Development and validation of a prognostic nomogram model in locally advanced NSCLC based on metabolic features of PET/CT and hematological inflammatory indicators.

BACKGROUND: We combined the metabolic features of 18F-FDG-PET/CT and hematological inflammatory indicators to establish a predictive model of the outcomes of patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiotherapy. RESULTS: A predictive nomogram was developed based on sex, CEA, systemic immune-inflammation index (SII), mean SUV (SUVmean), and total lesion glycolysis (TLG). The nomogram presents nice discrimination that yielded an AUC of 0.76 (95% confidence interval: 0.66-0.86) to predict 1-year PFS, with a sensitivity of 63.6%, a specificity of 83.3%, a positive predictive value of 83.7%, and a negative predictive value of 62.9% in the training set. The calibration curves and DCA suggested that the nomogram had good calibration and fit, as well as promising clinical effectiveness in the training set. In addition, survival analysis indicated that patients in the low-risk group had a significantly longer mPFS than those in the high-risk group (16.8 months versus 8.4 months, P < 0.001). Those results were supported by the results in the internal and external test sets. CONCLUSIONS: The newly constructed predictive nomogram model presented promising discrimination, calibration, and clinical applicability and can be used as an individualized prognostic tool to facilitate precision treatment in clinical practice.

1T-VS2@V2O3 Synergistic Nanoarchitecture-Based Lamellar Clusters as the High Conductivity Cathodes of Thermal Batteries.

Thermal batteries are solid-state, thermally activated batteries with long storage times and high reliability. FeS2 is used as a cathode material commonly, but the high internal resistance and low voltage platform limit the improvement of battery performance. Herein, the 1T-phase vanadium disulfide (VS2) is prepared via the scalable hydrothermal method and applied to thermal battery cathode materials for the first time. 1T-VS2 lamellar flower clusters have high electronic conductivity (1.583 S cm-1) at room temperature, which is 75 times higher than FeS2 (0.021 S cm-1). Mechanism analysis shows that 1T-VS2@V2O3 can be formed based on the part of 1T-VS2 being oxidized to V2O3 at the discharge temperature. Benefiting from the synergistic effect of vanadium sulfide and vanadium oxide as a cathode for thermal batteries enhanced specific capacity (292.4 mA h g-1) and mass energy density (572.5 W h kg-1) when cutoff voltage is 1 V. Additionally, the discharge results indicate that the cells utilizing 1T-VS2 cathodes provided a higher voltage platform of 2.11 V than 1.84 V for FeS2. This impressive work can offer a good strategy for boosting cathode materials for a high-performance thermal battery.

Causal effects of dietary habits on COVID-19 susceptibility, hospitalisation and severity: a comprehensive Mendelian randomisation study.

This study aimed to investigate the causal effect of dietary habits on COVID-19 susceptibility, hospitalisation and severity. We used data from a large-scale diet dataset and the COVID-19 Host Genetics Initiative to estimate causal relationships using Mendelian randomisation. The inverse variance weighted (IVW) method was used as the main analysis. For COVID-19 susceptibility, IVW estimates indicated that milk (OR: 0·82; 95 % CI (0·68, 0·98); P = 0·032), unsalted peanut (OR: 0·53; 95 % CI (0·35, 0·82); P = 0·004), beef (OR: 0·59; 95 % CI (0·41, 0·84); P = 0·004), pork (OR: 0·63; 95 % CI (0·42, 0·93); P = 0·022) and processed meat (OR: 0·76; 95 % CI (0·63, 0·92); P = 0·005) were causally associated with reduced COVID-19 susceptibility, while coffee (OR: 1·23; 95 % CI (1·04, 1·45); P = 0·017) and tea (OR: 1·17; 95 % CI (1·05, 1·31); P = 0·006) were causally associated with increased risk. For COVID-19 hospitalisation, beef (OR: 0·51; 95 % CI (0·26, 0·98); P = 0·042) showed negative correlations, while tea (OR: 1·54; 95 % CI (1·16, 2·04); P = 0·003), dried fruit (OR: 2·08; 95 % CI (1·37, 3·15); P = 0·001) and red wine (OR: 2·35; 95 % CI (1·29, 4·27); P = 0·005) showed positive correlations. For COVID-19 severity, coffee (OR: 2·16; 95 % CI (1·25, 3·76); P = 0·006), dried fruit (OR: 1·98; 95 % CI (1·16, 3·37); P = 0·012) and red wine (OR: 2·84; 95 % CI (1·21, 6·68); P = 0·017) showed an increased risk. These findings were confirmed to be robust through sensitivity analyses. Our findings established a causal relationship between dietary habits and COVID-19 susceptibility, hospitalisation and severity.

Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk.

INTRODUCTION: Despite numerous observational studies reporting a positive correlation between polyunsaturated fatty acids (PUFAs) and the risk of sepsis and mortality, the causation of such an association has yet to be firmly established. Thus, our study aimed to undertake the Mendelian randomization (MR) approach to scrutinize the potential causalities of PUFAs with sepsis and mortality risk. METHODS: We conducted the MR investigation using genome-wide association study (GWAS) summary statistics of PUFAs [including omega-3 fatty acids (omega-3), omega-6 fatty acids (omega-6), the ratio of omega-6 to omega-3 fatty acids (omega-6:3), docosahexaenoic acid (DHA), linoleic acid (LA)], sepsis, and sepsis mortality. We utilized the GWAS summary data from the UK Biobank. To establish reliable causality, we employed the inverse-variance weighted (IVW) method as the primary analytical approach, together with four additional MR methods. In addition, we performed heterogeneity and horizontal pleiotropy assessments using Cochrane's Q test and MR-Egger intercept test, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings. RESULTS: The IVW method showed that genetically predicted omega-3 [odd ratio (OR) 0.914, 95% confidence interval (CI) 0.845-0.987, P = 0.023] and DHA (OR 0.893, 95% CI 0.815-0.979, P = 0.015) were suggestively linked to a decreased risk of sepsis. Furthermore, genetically predicted DHA (OR 0.819, 95% CI 0.681-0.986, P = 0.035) was suggestively associated with a reduced risk of sepsis-related death. Conversely, the omega-6:3 ratio (OR 1.177, 95% CI 1.011-1.371, P = 0.036) was suggestively linked to an increased risk of sepsis-induced mortality. On the basis of the MR-Egger intercept assessment, it appears that our MR examination was not influenced by any horizontal pleiotropy (all P > 0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses. CONCLUSION: Our study supported the casual effect between PUFAs and susceptibility to sepsis and sepsis-related death. Our findings underline the importance of specific PUFAs levels, particularly for individuals with a genetic susceptibility to sepsis. Further research is needed to confirm these findings and investigate the underlying mechanisms.

Causal Associations Between Tobacco, Alcohol Use and Risk of Infectious Diseases: A Mendelian Randomization Study.

INTRODUCTION: The causal effects of smoking and alcohol use on the risk of infectious diseases are unclear, and it is hard investigate them in an observational study due to the potential confounding factors. The aim of this study was to use Mendelian randomization (MR) techniques to assess the causalities between smoking, alcohol use and risk of infectious diseases. METHODS: Univariable and multivariable MR analyses were performed using genome-wide association data for the age of initiation of regular smoking (AgeSmk, N = 341,427), smoking initiation (SmkInit, N = 1,232,091), cigarettes per day (CigDay, N = 337,334), lifetime smoking (LifSmk, N = 462,690), drinks per week (DrnkWk, N = 941,280), sepsis (N = 486,484), pneumonia (N = 486,484), upper respiratory tract infection (URTI, N = 486,484) and urinary tract infection (UTI, N = 486,214) among individuals of European ancestry. Independent genetic variants that were significantly (P < 5 × 10-8) associated with each exposure were considered as instruments. The inverse-variance-weighted method was used in the primary analysis, which was followed by a series of sensitivity analyses. RESULTS: Genetically predicted SmkInit was associated with an increased risk of sepsis (OR 1.353, 95% CI 1.079-1.696, P = 0.009), pneumonia (OR 1.770, 95% CI 1.464-2.141, P = 3.8 × 10-9) and UTI (OR 1.445, 95% CI 1.184-1.764, P = 3 × 10-4). Moreover, genetically predicted CigDay was associated with a higher risk of sepsis (OR 1.403, 95% CI 1.037-1.898, P = 0.028) and pneumonia (OR 1.501, 95% CI 1.167-1.930, P = 0.00156). Furthermore, genetically predicted LifSmk was associated with an increased risk of sepsis (OR 2.200, 95% CI 1.583-3.057, P = 2.63 × 10-6), pneumonia (OR 3.462, 95% CI 2.798-4.285, P = 3.28 × 10-30), URTI (OR 2.523, 95% CI 1.315-4.841, P = 0.005) and UTI (OR 2.036, 95% CI 1.585-2.616, P = 3.0 × 10-8). However, there was no significant causal evidence for genetically predicted DrnkWk in sepsis, pneumonia, URTI or UTI. Multivariable MR analyses and sensitivity analyses showed that the above results for causal association estimations were robust. CONCLUSION: In this MR study, we demonstrated the causal association between tobacco smoking and risk of infectious diseases. However, no evidence was found to support causality between alcohol use and the risk of infectious diseases.

Development and validation of a nomogram for the early prediction of acute kidney injury in hospitalized COVID-19 patients.

Introduction: Acute kidney injury (AKI) is a prevalent complication of coronavirus disease 2019 (COVID-19) and is closely linked with a poorer prognosis. The aim of this study was to develop and validate an easy-to-use and accurate early prediction model for AKI in hospitalized COVID-19 patients. Methods: Data from 480 COVID-19-positive patients (336 in the training set and 144 in the validation set) were obtained from the public database of the Cancer Imaging Archive (TCIA). The least absolute shrinkage and selection operator (LASSO) regression method and multivariate logistic regression were used to screen potential predictive factors to construct the prediction nomogram. Receiver operating curves (ROC), calibration curves, as well as decision curve analysis (DCA) were adopted to assess the effectiveness of the nomogram. The prognostic value of the nomogram was also examined. Results: A predictive nomogram for AKI was developed based on arterial oxygen saturation, procalcitonin, C-reactive protein, glomerular filtration rate, and the history of coronary artery disease. In the training set, the nomogram produced an AUC of 0.831 (95% confidence interval [CI]: 0.774-0.889) with a sensitivity of 85.2% and a specificity of 69.9%. In the validation set, the nomogram produced an AUC of 0.810 (95% CI: 0.737-0.871) with a sensitivity of 77.4% and a specificity of 78.8%. The calibration curve shows that the nomogram exhibited excellent calibration and fit in both the training and validation sets. DCA suggested that the nomogram has promising clinical effectiveness. In addition, the median length of stay (m-LS) for patients in the high-risk group for AKI (risk score ≥ 0.122) was 14.0 days (95% CI: 11.3-16.7 days), which was significantly longer than 8.0 days (95% CI: 7.1-8.9 days) for patients in the low-risk group (risk score <0.122) (hazard ratio (HR): 1.98, 95% CI: 1.55-2.53, p < 0.001). Moreover, the mortality rate was also significantly higher in the high-risk group than that in the low-risk group (20.6 vs. 2.9%, odd ratio (OR):8.61, 95%CI: 3.45-21.52). Conclusions: The newly constructed nomogram model could accurately identify potential COVID-19 patients who may experience AKI during hospitalization at the very beginning of their admission and may be useful for informing clinical prognosis.

Can Fluoxetine Combined with Cognitive Behavioral Therapy Reduce the Suicide and Non-Suicidal Self-Injury Incidence and Recurrence Rate in Depressed Adolescents Compared with Fluoxetine Alone? A Meta-Analysis.

Objective: The efficacy of medication and psychotherapy for adolescent depression is controversial, so we conducted a meta-analysis to evaluate the efficacy of combination therapy. Methods: We followed the PRISMA checklist in completing the meta-analysis. Relevant literature was searched in PubMed, Web of Science and Embase, Chinese databases CNKI and WanFang Data. We included the literature on the comparison of the fluoxetine plus psychotherapy or cognitive-behavioral therapy (CBT) and each treatment alone for adolescent depression published in 1980-2021. All statistical analyses were performed using Stata software. Results: After careful review, a total of 489 relevant articles were retrieved, and 13 studies were finally included. In comparison with the control group (fluoxetine alone), fluoxetine plus CBT achieved higher response rate (RR=1.12, 95% CI: 1.04, 1.21), lower incidence of adverse Reactions (RR=0.62,95% CI:0.40,0.96), lower proportion of suicide or self-injury (RR=0.94,95% CI:0.74,1.20), and lower one-year recurrence rate (RR=0.27, 95% CI: 0.16, 0.45). Before treatment, there were no significant differences in Hamilton Depression Scale score (HAMD), Children's Depression Rating Scale Revised (CDRS-R) score, and Clinical Global Impression (CGI) Severity score. After treatment, HAMD score (SMD=-1.01, 95% CI:-1.39,-0.63), CDRS-R score (SMD= -0.10,95% CI:-0.26,-0.07), and CGI score (SMD = -0.22, 95% CI: -0.54, -0.10) were significantly lower in the combined treatment group than in the control group. Conclusion: Adolescents simultaneously treated with fluoxetine and CBT had significantly reduced incidence of depressive symptoms, suicide or NSSI, adverse reactions, and one-year recurrence of symptoms, than adolescents treated with fluoxetine alone. This indicates fluoxetine plus CBT may be superior to fluoxetine alone for the clinical treatment of adolescent depression.

Inconsistent clinical outcomes following afatinib treatment in NSCLC patients harboring uncommon epidermal growth factor receptor mutation.

Background: Uncommon epidermal growth factor receptor (EGFR) mutations consist of a heterogeneous population of molecular alterations, and the available clinical data on the outcomes of patients with non-small-cell lung cancer (NSCLC) harboring uncommon EGFR mutations following afatinib treatment are limited. The purpose of this pooled analysis was to investigate the clinicopathological features of patients with uncommon EGFR mutations (um-EGFRms) along with their treatment response and survival outcomes following afatinib treatment. Methods: We performed a literature search in the NCBI PubMed database to identify relevant articles and conducted this pooled analysis based on 70 studies. The relationships between patient clinical characteristics, EGFR mutation type and the response to afatinib treatment were analyzed using univariate chi-square analysis, and survival analysis was performed using the Kaplan-Meier method. Results: Data from a total of 99 patients were included in the pooled analysis. The objective response rate (ORR) to treatment with afatinib was53.5%, with a median progression-free survival (mPFS) of 9.0 months. For patients administered first-line afatinib treatment, the ORR and median PFS were 73.5% and 15.6 months, respectively, which were both superior to those of patients treated with second- or later-line treatments (ORR:37.0%, p < 0.001; mPFS: 6.0months, p = 0.001). Moreover, patients with a single um-EGFRm were more likely to have a favorable response and prognosis benefit after treatment with afatinib than patients with multiple one (ORR: 63.3% vs 38.5%, p=0.017; mPFS: 15.6 months vs 6.0 months,p=0.010). Moreover, single um-EGFRm were independent predictive factors for better treatment response and superior PFS. Subgroup analysis indicated that patients harboring major um-EGFRms (i.e., L861Q, G719X, and S768I) exhibited the best treatment responses and prognoses (ORR: 74.1%, mPFS: 15.6 months), by contrast, patients harboring multiple um-EGFRms comprising 19del/L858R had the worst treatment responses and prognoses (ORR: 23.5%, mPFS: 5.6months). Conclusions: Patients with um-EGFRms exhibit favorable but inconsistent responses and survival outcomes following afatinib treatment, which closely related to the mutation pattern and cooccurring partner mutant genes. Administering afatinib for the treatment of patients with um-EGFRm might be considered an effective treatment option in some circumstances, but this recommendation requires further clinical studies for verification.

Insensitivity to T790M mutation? A pooled analysis of outcomes following osimertinib for the treatment of NSCLC patients harboring uncommon epidermal growth factor receptor mutation.

Background: In this pooled analysis, the aim was to investigate the clinicopathological characteristics of patients with uncommon epidermal growth factor receptor (EGFR) (ucm-EGFRms) along with their treatment responses and survival following osimertinib treatment. Methods: Univariate chi-square analysis was conducted to analyze the correlation between clinical characteristics, EGFR mutation type, and treatment response, and the Kaplan-Meier method was applied for survival analysis. Univariate logistic regression model and Cox proportional hazards model were performed to compare the efficacy and prognosis in subgroup analysis. Results: Seventy-two NSCLC patients in total were included in this pooled analysis. The objective response rate (ORR) for osimertinib treatment was 57.0%, with a median PFS of 7.1 months. Twenty-eight patients received osimertinib as first-line therapy with an ORR of 67.9%, which was higher than that in patients who received osimertinib as second- or later-line therapy, and their response rate was 50%, nevertheless, no statistically significant differences were found (p = 0.139). However, patients who received first-line osimertinib showed a more significant PFS benefit than those who received second- or later-line therapy (mPFS: 16.8 months vs 6.0 months HR: 2.453, 95%CI: 1.285-4.682, p =0.004). Subgroup analysis showed that patients with a single, non-ex20ins, ucm-EGFRm displayed a superior efficacy advantage and favorable survival benefit following osimertinib treatment, with an ORR of 68.8% and an mPFS at 15.1 months. By contrast, patients with a multiple ucm-EGFRm that contain T790M exhibited the worst outcome of osimertinib treatment, with an ORR of 47.6% and an mPFS of only 3.6 months, respectively. Conclusion: Patients with um-EGFRms exhibit favorable but inconsistent responses and survival outcomes following osimertinib treatment, which is closely related to the mutation pattern and cooccurring partner mutant genes. Administering osimertinib for the treatment of patients with um-EGFRm might be considered an effective treatment option in some circumstances.

Pterostilbene pre-treatment reduces LPS-induced acute lung injury through activating NR4A1.

CONTEXT: Pterostilbene (PTE), a common polyphenol compound, exerts an anti-inflammatory effect in many diseases, including acute lung injury (ALI). OBJECTIVE: This study explores the potential mechanism of PTE pre-treatment against lipopolysaccharide (LPS)-induced ALI. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were divided into control, ALI, 10 mg/kg PTE + LPS, 20 mg/kg PTE + LPS, and 40 mg/kg PTE + LPS groups. At 24 h before LPS instillation, PTE was administered orally. At 2 h before LPS instillation, PTE was again administered orally. After 24 h of LPS treatment, the rats were euthanized. The levels of inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid (BALF), the expression of nuclear receptor subfamily 4 group A member 1 (NR4A1), and the nuclear factor (NF)-κB pathway-related protein levels were detected. NR4A1 agonist was used to further investigate the mechanism of PTE pre-treatment. RESULTS: After PTE pre-treatment, the LPS induced inflammation was controlled and the survival rate was increased to 100% from 70% after LPS treatment 24 h. For lung injury score, it decreased to 1.5 from 3.5 after treating 40 mg/kg PTE. Compared with the control group, the expression of NR4A1 in the ALI group was decreased by 20-40%. However, the 40 mg/kg PTE pre-treatment increased the NR4A1 expression by 20-40% in the lung tissue. The results obtained with pre-treatment NR4A1 agonist were similar to those obtained by pre-treatment 40 mg/kg PTE. CONCLUSIONS: PTE pre-treatment might represent an appropriate therapeutic target and strategy for preventing ALI induced by LPS.

Current antipsychotic agent use and risk of venous thromboembolism and pulmonary embolism: a systematic review and meta-analysis of observational studies.

BACKGROUND: Antipsychotic agents (APS) are widely used drugs to treat psychotic symptoms and can effectively reduce both positive and negative symptoms of schizophrenia. For decades, some studies suggested that there is a relationship between using APS and the risk of venous thromboembolism (VTE) and pulmonary embolism (PE). However, results remain inconclusive. METHOD: This review has been registered in International Prospective Register of Systematic Reviews (PROSPERO, ID: CDR42020155620). Relevant studies were identified among observational studies published up to 1 October 2019 in the databases MEDLINE, EMBASE, and Cochrane Library. Random or fixed-effects models were used to calculate the pooled odds ratio (OR). RESULTS: In total, 28 observational studies were included. The results showed that compared with non-users, current APS users have significantly increased risks of VTE [OR 1.55 95% confidence interval (CI) 1.36, 1.76] and PE (OR 3.68, 95% CI 1.23, 11.05). Subgroup analyses suggested that new users were associated with a higher risk of VTE (OR 2.06, 95% CI 1.81, 2.35). For individual drugs, increased risk of VTE and PE was observed in taking haloperidol, risperidone, olanzapine, prochlorperazine but not in chlorpromazine, quetiapine or aripiprazole. However, careful interpretation is needed because of high heterogeneity among studies and scarce data. CONCLUSION: The present comprehensive meta-analysis further indicates a significantly increased risk of VTE and PE in current APS users compared with non-users. Subgroup analyses suggest that new users are more likely to develop VTE. However, due to significant heterogeneity among studies, conclusions should be considered with caution.

Efficacy of Sertraline Combined with Cognitive Behavioral Therapy for Adolescent Depression: A Systematic Review and Meta-Analysis.

OBJECTIVE: The efficacy of antidepressant drugs combined with psychotherapy is controversial; hence, this meta-analysis was conducted to assess the efficacy of the combination therapy. METHODS: Relevant literature was searched in PubMed, Web of Science and Embase, Chinese databases CNKI, and WanFang Data. We included the literature on the comparison of the sertraline combined with cognitive behavioral therapy (CBT) and each treatment alone for adolescent depression published in 2000-2021. Meta-analysis was performed using Stata16.0 software. RESULTS: A total of 421 relevant articles were retrieved, and 14 studies were finally included. In comparison with the control group (sertraline), sertraline combined with CBT achieved higher response rate (OR = 5.07, 95% CI: 3.00, 8.58) and lower incidence of adverse reactions (OR = 0.43, 95% CI: 0.24, 0.75). Before treatment, there were no significant differences in depression score, anxiety score, and symptom self-rating scale score between the two groups. After treatment, depression score (SMD = -2.79, 95% CI: -3.64, -1.94), anxiety score (SMD = -1.22, 95% CI: -1.96, -0.47), and symptom self-rating scale score (SMD = -1.73, 95% CI: -3.19, -0.27) were significantly lower in the combined treatment group than in the control group. CONCLUSION: Although the number of comparative trials is small, this study shows that sertraline is effective for adolescent depression, but sertraline combined with CBT is more effective. The latter can significantly reduce the incidence of depressive symptoms, anxiety, and adverse reactions in patients. Therefore, this combination therapy is recommended for the clinical treatment of adolescent depression.

Outcomes and safety of concomitant topiramate or metformin for antipsychotics-induced obesity: a randomized-controlled trial.

BACKGROUND: Although there are some existing data describing the usage of topiramate in patients with antipsychotic-induced obesity, study on its comparison with metformin is limited. This study aimed to explore the effectiveness and safety of concomitant topiramate on antipsychotic-induced obesity as well as its comparison with metformin. METHODS: 62 stabilized outpatients with antipsychotic-induced obesity were randomized into the topiramate group and the metformin group with 16-week treatment. The patients' weight, body mass index (BMI), waist-hip ratio, and their side effects were assessed and compared. Intention-to-treat and completer analyses were performed. Meanwhile, covariance analysis was conducted to control the impact of the significant difference in BMI between the two groups. RESULTS: The two groups had comparable characteristics, though their difference in baseline BMI was significant. (1) Intention-to-treat analyses: the random missing values were replaced using the last observation carried forward method when intention-to-treat analyses were conducted. Compared with the baseline, the weight, BMI, and waist-hip ratio in the topiramate group markedly decreased at each follow-up, whereas, in the metformin group, only waist-hip ratio significantly decreased at 4 weeks after treatment. Compared with the metformin, only weight and BMI in the topiramate group were significantly decreased at week 4 after treatment, and at week 8-16, weight, BMI and waist-hip ratio were remarkably declined. (2) Completer analyses: compared with the baseline, the weight, BMI, and waist-hip ratio in the topiramate group at week 4-16 were markedly decreased, whereas only waist-hip ratio with metformin was significantly decreased at week 4. Compared with the metformin, all BMI with topiramate were markedly decreased at week 4-16. Moreover, its weight and waist-hip ratio also were notably lowered at week 8. No significant differences in adverse events were found between the two groups. CONCLUSIONS: Topiramate, similar to metformin in reducing obesity as previously reported, also significantly reduced body weight, BMI, and waist-hip ratio in patients with antipsychotic-induced obesity and demonstrated well tolerance in psychiatric patients. Trial registration The trial was registered at http://www.chictr.org.cn , and the number was ChiCTR-IPR-17013122.

Calculation on surface energy and electronic properties of CoS2.

Density functional theory was employed to investigate the (111), (200), (210), (211) and (220) surfaces of CoS2. The surface energies were calculated with a sulfur environment using first-principle-based thermodynamics. It is founded that surfaces with metal atoms at their outermost layer have higher energy. The stoichiometric (220) surface terminated by two layer of sulfur atoms is most stable under the sulfur-rich condition, while the non-stoichiometric (211) surface terminated by a layer of Co atoms has the lower energy under the sulfur-poor environment. The electric structure results show that the front valence electrons of (200) surface are active, indicating that there may be some active sites on this face. There is an energy gap between the stoichiometric (220) and (211), which has low Fermi energy, indicating that their electronic structures are dynamically stable. Spin-polarized bands are calculated on the stoichiometric surfaces, and these two (200) and (210) surfaces are predicted to be noticeably spin-polarized. The Bravais-Friedel-Donnay-Harker (BFDH) method is adopted to predict crystal growth habit. The results show that the most important crystal planes for the CoS2 crystal growth are (111) and (200) planes, and the macroscopic morphology of CoS2 crystal may be spherical, cubic, octahedral, prismatic or plate-shaped, which have been verified by experiments.

Association of adenylate cyclase-2 gene polymorphism with bipolar disorder.

The pathogenesis of the Bipolar Disorder(BPD) is still unclear. Some studies suggest that abnormal signal transduction in specific pathways may play an important role in the pathogenesis of BPD (Sui et al., 2015). Adenylate cyclase (ADCY) is an essential component of the adenylate signaling pathway. Previous studies have shown that some SNPs within the adenylate cyclase gene could affect the therapeutic response to mood stabilizers and antidepressants. Moreover, in 2014, one whole-genome study suggested that the ADCY-2 gene may be associated with BPD (Mühleisen et al., 2014). This study aims to investigate the association between ADCY-2 gene polymorphism and BPD in Chinese Han population.

Aberrant cerebellar neural activity and cerebro-cerebellar functional connectivity involving executive dysfunction in schizophrenia with primary negative symptoms.

Deficit schizophrenia (DS) is a distinct subtype of schizophrenia characterized by primary and enduring negative symptoms. More severe executive dysfunctions were observed in DS patients, however, the associated neuroimaging characteristics, especially cerebellar functional anomalies in DS, remain largely unknown. We employed resting-state functional and structural MRI data of 106 male participants, including data from 29 DS patients, 39 non-deficit schizophrenia (NDS) patients and 38 healthy controls (HCs). Z-standardized fractional amplitude of low-frequency fluctuation (zfALFF) values were calculated in order to examine spontaneous regional brain activity. Cerebro-cerebellar functional connectivity and changes in the volume of gray matter in the cerebellum were also examined. Relative to the HCs, both DS and NDS patients exhibited decreased zfALFF in the bilateral cerebellar lobules VIII and IX. The zfALFF in the left Crus II was lower in DS patients compared to NDS patients. No significant difference was observed in the volume of cerebellar gray matter among the three groups. Compared with NDS patients, cerebro-cerebellar functional connectivity analysis revealed increased connectivity in the left orbital medial frontal cortex and right putamen regions in DS patients. Reduced zfALFF in the left Crus II in the DS group was significantly positively correlated with Stroop Color and Word scores, while negatively correlated with Trail-Making Test part B scores. The increased functional connectivity in the right putamen in DS patients was significantly positively correlated with Animal Naming Test and semantic Verbal Fluency Test scores. These results highlight cerebellar functional abnormality in DS patients and provide insight into the pathophysiological mechanism of executive dysfunction.

Overexpressed CXCR4 and CCR7 on the surface of NK92 cell have improved migration and anti-tumor activity in human colon tumor model.

Successive infusion of natural killer cells is increasingly being explored as a treatment for cancer patients. The inadequate homing of natural killer cells into the tumor site resulted in the poor efficacy of natural killer cells on solid tumors. For the adoptive transfer of tumor-directed natural killer cell has been proved effective, it is hypothesized that there must be more association between the tumor-produced chemokines and the natural killer cells-expressed chemokine receptors. Increased CXCL12 and CCL21 could ameliorated colorectal cancer via generating an anti-tumor environment by preferentially attracting natural killer cells which expressed the chemokine receptor CXCR4 and CCR7. This study demonstrated that overexpressed CXCR4 and CCR7 on the surface of NK92 cell enhanced their migration to human colon cells. Moreover, the administration of such natural killer cells resulted in tumor shrinkage and a significantly increased survival of experimental mice when compared to ones undergoing the treatment of xenografts with natural killer cells expressing only the mock control. These suggested that chemokine receptor engineered natural killer cells could be a promising tool to improve adoptive tumor immunotherapy.

MicroRNA-31/184 is involved in transforming growth factor-ß-induced apoptosis in A549 human alveolar adenocarcinoma cells.

AIMS: TGF-ß-induced alveolar epithelial cells apoptosis were involved in idiopathic pulmonary fibrosis (IPF). This study aimed to explore potential targets and mechanisms of IPF. MAIN METHODS: mRNA and microRNA arrays were used to analyze differentially expressed genes and miRNAs. Several essential targets of TGF-ß-SMADs and TGF-ß-PI3K-AKT pathways were detected. KEY FINDINGS: miR-31 and miR-184 expression levels were positively correlated with smad6 and smad2/akt expression levels in IPF patients. TGF-ß could induce miR-31 and suppress miR-184 levels in A549 cells. miR-31 was confirmed to bind to the smad6-3'UTR and functionally suppress its expression. Down-regulated SMAD6 enhanced SMAD2/SMAD4 dimer formation and translocation due to its failure to prevent SMAD2 phosphorylation. In contrast, anti-fibrotic functions of miR-184 were abolished due to TGF-ß directly suppressing miR-184 levels in A549 cells. When A549 was stimulated by TGF-ß combined with or without miR-31 inhibitor/miR-184 mimic, it was showed that depleted miR-31 and/or increased miR-184 significantly ameliorated TGF-ß-induced viability of A549 cells, as well as inhibited the expression of profibrotic factors, MMP7 and RUNX2. SIGNIFICANCE: Inhibiting miR-31 and/or promoting miR-184 protect against TGF-ß-induced fibrogenesis by respectively repressing the TGF-ß-SMAD2 and TGF-ß-PI3K-AKT signaling pathways, implying that miR-31/184 are potential targets and suggesting a new management strategy for IPF.

The efficacy, acceptability, and safety of five atypical antipsychotics in patients with first-episode drug-naïve schizophrenia: a randomized comparative trial.

BACKGROUND: Differences in effectiveness and tolerability between different atypical antipsychotics may affect schizophrenic patients' treatment adherence or prognosis. However, which kind of antipsychotic was more effective and safe in the treatment of schizophrenia is still being debated. This study attempted to understand whether there are any differences in efficacy, acceptability, and safety between the five atypical antipsychotics in patients with first-episode schizophrenia. METHODS: Two hundred cases of inpatients with first-episode drug-naïve schizophrenia were randomly assigned to 6-8 weeks of treatment with either of aripiprazole, risperidone, quetiapine, olanzapine, or ziprasidone from October 2012 to November 2014. The efficacy, acceptability, and safety measurement after 6-8 weeks of treatment of the five kinds of antipsychotics were evaluated by the deduction rate of Brief Psychiatric Rating Scale (BPRS) total score, the proportion of treatment discontinuation, and adverse events, respectively. Whether the treatment discontinuation or combination therapy for baseline antipsychotics after titration mainly depended on ineffective or less effective on an initial-assigned antipsychotic during the study period. RESULTS: BPRS total scores in each antipsychotic group were significantly decreased at the end of the study (P < 0.01), and only the deduction rate of BPRS total scores in the risperidone group was markedly higher than those in the groups of aripiprazole (P < 0.01) and olanzapine (P < 0.05) after controlling the impact of the differences of age of onset. There were significant differences between quetiapine (χ2 = 5.46, P = 0.019), olanzapine (χ2 = 5.6, P = 0.018), and ziprasidone regarding the proportion of maintaining on initially allocated therapy. In addition, the difference in treatment discontinuation between male and female patients was also significant (χ2 = 9.897, P = 0.002), and odds ratio of treatment discontinuation in male and female patients was 0.37 (95% CI 0.198-0.693); however, no difference in treatment discontinuation was found between five antipsychotics. Extrapyramidal symptoms in the groups of quetiapine and olanzapine were notably less than the other three kinds of antipsychotics (P < 0.05), but there were no significant differences in other adverse events between the five antipsychotic groups. CONCLUSIONS: Risperidone was more effective than aripiprazole and olanzapine in treating first-episode schizophrenia. The present study revealed the superiority of quetiapine and olanzapine over ziprasidone with remarkably less severe extrapyramidal adverse effects, especially with lower drop-out and treatment discontinuation. There were no differences in terms of other adverse events although the risk of treatment discontinuation was higher in female patients. Trial registration 2012-3-88. Registered 20 July 2012.