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Abstract Background Immunotherapy has revolutionized cancer treatment. Recent studies have suggested that the efficacy of immunotherapy can be further enhanced by the influence of gut microbiota. In this study, we aimed to investigate the impact of bacteria on the effectiveness of cancer immunotherapy by combining analysis of clinical samples with validation in animal models. Methods In order to characterize the diversity and composition of microbiota and its relationship with response to immune checkpoint inhibitors (ICIs), 16S ribosomal RNA (rRNA) and GC–MS sequencing was performed on 71 stool samples from patients with advanced non‐small cell lung cancer (NSCLC) prior to treatment with immune checkpoint blockade (ICB). Furthermore, fecal microbiota transplantation (FMT) was performed from different patients into mice and a subcutaneous tumor model established using the Lewis lung cancer cell line to evaluate the therapeutic effect of PD‐1 on mice with varying gut microbiota. Results The results demonstrated a significant association between elevated gut microbiota diversity and response to treatment with ICIs, p 0.05. The diversity of gut microbiota consistently correlated with an optimistic prognosis in NSCLC patients with immunotherapy, which could be functionally mediated by SCFAs. Conclusion The findings of the present study indicated that the diversity of gut microbiota and SCFAs is related to the efficacy of immunotherapy. FMT can effectively delay tumor progression, and enhance the effect of immunotherapy, thus providing evidence for improving the efficacy of immunotherapy in NSCLC patients.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Objective To analyze the clinical efficacy of full-visualization single-channel endoscopic lumbar interbody fusion (PE-PLIF) in the treatment of lumbar degenerative diseases, and to explore the application skills and significance of endoscopic spinal canal decompression and interbody fusion. Methods From January 2021 to December 2022, 50 patients who underwent PE-PLIF in The Affiliated Huai ‘an No.1 Hospital of Nanjing Medical University were selected retrospectively. A total of 56 lower lumbar segments were treated with spinal canal decompression and interbody fusion. The expandable cage implantation technique was used for spinal canal decompression, intervertebral fusion, and percutaneous pedicle screw internal fixation. The visual analogue scale (VAS) score of low back pain and lower limb pain, Oswestry disability index (ODI), and modified MacNab scoring system were used to evaluate the clinical efficacy before and after operation. Results The VAS scores of low back pain were 5.2±1.1, 2.2±0.7, 1.5±0.6, 1.3±0.7, 1.0±0.9 before operation, 1 day, 3 months, 6 months after operation and at the last follow-up, respectively. The VAS scores of lower limb pain were 7.2±1.0, 2.0±1.0, 0.5±0.3, 0.3±0.2, 0.3±0.2, respectively. The ODI was 66.3±7.4, 16.6±5.0, 12.4±3.6 and 10.7±3.3 before operation, 3 months, 6 months after operation and at the last follow-up, respectively. The VAS score and ODI score decreased after operation, and the differences were statistically significant compared with those before operation (P

Introduction Postoperative delirium (POD) is the most common acute fluctuating mental state change after hip fractures in older adults. Postoperative pain is a Grade A risk factor for POD and is closely related to the prognosis of patients undergoing hip fracture surgery. The fascia iliac block has a definite analgesic effect and few side effects, and several studies have reported that it reduces the occurrence of POD in patients undergoing general anaesthesia for hip fracture surgery. Liposomal bupivacaine is a local anaesthetic with a long half-life that significantly reduces the use of opioids and is conducive to patient prognosis and recovery. However, whether regional nerve block analgesia can decrease the occurrence of POD in elderly patients undergoing hip fracture surgery has not been reported.Methods and analysis This is a single-blinded, randomised, parallel-controlled prospective clinical study. Participants will be randomly assigned preoperatively to either the liposomal bupivacaine (ie, Exparel) or ropivacaine groups by block randomisation. Then, the occurrence of POD (primary outcome) and postoperative pain (secondary outcome) will be evaluated.Ethics and dissemination This research protocol complies with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 guidelines and is approved by the Ethics Committee of Shanghai General Hospital (ID 2023–437). The original data are expected to be released in July 2029 on the ResMan original data-sharing platform (IPD-sharing platform) of the China Clinical Trial Registry, which can be viewed on the following website: http://www.medresman.org.cn.PROSPERO registration number ChiCTR2300074022.

The accurate assessment of tree volume is crucial for developing forest management plans, and this can be achieved using tree volume models. In this study, data on individual trees were collected and calculated, including the diameter at breast height (D), ground diameter (DG), tree height (H), and tree volume (V). A total of 400 Populus × tomentosa Carrière, 400 Populus tomentosa Carr, and 400 Populus × canadensis Moench trees were sampled. Two compatible volume model systems were established using corresponding methods. The models consisted of the following five types: V-DH, V-D, V-DG, H-D, and DG-D. In our calculations, before the horizontal line was the dependent variable, and behind the horizontal line was the independent variable. Variations in preferences for the H-D models were observed among the tree species, with the logistic function proving the most suitable for Populus × tomentosa Carrière, Chapman–Richard function for Populus tomentosa Carr, and power function for Populus × canadensis Moench. Among the three volume models, the V-DH model exhibited a superior performance, with its R2 values ranging from 0.965 to 0.984 and mean estimated error (MPE) values ranging from 1.26% to 1.78%. Following this was the V-D model, with R2 values between 0.9359 and 0.9704 and MPE values between 1.71% and 2.46%. The V-DG model ranked third, with R2 values ranging from 0.8746 to 0.9501 and MPE values ranging from 2.33% to 3.16%. In the H-D model, the R2 and MPE values ranged from 0.4998 to 0.7851 and from 1.31% to 1.45%, respectively. For the DG-D model, the R2 values ranged from 0.9563 to 0.9868 and the MPE values ranged from 0.47% to 0.68%. Comparing both compatible methods, the nonlinear seemingly uncorrelated regression (NSUR) was more effective. The three volume models demonstrated high levels of accuracy and compatibility, providing a reliable scientific foundation for forest management and the formulation of harvesting plans in Beijing, with significant practical implications.

Abstract This phase I/II trial characterized the tolerability, safety, and antitumor activities of unecritinib, a novel derivative of crizotinib and a multi-tyrosine kinase inhibitor targeting ROS1, ALK, and c-MET, in advanced tumors and ROS1 inhibitor-naive advanced or metastatic non-small cell lung cancer (NSCLC) harboring ROS1 rearrangements. Eligible patients received unecritinib 100, 200, and 300 mg QD, and 200, 250, 300, and 350 mg BID in a 3 + 3 design during dose escalation and 300 and 350 mg BID during expansion. Phase II trial patients received unecritinib 300 mg BID in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) per independent review committee (IRC). Key secondary endpoints included intracranial ORR and safety. The ORR of 36 efficacy evaluable patients in the phase I trial was 63.9% (95% CI 46.2%, 79.2%). In the phase II trial, 111 eligible patients in the main study cohort received unecritinib. The ORR per IRC was 80.2% (95% CI 71.5%, 87.1%) and the median progression-free survival (PFS) per IRC was 16.5 months (95% CI 10.2, 27.0). Additionally, 46.9% of the patients who received recommended phase II dose of 300 mg BID experienced grade 3 or higher treatment-related adverse events. Treatment-related ocular disorders and neurotoxicity occurred in 28.1% and 34.4% of patients, respectively, but none was grade 3 or higher. Unecritinib is efficacious and safe for ROS1 inhibitor-naive patients with ROS1-positive advanced NSCLC, particularly patients with brain metastases at baseline, strongly supporting that unecritinib should become one of the standards of care for ROS1-positive NSCLC. ClinicalTrials.gov identifier: NCT03019276 and NCT03972189.

Abstract Background QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies. Methods In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated. Results Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3—not reached [NR]), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively. Conclusions QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.

Background Lung squamous cell carcinoma (LUSC) remains a leading cause of cancer-related deaths with few therapeutic strategies. Immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy in patients with LUSC. However, ICIs could also lead to a unique spectrum of immune-related adverse events (irAEs), which dampen the clinical outcome. In-depth characterization of the immune hallmarks of antitumor responses and irAEs remains an unmet need to maximize ICI-treatment benefits of patients.Methods We performed single-cell RNA sequencing (scRNA-seq) on pre-ICI and on-ICI treatment tumor biopsies. We used bulk RNA-seq data of matched pretreatment/on-treatment tumors and irAE affected organs to validate observations from scRNA-seq analysis. Two independent patient cohorts were collected to determine circulating tumor necrosis factor (TNF) protein expression levels.Results We found that increased proportions of a macrophage subcluster with highly expressed secreted phosphoprotein 1 (SPP1) and two tumor cell subclusters in irAE patients, whereas proportions of two cytotoxic CD8+ T cell subclusters were higher in patients with partial response (PR). TNF signaling pathway was conversely associated with treatment efficacy and irAE development in most macrophage and tumor cell subclusters. Cell–cell communications for TNF ligand-receptor pairs between macrophage/T cells and tumor cells were also bidirectionally remodeled in responders versus non-responders and irAE versus non-irAE patients. Bulk RNA-seq analysis on matched pretreatment/on-treatment tumors and irAE affected organs revealed remarkably enhanced macrophage abundance and TNF signaling pathway in on-treatment tumors and organs developed irAEs. Furthermore, we observed significantly increased circulating TNF protein in plasma or serum of irAE patients but not ICI responders, based on analysis of two independent LUSC patient cohorts and one published ICI patient cohort.Conclusions Our data depicts specific reprogramming of macrophage, T cells and tumor cells associated with ICI response and irAEs, elucidates divergent roles of TNF signaling in antitumor immunity and irAEs, and highlights the significance of TNF expression in irAE development in the LUSC setting.

Background Treatment options are limited for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after treatment failure with EGFR tyrosine kinase inhibitors (TKIs). This multicenter open-label, phase II study aims to evaluate the efficacy and safety of tislelizumab plus chemotherapy (cohort 1, TIS+chemo) or tislelizumab plus chemotherapy and bevacizumab (cohort 2, TIS+chemo+ beva) in EGFR-mutated non-squamous NSCLC patients who progressed on EGFR TKI therapies. Here, the primary analysis of the TIS+chemo cohort is reported.Methods In the TIS+chemo cohort, patients with EGFR-sensitizing mutations with prior EGFR TKI failure received tislelizumab plus carboplatin and nab-paclitaxel as induction treatment, followed by maintenance with tislelizumab plus pemetrexed. The primary endpoint was 1-year progression-free survival (PFS) rate. The planned sample size was 66 with a historical control of 7%, an expected value of 20%, a one-sided α of 0.05, and a power of 85%.Results Between July 11, 2020 and December 13, 2021, 69 patients were enrolled. As of June 30, 2022, the median follow-up was 8.2 months. Among the 62 patients in the efficacy analysis set, estimated 1-year PFS rate was 23.8% (90% CI 13.1% to 36.2%), and its lower bound of 90% CI was higher than the historical control of chemotherapy (7%), which met the primary endpoint. The median PFS was 7.6 (95% CI 6.4 to 9.8) months. Median overall survival (OS) was not reached (95% CI 14.0 to not estimable), with a 1-year OS rate of 74.5% (95% CI 56.5% to 86.0%). The objective response rate and disease control rate were 56.5% (95% CI 43.3% to 69.0%) and 87.1% (95% CI 76.1% to 94.3%), respectively. Patients who had progressed on first-generation/second-generation and third-generation EGFR-TKIs at baseline had shorter PFS than those who progressed on first-generation/second-generation EGFR-TKIs (median 7.5 vs 9.8 months, p=0.031). Patients with positive ctDNA had shorter PFS (median 7.4 vs 12.3 months, p=0.031) than those with negative ctDNA. No grade 5 treatment-emergent adverse events (TEAEs) were observed. Grades 3–4 TEAEs occurred in 40.6% (28/69) of patients. Grades 3–4 immune-related AEs occurred in 5 (7.2%) patients.Conclusion The study met the primary endpoint for the TIS+chemo cohort. Tislelizumab plus chemotherapy is effective with an acceptable safety profile for EGFR-mutated non-squamous NSCLC after EGFR TKI failure.

IntroductionThe efficacy of postoperative radiotherapy (PORT) is still unclear in non-small cell lung cancer (NSCLC) patients with pIIIA-N2 disease. Estrogen receptor (ER) was proven significantly associated with poor clinical outcome of male lung squamous cell cancer (LUSC) after R0 resection in our previous study.MethodsA total of 124 male pIIIA-N2 LUSC patients who completed four cycles of adjuvant chemotherapy and PORT after complete resection were eligible for enrollment in this study from October 2016 to December 2021. ER expression was evaluated using immunohistochemistry assay.ResultsThe median follow-up was 29.7 months. Among 124 patients, 46 (37.1%) were ER positive (stained tumor cells≥1%), and the rest 78 (62.9%) were ER negative. Eleven clinical factors considered in this study were well balanced between ER+ and ER- groups. ER expression significantly predicted a poor prognosis in disease-free survival (DFS, HR=2.507; 95% CI: 1.629-3.857; log-rank p=1.60×10-5). The 3-year DFS rates were 37.8% with ER- vs. 5.7% with ER+, with median DFS 25.9 vs. 12.6 months, respectively. The significant prognostic advantage in ER- patients was also observed in overall survival (OS), local recurrence free survival (LRFS), and distant metastasis free survival (DMFS). The 3-year OS rates were 59.7% with ER- vs. 48.2% with ER+ (HR, 1.859; 95% CI: 1.132-3.053; log-rank p=0.013), the 3-year LRFS rates were 44.1% vs. 15.3% (HR=2.616; 95% CI: 1.685-4.061; log-rank p=8.80×10-6), and the 3-year DMFS rates were 45.3% vs. 31.8% (HR=1.628; 95% CI: 1.019-2.601; log-rank p=0.039). Cox regression analyses indicated that ER status was the only significant factor for DFS (p=2.940×10-5), OS (p=0.014), LRFS (p=1.825×10-5) and DMFS (p=0.041) among other 11 clinical factors.ConclusionsPORT might be more beneficial for ER negative LUSCs in male, and the examination of ER status might be helpful in identifying patients suitable for PORT.

Accumulating evidence has revealed that the dysregulation of circular RNAs (circRNAs) plays crucial roles in the occurrence and progression of cancers. However, the aberrant expression profile and dysfunction of circRNAs in non-small cell lung cancer (NSCLC) have not been fully explored. Herein, we discovered that a circRNA, hsa_circ_0001666 (circ0001666), was highly expressed in NSCLC tissues and cell lines, and it was positively correlated with NSCLC tumor pathological grade and lymph node metastasis. Moreover, Kaplan-Meier survival analysis implied that NSCLC patients with high circ0001666 expression were negatively correlated with favorable survival. Functionally, circ0001666 could promote migration and invasion of NSCLC cells in vitro and in vivo. Mechanistically, circ0001666 could act as a sponge to miR-1184/miR-548I and upregulate the expression of AGO1, thereby promoting the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway in NSCLC cells. Collectively, these findings demonstrated that circ0001666 could serve as an oncogene to promote the migration and invasion of NSCLC via a novel miR-1184/miR-548I/AGO1 axis, which might be a promising therapeutic target for NSCLC treatment.

This study aimed to investigate the differences in complications between hepatitis B virus (HBV)-related and alcohol-related cirrhoses.

C10H16N12O6S2, triclinic, P1‾ $P\overline{1}$ (no. 2), a = 7.6977(2) Å, b = 11.5353(3) Å, c = 11.7533(3) Å, α = 67.973(2)°, β = 87.916(2)°, γ = 88.347(2)°, V = 966.69(5) Å3, Z = 2, R gt(F) = 0.0290, wR ref(F 2) = 0.0818, T = 170K.

Abstract Background Clinical options for lung squamous carcinoma (LUSC) are still quite limited. Carcinogenesis is an exceedingly complicated process involving multi-level dysregulations. Therefore, only looking into one layer of genomic dysregulation is far from sufficient. Methods We identified differentially expressed genes with consistent upstream genetic or epigenetic dysregulations in LUSC. Random walk was adopted to identify genes significantly affected by upstream abnormalities. Expression differentiation and survival analysis were conducted for these significant genes, respectively. Prognostic power of selected gene was also tested in 102 male LUSC samples through immunohistochemistry assay. Results Twelve genes were successfully retrieved from biological network, including ERα (ESRS1), EGFR, AR, ATXN1, MAPK3, PRKACA, PRKCA, SMAD4, TP53, TRAF2, UBQLN4 and YWHAG, which were closely related to sex hormone signaling pathway. Survival analysis in public datasets indicated ERα was significantly associated with a poor overall survival (OS) in male LUSC. The result of our immunohistochemistry assay also demonstrated this correlation using R0 resected tumors (n = 102, HR: 2.152, 95% CI: 1.089–4.255, p = 0.024). Although disease-free survival (DFS) difference was non-significant (n = 102, p = 0.12), the tendency of distinction was straight-forward. Cox analysis indicated ERα was the only independent prognostic factor for male patients’ OS after R0 resection (HR = 2.152, p = 0.037). Conclusion ERα was significantly related to a poor prognosis in LUSC, especially for male patients after radical surgery, confirmed by our immunohistochemistry data.

Since the concept, DNA damage repair has been stated as a natural biological event, and research has increasingly revealed its strong association to tumors, aging, immunity, biochemical detection, and other factors. The discovery of abnormal DNA repair in cancers has been heralded as a paradigm shift in the treatment of malignancies. A poly (ADP-ribose) polymerase (PARP) activates poly (ADP-ribosylation) to repair single-strand DNA breaks after DNA damage. In some cancers, such as breast cancer and gastric cancer, a PARP inhibitor can target the DNA damage response pathway, prevent DNA repair, and induce homologous recombination deficiency (HRD) tumors to create the phenomena of synthetic lethality. Increasingly, clinical trials are being submitted to research the uses of PARP inhibitors in various types of cancers. Small cell lung cancer (SCLC) is a quickly growing malignancy with numerous therapeutic limitations and a dismal prognosis. Sequencing of mutant genes revealed multiple gene connections that may contribute to its carcinogenesis, indicating a viable study direction. Furthermore, the therapy of SCLC with PARP inhibitors has been further explored. The mechanism of PARP action, as well as the advancement of its preclinical and clinical applications in SCLC, will be discussed in this review.

Background and objective Studies have shown that elevated serum lactate dehydrogenase (LDH) concentration can lead to poor prognosis in patients with small cell lung cancer and lung adenocarcinoma, but its relationship with the prognosis of patients with lung large-cell neuroendocrine carcinoma (L-LCNEC) is not clear. This study aims to explore the influence of L-LCNEC preoperative serum LDH concentration and postoperative LDH concentration change trend on the disease-free survival (DFS) of patients after surgery, so as to judge the clinical prognosis of L-LCNEC provides new ideas. Methods Collected the clinical data. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value, while the Kaplan-Meier and Cox proportional hazard model were used to analyze data. Results DFS was shortened in patients with high serum LDH concentration before operation and increased LDH concentration after operation (P

Abstract To explore a better treatment strategy for patients with advanced non‐small cell lung cancer harboring sensitive epidermal growth factor receptor mutations, a total of 271 patients were retrospectively analyzed. The patients were divided into two groups: the combination group (58 cases), which received concurrent icotinib, pemetrexed, and platinum treatment, and the sequential group (213 cases), which received the sequential pemetrexed and platinum therapy, followed by icotinib treatment. The primary end points were progression‐free survival (PFS) and PFS on the subsequent line of therapy (PFS2). PFS in the combination group was significantly higher compared with that in the sequential group (16.89 months vs. 9.90 months; p

Abstract Imbalance of macrophage polarization plays an indispensable role in acute lung injury (ALI), which is considered as a promising target. Matrix metalloproteinase-9 (MMP-9) is expressed in the macrophage, and has a pivotal role in secreting inflammatory cytokines. We reported that saquinavir (SQV), a first-generation human immunodeficiency virus-protease inhibitor, restricted exaggerated inflammatory response. However, whether MMP-9 could regulate macrophage polarization and inhibit by SQV is still unknown. We focused on the important role of macrophage polarization in CLP (cecal ligation puncture)-mediated ALI and determined the ability of SQV to maintain M2 over M1 phenotype partially through the inhibition of MMP-9. We also performed a limited clinical study to determine if MMP-9 is a biomarker of sepsis. Lipopolysaccharide (LPS) increased MMP-9 expression and recombinant MMP-9 (rMMP-9) exacerbated LPS-mediated M1 switching. Small interfering RNA to MMP-9 inhibited LPS-mediated M1 phenotype and SQV inhibition of this switching was reversed with rMMP-9, suggesting an important role for MMP-9 in mediating LPS-induced M1 phenotype. MMP-9 messenger RNA levels in peripheral blood mononuclear cells of these 14 patients correlated with their clinical assessment. There was a significant dose-dependent decrease in mortality and ALI after CLP with SQV. SQV significantly inhibited LPS-mediated M1 phenotype and increased M2 phenotype in cultured RAW 264.7 and primary murine bone marrow-derived macrophages as well as lung macrophages from CLP-treated mice. This study supports an important role for MMP-9 in macrophage phenotypic switching and suggests that SQV-mediated inhibition of MMP-9 may be involved in suppressing ALI during systemic sepsis.

Background and objective Lung cancer is the leading cause of cancer-related death, and small cell lung cancer (SCLC) has a poor prognosis in all types of lung cancer. This study evaluated the relationship between pretreatment serum apolipoprotein levels and prognosis in patients with SCLC, seeks a new index can guide diagnosis and treatment of SCLC. Methods This study retrospectively analyzed the clinical data of 122 patients with SCLC. The clinical results of patients with serum apolipoprotein levels within 2 weeks before treatment were collected, including apolipoprotein AI (ApoA-I), apolipoprotein B (ApoB), and the ratio of apolipoprotein B to apolipoprotein AI (ApoB/ApoA-I). Patients' progression-free survival (PFS) and overall survival (OS) are the main outcome indicators. The best critical to determine the index's value by X-tile tool. For survival analysis, Kaplan-Meier method was used for analysis, and Cox regression analysis method was used for single factor analysis and multifactor analysis. Results Compared with patients with low ApoA-I levels, patients with high ApoA-I levels (ApoA-I>1.12 g/L) had better OS (21.5 mon vs 12.3 mon, P=0.007) and PFS (7.3 mon vs 5.5 mon, P=0.017). In contrast, patients with higher ApoB/ApoA-I levels had worse median OS than patients with lower ApoB/ApoA-I levels (13.4 mon vs 20.7 mon, P=0.012). Multivariate Cox regression analysis showed that ApoA-I was an independent prognostic factor affecting PFS in SCLC patients (HR=0.67, 95%CI: 0.45-0.99, P=0.043). ApoB/ApoA-I is an independent risk factor for OS in patients with SCLC (HR=1.98, 95%CI: 1.21-3.23, P=0.007). Conclusion Serum ApoA-I level and ApoB/ApoA-I level before treatment can be important prognostic factors for SCLC, which is helpful to judge the prognosis of patients.

In recent years, lung cancer has become the leading cause of cancer-related deaths. There is increasing evidence that many lipids and lipid analogs are key regulators of tumorigenesis, and factors that affect blood lipid levels such as smoking, diet, and obesity may be associated with cancer risk. With the deepening of research on the relationship between lipids and tumorigenesis, exploring the correlation between blood lipids and lung cancer risk and prognosis has become a research hotspot. This article reviews the research progress of the relationship between blood lipid levels and the risk of lung cancer, blood lipid levels and the prognosis of lung cancer patients, and the adjustment of blood lipid drugs and the prevention and treatment of lung cancer.

The relentless debate on postoperative adjuvant radiotherapy in gastric adenocarcinoma (GA) has been lasting for decades. In this study, a new biomarker, named promoter methylation burden of DNA repair genes (RPMB), was established to identify the subgroup of patients who might benefit from adjuvant radiotherapy. Methylation profiles of 397 GA tumor samples were downloaded from The Cancer Genome Atlas (TCGA). RPMB for a patient was defined as the ratio of methylated DNA repair genes to the number of all DNA repair genes. Subgroup analyses in term of overall survival (OS) and disease-free survival (DFS) indicated that most of the subgroups favored the high-RMPB group. Kaplan-Meier analysis showed that overall the patients with high RPMB after R0 resection had a significantly better clinical outcome regarding DFS (hazard ratio [HR] = 0.013, p = 0.042). Additionally, high-RPMB patients, who underwent adjuvant radiotherapy with both ≥T2 tumor and positive lymph nodes, showed superior DFS in comparison with the low-RPMB group (HR = 5.35 × 10−10, n = 26, p = 0.010). RPMB might be considered as a promising biomarker for decision-making with regard to postoperative adjuvant radiotherapy for GA patients.

Abstract Hole drilling or contour milling for the large and complex workpieces such as automobile panels and aircraft fuselages makes a high combined demand on machining accuracy, stiffness and workspace of machining equipment. Therefore, a 5-DOF (degrees of freedom) parallel kinematic machine (PKM) with redundant constraints is proposed. Based on the kinematics analysis of the parallel mechanism using intermediate variables, the kinematics problems of the PKM are solved through equivalent kinematics model. The structural stiffness matrix method is adopted to model the stiffness of the parallel mechanism of the PKM, where the stiffness of each joint and branch component is obtained by stiffness formula and finite element analysis. And the stiffness model of the parallel mechanism is improved by correction coefficient matrix, each element of which is constructed as a polynomial function of three independent end variables of the parallel mechanism. The terminal stiffness matrices obtained by simulation result are used to determine the coefficients of polynomial function by least square fitting to describe the correction coefficient over the workspace of the parallel mechanism quantitatively. The experiment results prove that the modification method can greatly improve the stiffness model of the parallel mechanism. To enhance the machining accuracy of the PKM, the proposed kinematics model and the improved stiffness model are utilized to optimize the working stiffness of parallel machine by searching the best relative position of parallel machine and workpiece. A plate workpiece taken as example is examined in the case study section, which demonstrates the effectiveness of optimization method.

GSDME is a newly recognized executor of cellular pyroptosis, and has been recently implicated in tumor growth and immunity. However, knowledge about the molecular regulators underlying GSDME abundance remains limited. Here, we performed integrative bioinformatics analyses and identified that epithelial-mesenchymal transition (EMT) gene signatures exhibited positive correlation with GSDME levels across human cancers. A causal role was supported by the observation that EMT dictated GSDME reversible upregulation in multiple experimental models. Mechanistically, transcriptional activation of GSDME was directly driven by core EMT-activating transcription factors ZEB1/2, which bound to the GSDME promoter region. Of functional importance, elevated GSDME in mesenchymally transdifferentiated derivatives underwent proteolytic cleavage upon antineoplastic drug exposure, leading to pyroptotic cell death and consequent cytokine release. Taken together, our findings pinpointed a key transcriptional machinery controlling GSDME expression and indicated potential therapeutic avenues to exploit GSDME-mediated inflammatory pyroptosis for the treatment of mesenchymal malignancies.

C23H39ClN2O4, triclinic, P1‾$P‾{1}$ (no. 2), a = 9.0752(19) Å, b = 9.542(2) Å, c = 16.049(3) Å, α = 99.088(4)°, β = 94.422(4)°, γ = 107.146(4)°, V = 1300.0(5) Å3, Z = 2, Rgt(F) = 0.0646, wRref(F2) = 0.2298, T = 293.0 K.

C24H34N6Cl2Zn, monoclinic, P21/c (no. 14), a = 9.513(3) Å, b = 9.546(3) Å, c = 30.956(10) Å, β = 101.228(9)°, V = 2757.3(15) Å3, Z = 4, Rgt(F) = 0.0452, wRref(F2) = 0.1299, T = 293 K.

C39H37CuFeOP2S2, triclinic, P1̄ (no. 2), a = 9.6132(10) Å, b = 11.5667(12) Å, c = 16.8739(18) Å, α = 99.732(2)°, β = 96.342(2)°, γ = 93.446(2)°, V = 1832.0(3) Å3, Z = 2, Rgt(F) = 0.0455, wRref(F2) = 0.1212, T = 293.0 K.

C44H56N10S2O6Ni, triclinic, P1̄ (no. 2), a = 9.3077(14) Å, b = 9.9624(14) Å, c = 14.0449(19) Å, α = 70.889(3)°, β = 75.532(2)°, γ = 87.544(3)°, V = 1190.5(3) Å3, Z = 1, Rgt(F) = 0.0528, wRref(F2) = 0.1279, T = 293 K.

C26H20N10O6S2Pb, triclinic, P1̄ (no. 2), a = 9.3480(19) Å, b = 12.985(3) Å, c = 14.278(3) Å, α = 113.14(3)°, β = 92.05(3)°, γ = 102.75(3)°, V = 1539.8(7) Å3, Z = 2, Rgt(F) = 0.0336, wRref(F2) = 0.0874, T = 293.0 K.

Abstract Background Hepatic ischemia-reperfusion injury (IRI) is a common pathological phenomenon, which causes hepatic injury as well as remote organ injuries such as the lung. Several mediators, such as oxidative stress, Ca2+ overload and neutrophil infiltration, have been implied in the pathogenesis of liver and remote organ injuries following reperfusion. WNT1 inducible signaling pathway protein 1 (WISP1) is an extracellular matrix protein that has been associated with the onset of several malignant diseases. Previous work in our group has demonstrated WISP1 is upregulated and contributes to proinflammatory cascades in hepatic IRI. However, the role of WISP1 in the pathogenesis of lung injury after hepatic IRI still remains unknown. Methods Male C57BL/6 mice were used to examine the expression and role of WISP1 in the pathogenesis of lung injuries after hepatic IRI and explore its potential mechanisms in mediating lung injuries. Results We found WISP1 was upregulated in lung tissues following hepatic IRI. Treatment with anti-WISP1 antibody ameliorated lung injuries with alteration of cytokine profiles. Administration with rWISP1 aggravated lung injuries following hepatic IRI through excessive production of proinflammatory cytokines and inhibition of anti-inflammatory cytokines. Conclusions In this study, we concluded that WISP1 contributed to lung injuries following hepatic IRI through TLR4 pathway.

C10H16N6O3, monoclinic, P21/c$P{2}_{1}/c$ (no. 14), a = 7.2312(1) Å, b = 17.7721(3) Å, c = 11.0146(2) Å, β = 104.557°, V = 1370.08(4) Å3, Z = 4, Rgt (F) = 0.0532, wRref (F2) = 0.1537, T = 170.0 K.

C6H12N6O4, monoclinic, P21/n (no. 14), a = 7.3652(3) Å, b = 16.8683(7) Å, c = 8.3779(3) Å, β = 101.525(4)°, V = 1019.87(7) Å3, Z = 4, Rgt(F) = 0.0349, wRref(F2) = 0.1018, T = 170 K.

Abstract Background Large‐cell neuroendocrine carcinoma of the lung (LCNEC) and small‐cell lung carcinoma (SCLC) are neuroendocrine neoplasms. However, the underlying mechanisms of common and distinct genetic characteristics between LCNEC and SCLC are currently unclear. Herein, protein expression profiles and possible interactions with miRNAs were provided by integrated bioinformatics analysis, in order to explore core genes associated with tumorigenesis and prognosis in SCLC and LCNEC. Methods GSE1037 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in LCNEC and SCLC, as compared with normal lung tissues, were selected using the GEO2R online analyzer and Venn diagram software. Gene ontology (GO) analysis was performed using Database for Annotation, Visualization and Integrated Discovery. The biological pathway analysis was performed using the FunRich database. Subsequently, a protein–protein interaction (PPI) network of DEGs was generated using Search Tool for the Retrieval of Interacting Genes and displayed via Cytoscape software. The PPI network was analyzed by the Molecular Complex Detection app from Cytoscape, and 16 upregulated hub genes were selected. The Oncomine database was used to detect expression patterns of hub genes for validation. Furthermore, the biological pathways of these 16 hub genes were re‐analyzed, and potential interactions between these genes and miRNAs were explored via FunRich. Results A total of 384 DEGs were identified. A Venn diagram determined 88 common DEGs. The PPI network was constructed with 48 nodes and 221 protein pairs. Among them, 16 hub genes were extracted, 14 of which were upregulated in SCLC samples, as compared with normal lung specimens, and 10 were correlated with the cell cycle pathway. Furthermore, 57 target miRNAs for 8 hub genes were identified, among which 31 miRNAs were correlated with the progression of carcinoma, drug‐resistance, radio‐sensitivity, or autophagy in lung cancer. Conclusion This study provided effective biomarkers and novel therapeutic targets for diagnosis and prognosis of SCLC and LCNEC.

A routine pipeline seems very common in many cancer studies that expression differentiation might be helpful in identifying prognostic molecules. There also exists a striking unanimity that molecules upregulated in cancer usually shorten survival, while downregulated ones have the opposite effect. In this study, based on the transcriptional profiles of 18 malignancies, cancer and corresponding adjacent normal tissues were used to calculate differential scores. Cox correlation coefficients of global genes were also calculated to denote survival association. The relationship between expression differentiation and survival association has been extensively studied in 18 malignancy types. Contradictory to our stereotypic research pattern, expression differentiation between cancer and adjacent normal tissues was proven irrelevant to corresponding survival correlation. Surprisingly, the more stringent cutoff we used in differentially expressed gene identification, the less prognostic information we would obtain from the collected gene groups. Moreover, the direction of dysregulated genes in cancer was irrelevant to the direction of corresponding survival correlation. Cancer-normal expression differentiation is irrelevant to genes’ survival correlation in multiple cancers and, therefore, not helpful in identifying prognostic genes. For future studies, it is more sensible to look into another alternative rather than collect differentially expressed molecules in the initial step.

Abstract Background In recent years, systemic chemotherapy and molecular targeted therapy have become standard first-line treatments for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The objective of this survey was to investigate first-line anticancer treatment patterns and gene aberration test status of patients with advanced nonsquamous NSCLC in China. Methods Patients included in this study had unresectable Stage IIIB/IV nonsquamous NSCLC and were admitted during August 2015 to March 2016 into one of 12 tertiary hospitals throughout China for first-line anticancer treatment. Patient data (demographics, NSCLC histologic type, Eastern Cooperative Oncology Group [ECOG] Performance Status [PS], gene aberration test and results [if performed], and first-line anticancer treatment regimen) were extracted from medical charts and entered into Medical Record Abstraction Forms (MERAFs), which were collated for analysis. Results Overall, 1041 MERAFs were collected and data from 932 MERAFs were included for analysis. Patients with unresectable Stage IIIB/IV nonsquamous NSCLC had a median age of 59 years, 56.4% were male, 58.2% were never smokers, 95.0% had adenocarcinoma, and 92.9% had an ECOG PS ≤1. A total of 665 (71.4%) patients had gene aberration tests; 46.5% (309/665) had epidermal growth factor receptor (EGFR) gene mutations, 11.5% (48/416) had anaplastic lymphoma kinase (ALK) gene fusions, and 0.8% (1/128) had a c-ros oncogene 1 gene fusion. The most common first-line treatment regimen for unresectable Stage IIIB/IV nonsquamous NSCLC was chemotherapy (72.5%, 676/932), followed by tyrosine kinase inhibitors (TKIs; 26.1%, 243/932), and TKIs plus chemotherapy (1.4%, 13/932). Most chemotherapy regimens were platinum-doublet regimens (93.5%, 631/676) and pemetrexed was the most common nonplatinum chemotherapy-backbone agent (70.2%, 443/631) in platinum-doublet regimens. Most EGFR mutation-positive patients (66.3%, 205/309) were treated with EGFR-TKIs. Conclusions Findings from our survey of 12 tertiary hospitals throughout China showed an increased rate of gene aberration testing, compared with those rates reported in previous surveys, for patients with advanced nonsquamous NSCLC. In addition, pemetrexed/platinum-doublet chemotherapy was the predominant first-line chemotherapy regimen for this population. Most patients were treated based on their gene aberration test status and results.

C22H28Cl2N4Ni, monoclinic, P21/c (no. 14), a = 9.7332(19) Å, b = 14.886(3) Å, c = 18.623(5) Å, β = 117.45(2)°, V = 2394.5(10) Å3, Z = 4, Rgt(F) = 0.0450, wRref(F2) = 0.1466, T = 293.0 K.

C16H24O6, triclinic, P1̄ (no. 2), a = 6.3410(13) Å, b = 7.3430(15) Å, c = 10.241(2) Å, α = 94.06(3)°, β = 103.89(3)°, γ = 113.13(3)°, V = 418.3(8) Å3, Z = 1, Rgt(F) = 0.0546, wRref(F2) = 0.1691, T = 295(3) K.

C18H28O6, monoclinic, C2/c (no. 15), a = 15.061(3) Å, b = 13.791(3) Å, c = 10.106(2) Å, β = 118.60(3)°, V = 1843.0(8) Å3, Z = 4, Rgt(F) = 0.0462, wRref(F2) = 0.1315, T = 294.3 K.

C18H26N4NiO4, triclinic, P1̄ (no. 2), a = 7.7547(16) Å, b = 7.8666(16) Å, c = 8.2798(17) Å, α = 90.46(3)°, β = 96.24(3)°, γ = 93.25(3)°, V = 501.24(18) Å3, Z = 1, Rgt(F) = 0.0294, wRref(F2) = 0.0873, T = 310 K.

C17H14N2OFCl, triclinic, P1̄ (no. 2), a = 8.2387(19) Å, b = 9.764(2) Å, c = 10.644(3) Å, α = 72.023(4)°, β = 72.770(4)°, γ = 78.581(4)°, V = 772.5(3) Å3, Z = 2, Rgt(F) = 0.0444, wRref(F2) = 0.1099, T = 294.15 K.

Lung cancer is the most commonly diagnosed type of cancer and the leading cause of cancer-associated death worldwide. MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules of ∼20–25 nucleotides in length. Single nucleotide polymorphisms are a class of genetic variation in the human genome, which when present in miRNA genes are associated with the risk of developing cancer. This study aimed to identify whether the miRNA (miR)-608 polymorphism rs4919510 influenced the incidence of lung cancer, and to explore the underlying mechanisms of miR-608 in the pathogenesis of the disease. A total of 37 patients with non-small cell lung cancer (NSCLC) were selected to determine the expression levels of miR-608; 96 NSCLC patients and 136 cancer-free healthy controls were recruited to determine the incidence of miR-608 rs4919510 in lung cancer patients. Additionally, the impact of miR-608 on the expression of predicted target genes, cell migration, viability, proliferation, and apoptosis was also assessed. We found that the presence of miR-608 rs4919510 did not affect the susceptibility of patients to NSCLC or the maturation of miR-608. miR-608 expression levels were found to be downregulated in NSCLC tissues. Furthermore, overexpression of miR-608 promoted doxorubicin-induced apoptosis in NSCLC cell lines A549 and HCC4006 by inhibiting the expression of transcription factor activating enhancer-binding protein 4 (TFAP4), and high expression levels of TFAP4 were observed in NSCLC tissues. Therefore, our results may provide valuable insights for the chemotherapeutical treatment of NSCLC.

Background: Postoperative preablative stimulated thyroglobulin (ps-Tg) has been evaluated in predicting prognosis and success of ablation regarding differentiated thyroid cancer (DTC); however, its relationship with recurrence risk and radioiodine decision-making remains uncertain, especially in Chinese DTC patients. We aimed to evaluate the association between ps-Tg and recurrence risk stratification in DTC, to provide incremental values for ps-Tg in postoperative assessment and radioiodine management. Methods: Seven hundred and seven patients with DTC were included; low-risk (L; n = 90), intermediate-risk (I; n = 283), and high-risk (H; n = 334, 117 with distant metastasis [M1]) patients were divided according to recurrence risk stratification. The M1 group was further analyzed regarding evidence of metastasis. Cut-off values of ps-Tg were obtained using receiver operating characteristic analysis. Results: Patients with more advanced disease at initial risk stratification were more likely to have higher ps-Tg levels (I vs. L: P < 0.05; H vs. I: P < 0.001; H vs. L: P < 0.001). The corresponding cut-off value of ps-Tg for distinguishing sensitivity and specificity in each of the two groups was 2.95 ng/ml (I vs. L: 61.5%, 63.3%), 29.5 ng/ml (H vs. I: 41.9%, 92.6%), 47.1 ng/ml (M1 vs. M0 in the H group: 79.5%, 88.9%) and 47.1 ng/ml (M1 vs. M0 in all patients: 79.5%, 93.7%). With the cut-off value at 47.1 ng/ml, ps-Tg was the only factor that could be used to identify distant metastases, and consequently if measured before radioiodine therapy would prevent 10.26% of patients with M1 from undertreatment. Conclusions: Ps-Tg, as an ongoing reassessment marker, favors differential recurrence risk grading and provides incremental values for radioiodine treatment decision-making.

Liver ischemia and reperfusion (I/R) induce local and distant tissue injuries, contributing to morbidity and mortality in a wider range of pathologies. This is especially seen under uncontrolled aseptic inflammatory conditions, leading to injury of remote organs, such as lung injury, and even failure. Saquinavir (SQV) is a kind of HIV protease inhibitor that possesses an anti-inflammatory property. In this study, we investigated whether SQV suppresses Toll-like receptor 4- (TLR4-) dependent signaling pathways of high-mobility group box 1 (HMGB1) and P38/JNK, conferring protection against murine liver I/R-induced lung injury. To investigate our hypothesis, C57BL/6 mice and TLR4 knockout mice (TLR4−/−) were used to perform the study. SQV administration markedly attenuated remote lung tissue injury after 1-hour ischemia and 6-hour reperfusion of the liver. To our expectation, SQV attenuated I/R-induced lung edema, hyperpermeability, and pathological injury. The beneficial effects of SQV were associated with decreased levels of circulating and lung tissue inflammatory cytokines, such as IL-6, IL-1β, TNF-α, and iNOS. The protective effect of SQV was also associated with decreased lung tissue expression of HMGB1, TLR-4, and p-P38/JNK, but not p-ERK in wild-type liver I/R mice. Overall, this study demonstrated a new role of SQV, facilitating negative regulation of HMGB1- and P38/JNK-mediated TLR-4-dependent signaling pathways, conferring protection against liver I/R-induced lung injury.

Urban heat islands are one of the most critical urban environment heat problems. Landsat ETM+ satellite data were used to investigate the land surface temperature and underlying surface indices such as NDVI and NDBI. A comparative study of the urban heat environment at different scales, times and locations was done to verify the heat island characteristics. Since remote sensing technology has limitations for dynamic flow analysis in the study of urban spaces, a CFD simulation was used to validate the improvement of the heat environment in a city by means of wind. CFD technology has its own shortcomings in parameter setting and verification, while RS technology is helpful to remedy this. The city of Wuhan and its climatological condition of being hot in summer and cold in winter were chosen to verify the comparative and combinative application of RS with CFD in studying the urban heat island.

BackgroundLung cancer is an important and common cancer that constitutes a major public health problem, but early detection of small cell lung cancer can significantly improve the survival rate of cancer patients. A number of serum biomarkers have been used in the diagnosis of lung cancers; however, they exhibit low sensitivity and specificity.MethodsWe used biochemical methods to measure blood levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), Na+, Cl-, carcino-embryonic antigen (CEA), and neuron specific enolase (NSE) in 145 small cell lung cancer (SCLC) patients and 155 non-small cell lung cancer and 155 normal controls. A gene expression programming (GEP) model and Receiver Operating Characteristic (ROC) curves incorporating these biomarkers was developed for the auxiliary diagnosis of SCLC.ResultsAfter appropriate modification of the parameters, the GEP model was initially set up based on a training set of 115 SCLC patients and 125 normal controls for GEP model generation. Then the GEP was applied to the remaining 60 subjects (the test set) for model validation. GEP successfully discriminated 281 out of 300 cases, showing a correct classification rate for lung cancer patients of 93.75% (225/240) and 93.33% (56/60) for the training and test sets, respectively. Another GEP model incorporating four biomarkers, including CEA, NSE, LDH, and CRP, exhibited slightly lower detection sensitivity than the GEP model, including six biomarkers. We repeat the models on artificial neural network (ANN), and our results showed that the accuracy of GEP models were higher than that in ANN. GEP model incorporating six serum biomarkers performed by NSCLC patients and normal controls showed low accuracy than SCLC patients and was enough to prove that the GEP model is suitable for the SCLC patients.ConclusionWe have developed a GEP model with high sensitivity and specificity for the auxiliary diagnosis of SCLC. This GEP model has the potential for the wide use for detection of SCLC in less developed regions.

Patients with pituitary adenomas usually receive "stress dose" steroids in the peri-operative peroids. Though randomized controlled trials(RCT) have not been performed to assess the necessity of steroid coverage, there are several studies that explained the changes of adrenal function during peri-operative peroids. The aim of the present study is to investigate whether it is necessary to employ conventional peri-operative glucocorticoid replacement therapy to all the patients undergoing surgery.We searched studies addressing peri-operative steroids coverage for pituitary adenomas in the Web of Science, Medline and the Cochrane Library. Then we extracted studies about peri-operative morning serum cortisol(MSC) levels, morbidity of early postoperative adrenal insufficiency, postoperative diabetes insipidus, relationships between MSC levels and adrenal integrity. We used RevMan Software to combine the results for meta-analysis. We used fixed-effects models for there was no significant heterogeneity existed.There are 18 studies from 11 countries published between 1987 and 2013 including 1224 patients. The postoperative serum cortisol levels were significantly increased compared with the preoperative one in hypothalamic-pituitary-adrenal axis(HPAA) functions preserved patients(P

In the future development of natural gas transportation industry, emerging ITS technology will be applied more and more, aiming at integrating precise positioning technology, geographic information system technology, database technology, multimedia technology and modern communication technology, sensor network technology and video capture technology, so as to achieve the transport steam (oil) vehicles in real time monitoring and management. The main research content of this paper is to design and research the monitoring and locating system of luck (oil) vehicle based on 4G on Android System. Real-time monitoring and alarming by sensor module, real-time video recording and uploading through camera module, real-time position recording and uploading through GPS module, vehicle navigation module and quick alarm module, which is composed of five parts. The system is the application of new intelligent transport technology in the field of special vehicle transport. It apply electronic information technology and internet of things technology to the vehicle system, so we can monitor natural gas and other special dangerous goods anytime, anywhere.

The hierarchical community detection is able to demonstrate the intrinsic structure of the network, but a deficiency is that the final structure is invariable. In this study, a flexible extension of the hierarchical approach is proposed. The modularity increasement is substituted by a ratio that should be larger than a threshold. We are able to adjust the hierarchical structure by modifying the threshold. The experiments display that such a variation of hierarchical structure is sensible if the modularity metric Q does not change too much.

Abstract Background The fungus of Ganoderma is a traditional medicine in Asia with a variety of pharmacological functions including anti-cancer activities. We have purified an extracellular heteropolysaccharide fraction, PS-F2, from the submerged mycelia culture of G. formosanum and shown that PS-F2 exhibits immunostimulatory activities. In this study, we investigated the molecular mechanisms of immunostimulation by PS-F2. Results PS-F2-stimulated TNF-α production in macrophages was significantly reduced in the presence of blocking antibodies for Dectin-1 and complement receptor 3 (CR3), laminarin, or piceatannol (a spleen tyrosine kinase inhibitor), suggesting that PS-F2 recognition by macrophages is mediated by Dectin-1 and CR3 receptors. In addition, the stimulatory effect of PS-F2 was attenuated in the bone marrow-derived macrophages from C3H/HeJ mice which lack functional Toll-like receptor 4 (TLR4). PS-F2 stimulation triggered the phosphorylation of mitogen-activated protein kinases JNK, p38, and ERK, as well as the nuclear translocation of NF-κB, which all played essential roles in activating TNF-α expression. Conclusions Our results indicate that the extracellular polysaccharides produced by G. formosanum stimulate macrophages via the engagement of multiple pattern-recognition receptors including Dectin-1, CR3 and TLR4, resulting in the activation of Syk, JNK, p38, ERK, and NK-κB and the production of TNF-α.