based on the land cover areas of the three ecosystems. This study found that three ecosystems were net annual carbon sinks during the study period. Forest was the strongest (−592.8 and −488.1 gC m−2 a−1), followed by non-timber forest (−371.0 gC m−2 a−1), and cropland was the smallest (−92.5 and −71.6 gC m−2 a−1), after taking fallow period into account. Weeds were a significant source of carbon flux in non-timber forest ecosystems. It was also found that variations in daily NEE were controlled by photosynthetically active radiation and soil volumetric water content, with weak effects related to temperature also being observed. However, when the temperature exceeded 21 °C, GPP and Re were significantly reduced in cropland. Finally, it was discovered that the total carbon sink of the three ecosystems in the watershed for one year was −52.15 Gg C. Overall, we found that small watersheds dominated by forest ecosystems in Southwestern China have a strong carbon sink capacity.

Abstract Background Drug repurposing refers to the application of existing drugs to new therapeutic indications. As phenotypic indicators of human drug response, drug side effects may provide direct signals and unique opportunities for drug repurposing. Objectives We aimed to identify drugs frequently associated with hypohidrosis or anhidrosis adverse reactions (that is, the opposite condition of hyperhidrosis) from the pharmacovigilance database, which could be potential candidates as anti-hyperhidrosis treatment agents. Methods In this observational, retrospective, pharmacovigilance study, adverse event reports of hypohidrosis or anhidrosis in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) were assessed between January 2004 and December 2021 using reporting odds ratio (ROR) estimates and categorized by the World Health Organization Anatomical Therapeutic Chemical (ATC) classification code. The onset time of drug-associated hypohidrosis or anhidrosis was also examined. Results There were 540 reports of 192 drugs with suspected drug-associated hypohidrosis or anhidrosis in the FAERS database, of which 39 drugs were found to have statistically significant signals. Nervous system drugs were most frequently reported (187 cases, 55.82%), followed by alimentary tract and metabolism drugs (35 cases, 10.45%), genitourinary system and sex hormones (28 cases, 8.36%), and dermatologicals (22 cases, 6.57%). The top 3 drug subclasses were antiepileptics, drugs for urinary frequency and incontinence, and antidepressants. Taking disproportionality signals, pharmacological characteristics of drugs and appropriate onset time into consideration, the main putative drugs for hyperhidrosis were glycopyrronium, solifenacin, oxybutynin, and botulinum toxin type A. Other drugs, such as topiramate, zonisamide, agalsidase beta, finasteride, metformin, lamotrigine, citalopram, ciprofloxacin, bupropion, duloxetine, aripiprazole, prednisolone, and risperidone need more investigation. Conclusions Several candidate agents among hypohidrosis or anhidrosis-related drugs were identified that may be redirected for diminishing sweat production. There are affirmative data for some candidate drugs, and the remaining proposed candidate drugs without already known sweat reduction mechanisms of action should be further explored.

Abstract Background Immune checkpoint inhibitors (ICIs) have been shown to significantly improve the survival of patients with advanced lung adenocarcinoma (LUAD). However, only limited proportion of patients could benefit from ICIs. Novel biomarkers with strong predictability are needed for clinicians to maximize the efficacy of ICIs. Our study aimed to identify potential biomarkers predicting ICIs efficacy in LUAD. Methods The Cancer Genome Atlas (TCGA) PanCancer Atlas studies in cBioportal were used to evaluate the mutation frequency of ANK2 across multiple cancers. Clinical and mutational data for LUAD from ICIs-treated cohorts (Hellmann et al. and Rizvi et al.) were collected to explore the correlation between ANK2 mutation and clinical outcomes. In addition, the relationship between ANK2 expression and clinical outcomes was analyzed using LUAD data from TCGA and Gene Expression Omnibus. Furthermore, the impact of ANK2 mutation and expression on the tumor immune microenvironment of LUAD was analyzed using TCGA and TISIDB databases. Results Patients with ANK2 mutation benefited more from ICIs. In ICIs-treated cohort, prolonged progression-free survival (PFS) (median PFS: NR (not reached) vs. 5.42 months, HR (hazard ratio) 0.31, 95% CI 0.18–0.54; P = 0.0037), improved complete response rate (17.65% vs. 1.85%, P = 0.0402), and improved objective response rate (64.71% vs. 24.07%, P = 0.0033) were observed in LUAD patients with ANK2 mutation compared to their wild-type counterparts. Regarding ANK2 expression, it was observed that ANK2 expression was decreased in LUAD (P

Purpose: The prognostic nutritional index (PNI), which is derived from the albumin concentration and absolute lymphocyte number, is an effective indicator of cancer patients’ nutritional and immunological status. According to multiple studies, PNI was strongly linked to the prognosis of patients with non-small cell lung cancer (NSCLC). The predictive value of PNI for survival outcomes in NSCLC patients receiving immune checkpoint inhibitors (ICIs) is still in dispute at present. This meta-analysis is devoted to fill this information gap and investigate the predictive ability of PNI in NSCLC patients treated with ICIs. Methods: The PubMed, Embase, Cochrane Library databases, and conference proceedings were searched for eligible studies without language restriction. Overall survival (OS) and progression-free survival (PFS) were included. The predictive value of PNI was estimated using hazard ratios and their 95% confidence intervals. Results: Thirteen relevant retrospective cohort studies were included and these studies included 1119 patients with stage III-IV NSCLC. Lower PNI status was found to be an independent risk factor for worse survival outcomes in patients with NSCLC (OS HR = 2.68; 95%CI: 1.76–4.06; P

Abstract. Primary palmar hyperhidrosis (PPH) is a pathologic condition of excessive sweating on hands that has adverse impacts on patients’ social activity, professional life, and psychological state. Endoscopic thoracic sympathicotomy (ETS) is by far the treatment choice for PPH with the most stable and durable curative effects, but special attention should be given to the side effects of the surgery, especially compensatory hyperhidrosis (CH). This consensus is the second version of the Chinese Expert Consensus on the Surgical Treatment of PPH by the China Expert Committee on Palmar Hyperhidrosis (CECPH), which was published 10 years ago. This consensus emphasizes the need for special attention and careful assessment of the patients’ feelings, as well as their emotional and mental state, and emphasizes that distress due to palmar sweating and the desire for treatment are prerequisites for diagnosis. It also provides a more nuanced delineation of CH and reviews all new attempts to prevent and treat this side effect. New evidence of the epidemiology, pathogenesis of PPH, and indications for surgery were also assessed or recommended.

Objectives It is unclear whether the use of antineoplastic drugs for patients with lung cancer in China has changed after the implementation of the national drug price negotiation in 2016 and continual update of clinical guidelines. This study aims to evaluate the trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer in major cities of China.Design We conducted a retrospective observational study using data from January 2016 to December 2020.Setting This study used prescription records based on inpatient and outpatient hospital data from 97 hospitals in 9 major cities of China.Participants A total of 218 325 antineoplastic drug prescriptions in patients with lung cancer were retrospectively collected from the Hospital Prescription Analysis Cooperative Project during the study period.Outcome measures Trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer.Results The yearly antineoplastic prescriptions increased by 85.6% from 28 594 in 2016 to 53 063 in 2020 (Z=1.71, p=0.086). Significant increases were seen in the prescriptions for protein kinase inhibitors (PKIs) and monoclonal antibodies (mAbs), whereas significant decreases were observed in antimetabolites, plant alkaloids and platinum compounds. The yearly cost increased progressively by 145.0% from ¥113.6 million in 2016 to ¥278.3 million in 2020 (Z=2.20, p=0.027). The top three anticancer drug classes in terms of total cost were PKIs, antimetabolites and mAbs. In prescribing patterns of antineoplastic agents for lung cancer, monotherapy, and triple or more drug combinations gradually increased, while dual combinations decreased significantly from 30.8% to 19.6%.Conclusions Prescription practices among patients with lung cancer in China underwent major changes during the study period. The observed trends can aid in understanding the present medication use status of patients with lung cancer in China and provide information for future drug management.

Ecological red lines (ERLs) are one of innovation regional ecological management systems, and a major strategy of construction of ecological civilization of China. Assessments of ecosystem services and the ecological sensitivity of the environment are the conventional methods for ERL delineation, which cannot quickly identify protection patterns, and also lacks the recognition of geological and geographical processes mechanism and influencing factors of ERLs. However, this omission may lead to inaccurate ERL delineation in mountainous areas. This study constructed an ecological–geological (eco–geo) environment vulnerability assessment index system to quickly identify protection patterns and optimize conventional ERL, taking Sichuan Province of Southwest China as the study region. The results showed that the conventional ERL covered 148,000 km2, accounting for 30.45 % of the total area. The extreme and severe vulnerability areas in the eco–geo environment together covered 189,700 km2, accounting for 39.10 %. The conventional ERL was almost completely included in the extreme vulnerability zone. Two optimization methods were analyzed by overlaying the vulnerability zone (extreme/extreme and severe) on nature reserves and the conventional ERLs. The first scheme covered an area of 188,600 km2 and 238,400 km2 for extreme and extreme and severe vulnerability, respectively; this reflected a more comprehensive vulnerability and protection pattern. The second scheme covered 197,600 km2 and 241,700 km2 for extreme and extreme and severe vulnerability, respectively, and could rapidly identify the vulnerability zones and protected areas. The study found that the geological and geographical processes in mountainous areas were the key factors shaping the ERLs. The assessment and the two schemes on provincial scale were practical, referential for similar mountainous area of China, and also be applied to other scales, serving the comprehensive management of ERL and the regional ecological security.

Abstract The application of chemotherapy in non‐small cell lung cancer (NSCLC) is limited by the toxicity to normal cells and the development of multi‐drug resistance. Targeted chemotherapy using cytotoxic analogs against specific receptors on cancer cells could be a less toxic and more efficacious approach. We identified that the expressions of somatostatin receptor (SSTR) 2 and 5 in tumor tissues from NSCLC patients were higher than those in the adjacent normal tissues by immunohistochemistry, and therefore, cytotoxic somatostatin analogues might be applied for SSTRs‐mediated targeted therapy against NSCLC. Two cytotoxic analogs, paclitaxel‐octreotide (PTX‐OCT) and 2paclitaxel‐octreotide (2PTX‐OCT), were synthesized by linking one or two molecules of paclitaxel to one molecule of somatostatin analog octreotide. PTX‐OCT and 2PTX‐OCT significantly inhibited the growth and induced apoptosis of SSTR2‐ and SSTR5‐positive A549 cells, compared with the control (p

BackgroundThe emergence of immune checkpoint inhibitors (ICIs) has significantly improved the clinical outcomes of patients with metastatic melanoma. However, survival benefits are only observed in a subset of patients. The fibroblast growth factor receptor (FGFR) family genes are frequently mutated in melanoma, yet their impacts on the efficacy of ICIs remain unclear. Our study aimed to explore the association of FGFR mutations with ICIs efficacy in metastatic melanoma.MethodsThe Cancer Genome Atlas (TCGA) data (PanCancer Atlas, skin cutaneous melanoma (SKCM), n = 448) in cBioPortal were collected as a TCGA cohort to investigate the association between FGFR mutations and prognosis of melanoma patients. To explore the impact of FGFR mutations on the efficacy of ICIs in melanoma, clinical and tumor whole-exome sequencing (WES) data of four ICI-treated studies from cBioPortal were consolidated as an ICIs-treated cohort. Moreover, the relationship between FGFR mutations and immunogenicity (tumor mutation burden (TMB), neo-antigen load (NAL), mismatch repair (MMR)-related genes and DNA damage repair (DDR)-related genes) of melanoma was evaluated utilizing data from the ICIs-treated cohort. The influence of FGFR mutations on the tumor immune microenvironment (TIME) of melanoma was also analyzed using the TCGA cohort.ResultsIn the TCGA cohort, survival in melanoma patients with or without FGFR mutations was nearly equivalent. In the ICIs-treated cohort, patients with FGFR mutations had better survival than those without (median overall survival: 60.00 vs. 31.00 months; hazard ratio: 0.58, 95% CI: 0.42-0.80; P = 0.0051). Besides, the objective response rate was higher for patients harboring FGFR mutations (55.56%) compared to wild-type patients (22.40%) (P = 0.0076). Mechanistically, it was revealed that FGFR mutations correlated with increased immunogenicity (e.g., TMB, NAL, MMR-related gene mutations and DDR-related gene mutations). Meanwhile, FGFR mutant melanoma tended to exhibit an enhanced antitumor TIME compared with its wild-type counterparts.ConclusionsOur study demonstrated that FGFR mutations is a promising biomarker in stratifying patients with advanced melanoma who might benefit from ICIs therapy.

Neutrophils play a key role in the occurrence and development of cancer. However, the relationship between neutrophils and cancer prognosis remains unclear due to their great plasticity and diversity. To explore the effects of neutrophils on the clinical outcome of bladder cancer, we acquired and analyzed gene expression data and clinical information of bladder cancer patients from IMvigor210 cohort and The Cancer Genome Atlas dataset (TCGA) database. We established a neutrophil-based prognostic model incorporating five neutrophil-related genes (EMR3, VNN1, FCGRT, HIST1H2BC, and MX1) and the predictive value of the model was validated in both an internal and an external validation cohort. Multivariate Cox regression analysis further proved that the model remained an independent prognostic factor for overall survival and a nomogram was constructed for clinical practice. Additionally, FCGRT was identified as the key neutrophil-related gene linked to an adverse prognosis of bladder cancer. Up-regulation of FCGRT indicated activated cancer metabolism, immunosuppressive tumor environment, and dysregulated functional status of immune cells. FCGRT overexpression was also correlated with decreased expression of PD-L1 and low levels of tumor mutation burden (TMB). FCGRT predicted a poor response to immunotherapy and had a close correlation with chemotherapy sensitivity. Taken together, a novel prognostic model was developed based on the expression level of neutrophil-related genes. FCGRT served as a promising candidate biomarker for anti-cancer drug response, which may contribute to individualized prognostic prediction and may contribute to clinical decision-making.

BackgroundLiver metastasis is the most common type of lung cancer metastasis, and is a significant prognostic factor in lung cancer. However, the effect of liver metastases on the efficacy of immune checkpoint inhibitors (ICIs) remains inconsistent and controversial. The aim of this study was to explore the relationship between liver metastases and ICI efficacy in patients with advanced lung cancer based on data from randomized controlled trials (RCTs) and observational studies.MethodsPubMed, EMBASE, Cochrane Library databases, conference proceedings, as well as grey literature websites were searched for eligible studies without language restrict ion. Study quality was assessed using Cochrane tools and the Newcastle–Ottawa Quality Assessment Scale (NOS). Outcomes of interest were overall survival (OS) and progression-free survival (PFS). The difference in efficacy between patients with and without liver metastases was calculated by pooling ratios of hazard ratios (HR), as calculated using the deft approach.ResultsA total of 16 RCTs and 14 observational trials were included. Analyses of RCTs revealed a survival benefit for ICI treatment (i.e., ICI monotherapy, ICI + Chemotherapy, dual ICI therapy and dual ICI + Chemotherapy) versus standard therapies among non-small cell lung cancer (NSCLC) patients with liver metastases (PFS HR, 0.77; 95%CI, 0.61–0.97; OS HR, 0.78; 95%CI, 0.68–0.90). NSCLC patients with liver metastases achieved less PFS benefit and comparable OS benefit from ICI treatment compared with those without liver metastases (ratios of PFS–HRs, 1.19; 95%CI, 1.02–1.39; P=0.029; Ratios of OS–HRs, 1.10; 95%CI, 0.94–1.29; P=0.24). For patients with small cell lung cancer (SCLC), ICI treatment achieved a marginal effect on patients with liver metastases as compared with standard therapies (OS HR, 0.94; 95%CI, 0.73–1.23). SCLC patients with liver metastases benefited less from ICI treatment than patients without liver metastases (ratio of OS–HRs, 1.22; 95%CI, 1.01–1.46; P=0.036). In real-world data analysis, liver metastasis could be used as an independent prognostic risk factor, increasing the risk of death by 21% in lung cancer patients receiving ICI treatment compared with those without liver metastases (OS HR, 1.21; 95%CI, 1.17–1.27; P

Abstract Lung cancer is the leading cause of cancer‐related death worldwide, with an estimated 1.2 million deaths each year. Despite advances in lung cancer treatment, 5‐year survival rates are lower than ~15%, which is attributes to diagnosis limitations and current clinical drug resistance. Recently, more evidence has suggested that epigenome dysregulation is associated with the initiation and progress of cancer, and targeting epigenome‐related molecules improves cancer symptoms. Interestingly, some groups reported that the level of methylation of histone 3 lysine 4 (H3K4me3) was increased in lung tumors and participated in abnormal transcriptional regulation. However, a mechanistic analysis is not available. In this report, we found that the SET domain containing 1A (SETD1A), the enzyme for H3K4me3, was elevated in lung cancer tissue compared to normal lung tissue. Knockdown of SETD1A in A549 and H1299 cells led to defects in cell proliferation and epithelial‐mesenchymal transition (EMT), as evidenced by inhibited WNT and transforming growth factor β (TGFβ) pathways, compared with the control group. Xenograft assays also revealed a decreased tumor growth and EMT in the SETD1A silenced group compared with the control group. Mechanistic analysis suggested that SETD1A might regulate tumor progression via several critical oncogenes, which exhibited enhanced H3K4me3 levels around transcriptional start sites in lung cancer. This study illustrates the important role of SETD1A in lung cancer and provides a potential drug target for treatment.

BackgroundAlthough immune checkpoint inhibitors (ICIs) generally show poor therapeutic efficacy in patients with epidermal growth factor receptor (EGFR) mutations, certain research indicate that a small proportion of these patients do respond to ICIs. The present study sought to identify the features of patients with EGFR mutations who might benefit from ICIs from multiple studies and discussed the optimal treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations.MethodsThe profiles of 114 advanced NSCLC patients with EGFR mutations who received ICIs treatment were retrospectively reviewed. EGFR subtypes, programmed cell death ligand 1 (PD-L1) expression, and clinical characteristics regarding their impact on the efficacy of ICIs were investigated.ResultsPatients with major EGFR mutations (L858R or 19Del) had a shorter progression-free survival (PFS) and a lower objective response rate (ORR) as compared to patients with rare (20ins or G719X) and other EGFR mutations. Although not statistically significant, median overall survival (OS) tended to be longer in patients with negative (

The application of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer has significantly improved patient survival. However, most patients fail to respond to ICIs or develop drug resistance during treatment. Therefore, novel biomarkers are needed to predict the efficacy of ICIs or provide clues on how to overcome drug resistance. Here, it was revealed that cell division cycle 25C (CDC25C) expression was upregulated in lung adenocarcinoma (LUAD) compared to that of normal lung tissue in multiple databases. This was further verified by q-PCR. Furthermore, higher CDC25C expression was associated with shorter overall survival and worse pathological stage. Most importantly, a higher CDC25C expression was associated with shorter progression-free survival in LUAD patients treated with nivolumab, suggesting the role of the cell cycle in immunotherapy. In addition, CDC25C expression was significantly associated with immune cell infiltration and immune-related signatures in the LUAD tumor microenvironment. Moreover, CDC25C was differentially expressed and correlated with overall survival in multiple tumors, indicating that CDC25C is a broad-spectrum biomarker. Taken together, our study demonstrates that CDC25C is a prognostic biomarker for LUAD patients, especially for patients treated with ICIs. Our study also provides strong evidence for the role of the cell cycle in ICIs therapy and tumor microenvironment.

Background The biological behavior of cells change after they develop drug resistance, and the degree of resistance will be affected by the tumor microenvironment. Here, we aimed to explore the changes in the biological behavior of tumors and to observe the differences in the release of cytokines and chemokines which can influence the tumor microenvironment. We also aimed to study how TKIs‐resistant cell lines recruit macrophages to reduce the sensitivity of the cells following gefitinib administration. Methods We generated and maintained gefitinib‐resistant cell lines to study the differences between gefitinib‐sensitive cell lines according to clone formation, cell growth curve analysis, whole‐exome sequencing, and qPCR ARRAY technology. We used the WNT/β‐catenin inhibitor, WNT/β‐catenin activator and overexpression β‐catenin lentivirus to observe the changes in CCL2. M2 macrophages and gefitinib‐resistant cell lines HCC827/GR were cocultured to detect the viability gefitinib for inducing cell death. Results The proliferation and migratory activities were much more pronounced in HCC827/GR cells. CCL2 expression was also enhanced and regulated by β‐catenin in HCC827/GR. CCL2 promoted the chemotactic ability of M2 macrophages. M2 macrophages reduced the antitumor effect of gefitinib treatment by activating AKT/mTOR. Conclusions Gefitinib‐resistant cell lines have stronger proliferation and migration capabilities, and attract macrophages by releasing more CCL2 to reduce the sensitivity of cells to gefitinib.

Background The aim of this study was to investigate whether tobacco extracts could regulate PD‐L1 expression and enhance malignant biological differences in gefitinib‐resistant cell lines. Methods We constructed gefitinib‐resistant cells and observed the biological differences in gefitinib‐resistant cells. The cells were stimulated with medium containing 5% volume of tobacco extract, and the change in PD‐L1 expression and the mammalian target of rapamycin (mTOR) and p‐mTOR expression in gefitinib‐resistant cells treated with tobacco extracts was observed. We discussed the relationship between PD‐L1 and mTOR. Results Tobacco extracts could promote PD‐L1 expression in the cell line. Western blot analysis showed that mTOR and p‐mTOR were significantly enhanced in gefitinib‐resistant cell lines cultured in the tobacco extracts. The mTOR signaling pathway was involved in PD‐L1 expression and in regulating the expression of cytokines IL‐6 and IL‐23. In addition, the tobacco extracts could promote macrophage migration via mTOR/IL‐6. Conclusions PD‐L1 can transmit inhibitory signals and reduce the proliferation of CD8 + T cells in lymph nodes. Tobacco extracts upregulate PD‐L1 expression via mTOR/IL‐6. These results imply that lung cancer patients should not smoke and stay away from a smoke environment.

Background We investigated the safety and feasibility of intraoperative near‐infrared (NIR) imaging using indocyanine green (ICG) during sympathectomy in the management of primary palmar hyperhidrosis (PPH). Methods We performed a retrospective review of 142 patients (ICG group) who underwent endoscopic thoracic sympathectomy (ETS) between February 2018 and April 2019. All patients received a 5 mg/kg infusion of ICG 24 hours preoperatively. The vital signs before and after ICG injection and adverse reactions were recorded. Meanwhile, 498 patients (Non‐ICG group) who underwent ETS by normal thoracoscopy during August 2017 to April 2019 were also reviewed to compare the abnormal white blood cell (WBC) counts, alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), and creatinine (Cr) levels before and after operation between two groups. Results For ICG group, the vital signs including body temperature, heart rate and blood pressure before and after ICG injection were stable. There was no significant difference in the abnormal WBC counts, ALT, AST, BUN, and Cr levels before and after operation between two groups. Only one patient had mild adverse reaction (0.7%) after ICG injection. The visibility rate of all sympathetic ganglions was 96.7% (1369/1415). The visibility rate from T1 to T5 was 98.23% (278/283), 98.23% (278/283), 97.17% (275/283), 95.76% (271/283), and 94.35% (267/283), respectively. There was no significant difference in the visibility rate with regard to age, gender, height, weight, body mass index, and PPH grade. Conclusions NIR fluorescence imaging with ICG for identifying sympathetic ganglions is relatively safe and feasible. Key points • Significant findings of the study. NIR fluorescence imaging with ICG for identifying sympathetic ganglions is relatively safe and feasible. • What this study adds. This technology may take the place of the rib‐oriented method as standard practice for the precise localization of sympathetic ganglions, and may improve the effect of sympathectomies.

IntroductionPulmonary artery sling (PAS) is a rare congenital vascular anomaly that results when the left pulmonary artery arises from the right pulmonary artery. There is little relevant literature on lobectomy for the treatment of lung cancer in patients with PAS, and the prognosis is unknown.Case DescriptionA 54-year-old asymptomatic man was found to have a nodule on the left lower lobe of the lung, which measured 2.5 cm. The patient also had PAS. Three-dimensional computed tomography angiography confirmed that the left pulmonary artery arose from the right pulmonary artery and passed between the main trachea and the esophagus toward the left thorax. No obvious contraindication was found in the preoperative examination, and the patient successfully underwent lobectomy of the left lower lobe by video-assisted thoracoscopic surgery. Histological examination of the lesion revealed invasive adenocarcinoma. The postoperative course was uneventful, and no complications occurred in the subsequent 3 years of follow-up.ConclusionsLobectomy in a lung cancer patient with PAS did not increase perioperative risk and had no significant effect on prognosis.

Vegetation dynamics and their responses to climate change are of significant spatial and temporal heterogeneity. The Sichuan–Tibet Railway (STR) is a major construction project of the 14th Five-Year Plan for Economic and Social Development of the People’s Republic of China that is of great significance to promoting the social and economic development of Sichuan–Tibet areas. The planned railway line crosses areas with a complex geological condition and fragile ecological environment, where the regional vegetation dynamics are sensitive to climate change, topographic conditions and human activities. So, analyzing the vegetation variations in the complex vertical ecosystem and exploring their responses to hydrothermal factors are critical for providing technical support for the ecological program’s implementation along the route of the planned railway line. Based on MOD13Q1 Normalized Difference Vegetation Index (NDVI) data for the growing season (May to October) during 2001–2020, a Theil-Sen trend analysis, Mann–Kendall test, Hurst exponent analysis and partial correlation analysis were used to detect the vegetation dynamics, predict the vegetation sustainability, examine the relationship between vegetation change and hydrothermal factors, regionalize the driving forces for vegetation growth and explore the interannual variation pattern of driving factors. The growing season NDVI along the Ya’an–Linzhi section of the STR showed a marked rate of increase (0.0009/year) during the past 20 years, and the vegetation’s slight improvement areas accounted for the largest proportion (47.53%). Among the three hydrothermal parameters (temperature, precipitation and radiation), the correlation between vegetation growth and the temperature was the most significant, and the vegetation response to precipitation was the most immediate. The vegetation changes were affected by the combined impact of climatic and non-climatic factors, and the proportion of hydrothermal factors’ combined driving force slightly increased during the study period. Based on the Hurst exponent, the future vegetation sustainability of the area along the Ya’an–Linzhi section of the STR faces a risk of degradation, and more effective conservations should be implemented during the railway construction period to protect the regional ecological environment.

A diaphragmatic tumor is usually caused by metastasis from lung cancer, malignant mesothelioma, and malignant thymoma. Endometrial cancer is rarely involved in metastasis to the diaphragm. A right anterior mediastinal tumor was found in a 60-year-old woman who was initially diagnosed with endometrial carcinoma. There was initially no relationship between the right anterior mediastinal tumor and endometrial carcinoma. Radical curative surgery was performed for endometrial carcinoma. The endometrial carcinoma stage was IA. The patient was admitted to the Department of Thoracic Surgery 6 months after the curative surgery. Intraoperative exploration showed a tumor growing in the right diaphragm. Right diaphragmotomy was performed. Immunohistochemistry showed metastasis of endometrial carcinoma to the diaphragm. Endometrial cancer solitary metastasis to the diaphragm is rare. Clinicians should be aware of this possibility. Surgical treatment followed by a pathological examination is the most useful method for determining the diagnosis of a diaphragmatic tumor due to metastasis of endometrial cancer.

The co-gasification behaviors of composite samples of biomass and lean coal were investigated under a CO2 atmosphere. The composite behaviors were determined based on thermogravimetric analysis and the Coats-Redfern method. These methods were used to analyze the kinetics of the processes. The results showed that the temperature ranges of the lean coal, biomasses, and the gasification ability of each biomass were different, and the coordination effects of each biomass varied. The addition of alkali metals had little influence on the pyrolysis efficiency and the peak temperature of composite samples of soybean stalk and lean coal, but it did promote gasification. In the processes of pyrolysis and gasification, composite samples of soybean stalk and lean coal exhibited lower activation energies than unmixed samples, but there was no significant enhancement with the extra alkali metal.

Glycodelin is a kind of glycoprotein expressed in secretory endometrium, pregnancy deciduas, and amniotic fluid originally, which is vital for the maintenance of normal human reproductive activities. Recent researches have reported that glycodelin is specifically expressed in various malignancies, including female-specific cancers such as endometrial cancer, ovarian cancer and breast cancer, and non-gender specific cancers including lung cancer, and colon cancer, and glycodelin expression correlates with the diagnosis and prognosis of cancer patients. This review focuses on the expression of glycodelin in different cancers and its role in cancer development and progression. Glycodelin possesses the abilities to regulate cancer cell proliferation, differentiation, and invasion, promote cancer angiogenesis, and modulate the differentiation and function of immune cells including T cells, dendritic cells, monocyte-macrophages, natural killer cells and B cells participating in cancer development. The expression of glycodelin can be regulated by stromal cells, lysophosphatidic acid, histone deacetylase inhibitors, and relaxin. In summary, glycodelin is a promising biomarker for the diagnosis and prognosis of cancer patients, and depending on its distinct immunoregulatory effects, glycodelin can be a prospective target for cancer immunotherapy.

Background and objective Solitary pulmonary nodules (SPN) is a knotty problem in clinical work. The clinical manifestation and pathological features of SPN in sizes may be obviously different. The aim of this study is to analyze the relationship between the diameters and clinicopathologic characteristics of SPN. Methods 390 patients (212 male, 178 female, ranging from 17 years to 86 years, median age 57.1 years) with SPN who were postoperatively diagnosed by pathology between Jan. 2000 and Jun. 2009 are enrolled to this study. In these cases, the number of SPN diameters which are smaller than 0.5 cm (including 0.5 cm) (group A) is 16, between 0.5 cm and 1 cm (including 1 cm, not including 0.5 cm) (group B) is 58, between 1 cm and 2 cm (group C) is 163, and between 2 cm and 3 cm (group D) is 153. The clinical manifestation, and postoperative pathological characters are analyzed in various diameter ranges. Results All procedures were carried out securely, including tumor enucleation (n=20), wedge resection (n=153), lobectomy (n=217). There are 130 benign cases (33.3%) and 260 malignant cases (66.7%). 58.5% SPN are detected incidently with no symptoms. There is an increasing incidence of clinical symptoms as the increasing diameter of SPN. All the cases are divided into 4 groups, the prevalence of malignant are separated 43.7% (group A), 50.0% (group B), 63.2% (group C), 79.1% (group D). The diameter of SPN is positively correlated with incidence of malignancy (χ2=22.535, P

The Chinese government aims to deal with poverty by 2020 for people living in ethnic and rural regions, including mountainous ethnic regions with the highest concentration of poverty and chronic poverty. Based on a sustainable livelihood Framework, five capitals and 33 evaluation indices of livelihood were built, and 13 counties’ resources of the Aba Tibetan and Qiang Autonomous Prefecture were compared in order to calculate the degree of poverty. Topographic factors index of settlement sites (TFIS) were constructed by eight topographic factors, and diagnoses of the dominant factors of differentiation of 2699 settlements were calculated by using the geographical detector model to establish the poverty alleviation policies and models for different regions. The results showed that the livelihood capital evaluation indices were different (0.56–1.88), and natural capitals (mean value 1.56) had obvious advantages, but physical (mean value 0.56), financial (mean value 0.78), and human capital were lower (mean value 0.93), limiting the rate of transforming the ecological resources advantage into the economy. In the TFIS, the settlement points indicate topographic factors of natural breakpoint classification superposition, including elevation, slope, relief amplitude, surface incision, variance coefficient in elevation, surface roughness, distance to roads, and distance to rivers. These are within the 8–34 range, and their power determinant value to TFIS are 0.02, 0.70, 0.77, 0.76, 0.51, 0.66, 0.06, and 0.09. Livelihood capital evaluation indices and TFIS classification one (8–14) are positively correlated, and negative correlation (22–26 and 27–34) is at the 0.05 level. The county's poverty alleviation measures and development under different livelihood indices and TFIS indicate that the ecotourism industry has become the inevitable choice for promoting rapid and coordinated development of economy, society, and the environment in ethnic regions.

The hot deformation behavior and microstructural evolution of Ti-44Al-5V-1Cr alloy were investigated by hot compression tests at temperatures of 1000–1250 °C and strain rates of 0.001–1 s−1. It was indicated that the dependence of peak stress on deformation temperature and strain rate could be accurately described by a hyperbolic sine type equation. The activation energy, Q, was estimated to be 632 kJ/mol. The hot processing map was developed at different strains on the basis of dynamic materials modeling and the Murty criteria. As a result, the instability zones occurred in the regions of low temperature (0.1 s−1). The flow soft mechanism of the instability regions is stress relaxation caused by localization deformation at lamellar boundaries. Dynamic recrystallization is the mainly refining and spheroidizing mechanism of lamellar microstructures. The optimum hot working condition of as-cast TiAl alloy occurs in the temperature range of 1175–1225 °C and the strain rate range 0.05–0.1 s−1. The large-size TiAl alloy rectangular bars with crack-free appearance were successfully prepared by hot extrusion. After annealing, the fine and uniform microstructure with excellent deformation ability was obtained.

Background and objective To determine the value of mediastinoscopy in the mediastinal staging of lung cancer with clinical N2 disease. Methods We retrospectively reviewed 87 patients received mediastinoscopy for known or suspected lung cancer, including 83 cervical mediastinoscopies and 4 parasternal mediastinoscopies. All patients were staged clinical N2 for enlarged ipsilateral mediastinal and/or subcarinal lymph nodes (short axis > 1.0 cm)on computed tomography scan. Results Of the 87 patients, 61 cases proved N2 disease on mediastinoscopy. The other 26 mediastinoscopy-negative patients underwent thoracotomy for lung resection and mediastinal lymph node dissection in the same operative session. Final pathologic N staging were consistent for mediastinoscopic sampling and surgical dissection in 24 patients. N2 disease was found in 2 patients (false-negative of mediastinoscopy). The sensitivity, specificity, and accuracy of mediastinoscopy were 96.8%, 100%, and 97.7%, respectively. There was no mortality and only 1 complication(1.1%) for all 87 mediastinoscopic procedures. Conclusion Mediastinoscopy is a highly effective and safe procedure for the mediastinal staging of lung cancer with clinical N2 disease.

Immune checkpoint inhibitors (ICIs) have a demonstrable treatment response in patients with resectable non-small cell lung cancer (NSCLC). However, immune-related adverse events and tumor progression in patients administered ICIs are of great concern. The present case study is of a 59-year-old male with NSCLC (squamous, stage IIIA) who received neoadjuvant immunotherapy combined with chemotherapy before surgery. The patient first developed hyperthyroidism and then hypothyroidism, indicating that ICI-related thyroid dysfunction had occurred. Furthermore, the patient suffered from tumor progression and could not undergo resection. The present case called attention to the prevention and management of irAEs, and the precaution that should be taken with regard to tumor progression. The case also suggested that the development of ICI-related thyroid dysfunction may not predict an improved response to ICI therapies, which needs further evidence to illustrate. [ABSTRACT FROM AUTHOR]