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Goodpasture’s syndrome (GPS) is a rare but severe vasculitis disease, characterized by rapidly progressive glomerulonephritis (RPGN), diffuse pulmonary hemorrhage in the presence of anti-glomerular basement membrane antibody (anti-GBM antibody). Central nervous system (CNS) was rarely involved, especially in the absence of anti-neutrophil cytoplasmic antibodies (ANCA). Typically, CNS vasculitis was one of important causes. Herein we present a case of GPS presenting RPGN, clonic-tonic seizures and bloody sputum. She underwent renal puncture and bleeding complication occurred afterwards. Due to the insufficiency of conservative therapy including transfusion, fluid infusion, selective renal arteriography embolization was then employed. Angiogram results showed beading changes of renal artery. Brain CT scan was found negative, but MRA imaging demonstrated the obvious involvement of cranial vessels. The changes of renal and cranial vascular involvement were highly suspicious of nervous vasculitis based on the primary disease. The patient was treated with corticoids and plasma exchange. Patient’s condition improved quickly and anti-GMB antibodies proved to be negative, but renal failure persisted, dependent on long-term hemodialysis. We described for the first-time association of Goodpasture’s syndrome with both renal and nervous vascular involvements.

Background: Encapsulating peritoneal sclerosis (EPS) is an uncommon, but serious complication in patients with continuous ambulatory peritoneal dialysis (PD) who have a considerable mortality rate. This study aimed to identify risk factors and outcomes of EPS in Chinese patients on PD. Methods: Sixteen patients on PD who met the International Society for Peritoneal Dialysis criteria for diagnosis of EPS in the First Affiliated Hospital of Sun Yat-Sen University from 1997 to 2018 were included. Patients without EPS were matched for age, sex and the duration of PD and selected at a 1:3 ratio for the controls. A case–control study was conducted to analyse the clinical profile and risk factors associated with EPS in patients. Results: The prevalence of EPS in patients on PD in our centre was 0.55%. The percentage of EPS significantly increased with the duration of PD. In univariate regression analysis, a history of peritonitis (odds ratios (OR): 2.83; 95% confidence interval (CI): 0.82–9.68; p = 0.08), peritoneal glucose exposure (OR: 1.12; 95% CI: 1.03–1.22; p < 0.01) and a high peritoneal transport status (OR: 14.70; 95% CI: 1.85–117.02; p < 0.01) were associated with EPS in patients on PD. However in the multivariate model, only a high peritoneal transport status (adjusted odds ratios (aOR): 13.65; 95% CI: 1.69–109.96; p = 0.01) was independently associated with EPS. Conclusion: The rate of EPS significantly increases with the duration of PD. Progressive peritoneal dysfunction, especially a high peritoneal transport status, is associated with a higher risk of EPS in this population.

Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) is an important virulence factor that blocks the host immune response and facilitates M. tuberculosis growth in host cells. MptpB inhibitors are potential components of tuberculosis combination treatment. Herein, we present the development of new biphenyls MptpB inhibitors with greatly improved MptpB inhibition based on our reported thiobarbiturate lead 6 by rational design with the structure-based strategy. The eight biphenyls bearing thiobarbiturate fragment target compounds showed more potent MptpB inhibition (IC

Background Primary small cell carcinoma of the esophagus (PSCCE) is a rare and aggressive malignancy. It has a poor survival rate, and there is no consensus as to a standard therapeutic modality. In this study, we aimed to investigate the prognostic factors and evaluate the outcomes of patients with PSCCE who had been treated with different therapeutic methods. Methods We retrospectively evaluated 113 consecutive patients with PSCCE who received treatment at our center from 2003 to 2016. The primary endpoint was overall survival (OS). The Cox regression model was used to analyze the prognostic factors. The survival analysis was calculated using the Kaplan-Meier and log-rank methods. Results The 12- and 36-month OS rates of all 113 enrolled patients were 45% and 12%, respectively. A significantly prolonged OS rate was associated with lymph node stages N0-N1 (P=0.022), the Veterans' Administration Lung Study Group (VALSG) system limited-disease (LD) staging (P=0.040), and multimodality treatments (P=0.047). Patients with regional lymph node metastasis benefited more from surgery combined with chemotherapy than surgery or chemotherapy alone (P=0.046). Concerning chemotherapy, cisplatin plus etoposide was the regimen most commonly used to treat PSCCE patients (67.5%). Conclusions An early lymph node stage, the VALSG LD staging, and multimodality treatments were identified as independent prognostic factors of PSCCE. Surgery combined with adjuvant chemotherapy was especially necessary for LD stage PSCCE patients with lymph node stages N1-3.

We consider an ensemble of atoms with $\Lambda$-type level structure trapped in a single-mode cavity, and propose a geometric scheme of coherent manipulation of quantum states on the subspace of zero-energy states within the quantum Zeno subspace of the system. We find that the particular subspace inherits the decoherence-free nature of the quantum Zeno subspace and features a symmetry-protected degeneracy, fulfilling all the conditions for a universal scheme of arbitrary unitary operations on it., Comment: 5 pages with 3 figures. Supplemental Material is available upon request

Purpose: The efficacy and safety of nimotuzumab (NTZ) added to concurrent chemoradiotherapy (CCRT) was investigated in patients with stage III-IVa nasopharyngeal carcinoma (NPC).Methods: Patients with stage III-IVa NPC treated with CCRT, with or without NTZ, were screened between January 2015 and December 2017. Overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between these groups. Propensity score matching (PSM) was applied to reduce the selection bias. Nomogram models were developed to predict survival of CCRT with or without NTZ. Results: A total of 426 patients were included after PSM, with 213 patients in each regimen. Compared with NPC patients receiving CCRT alone, patients who received NTZ plus CCRT treatment had significantly better OS (5-year OS, 76.1% vs. 72.3%, P = 0.004), PFS (5-year PFS, 73.2% vs. 69.0%, P = 0.002), and LRFS (5-year LRFS, 73.2% vs. 69.0%, P = 0.028). A multivariate Cox regression analysis demonstrated that, compared with receiving CCRT alone, NTZ plus CCRT was an independently positive factor for OS, PFS, and LRFS. In addition, no significant difference was observed in the major toxicities among the two treatments (all P>0.05). Nomogram models that identified significant prognostic factors were produced.Conclusion: The present study suggested the NTZ plus CCRT treatment presented favorable clinical outcomes for stage III-IVa NPC patients with good tolerance and similar toxicity compared to CCRT alone. A prospective, randomized clinical trial is essential to validate the current findings.

Background It is generally believed that the preoperative serum carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) levels are independent predictors of prognosis in multiple malignant tumors. However, their predictive value in esophageal squamous cell carcinoma (ESCC) is still unknown. Therefore, the main purpose of this study is to detect the serum CEA and SCC-Ag levels of ESCC patients before operation, in order to clarify the clinical significance of them as prognostic factors. Methods We conducted a retrospective review of 348 patients with ESCC treated by esophagectomy between February 2009 and October 2012. We Analyzed the influence of serum CEA and SCC-Ag level on prognosis. We used a receiver operating characteristic (ROC) curve to identify the serum CEA and SCC-Ag level for predicting survival. We used Log-rank test to compare survival curves, and Cox regression analysis to clarify significant prognostic factors. Results The cutoffs for CEA and SCC-Ag were 2.28 ng/mL and 0.75 ng/mL, respectively, Under curve area of CEA was 0.600 (95% CI: 0.541–0.660; P=0.001) and under curve area of SCC-Ag was 0.567 (95% CI: 0.507–0.628; P=0.030). According to the Kaplan-Meier curves, the overall survival rate (OS) and disease-free survival rate (DFS) of patients with CEA ≤2.28 ng/mL were higher than those with CEA >2.28 ng/mL. Meanwhile, patients with serum levels of SCC-Ag ≤0.75 ng/mL had a more favorable OS and DFS than those of patients with SCC-Ag >0.75 ng/mL. Cox regression analysis showed that the total mortality of patients with CEA >2.28 ng/mL was higher than that of patients with CEA ≤2.28 ng/mL (HR 1.76; 95% CI: 1.39–2.39; P0.75 ng/mL was an independent negative prognostic factor for DFS (HR 1.86; 95% CI: 1.17–2.96; P=0.009). As the nomogram showed, the survival rate of ESCC patients with high preoperative serum CEA and SCC-Ag levels was relatively low. Conclusions High levels of serum CEA and SCC-Ag were independent and significant predictors of ESCC patients after surgical treatment.

Objective The impact of negative lymph nodes (NLNs) count on prognosis in esophageal cancer (EC) was analyzed using two institutions surgical database. Methods We conducted a retrospective study of 768 EC patients treated by surgical resection between January 2010 and December 2012. The effects of the NLNs count on prognosis was analyzed. Cox regression model was conducted to determine the significant prognostic elements. Results The number of NLNs was studied as a categorical variable based on the quartiles (Q1: ≤15, Q2: 16-21, Q3: 22-30, Q4: ≥31). And a better overall survival (OS) was observed with increasing number of NLNs (HR= 0.762; 95% CI, 0.596-0.974 for Q2, HR= 0.666; 95% CI, 0.516-0.860 for Q3 and HR= 0.588; 95% CI, 0.450-0.768 for Q4) (all P

Fiscpropionates A-F (1-6), six new polypropionate derivatives featuring an unusual long hydrophobic chain, were isolated from the deep-sea-derived fungus Aspergillus fischeri FS452. Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configurations were determined by J-HMBC analysis, electronic circular dichroism (ECD) calculations, and the modified Mosher's method. This is the first discovery of polypropionates from marine-derived fungi, and compounds 4 and 5 represent the first examples of polypropionate derivatives containing a 3-hydroxypiperidin-2-one as part of an imide linkage. In addition, compounds 1-4 exhibited significant inhibitory activities against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with the IC50 values of 5.1, 12, 4.0, and 11 μM, respectively. Enzyme kinetic experiments suggested that they all acted through a noncompetitive mechanism. A preliminary structure-activity relationship is discussed.

Background Of all malignancies, lung cancer is the leading cause of death, and non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers. In this study, the long non-coding RNA (lncRNA) THUMPD3-AS1 was observed to be highly expressed in NSCLC and correlated with TNM stages and relapse, suggesting that THUMPD3-AS1 is involved in the regulation of NSCLC. Methods The aim of this study was to investigate the regulatory function and mechanism of THUMPD3-AS1 in NSCLC cells by cellular function and molecular biology experiments. Results Overexpression and knockdown analysis revealed that THUMPD3-AS1 promoted tumor progression by increasing cell proliferation and self-renewal of NSCLC cells. Moreover, THUMPD3-AS1 may act as an endogenous sponge of microRNA-543 (miR-543) which can regulate the target gene ONECUT2 in NSCLC cells. Conclusion Our study indicated that THUMPD3-AS1 regulated NSCLC cell self-renewal by regulating the expression of miR-543 and ONECUT2, and THUMPD3-AS1 can potentially act as a biomarker or therapeutic target in NSCLC.

Background The development of lung adenocarcinoma (LUAD) involves the interactions between cell proliferation and death. Autophagy-dependent ferroptosis, a distinctive cell death process, was implicated in a multitude of diseases, whereas no research revealing the relationship between autophagy-dependent ferroptosis and LUAD pathogenesis was reported. Thus, the primary objective was to explore the role and potential function of the autophagy-dependent ferroptosis-related genes in LUAD. Methods Clinical information and transcriptome profiling of patients with LUAD were retrieved and downloaded from open-source databases. Autophagy-dependent ferroptosis-related genes were screened by published articles. The critical gene was identified as the intersection between the differentially expressed genes and prognosis-related genes. Patients were divided into high- and low-risk groups using the expression level of the critical gene. The validity of the key gene prognosis model was verified by survival analysis. The correlation between the clinical characteristics of LUAD and the expression level of the key gene was analyzed to explore the clinical significance and prognosis value. And the roles of the key gene in response to chemotherapy, immune microenvironment, and tumor mutation burden were predicted. The validation of key gene expression levels was further performed by quantitative real-time PCR and immunohistochemistry staining. Results FANCD2, an essential autophagy-dependent ferroptosis-related gene by searching database, was confirmed as an independent prognostic factor for LUAD occurrence. The high expression level of FANCD2 was associated with an advantaged TNM stage, a less chemotherapy sensitivity, a low ImmuneScore, which indicated a deactivation status in an immune microenvironment, a high tumor mutation burden, and poor survival for LUAD patients. Pathway enrichment analysis showed that FANCD2 responded to oxidative stress and neutrophil-mediated immunity. Quantitative real-time PCR and immunohistochemistry staining showed that the expression level of FANCD2 is higher in LUAD patients than in normal tissue samples, which was in accordance with the database report. Conclusion FANCD2, an essential gene related to autophagy-dependent ferroptosis, could work as a biomarker, predicting the survival, chemotherapy sensitivity, tumor immunity, and mutation burden of LUAD. Researching autophagy-dependent ferroptosis and targeting the FANCD2 may offer a new perspective for treating and improving prognosis in LUAD.

Background. The development of lung adenocarcinoma (LUAD) involves the interactions between cell proliferation and death. Autophagy-dependent ferroptosis, a distinctive cell death process was implicated in a multitude of diseases, whereas no research revealing the relationship between autophagy-dependent ferroptosis and LUAD pathogenesis was reported. Thus, the primary objective was to explore the role and potential function of the autophagy-dependent ferroptosis-related genes in LUAD.Methods. Clinical information and transcriptome profiling of patients with LUAD were retrieved and downloaded from open-source databases. Autophagy-dependent ferroptosis-related genes were screened by published articles. The key gene was identified as the intersection between the differentially expressed genes and prognosis-related genes. Patients were divided into high- and low-risk groups using the expression level of the key gene. The validity of the key gene prognosis model was verified by survival analysis. The correlation between the clinical characteristics of LUAD and the expression level of the key gene was analyzed to explore the clinical significance and prognosis value. And the roles of the key gene in response to chemotherapy, immune microenvironment and tumor mutation burden were predicted. The validation of key gene expression levels were further performed by quantitative real-time PCR and immunohistochemistry staining.Results. FANCD2, a key autophagy-dependent ferroptosis-related gene by searching database, was confirmed as an independent prognostic factor for LUAD occurrence. The high expression level of FANCD2 was associated with an advantaged TNM stage, a less chemotherapy sensitivity, a low ImmuneScore, which indicated a deactivation status in immune microenvironment, a high tumor mutation burden, and a poor survival for LUAD patients. Pathway enrichment analysis showed that FANCD2 were involved in response to oxidative stress and neutrophil mediated immunity. Quantitative real-time PCR and immunohistochemistry staining showed that the expression level of FANCD2 is higher in LUAD patients than normal tissue samples, which was in accordance with the database report.Conclusion. FANCD2, a key gene related to autophagy-dependent ferroptosis, could work as a biomarker, which predicts the survival, chemotherapy sensitivity, tumor immunity and mutation burden of LUAD. Research of autophagy-dependent ferroptosis and targeting the FANCD2 may offer a new perspective for the treatment and improvement of prognosis in LUAD.

Ningbo Fan,1,* Dongni Chen,1,* Jiabo Zheng,2 Zhesheng Wen,1 Peng Lin11Department of Thoracic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China*These authors contributed equally to this workPurpose: The inflammatory microenvironment and hemostatic system are involved in several stages of tumor progression. The aim of this study was to assess the prognostic effect of fibrinogen-to-lymphocyte ratio (FLR) in esophageal squamous cell carcinoma (ESCC) patients who underwent radical esophagectomy.Patients and methods: We retrospectively reviewed 673 consecutive patients with ESCC who underwent radical esophagectomy from January 2009 to December 2012 at a major cancer hospital in Guangzhou, southern China. The cutoff points were defined by the X-tile software. The prognostic value of FLR for overall survival (OS), disease-free survival (DFS), and first-year mortality after surgery were analyzed using Cox proportional hazard regression model and logistic regression model. Survival was estimated by the Kaplan–Meier estimator and compared using the log-rank test.Results: The optimal cutoff point of FLR was 3.03. Compared with the FLR-low (≤3.03) group, the FLR-high (>3.03) group included older patients (χ2=7.267, P=0.007), showed higher postoperative overall morbidity (24.7% vs 14.8%, χ2=5.414, P=0.020) and tended to die within one year (23.5% vs 10.9%, χ2=10.871, P=0.001). The FLR-high group showed significant lower 5-year OS rates (41.2% vs 53.7%, log-rank=6.827, P=0.009) and 5-year DFS rates (35.3% vs 48.0%, log-rank=5.954, P=0.015) than the FLR-low group. Multivariate analyses suggested that high FLR was an independent negative predictor of OS (HR: 1.448, 95%CI: 1.073–1.952, P=0.015), DFS (HR: 1.445, 95%CI: 1.084–1.925, P=0.012) and first-year mortality (HR: 2.123, 95%CI: 1.157–3.898, P=0.015).Conclusion: The preoperative FLR level could be used as a simple, noninvasive, inexpensive, and potentially effective indicator to evaluate the prognosis of ESCC patients following radical esophagectomy.Keywords: esophageal squamous cell carcinoma, prognostic indicator, fibrinogen, lymphocyte

By considering a 3-mode optomechanical system formed by two cavities interacting with a common mechanical mode, we demonstrate that phonon-counting measurements lead to a significant enhancement of entanglement in the output of the two cavities. This conclusion still holds for an inefficient detector, but the dependence on system parameters changes qualitatively from the ideal limit of perfect projective measurements. We find non-trivial optimal points for the entanglement as functions of detector efficiency, measurement outcome, and optical drive strengths. We characterize both the highest achievable entanglement as well as a ‘typical’ value, obtained at the most likely measurement outcome. Numerical results are well understood within an approximate analytical approach based on perturbation theory around the ideal detector limit.

Background Long non-coding RNAs (lncRNAs) play vital roles in the development and progression of non-small-cell lung cancer (NSCLC); however, the role of most lncRNAs in NSCLC remains unknown. This study explored the clinical significance, biological function and underlying mechanism of lnc-GAN1 in NSCLC. Methods With a custom lncRNA microarray we found that lnc-GAN1 is markedly downregulated in NSCLC tissues. Then lnc-GAN1 expression level was measured using qRT-PCR in NSCLC tissues and cell lines. Survival was assessed using the Kaplan-Meier method. The biological functions of lnc-GAN1 in lung cancer cells were evaluated in vitro and in vivo. RNA fluorescence in situ hybridization and subcellular localization assays revealed the subcellular distribution of lnc-GAN1 in cells. Bioinformatic analysis was adopted to predict miRNAs and signaling pathways regulated by lnc-GAN1. RNA immunoprecipitation and Dual-luciferase reporter assays were used to assess the interaction between lnc-GAN1 and miR-26a-5p in lung cancer cells. Results lnc-GAN1 is downregulated in HCC tissues and associated with larger tumor size and poor overall survival and disease-free survival; its ectopic expression suppresses cell proliferation, colony formation, and cell cycle progression and induces apoptosis in NSCLC cells; it also inhibits tumor growth in the NSCLC xenograft model. We further proved that lnc-GAN1 is localized in cytoplasm and transcribed independently from its parental gene GAN. Mechanistically, lnc-GAN1 acts as a sponge for miR-26a-5p by two seed sequences, and the two non-coding RNAs have a negative relationship in NSCLC tissues; we further prove that PTEN is a direct target of miR-26a-5p and lnc-GAN1 inhibits cell cycle signaling pathway by activating PTEN, whose expression level correlated negatively with miR-26a-5p level but positively with lnc-GAN1 level in NSCLC samples. Conclusions Lnc-GAN1 is downregulated and associated with poor survival of NSCLC patients, and mechanistically acts as a tumor suppressor via sponging and inhibiting miR-26a-5p to upregulate PTEN. This study provides a potential prognostic biomarker and treatment target for NSCLC.

Founded in 1980s, universities for the aged in our country only have a history of over 30 years which is not only emerging but also immature against the whole history of education. Because of the particularity of the students, there are lots of aspects worthy of researching and considering in education and teaching of the universities for the aged. In terms of the vocal music teaching of the universities for the aged, there are lots of problems which need to be solved in many aspects such as the student conditions, teaching management, etc. This essay aims to put forward the effective strategies to solve the above problems in the current elderly universities and promote the vocal music teaching of the universities for the aged to move forward to standardization and specialization.

Background: Lung adenocarcinoma (LUAD) is a heterogeneous disease with high mortality. Close attention has been paid to immunotherapy in LUAD treatment. However, immunotherapy has produced different therapeutic effects because of immune heterogeneity. Long noncoding RNAs (lncRNAs) are survival prognostic indicators with functions in the immune process. The present study was designed to examine the predictive power of immune-related lncRNAs in LUAD prognosis and investigated potential molecular mechanisms. Methods: Transcriptome profiling and LUAD sample clinical information were retrieved from online database. The immune-related lncRNAs signature was identified by Cox regression. Survival analysis was used to verify the validity of the prognosis model. Then, possible biological functions were predicted and the abundance of infiltrating immune cells in LUAD samples were further analyzed. Results: An immune-associated lncRNAs signature was established by combining six lncRNAs. Patients with LUAD were stratified into high- and low-risk groups using the six lncRNAs signature. Patients in different risk levels had significantly different prognoses (P Conclusion: A reliable immune-related lncRNAs prognosis model for LUAD was identified. lncRNAs played a vital role in the tumor immune process and were associated with the LUAD prognosis. Research of lncRNAs in B-cell immune infiltration could provide new insight into the immunotherapy of LUAD.

The secreted Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase B (MptpB) is an essential virulence factor required for the intracellular survival of Mtb within host macrophages. MptpB has become a promising target for the development of novel anti-tuberculosis (TB) drugs. In this study, two new fusarielins, fusarielins M (1) and N (2), and a biogenetically related known compound, fusarielin G (3) were isolated from the marine-derived fungus Fusarium graminearum SYSU-MS5127. Their inhibitory effects on MptpB were evaluated. Among these compounds, fusarielin M substantially inhibited MptpB with a half-maximal inhibitory concentration (IC50) of 1.05 ± 0.08 μM, and an inhibition constant (Ki) of 1.03 ± 0.39 μM. Surface plasmon resonance analysis was used to characterize the interaction between fusarielin M and MptpB in vitro. Fusarielin M also exhibited cellular activity in blocking MptpB-mediated Erk1/2 and p38 inactivation in macrophages. Importantly, fusarielin M (20 μM) substantially reduced intracellular mycobacterial growth within macrophages, causing a 62% reduction in the bacterial burden. The binding mode of fusarielin M was further explored via molecular docking which suggested that fusarielin M binds to the active site of MptpB, forming a hydrogen bond with the side chain of Asp165; this is unique in the P-loop of MptpB compared to conventional human PTPs. The contact between fusarielin M and Asp165 in the catalytic loop provides a potential basis for inhibitor selectivity. Therefore, fusarielin M shows great potential as an anti-TB drug candidate.

Background Although previous studies have discussed whether the minimally invasive esophagectomy (MIE) is superior to open surgery, the data concerning esophageal squamous cell carcinoma (ESCC) patients underwent neoadjuvant treatment followed by radical resection is limited. The purpose of our study was to compare the short- and long-term clinical outcomes of the two surgical approaches in treating ESCC patients. Methods Between January 2010 and December 2016, ESCC patients who had received neoadjuvant therapy and underwent Mckeown esophagectomy at our institute were eligible. The baseline characteristics, pathological data, short-and long-term outcomes of these patients were collected and compared based on the surgical approach. Results A total of 195 patients was included in the current study. Compared to patients underwent open surgery, patients underwent MIE had shorter operative time and less intraoperative bleeding (390 min vs 330 min, P = 0.001; 204 ml vs 167 ml, P = 0.021). In addition, the risk of anastomotic leakage was decreased in MIE group (20.0% vs 3.3%, P P = 0.013). Conclusion Minimally invasive Mckeown esophagectomy is safe and feasible for ESCC patients who underwent neoadjuvant therapy. MIE approach presented better perioperative results than open esophagectomy. The effect of surgical approaches on survival was depending on the scheme of neoadjuvant treatment.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common symptom, but prophylactic measures cannot still be carried out effectively. In addition, the efficacy of vitamin E in preventing peripheral neurotoxicity caused by chemotherapy is inconclusive. Therefore, we collected the relevant randomized controlled trials (RCTs) and performed a meta-analysis to examine whether the vitamin E has a positive effect in CIPN. Methods: We searched PubMed, EMBASE, Cochrane, and other databases in December 2019 for eligible trials. Two reviewers conducted the analysis independently when studies were homogeneous enough. Results: Eight RCTs, involving 488 patients, were identified. Upon pooling these RCTs, patients who received vitamin E supplementation of 600 mg/day had a lower incidence of CIPN (risk ratio [RR] 0.31; 95% confidence interval [CI] 0.14–0.65; p = 0.002) than the placebo group. Vitamin E played a key role in decreasing the incidence of peripheral neuropathy in the cisplatin chemotherapy group (RR 0.28; 95% CI 0.14–0.54; p = 0.0001). Moreover, vitamin E supplementation significantly decreased patients’ sural amplitude after 3 rounds of chemotherapy (RR −2.66; 95% CI −5.09 to −0.24; p = 0.03) in contrast with that of placebo supplementation, while no significant difference was observed when patients were treated with vitamin E after 6 rounds of chemotherapy. In addition, the vitamin E-supplemented group had better improvement in the neurotoxicity score and lower incidence of reflexes and distal paraesthesias than the control group. Conclusion: Available data in this meta-analysis showed that vitamin E supplementation can confer modest improvement in the prevention of CIPN.

Background Previous findings have indicated that the tumor, nodes, and metastases (TNM) staging system is not sufficient to accurately predict survival outcomes in patients with non-small lung carcinoma (NSCLC). Thus, this study aims to identify a long non-coding RNA (lncRNA) signature for predicting survival in patients with NSCLC and to provide additional prognostic information to TNM staging system. Methods Patients with NSCLC were recruited from a hospital and divided into a discovery cohort (n = 194) and validation cohort (n = 172), and detected using a custom lncRNA microarray. Another 73 NSCLC cases obtained from a different hospital (an independent validation cohort) were examined with qRT-PCR. Differentially expressed lncRNAs were determined with the Significance Analysis of Microarrays program, from which lncRNAs associated with survival were identified using Cox regression in the discovery cohort. These prognostic lncRNAs were employed to construct a prognostic signature with a risk-score method. Then, the utility of the prognostic signature was confirmed using the validation cohort and the independent cohort. Results In the discovery cohort, we identified 305 lncRNAs that were differentially expressed between the NSCLC tissues and matched, adjacent normal lung tissues, of which 15 are associated with survival; a 4-lncRNA prognostic signature was identified from the 15 survival lncRNAs, which was significantly correlated with survivals of NSCLC patients. This signature was further validated in the validation cohort and independent validation cohort. Moreover, multivariate Cox analysis demonstrates that the 4-lncRNA signature is an independent survival predictor. Then we established a new risk-score model by combining 4-lncRNA signature and TNM staging stage. The receiver operating characteristics (ROC) curve indicates that the prognostic value of the combined model is significantly higher than that of the TNM stage alone, in all the cohorts. Conclusions In this study, we identified a 4-lncRNA signature that may be a powerful prognosis biomarker and can provide additional survival information to the TNM staging system.

BACKGROUND: It is widely accepted that the pretreatment neutrophil-to-lymphocyte ratio (NLR) is an independent predictor of prognosis in multiple malignancies, including esophageal squamous cell carcinoma (ESCC). However, its predictive value in middle thoracic esophageal carcinoma is still unclear. Therefore, the purpose of this study was to investigate the preoperative serum levels of NLR in middle thoracic esophageal carcinoma patients to clarify their clinical significance as predictors of prognosis. METHODS: This study investigated 556 patients with middle thoracic ESCC treated by esophagectomy from January 2010 to December 2012. The prognostic impact of serum NLR level was analyzed. A receiver operating characteristic (ROC) curve was used to identify the NLR for predicting survival. Correlation between the NLR and clinicopathological characteristics was analyzed by χ(2) test. Prognostic influence was calculated by using the Kaplan-Meier method and the difference was compared by log-rank test. Cox regression analysis was performed to evaluate the significant prognostic factors. RESULTS: The cutoff value for the NLR was 2.43 ng/mL, the area under the curve was 0.553 (95% CI: 0.504–0.601; P=0.035), and the sensitivity and specificity were 53.3% and 58.7% respectively. It is demonstrated that preoperative NLR (P=0.003), T stage (P2.43 ng/mL could serve as an indicator of poor prognosis in middle thoracic ESCC patients after surgical treatment.

A two-stage interval fuzzy credibility constraint programming method is proposed to deal with the uncertainties of fuzzy variables, discrete intervals and probability distributions, and to reflect the dynamic uncertainties and related decision-making processes. Lincang City is located in the southwest border of China. It is a frontier window and an important channel for China to face the "radiation center" of Southeast Asia and South Asia. It is the only intersection of the Tropic of cancer and the geographic water distribution lines of the Pacific Ocean and the Indian Ocean. Its hydrological and water resources are unique.Considering lincang city, yunnan province as the research object, and considering the uncertainty of the amount of available water resources within the region, a two-stage fuzzy credibility constraint programming model was built to optimize the allocation of regional water resources.The objective function of the model is to maximize the economic returns of the system. Fuzzy variables, discrete intervals and probability distribution are introduced to represent the multiple uncertainties in the system. The confidence level is set to solve the problem of fuzzy risk with violation probability. The results show that the model can effectively deal with the uncertainty of the allocation system, and reflect the trade-off between the system benefits and risks, so as to reduce the risk of water shortage and low economic penalty, and achieve efficient allocation of water resources.

Background Chemotherapy often causes chemotherapy-induced peripheral neuropathy (CIPN), but effective prevention measures are still lacking. Whether vitamin E can prevent peripheral neurotoxicity caused by chemotherapy is inconclusive. Therefore, we collected related randomized controlled trials (RCTs) and conducted a meta-analysis to examine whether vitamin E could prevent CIPN. Methods We searched PubMed, EMBASE and the Cochrane databases in November 2019 for eligible trials. Two reviewers conducted the analysis independently when studies were homogeneous enough. Results Eight RCTs, involving 555 patients, were identified. Upon pooling these RCTs, patients who received vitamin E supplementation of 600 mg/day had a significantly lower incidence of peripheral neuropathy (RR 0.31; 95% CI 0.14 to 0.65; P = 0.002) induced by chemotherapy compared with the placebo group. Vitamin E played a key role in decreasing the incidence of peripheral neuropathy in the cisplatin chemotherapy group (RR 0.28; 95% CI 0.14 to 0.54; P = 0.0001). With regard to improvements in sural amplitude, vitamin E supplementation significantly decreased patients’ sural amplitude after three rounds of chemotherapy (RR -2.66; 95% CI -5.09 to -0.24; P =0.03) in contrast with that of placebo supplementation, while no significant difference was observed when patients were treated with vitamin E after six rounds of chemotherapy. In addition, the vitamin E group had better improvement in the neurotoxicity score (RR -2.65; 95% CI -4.01to -1.29; P = 0.0001) and a lower incidence of reflexes and distal paraesthesias (RR 0.50; 95% CI 0.29 to 0.87; P = 0.01) compared to the control group. Conclusion Available data included in this meta-analysis showed that vitamin E supplementation can confer modest improvement in the prevention of CIPN. However, large-scale, well-designed RCTs are needed to confirm the exact role of vitamin E supplementation in the prevention of CIPN.

supplmental_table_2 for Comparison of Outcomes Between McKeown and Sweet Esophagectomy in the Elderly Patients for Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Analysis by Dongni Chen, Yihuai Hu, Youfang Chen, Jia Hu and Zhesheng Wen in Cancer Control

Fiscpropionates A-F (

Background: Lupus nephritis (LN) is classified by renal biopsy into proliferative and nonproliferative forms, with distinct prognoses, but renal biopsy is not available for every LN patient. The present study aimed to establish an alternate tool by building a predictive model to evaluate the probability of proliferative LN. Methods: In this retrospective cohort with biopsy-proven LN, 382 patients in development cohort, 193 in internal validation cohort, and 164 newly diagnosed patients in external validation cohort were selected. Logistic regression model was established, and the concordance statistics (C-statistics), Akaike information criterion (AIC), integrated discrimination improvement, Hosmer-Lemeshow test, and net reclassification improvement were calculated to evaluate the performance and validation of models. Results: The prevalence of proliferative LN was 77.7% in the whole cohort. A model, including age, gender, systolic blood pressure, hemoglobin, proteinuria, hematuria, and serum C3, performed well on good-of-fit and discrimination in the development chohort to predict the risk of proliferative LN (291 for AIC and 0.84 for C-statistics). In the internal and external validation cohorts, this model showed good capability for discrimination and calibration (0.84 and 0.82 for C-statistics, and 0.99 and 0.75 for Pvalues, respectively). Conclusion: This study developed and validated a model including demographic and clinical indices to evaluate the probability of presenting proliferative LN to guide therapeutic decisions and outcomes. Key words: Biopsy; Lupus Nephritis; Nomogram; Predictive Value of Tests; Risk Factors

The gram-negative bacterium Legionella pneumophila invades human's lung and causes Legionnaires' disease. To benefit its survival and replication in cellular milieu, L. pneumophila secrets at least 330 effector proteins into host cells. We found that the effector WipA has the protein tyrosine phosphatase (PTP) activity but does not depend on the classical CX5R motif for activity, suggesting that WipA is an unconventional PTP. Meanwhile, the presence of three other highly conserved motifs typically seen in protein serine/threonine phosphatases and the poor inhibition of WipA activity by okadaic acid led us to propose that WipA is a bacterial protein phosphatase. In addition, the determination of the 2.55-A crystal structure of WipA revealed that WipA resembles cold-active protein tyrosine phosphatase (CAPTPase), and therefore very likely shares the same catalytic mechanism.

Under guidance of 1H NMR, ten new polypropionate derivatives, decempyrones A–J (1–10) along with two known analogues (11 and 12), were isolated from the marine-derived fungus Fusarium decemcellulare SYSU-MS6716. The planar structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, and HR-ESIMS). The absolute configuration of the chiral centers in the side chain is a major obstacle for the structure identification of natural polypropionate derivatives. Herein, the J-based configurational analysis (JBCA), chemical degradation, geminal proton rule, and the modified Mosher’s method were adopted to fix their absolute configurations in the side chain. Compounds 3 and 10 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide with IC50 values 22.4 ± 1.8 and 21.7 ± 1.1 μM. In addition, compounds 3 and 10 displayed MptpA inhibitory activity with an IC50 value of 19.2 ± 0.9 and 33.1 ± 2.9 µM. Structure-activity relationships of the polypropionate derivatives were discussed.

In this research, an integrated prediction-optimization approach (IPOA) was developed to manage coupled risks of water and energy nexus (WEN) systems. This approach combined Markov-chain based unbiased grey model (MC-UGM), Copula analysis and inexact optimization into a general modeling framework. The proposed approach was employed for dealing with the joint probability distributions of water and energy resources, and further supporting coordinated decision-making under uncertainties. Then, Beijing Tianjin Hebei Integrated Region (BTHIR), as the leading economic center of north China, was employed as the demonstrative site for the developed approach. Results indicated that IPOA could help predict water and energy demands, excavate the interactions between water and energy, identify and deal with the uncertain and complex features of the WEN system in the region. Optimal allocation schemes of water and energy under multiple coupled risks for multiple users in BTHIR were obtained. It can be found that under certain coupled risks, the lower for water risk, and the greater for energy risks. Also, the net benefits of WEN systems would continue to increase over time. Under most of the risk levels, water resource in BTHIR would be mainly allocated for domestic and industrial sectors. Energy resource would be mainly allocated for secondary and tertiary industrial sectors. The developed IPOA could not only realize the identification and quantification of inherent interactions between energy and water, but also help decision makers formulate reasonable policies balancing system benefits and coupled risks. Besides, IPOA can improve the robustness of utilization decisions regarding water and energy, which could help promote the coordinated development for BTHIR.

Background The Toll-like receptor plays an essential role in controlling immunity and inflammation. This study was to investigate the relationships of genetic variants in TLR2 and TLR3 with hepatitis B virus (HBV) natural clearance and HBV-related hepatocellular carcinoma (HCC) risk in a Chinese male population. Methods We analyzed 5 polymorphisms of TLR2 (rs3804099 and rs3804100) and TLR3 (rs5743305, rs3775296 and rs3775291) in a population consisting of 686 participants with HBV natural clearance, 293 chronic HBV carriers and 395 HBV-positive HCC patients, using the improved multiplex ligase detection reaction method. Results After adjustment for age and smoking and drinking status, no associations were observed either between the 5 single-nucleotide polymorphisms (SNPs) and the HBV natural clearance participants, or between the 5 SNPs and HCC patients. Whereas the stratified analysis showed that under the dominant models, nondrinkers with TLR2 rs3804100 and participants younger than 40 years old with TLR3 rs3775291 were significantly associated with HCC risk when compared with persistent HBV carriers (adjusted odd ratio [OR] = 0.49, 95% confidence interval [95% CI], 0.31-0.78, p = 0.003; and adjusted OR = 0.50, 95% CI, 0.29-0.86, p = 0.013, respectively). Furthermore, the TTTCT haplotype was found to promote the progress of HBV clearance and inhibit development of HBV-related HCC (OR = 0.77, 95% CI, 0.61-0.97, p = 0.029; and OR = 0.72, 95% CI, 0.55-0.94, p = 0.016, respectively). And the CCACC and CCTCT haplotypes were observed to decrease susceptibility to HCC (OR = 0.64, 95% CI, 0.40-1.00, p = 0.048; and OR = 0.43, 95% CI, 0.28-0.68, pConclusions This study revealed that TLR2 rs3804100 and TLR3 rs3775291 polymorphisms may be protective factors for HBV-related HCC.

As a eukaryotic-like Ser/Thr protein kinase, Mycobacterium tuberculosis virulent effector protein kinase G (PknG) mediates mycobacterial survival by regulating bacterial cell metabolic processes and preventing phagosome-lysosome fusion in host macrophages. Targeting PknG is an effective strategy for development of anti-tuberculosis (TB) drugs. In the study, we found that sclerotiorin, derived from marine fungi from the South China Sea, exhibited moderately strong inhibitory effects on recombinant PknG, with an IC50 value of 76.5 μM, and acted as a non-competitive inhibitor. The dissociation constant (KD) of sclerotiorin determined by MST was 11.4 μM, demonstrating a moderate binding strength between them. Sclerotiorin could substantially impair the mycobacterial survival in infected macrophages while the macrophage viability remained unaffected, though it did not inhibit the mycobacterial growth in culture. When sclerotiorin was used in combination with rifampicin, intracellular mycobacterial growth decreased as sclerotiorin concentration increased. Docking analysis suggested a binding mechanism of inhibition with performing interactions with the P-loop and catalytic loop of PknG. In summary, we reported that sclerotiorin had moderately strong PknG inhibitory activity, but no cytotoxicity, and it could substantially decrease the mycobacterial growth inside macrophages, suggesting that sclerotiorin has potential to supplement antibiotic therapy for TB.

An unusual alkaloid, talaramide A (1), was obtained from the mangrove endophytic fungus Talaromyces sp. (HZ-YX1). The structure of 1 was established by analysis of NMR spectroscopic data, X-ray diffraction data, and electronic circular dichroism (ECD) spectra. Talaramide A (1) is the second example of an alkaloid that possesses a unique oxidized tricyclic system. A possible biosynthetic pathway for 1 was proposed. Compound 1 showed promising inhibition of mycobacterial PknG activity with an IC50 value of 55 μM.

In the experiment, order anode oxidation TiO 2 nanotube arrays (TNTs) film was prepared and achieved Cu electrolytic deposition synchronously in the electrolyte of NH 4 F, ethylene glycol and CuNO 3 by periodic reverse voltage pulsed power. With the concentration of Cu(NO) 2 ·3H 2 O and reverse voltage changing, the loading condition of Cu compound in the TNTs can also be changed. The photocatalytic performance of TNTs film and Cu 2 O-TNTs film after annealing at 450 ℃ were studied by degrading methylene blue (MB) under the condition of ultraviolet light. The morphology, structure, optical property were studied by means of SEM, EDS, XRD, XPS, photoluminescence spectroscopy (PL) and ultraviolet-visible diffuse reflection spectrum (UV-vis DRS). The results show that Cu loaded had no influence to morphology of the nanotubes, and the optical property of TNTs can be further improved after loading Cu by narrowing the band gap of TiO 2 about 0.22 and decreasing the recombination rate of photoelectrons and holes. When the addition concentration of Cu 2 O-TNTs in the MB solution was 0.25 cm 2 /mL, the degradation rate reached 72.63% from 43.45%. When increased concentration to 0.75 cm 2 /mL, the degradation rate of MB reached 96.79%. The photocatalytic performance of Cu 2 O-TNTs film prepared by using single-step anodic method performed well under ultraviolet light.

BACKGROUND: Patients with esophageal cancer (EC) frequently have multiple primary cancers. We conducted the present study to assess the risk of multiple primary malignancies for patients with squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus and to investigate the influence of multiple primary tumors on the prognosis of EC patients. METHODS: Using the data of 44,091 EC patients from the Surveillance Epidemiology and End Results (SEER) database, we calculated the standardized incidence ratios (SIRs) for overall multiple primary cancers and cancers at particular sites among EC survivors. The SIRs of esophageal SCC and AC patients were compared using Poisson regression. The Kaplan-Meier (KM) method was used for survival analysis. RESULTS: Multiple primary cancer risk was significantly increased among both esophageal SCC and AC survivors (SIR: 2.28 and 1.57, respectively; P

OBJECTIVESOur goal was to compare short- and long-term outcomes between 3-field lymphadenectomy (3-FL) and modern 2-field lymphadenectomy (2-FL) in patients with thoracic oesophageal squamous cell carcinoma.METHODSWe reviewed clinical outcomes for 298 patients with thoracic oesophageal squamous cell carcinoma who underwent 3-FL or modern 2-FL from March 2008 to December 2013 at a major cancer hospital in Guangzhou, southern China. Propensity score matching was used to balance baseline differences, and 83 pairs of cases were selected. Postoperative complications, recurrence patterns and survival outcomes were compared between the 2 groups.RESULTSCompared with modern 2-FL, 3-FL led to higher overall operative morbidity rates [78.3% vs 61.4%, odds ratio (OR) 2.266, 95% confidence interval (CI) 1.143–4.490; P = 0.019], with higher recurrent nerve palsy rates (47.0% vs 19.3%, OR 3.712, 95% CI 1.852–7.438; P CONCLUSIONSAdditional cervical lymphadenectomy did not lead to added survival benefit when compared with modern 2-FL in patients with thoracic oesophageal squamous cell carcinoma. Recurrence was similar in patients undergoing 3-FL and modern 2-FL. 3-FL resulted in more postoperative complications.

A putative three-gene cluster for asperterpenoid A was identified. Step-wise reconstitution of this gene cluster in Aspergillus oryzae reveals that astC encodes a sesterterpene cyclase to synthesize preasperterpenoid A, which is dually oxidized by a P450 enzyme AstB to give asperterpenoid A along with a minor product asperterpenoid B, and asperterpenoid A is further oxidized by another P450 eznyme AstA to afford a new sesterterpenoid asperterpenoid C. Unexpectedly, asperterpenoids A and B, but not the final product asperterpenoid C, exhibit potent inhibitory activity against Mycobacterium tuberculosis protein tyrosine phosphatase B with IC50 values of 3-6 μM.