The associations between dysregulation of human blood metabolites and lung cancer risk: evidence from genetic data.

BACKGROUND: Metabolic dysregulation is recognized as a significant hallmark of cancer progression. Although numerous studies have linked specific metabolic pathways to cancer incidence, the causal relationship between blood metabolites and lung cancer risk remains unclear. METHODS: Genomic data from 29,266 lung cancer patients and 56,450 control individuals from the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium (TRICL-ILCCO) were utilized, and findings were replicated using additional data from the FinnGen consortium. The analysis focused on the associations between 486 blood metabolites and the susceptibility to overall lung cancer and its three major clinical subtypes. Various Mendelian randomization methods, including inverse-variance weighting, weighted median estimation, and MR-Egger regression, were employed to ensure the robustness of our findings. RESULTS: A total of 19 blood metabolites were identified with significant associations with lung cancer risk. Specifically, oleate (OR per SD = 2.56, 95% CI: 1.51 to 4.36), 1-arachidonoylglyceropholine (OR = 1.79, 95% CI: 1.22 to 2.65), and arachidonate (OR = 1.67, 95% CI: 1.16 to 2.40) were associated with a higher risk of lung cancer. Conversely, 1-linoleoylglycerophosphoethanolamine (OR = 0.57, 95% CI: 0.40 to 0.82), ADpSGEGDFXAEGGGVR, a fibrinogen cleavage peptide (OR = 0.60, 95% CI: 0.47 to 0.77), and isovalerylcarnitine (OR = 0.62, 95% CI: 0.49 to 0.78) were associated with a lower risk of lung cancer. Notably, isoleucine (OR = 9.64, 95% CI: 2.55 to 36.38) was associated with a significantly higher risk of lung squamous cell cancer, while acetyl phosphate (OR = 0.11, 95% CI: 0.01 to 0.89) was associated with a significantly lower risk of small cell lung cancer. CONCLUSION: This study reveals the complex relationships between specific blood metabolites and lung cancer risk, highlighting their potential as biomarkers for lung cancer prevention, screening, and treatment. The findings not only deepen our understanding of the metabolic mechanisms of lung cancer but also provide new insights for future treatment strategies.

Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non-small cell lung cancer.

The third most prevalent type of epidermal growth factor receptor (EGFR) mutation, EGFR exon 20 insertions (EGFRex20ins), involves 2%-12% of all cases of EGFR-positive non-small cell lung cancer (NSCLC). Approximately 90% of the mutations occur within the loop structure region, and the most frequently reported subtypes are A767_V769dup and S768_D770dup, which together account for almost 50% of instances. Apart from the unique subtype of A763_Y764insFQEA, NSCLCs with EGFRex20ins are resistant to approved EGFR tyrosine kinase inhibitors (TKIs) and are also insensitive to chemotherapy or immunotherapy. A new modality of treatment for NSCLC patients with EGFRx20ins has been established with the approval of mobocertinib and amivantamab. There are also numerous novel targeted treatments for NSCLC with EGFRex20ins in development, which are anticipated to improve this patient population's survival even further. This review provides a reference for the clinical management of these patients by summarizing the most recent epidemiological, and clinicopathological characteristics, diagnostic techniques, and therapeutic advances of EGFRex20ins in NSCLC.

Efficacy and safety of video-assisted thoracoscopic surgery and thoracotomy in the treatment of pulmonary hydatid disease in the Tibetan Plateau: a retrospective study.

Background: Although video-assisted thoracoscopic surgery (VATS) plays an increasingly significant part in treating thoracic disease, the role of thoracotomy is not replaced in cystic echinococcosis. The aim of this study was to demonstrate the application of VATS and traditional thoracotomy in the treatment of pulmonary hydatid disease in Shigatse of the Tibet Plateau and to compare the clinical safety and efficacy of these two surgical approaches. Methods: A total of 53 patients with pulmonary hydatid who received thoracoscopic cystectomy with needle aspiration from January 2015 to December 2020 were enrolled in the study, and 126 patients who received thoracotomy during the same period were matched as the control group. The clinical characteristics, operative time, incidence of perioperative complications, length of stay, and hospitalization cost of the VATS and thoracotomy groups were analyzed to compare the safety and efficacy. Patients were followed up through telephone and outpatient service. In order to balance potential confounding baseline factors, propensity-score matching (PSM) was applied to establish a 1:1 VATS to thoracotomy group ratio. Results: There were statistically significant differences between the VATS group and the thoracotomy group in operative time, blood loss, drainage volume, and postoperative hospital stay (P<0.05), with the VATS group being superior to the thoracotomy group. There were no significant differences in postoperative complications, adverse imaging outcomes, or recurrence rates between the 2 groups. In terms of complications, there was no significant difference in the incidence of postoperative air leakage, atelectasis, or other common complications between the 2 groups, while the frequency of postoperative fever and incision infection in the thoracotomy group was significantly higher than that in the VATS group (P<0.05). Moreover, the postoperative recurrence rate between the 2 groups showed no significant difference after a 3-year follow-up. Conclusions: Compared to traditional thoracotomy, VATS had acceptable efficacy and safety and it could further accelerate postoperative recovery and reduce the cost in the treatment of pulmonary hydatid disease in the Tibetan Plateau. Thus, VATS should be promoted more widely to other Tibetan regions.

Clinicopathological and prognostic implications of ALK rearrangement in patients with completely surgically resected lung adenocarcinoma.

BACKGROUND: The prognostic significance of ALK rearrangement is still contradictory. Here, we aimed to investigate the clinical characteristics and outcomes of lung adenocarcinoma patients with ALK rearrangement, and analyze whether these patients benefited from targeted therapy. METHODS: This was a retrospective cohort study of 80 ALK-rearranged lung adenocarcinoma patients who had undergone radical surgery and another 3031 ALK mutation-negative patients were retrospectively reviewed for inclusion in this case-controlled analyses. Overall survival (OS) was evaluated using the Kaplan--Meier method. Univariate analysis (UVA) and multivariate analysis (MVA) by the Cox proportional hazards regression identified risk factors that predicted OS. RESULTS: Compared to ALK-negative patients, the ALK rearranged patients were younger, with more non-smokers, more females, a larger primary tumor was demonstrated, and were a higher pathological stage. In particular, the risk of lymph node metastasis was higher. For patients with surgically-resected tumors, the prognosis was better for ALK rearranged patients (HR = 0.503; 95% CI: 0.259-0.974, p = 0.041). In addition, for stage II-III patients, targeted therapy was an independent prognostic factor of better OS (HR = 0.159; 95% CI: 0.032-0.801, p = 0.026). CONCLUSIONS: ALK rearranged lung adenocarcinoma patients who have undergone radical surgery have distinct clinical features. Patients with ALK rearrangement may have a favorable prognosis, and stage II-III patients may benefit from targeted treatment.

Dissecting the single-cell transcriptome network in patients with esophageal squamous cell carcinoma receiving operative paclitaxel plus platinum chemotherapy.

Esophageal squamous cell carcinoma (ESCC) accounts for 90% of all cases of esophageal cancers worldwide. Although neoadjuvant chemotherapy (NACT-ESCC) improves the survival of ESCC patients, the five-year survival rate of these patients is dismal. The tumor microenvironment (TME) and tumor heterogeneity decrease the efficacy of ESCC therapy. In our study, 113,581 cells obtained from five ESCC patients who underwent surgery alone (SA-ESCC) and five patients who underwent preoperative paclitaxel plus platinum chemotherapy (NACT-ESCC), were used for scRNA-seq analysis to explore molecular and cellular reprogramming patterns. The results showed samples from NACT-ESCC patients exhibited the characteristics of malignant cells and TME unlike samples from SA-ESCC patients. Cancer cells from NACT-ESCC samples were mainly at the 'intermediate transient stage'. Stromal cell dynamics showed molecular and functional shifts that formed the immune-activation microenvironment. APOE, APOC1, and SPP1 were highly expressed in tumor-associated macrophages resulting in anti-inflammatory macrophage phenotypes. Levels of CD8+ T cells between SA-ESCC and NACT-ESCC tissues were significantly different. Immune checkpoints analysis revealed that LAG3 is a potential immunotherapeutic target for both NACT-ESCC and SA-ESCC patients. Cell-cell interactions analysis showed the complex cell-cell communication networks in the TME. In summary, our findings elucidate on the molecular and cellular reprogramming of NACT-ESCC and ESCC patients. These findings provide information on the potential diagnostic and therapeutic targets for ESCC patients.

Dissecting the single-cell transcriptome network underlying esophagus non-malignant tissues and esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is among the most prevalent causes of cancer-related death in adults. Tumor microenvironment (TME) has been associated with therapeutic failure and lethal outcomes for patients. However, published reports on the heterogeneity and TME in ESCC are scanty. METHODS: Five tumor samples and five corresponding non-malignant samples were subjected to scRNA-seq analysis. Bulk RNA sequencing data were retrieved in publicly available databases. FINDINGS: From the scRNA-seq data, a total of 128,688 cells were enrolled for subsequent analyses. Gene expression and CNV status exhibited high heterogeneity of tumor cells. We further identified a list of tumor-specific genes and four malignant signatures, which are potential new markers for ESCC. Metabolic analysis revealed that energy supply-related pathways are pivotal in cancer metabolic reprogramming. Moreover, significant differences were found in stromal and immune cells between the esophagus normal and tumor tissues, which promoted carcinogenesis at both cellular and molecular levels in ESCC. Immune checkpoints, regarded as potential targets for immunotherapy in ESCC were significantly highly expressed in ESCC, including LAG3 and HAVCR2. Eventually, we constructed a cell-to-cell communication atlas based on cancer cells and immune cells and performed the flow cytometry, qRT-PCR, immunofluorescence, and immunohistochemistry analyses to validate the results. INTERPRETATION: This study demonstrates a widespread reprogramming across multiple cellular elements within the TME in ESCC, particularly in transcriptional states, cellular functions, and cell-to-cell interactions. The findings offer an insight into the exploration of TME and heterogeneity in the ESCC and provide new therapeutic targets for its clinical management in the future. FUNDING: The work was supported by the Shanghai Pujiang Program (2020PJD009) and Research Development Fund of Zhongshan Hospital, Fudan University (2019ZSFZ002 and 2019ZSFZ19).

A nomogram to predict prognosis of patients with lung adenosquamous carcinoma: a population-based study.

BACKGROUND: Adenosquamous carcinoma (ASC) of the lung is an infrequent variant of lung cancer. This study aimed to identify independent risk factors and to develop a predictive model for the prognosis of ASC patients. METHODS: Patient data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (2004 to 2016) and database in our department (2010 to 2014). Overall survival (OS) was evaluated by the Kaplan-Meier method. Significant prognostic factors were identified by univariate analysis (UVA) and multivariate analysis (MVA) using the Cox proportional hazards regression. Competing risk model analyses were performed using cancer-specific survival outcomes. A nomogram was developed to predict patient 3-year and 5-year OS and was validated using data from the two databases. RESULTS: A total of 4,600 patients with ASC were included and divided into a training cohort (n=3,202) and two validation cohorts (n=1,372, n=26). Patients with ASC had significantly older age, lower grades of tumor differentiation or incidences of nodal, and distant invasions than adenocarcinoma and squamous cell carcinoma (SCC) of the lung (P<0.001), while the median survival time of ASC patients was intermediate [21.0 (19.3-22.7) months]. Age, sex, primary site of tumor, histological grade, T stage, N stage, M stage of the tumor, as well as surgery to the primary tumor site and chemotherapy were identified as independent factors for ASC (P<0.001). A reliable nomogram was established with a group of validation plots and concordance indices (C-indices) (internal: 0.755±0.010; external: 0.748±0.049 and 0.721±0.045). CONCLUSIONS: Age, sex, primary site of tumor, histological grade, T stage, N stage, M stage of the tumor, as well as surgery to the primary site of tumors and chemotherapy were independent risk factors for ASC patients. A validated nomogram was constructed to predict the prognosis based on the patient clinical characteristics.

Long-term outcomes following neoadjuvant or adjuvant chemoradiotherapy for stage I-IIIA non-small cell lung cancer: a propensity-matched analysis.

BACKGROUND: This study aimed to evaluate the long-term survival outcomes of patients undergoing neoadjuvant chemoradiotherapy or adjuvant chemoradiotherapy for T1-4N0-1M0 disease. METHODS: Patients with pT1-4N0-1M0 between 2010 and 2015 who received pre- or postoperative (R0 resection) chemoradiotherapy were identified. The exclusion criteria included N2 or M1 disease, immunotherapy, and targeted therapy. The staging was recalculated according to the new 8th edition TNM classification. Survival and predictors were assessed using Kaplan-Meier and multivariate Cox proportional-hazards model. Propensity-score matching with a ratio of 2:1 was performed to reduce bias in various clinicopathological factors. RESULTS: Of the 1,769 patients who met the inclusion criteria, 407 and 814 were included in the neoadjuvant and adjuvant chemoradiotherapy group, respectively, after propensity-score matching. The 5-year overall survival (OS) and cancer-specific survival (CSS) were 38.1% and 40.0% for neoadjuvant chemoradiotherapy and 26.3% and 26.5% for adjuvant chemoradiotherapy, respectively [P<0.0001, hazard ratio (HR): 0.7418, 95% confidence interval (CI): 0.6434-0.8553; P<0.0001, HR: 0.7444, 95% CI: 0.6454-0.8587)]. When stratified by stage, stage IIA (P=0.4166, HR: 0.8575, 95% CI: 0.5917-1.243) and IIIA (P=0.0740, HR: 0.7687, 95% CI: 0.5748-1.028) did not show improved 5-year OS in patients receiving neoadjuvant chemoradiotherapy. When stratified by age, similar trends were observed for patients aged more than 75 years. The multivariable analysis showed a significant association of neoadjuvant chemoradiotherapy with better survival. CONCLUSIONS: Neoadjuvant chemoradiotherapy might improve the long-term survival of patients with stage I-IIIA non-small cell lung cancer (NSCLC). For patients aged more than 75 years, neoadjuvant chemoradiotherapy was not associated with an improvement in survival.

Development and validation of a nomogram for predicting the overall survival of patients with lung large cell neuroendocrine carcinoma.

BACKGROUND: Lung large cell neuroendocrine carcinoma (L-LCNEC) is a rare and rapidly progressing lung cancer. We aimed to formulate a nomogram model to predict the survival of L-LCNEC patients. METHODS: Clinical data of patients with L-LCNEC, lung large cell cancer (L-LCC) and small cell lung cancer (SCLC) were derived from the Surveillance, Epidemiology, and End Results (SEER) database. The characteristics and prognosis of L-LCNEC were investigated by comparing with that of L-LCC and SCLC, respectively. All L-LCNEC patients were randomly assigned into training group and validation group. A prognostic nomogram model was established for the overall survival (OS) in L-LCNEC patients. Furthermore, we enrolled 112 L-LCNEC patients from our department to validate the nomogram model. RESULT: 3,076 L-LCNEC, 11,163 L-LCC, and 78,097 SCLC patients were collected and enrolled in our analyses. Compared with L-LCC and SCLC, differences were observed in L-LCNEC in age, sex, race, marital status, SEER registry, TNM stage, and treatment. Furthermore, higher proportions of L-LCNEC were located at the upper lobe and unilateral lung compared with SCLC. L-LCNEC has similar survival to L-LCC, but better than SCLC. We identified that the age, gender, T, N, and M classification, and treatment were the independent prognostic predictors. A nomogram model was formulated to predict the OS. Calibration curves were performed to show optimal coherence between predicted probability of survival and actual survival, with a concordance index of 0.775. The external cohort included 112 patients and all of them underwent surgical treatment. The external validation demonstrated the reliability of this model. CONCLUSIONS: The nomogram demonstrated its discrimination capability to predict the OS for L-LCNEC patients.

Benefits of surgery in the multimodality treatment of stage IIB-IIIC small cell lung cancer.

Surgery combined with chemotherapy/radiotherapy is recommended for early stage small cell lung cancer (SCLC); however, the role of surgery in the multimodality treatment of advanced disease remains controversial. The clinical data of patients between 2000 and 2015 were obtained from the Surveillance, Epidemiology, and End Results database. The surgery group included 998 patients with stage IIB-IIIC. A matched non-surgery group (n = 2994) was generated by propensity score matching. The Kaplan-Meier method and log-rank tests were used for survival analyses. Univariate and multivariate analyses were used to identify significant prognostic factors. After matching, there were no significant differences between the two groups in race, age, sex, T classification, N classification, TNM stage, marital status, primary sites, and origin record NAACCR Hispanic Identification Algorithm (NHIA). The surgery group showed better overall survival and cancer-specific survival than the non-surgery group. Univariate and multivariate analyses showed that therapy methods, age, sex, T classification, and N classification were independent prognostic predictors for stage IIB-IIIC SCLC (all P < 0.05). Stratified analyses showed that survival outcomes favored surgery in any age groups, men and women, any T classification except T3, and N0-2 but not N3 compared with non-surgical treatment. The survival differences favored surgery in stage IIB and IIIA SCLC, although they were not significant in stage IIB and IIIC SCLC. Therefore, surgery was associated with improved survival in stage IIB and IIIA SCLC, but not in stage IIIB and IIIC SCLC.

Identification and validation of an immune cell infiltrating score predicting survival in patients with lung adenocarcinoma.

BACKGROUND: Immune infiltration may predict survival and have clinical significance in lung cancer. However, immune signatures derived from immune profiling based on bulk tumor transcriptomes have not been systematically established in lung adenocarcinoma. We aimed to construct an immune cell infiltrating score, using a new algorithm for evaluating immune infiltration, to improve the prognostic model of lung adenocarcinoma. METHODS: Public datasets of lung adenocarcinoma from the Gene Expression Omnibus and The Cancer Genome Atlas were adopted as the training and validation cohorts. Fractions of different immune cell subtypes in each sample were estimated using the CIBERSORT algorithm. The immune infiltrating score was further developed by a least absolute shrinkage and selection operator regression model. The prognostic value and clinical relationship of the model was then further explored. RESULTS: An immune infiltrating score model was established on the basis of the immune cells in the training cohort. A high score was associated with significantly worse survival in patients with lung adenocarcinoma (P < 0.001). The prognostic value of the score was confirmed in the validation cohort. The immune infiltrating score could improve the accuracy of predictions of survival when combined with the staging system. Furthermore, the score was potentially associated with patient smoking status and histologic subtype of lung adenocarcinoma. Its possible association with the efficacy of adjuvant chemotherapy was not statistically significant. CONCLUSION: The immune cell infiltrating score has prognostic significance in predicting overall survival in patients with lung adenocarcinoma.

[Clinical Characteristics and Prognostic Factors of Lung Adenosquamous Carcinoma 
in SEER Database between 2010 and 2015].

BACKGROUND: The incidence and the mortality of lung cancer rank first among all malignant tumors and it seriously affects human health. The common types of non-small cell lung cancer (NSCLC) are adenocarcinoma and squamous carcinoma with clinical research and more attention, while adenosquamous carcinoma is a rare pathological subtype of lung cancer, which clinical features and prognostic factors are not yet fully understood. The purpose of this study is to analyze the clinical features and prognosis of lung adenosquamous carcinoma, and construct a nomogram to predict the patients' prognosis. METHODS: We obtained the data of adenosquamous carcinoma patients diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database of the United States, and compared their clinical features and prognosis with those of lung adenocarcinoma and lung squamous cell carcinoma patients in the same period. Then we used univariate and multivariate analyses to explore the independent prognostic factors of adenosquamous carcinoma. Finally, we constructed and validated a nomogram to visually predict the outcomes of lung adenosquamous carcinoma. RESULTS: 1,453 patients with lung adenosquamous carcinoma were finally included. Compared with patients with lung adenocarcinoma and lung squamous cell carcinoma, the distributions of lung adenocarcinoma patients in most of the variables were medium between lung adenocarcinoma and squamous cell carcinoma. The prognosis of adenosquamous carcinoma was better than that of lung squamous cell carcinoma, but worse than that of lung adenocarcinoma. Multivariate analysis showed that age, differentiation, tumor-node-metastasis (TNM), surgery, and chemotherapy were independent prognostic factors (all P were less than 0.001). We constructed a nomogram with a C-index of 0.783 (0.767-0.799). The distinction test and consistency test showed that the nomogram could predict the patient's prognosis effectively. CONCLUSIONS: Lung adenosquamous carcinoma has unique clinical, pathological, and prognostic characteristics. Age, differentiation, T, N, M, surgery, and chemotherapy status are independent predictors of prognosis in patients with adenosquamous carcinoma. Our nomogram can efficiently predict the prognosis of patients.

Straightforward Loading of Imidazole Molecules into Metal-Organic Framework for High Proton Conduction.

A one-step straightforward strategy has been developed to incorporate free imidazole molecules into a highly stable metal-organic framework (NENU-3, ([Cu12(BTC)8(H2O)12][HPW12O40])·Guest). The resulting material Im@(NENU-3) exhibits a very high proton conductivity of 1.82 × 10-2 S cm-1 at 90% RH and 70 °C, which is significantly higher than 3.16 × 10-4 S cm-1 for Im-Cu@(NENU-3a) synthesized through a two-step approach with mainly terminal bound imidazole molecules inside pores. Single crystal structure reveals that imidazole molecules in Im-Cu@(NENU-3a) isolate lattice water molecules and then block proton transport pathway, whereas high concentration of free imidazole molecules within Im@(NENU-3) significantly facilitate successive proton-hopping pathways through formation of hydrogen bonded networks.

CMISG1701: a multicenter prospective randomized phase III clinical trial comparing neoadjuvant chemoradiotherapy to neoadjuvant chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0) (NCT03001596).

BACKGROUND: Neoadjuvant chemoradiation is not recommended as an approach for treatment of esophageal squamous cell carcinoma due to its significant postoperative mortality. However, it is assumed the combination of neoadjuvant chemoradiation with minimally invasive esophagectomy (MIE) may reduce postoperative mortality, which can revive preoperative chemoradiation. No randomized controlled studies comparing neoadjuvant chemoradiation plus MIE with neoadjuvant chemotherapy plus MIE have been performed so far. The present trial is initiated to obtain valid information whether neoadjuvant chemoradiation plus MIE yields better survival without worse postoperative morbidity and mortality in the treatment of locally advanced resectable esophageal squamous cell carcinoma(cT3-4aN0-1M0). METHODS/DESIGN: CMISG1701 is a multicenter, prospective, randomized, phase III clinical trial, investigating the safety and efficacy of neoadjuvant chemoradiation plus MIE compared with neoadjuvant chemotherapy plus MIE. Patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0) are eligible for the study. A total of 264 patients are randomly assigned to neoadjuvant chemoradiation (arm A) or neoadjuvant chemotherapy (arm B) with a 1:1 allocation ratio. The primary outcome is overall survival assessed with a minimum follow-up of 36 months. Secondary outcomes are progression-free survival, recurrence-free survival, postoperative pathologic stage, treatment-related complications, postoperative mortality as well as quality of life. DISCUSSION: The objective of this trial is to identify the superior protocol with regard to patient survival, treatment morbidity/mortality and quality of life between neoadjuvant chemoradiation plus MIE and neoadjuvant chemotherapy plus MIE. TRIAL REGISTRATION: NCT03001596 (December 17, 2016).

Evaluation of the 7(th) edition of the UICC-AJCC tumor, node, metastasis classification for esophageal cancer in a Chinese cohort.

BACKGROUND: To assess and evaluate the prognostic value of the 7(th) edition of the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC) tumor, node, metastasis (TNM) staging system for Chinese patients with esophageal cancer in comparison with the 6(th) edition. METHODS: A retrospective review was performed on 766 consecutive esophageal cancer patients treated with esophagectomy between 2008 and 2012. Patients were staged according to the 6(th) and 7(th) editions for esophageal cancer respectively. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed using Cox regression model. RESULTS: Overall 3-year survival rate was 59.5%. There were significant differences in 3-year survival rates among T stages both according to the 6(th) edition and the 7(th) edition (P<0.001). According to the 7(th) edition, the 3-year survival rates of N0 (75.4%), N1 (65.2%), N2 (39.7%) and N3 (27.3%) patients were significant differences (P<0.001). Kaplan-Meier curve revealed a good discriminatory ability from stage I to IV, except for stage IB, IIA and IIB in the 7(th) edition staging system. Based on the 7(th) edition, the degree of differentiation, tumor length and tumor location were not independent prognostic factors on multivariate analysis. The multivariate analyses suggested that pT-, pN-, pTNM-category were all the independent prognostic factors based on the 6(th) and 7(th) edition staging system. CONCLUSIONS: The 7(th) edition of AJCC TNM staging system of esophageal cancer should discriminate pT2-3N0M0 (stage IB, IIA and IIB) better when considering the esophageal squamous cell cancer patients. Therefore, to improve and optimize the AJCC TNM classification for Chinese patients with esophageal cancer, more considerations about the value of tumor grade and tumor location in pT2-3N0M0 esophageal squamous cell cancer should be taken in the next new TNM staging system.

Decreased expression of miR-204 in plasma is associated with a poor prognosis in patients with non-small cell lung cancer.

In order to identify novel non-invasive biomarkers with high accuracy for the screening of non-small cell lung cancer (NSCLC), we investigated the predictive power of 4 microRNAs (miR-146, miR-204, miR-106a and miR-124) in plasma samples obtained from patients with NSCLC and healthy controls (n=50; training phase) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We found that the levels of miR-204 in the patients with NSCLC were significantly dysregulated compared with the healthy controls, and thus this miRNA was selected for further validation. For the validation phase, RT-qPCR was performed on plasma samples from patients with NSCLC and healthy controls (n=176) in order to examine the expression levels of the candidate miRNA, miR-204. The results revealed that the plasma levels of miR-204 were significantly downregulated in the patients with NSCLC compared with the healthy controls (p<0.001). The value of the area under the receiver operating characteristic (ROC) curve obtained for miR-204 was 0.809 (sensitivity, 76%; specificity, 82%), which was higher than the values obtained for carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). The expression of miR-204 in plasma significantly correlated with the tumor stage (p=0.009) and distant metastasis (p=0.048). A log-rank test revealed that lower plasma levels of miR-204 were associated with a shorter overall survival and disease-free survival (p=0.006 and 0.0065, respectively). Both univariate and multivariate Cox regression analyses indicated that a lower miR-204 expression level in plasma was a prognostic factor with a relative risk of death of 1.936 and 1.712, respectively. On the whole, our results suggest that the decreased expression of miR-204 in plasma is a promising biomarker for the detection of NSCLC and the prediction of poor survival in patients with the disease.

Randomized controlled trial comparing changes in serum prolactin and weight among female patients with first-episode schizophrenia over 12 months of treatment with risperidone or quetiapine.

BACKGROUND: Increased serum prolactin and weight gain are common side effects of atypical antipsychotics but few studies have assessed the long-term pattern of these adverse effects. AIM: Compare the effects of risperidone and quetiapine on serum prolactin and weight over 12 months of treatment among female patients with first-episode schizophrenia. METHODS: Eighty female inpatients with first-episode schizophrenia were randomly assigned to receive risperidone (n=40) or quetiapine (n=40) for 12 months. Prolactin concentration, weight and height were measured one day before starting treatment and 1, 3, 6, 9 and 12 months after initiating treatment. Severity of symptoms was assessed at the same time periods using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Thirty-one patients in the risperidone group and 33 patients in the quetiapine group completed the 12 months of treatment. PANSS scores decreased at each follow-up assessment for both groups; the improvement was significantly greater in the risperidone group after 3 months and 6 months of treatment but by the 9th month of treatment the level of improvement in the two groups was similar. In the quetiapine group serum prolactin remained stable throughout the 12 months but in the risperidone group the serum prolactin level increased 3.5- to 5.2-fold over the one-year follow-up. Weight gain was seen in both groups, particularly during the first 3 months of treatment: 62% of the increase in BMI in both groups had occurred by the end of the 3rd month of treatment. No between-group differences in weight changes were observed. The correlation between changes in weight and changes in prolactin levels were weakly positive: rs=0.17(p=0.104) in the risperidone group and r=0.07 (p=0.862) in the quetiapine group. CONCLUSIONS: Risperidone and quetiapine had similar efficacy in the first year of treatment of first-episode schizophrenia though risperidone was more rapidly effective. Use of risperidone was associated with chronic hyperprolactinemia but this did not occur with quetiapine. Long-term use of both drugs was associated with sustained weight gain; the timing and magnitude of the weight gain is similar for the two drugs. Weight gain was not strongly related to changes in prolactin levels.

Diazoxide-mediated growth inhibition in human lung cancer cells via downregulation of beta-catenin-mediated cyclin D1 transcription.

Treatment of various types of cells with the mitochondrial ATP-sensitive K(+) channel opener, diazoxide, preconditions cells to subsequent injuries and inhibits apoptosis. However, the role and mechanism(s) of diazoxide in solid tumor cell growth are largely unknown. Here we demonstrate that diazoxide inhibited the proliferation of lung cancer cells as well as the transcription of cell cycle-related protein Cyclin D1. Cyclin D1 overexpression inhibited the negative role of diazoxide in cell cycle progression. We further explored the mechanisms by which diazoxide affected Cyclin D1 transcription and found that the beta-catenin transcription factor was downregulated by diazoxide, with a corresponding decrease in Cyclin D1 promoter activity. Taken together, these results suggest that diazoxide inhibits lung cancer cell proliferation via downregulation of Cyclin D1 transcription, which may have important therapeutic implications in lung cancer patients.

[Multi-points pulse information acquisition and 3-D reconstruction based on grid-net images].

A method of acquiring radial pulse information from the grid-net area on every pulse image frame is proposed based on the principle of lens imaging and the characteristics of image data. The radial pulse image data are collected by the pulse image sensor. Multi-points out-of-plane displacements of the pulse are acquired by the method. And the membrane surfaces are reconstructed, then the 3D information of the pulse can be observable.