The impact of SOX4-activated CTHRC1 transcriptional activity regulating DNA damage repair on cisplatin resistance in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the predominant subtype within the spectrum of lung malignancies. CTHRC1 has a pro-oncogenic role in various cancers. Here, we observed the upregulation of CTHRC1 in LUAD, but its role in cisplatin resistance in LUAD remains unclear. Bioinformatics analysis was employed to detect CTHRC1 and SRY-related HMG-box 4 (SOX4) expression in LUAD. Gene Set Enrichment Analysis predicted the enriched pathways related to CTHRC1. JASPAR and MotifMap databases predicted upstream transcription factors of CTHRC1. Pearson analysis was conducted to analyze the correlation between genes of interest. The interaction and binding relationship between CTHRC1 and SOX4 were validated through dual-luciferase and chromatin immunoprecipitation assays. Quantitative real-time polymerase chain reaction determined the expression of CTHRC1 and SOX4 genes. CCK-8 was performed to assess cell viability and calculate IC50 value. Flow cytometry examined the cell cycle. Comet assay and western blot assessed DNA damage. CTHRC1 and SOX4 were upregulated in LUAD. CTHRC1 exhibited higher expression in cisplatin-resistant A549 cells compared to cisplatin-sensitive A549 cells. Knockdown of CTHRC1 enhanced DNA damage during cisplatin treatment and increased the sensitivity of LUAD cells to cisplatin. Additionally, SOX4 modulated DNA damage repair (DDR) by activating CTHRC1 transcriptional activity, promoting cisplatin resistance in LUAD cells. SOX4 regulated DDR by activating CTHRC1, thereby enhancing cisplatin resistance in LUAD cells. The finding provides a novel approach to address clinical cisplatin resistance in LUAD, with CTHRC1 possibly serving as a candidate for targeted therapies in addressing cisplatin resistance within LUAD.

Synthesis of Azepino[4,5-b]indole via Ring Expansion of Tetrahydro-ß-carbolines Ammonium Ylide.

The formal cyclization strategy was generally used to construct azepino[4,5-b]indole. Herein, we reported a novel and expeditious protocol for the synthesis of quaternary carbon azepino[4,5-b]indole via ring expansion of ammonium ylide, which was formed by the reaction of tetrahydro-ß-carbolines with the diazo compound. The easily available substrates, mild reaction conditions, and broad functional tolerance rendered this method a practical strategy that may significantly afford an efficient method of scaffold hopping in drug discovery.

Suicide death, suicidal ideation and suicide attempt in patients with diabetes: A systematic review and meta-analysis.

AIMS: Diabetes has been indicated to be a risk factor for suicide. We aim to estimate the prevalence of suicide in patients with diabetes. DESIGN: A meta-analysis using PRISMA methodology was adopted to examine the incidence of suicide in diabetic patients. DATA SOURCES: From inception to October 2022, three online databases (PubMed, China National Knowledge Infrastructure and Web of Science) were used to search studies. REVIEW METHODS: We used random-effects model to analysis. And our primary outcome was the incidence of suicide death per 100 person-years, and other outcomes were prevalence of suicidal ideation and suicide attempt. To explore the sources of heterogeneity in our study, we performed subgroup and meta-regression analyses. RESULTS: The suicide death rate in diabetic patients was 0.027 per 100 person-years, with a higher rate for Type 1 Diabetes Mellitus compared to Type 2 Diabetes Mellitus. The prevalence of suicidal ideation in diabetes patients was 0.175, with a higher prevalence in Type 1 Diabetes Mellitus compared to Type 2 Diabetes Mellitus. The prevalence of suicide attempts in diabetes patients was 0.033, indicating a higher rate for Type 2 Diabetes Mellitus compared to Type 1 Diabetes Mellitus. CONCLUSIONS: The results indicate a high rate of suicide among people with diabetes, and this study identifies populations and regions at high risk for suicide. Our review emphasizes interventions in mental health and the improvement of suicide prevention programmes. IMPACT: The study investigated suicide death, suicidal ideation and suicide attempt in diabetic individuals. Suicide rates are elevated among diabetic patients, and various patient groups face distinct suicide risks. It is important to prioritize the mental well-being of diabetic individuals and enhance interventions, including personalized approaches, to inform public health efforts aimed at preventing and addressing suicide among diabetic patients. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Gender differences in suicidal ideation, suicide attempts, and suicide death among people living with HIV: A systematic review and meta-analysis.

OBJECTIVE: Although excess mortality, especially suicide, is a critical trait in people living with HIV, consensus about gender differences in these areas is lacking. We conducted meta-analyses to examine gender differences in suicidal ideation, suicide attempts, and suicide death among people living with HIV. METHODS: We systematically searched PubMed and Web of Science for studies written in English. In this review, suicide among people living with HIV includes suicide death, suicidal ideation, and suicide attempts. Studies reporting the suicide prevalence among males and females living with HIV were eligible for inclusion in our review. Odds ratios (ORs) and 95% confidence intervals (CIs) served as the effect size index. Fixed-effects or random-effects meta-analyses were chosen based on the size of the heterogeneity. RESULTS: A total of 27 studies comprising 801 017 participants from 11 countries were included in the meta-analysis. The overall prevalence of suicidal ideation was 18.0% (95% CI 13.3%-22.8%) in males and 20.8% (95% CI 16.4%-25.1%) in females, and there was a statistically significant higher risk of suicidal ideation in females living with HIV (OR 1.30; 95% CI 1.09-1.56; p < 0.05). The overall prevalence of suicide attempts was 16.8% (95% CI 9.0%-24.5%) in males and 24.7% (95% CI 12.4%-37.1%) in females, and there was a statistically significant higher risk of suicide attempts in females living with HIV (OR 1.34; 95% CI 1.02-1.75; p < 0.05). The pooled prevalence of suicide death was 1.2% (95% CI 0.5%-1.9%) among males and 0.2% (95% CI 0.1%-0.3%) among females, and the risk of suicide death between genders was not statistically significant (OR 0.78; 95% CI 0.50-1.24; p = 0.298). CONCLUSIONS: There were gender differences in suicidal ideation and suicide attempts among people living with HIV. Females living with HIV were more likely to experience suicidal ideation and make suicide attempts, but there were no statistically significant gender differences in suicide death. Appropriate initiatives to optimize the recognition, treatment, and management suicide behaviours of males and females living with HIV may narrow this gender gap.

Wilms' tumour gene 1 (WT1) enhances non-small cell lung cancer malignancy and is inhibited by microRNA-498-5p.

BACKGROUND: Wilms' tumour gene 1 (WT1) is clearly recognized as a tumour promoter in diversiform of human malignancies. Nevertheless, knowledge of its expression, functions and potential molecular mechanisms in non-small cell lung cancer (NSCLC) remains elusive. METHODS: Differential expression of WT1 mRNA and protein between NSCLC and normal tissues were assessed by analyzing RNA-seq data from Oncomine and protein data from Human Protein Atlas, respectively. Subsequently, prognosis significance and immune cell infiltration were analyzed by Kaplan-Meier plotter and CIBERSORT. 60 pairs of local NSCLC tissues were involved to validate WT1 expression by quantitative PCR (qPCR) and Western blot. Moreover, Cell Counting Kit-8 (CCK-8), colony formation, transwell, dual luciferase reporter assays and in vivo xenograft tumour growth experiments were conducted to explore the function and mechanism of WT1 in NSCLC. RESULTS: Our solid data indicated that WT1 was increased in NSCLC tissues and cell lines in comparison with their matched controls. In particular, its upregulation correlated with worse prognosis and immune infiltration of the patients. Functional assays demonstrated that knockdown of WT1 inhibited NSCLC malignancy, including inhibiting cell proliferation, survival and invasion. Further exploration discovered that microRNA-498-5p (miR-498-5p) was the upstream suppressor of WT1 by directly targeting the 3' untranslated region (UTR) of WT1 mRNA. Moreover, expression of miR-498-5p was notably decreased and inversely correlated with WT1 in NSCLC tissues. Finally, we proved that miR-498-5p was a potent tumour suppressor in NSCLC by suppressing cell proliferation, survival and invasion, while WT1 restoration could in turn disrupt this suppression both in vitro and in vivo. CONCLUSION: The abnormal increase in WT1 contributes to the malignant properties of NSCLC cells, and miR-498-5p is a natural inhibitor of WT1. Our findings might facilitate the development of novel therapeutic strategies against NSCLC in the future.

Incidence, prevalence and risk factors of device-related pressure injuries in adult intensive care unit: A meta-analysis of 10,084 patients from 11 countries.

Device-related pressure injuries (DRPIs) prevail in the intensive care unit (ICU) and have much to do with medical devices and patients' conditions. This meta-analysis aims to systematically assess the incidence, prevalence and risk factors related to DRPIs among adults in ICU. Web of Science, Cochrane Library, MEDLINE, PubMed and CINAHL were searched from inception to March 2023. Observational studies were included, and the Newcastle-Ottawa scale (NOS) was used to assess literature quality. The primary outcomes were the incidence, prevalence and risk factors regarding DRPIs among adults in ICU. The 19 studies conformed to the criteria for inclusion in the review. The estimated pooled incidence of DRPIs was 14.7% (95% CI: 9.7%-19.6%) in 10 studies (4866 participants). The estimated pooled prevalence of DRPIs was 19.0% (95% CI: 13.6%-24.3%) in 9 studies (5218 participants). The most significant risk factor for DRPIs was using mechanical ventilation. The pooled analysis of the four studies showed that DRPIs were more likely to occur in patients who required mechanical ventilation compared with patients who did not use mechanical ventilation (OR: 9.67, 95% CI: 5.03-18.61, p < 0.001) and using vasopressors, age, length of ICU stays, APACHE II score, Braden score, fever, sex, oedema, diabetes and number of medical devices, SOFA score was also related to pressure injuries risk. The incidence and prevalence of DRPIs in adult ICU were high, and the most significant risk factor for DRPIs was using mechanical ventilation. It is imminent to identify patients of increased risk with DRPIs early.

Palliative care for cancer patients during the COVID-19 pandemic: A narrative synthesis from 36 studies of 16 countries.

BACKGROUND: During the COVID-19 epidemic, palliative care has become even more indispensable for cancer patients. AIM: To identify the changes in palliative care for cancer patients and improvements in palliative care quality during the COVID-19 pandemic. DESIGN: A systematic review and narrative synthesis was conducted in PubMed, Embase and Web of Science. An evaluation tool using mixed methods was used to assess the quality of the study. The main relevant themes identified were used to group qualitative and quantitative findings. RESULTS: A total of 36 studies were identified, primarily from different countries, with a total of 14,427 patients, 238 caregivers and 354 health care providers. Cancer palliative care has been experiencing several difficulties following the COVID-19 pandemic, including increased mortality and infection rates as well as delays in patient treatment that have resulted in poorer prognoses. Treatment providers are seeking solutions such as electronic management of patients and integration of resources to care for the mental health of patients and staff. Telemedicine plays an important role in many ways but cannot completely replace traditional treatment. Clinicians strive to meet patients' palliative care needs during special times and improve their quality of life. CONCLUSIONS: Palliative care faces unique challenges during the COVID-19 epidemic. With adequate support to alleviate care-related challenges, patients in the home versus hospital setting will be able to receive better palliative care. In addition, this review highlights the importance of multiparty collaboration to achieve personal and societal benefits of palliative care. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Effect of matrix metalloproteinases on the healing of diabetic foot ulcer: A systematic review.

BACKGROUND: This study aims to discuss the expression of matrix metalloproteinase in wound healing of diabetic foot ulcers and further summarize the strategies of targeted matrix metalloproteinase and its inhibitors in the treatment of diabetic foot ulcers. METHODS: Following PRISMA-SCR guidelines, databases (PubMed, Home-PMC-NCBI, CINAHL, Web of Science) were systematically searched from inception to 19 June 2022. Newcastle-Ottawa Scale (NOS) was used to evaluate the bias risk of the included studies. RESULTS: Eight studies are finally eligible for our systematic review. The combined data analysis of 8 studies showed that there were no significant difference in age(p = 0.110), duration of diabetes(p = 0.197), glycosylated hemoglobin content(p = 0.489), size(p = 0.133) and depth(p＞0.05) of initial ulcer between the ulcer wound healing group and the non-healing group. MMP-1, 2, 8, 9, and TIMP-1, 2 affected the healing of DFUs. In the DFUs healing group, the concentrations of MMP (MMP-1, 2, 8, 9) decreased, and the concentration of TIMP-1 increased. CONCLUSION: Our study showed that high levels of MMP-1, 2, 9 delayed the healing of diabetic foot ulcers, and high expression of MMP-8 in tissues improved wound healing. This study also summarized the effective intervention strategies for the treatment of diabetic foot ulcers.

Factors associated with lack of tracheal sealing by a cuff inflated to more than 30 cmH2O during mechanical ventilation: A cross-sectional study.

Objectives: The cuff pressures > 30 cmH2O may create a seal in the trachea. The objective of this study was to identify risk factors associated with lack of tracheal sealing by an endotracheal cuff inflated to > 30 cmH2O in patients undergoing mechanical ventilation. Methods: This prospective cross-sectional study was conducted from 2019 to 2020 in the cardiothoracic intensive care unit and respiratory medical care unit of a Hospital in Nantong, China. Patients aged >16 years undergoing cardiothoracic surgery with mechanical ventilation using endotracheal intubation were included. Patient characteristics and ventilator parameters were analyzed. Cuff pressure was maintained with the minimum leak technique (MLT) and measured with a cuff pressure gauge. Cuff pressure was measured for 30 seconds when ventilation was accompanied by no leak, simultaneously detected by the ventilator or auscultation with a stethoscope. Result: Of 352 patients undergoing mechanical ventilation, 51 patients (14.5%) had a cuff pressure of >30 cmH2O. Multivariable analysis showed that cuff manufacturer (Guangzhou Weili) and nasal endotracheal intubation significantly increased the risk of an unsealed trachea. Peak inspiratory pressure, cuff diameter and male sex had a strong inverse association with an unsealed trachea. Conclusions: These findings suggest that an endotracheal cuff pressure of 20 to 30 cmH2O is adequate for most patients, but lack of a tracheal seal still occurs in a small number of people. An unsealed trachea is most likely because cuff and tracheal diameters do not match. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx Unique identifier: ChiCTR-COC-15006459.

Incidence and risk factors of suicide in patients with lung cancer: a scoping review.

PURPOSE: To explore the high-risk period of the occupation of suicide after diagnosis; and clarify the risk factors of suicidal behaviors (suicidal ideation, suicide attempt, and suicidal death) behind the lung cancer patients during the cancer cure process. METHODS: This scoping review was conducted through the whole month of April 2021. We extracted data of the suicide mortality after diagnosis and latent risk factors of suicidal behaviors among lung cancer patients where we used to study from the two online databases which are PubMed and Web of Science. Two online databases were searched and written in English without age restriction. To note that the standardized mortality ratio (SMR), person-years, and odds ratio (OR) associated with lung cancer were documented. RESULTS: Out of 570 records, 23 studies mentioned suicidal behaviors and lung cancer met the included criteria. Eleven (n = 47.8%) of the selected publications reported changes in suicide mortality. None of them reported suicidal ideation or suicide attempt after diagnosis. The individuals with lung cancer have significantly higher rates of suicidal death (SMR, 2.04-13.4) during the first years after diagnosis and decrease over subsequent years (SMR, 0.66-3.17). The median time from cancer diagnosis to suicide death was around 7 months. Across all studies with the 22 studies that examined factors, we extracted the data of the suicidal ideation (n = 3), suicide attempt (n = 1), and suicidal death (n = 18) in individuals. For patients with suicidal ideation, there was a significantly higher incidence in males than in females. Among patients who attempted suicide, the incidence of mental illness is greater than the incidence of physical illness. Factors for suicidal death, including gender (male, 56.3-100%), prognosis tumors (poor, 25.8-66.3%), marital status (widowhood or unmarried, 19-75.7%), and age of patients (> 70 years, 24.5-47%) with lung cancer, play a vital role. Treatment of lung cancer is expected to affect a patient in his/her mental state. CONCLUSION: Overall, our finding indicates that lung cancer patients have been presented with a higher incidence of suicide death in a specific period, especially the early years after diagnosis. Discovering risk factors for suicide helps prevent potential suicide. It is essential to screen lung cancer patients for suicidal ideation, especially those with high-risk factors. Future prospective studies are necessary to confirm these findings to support care.

C-reactive protein and diabetic foot ulcer infections: A meta-analysis.

BACKGROUND: Accurate identification of diabetic foot ulcer infection (IDFU) through inflammatory markers is still a challenge in clinical practice. OBJECTIVES: This meta-analysis aims to investigates whether there is a significant indigenous association between CRP level and diabetic foot ulcer infection. METHODS: The studies on the diagnosis of IDFU by inflammatory marker C-reactive protein published before November 2021 in PubMed, Web of Science, Embase, and Cochrane Library were searched. Since the included seven studies were cohort studies and cross-sectional studies, the quality evaluation was founded on the standard of Newcastle-Ottawa Scale (NOS), which was convenient and straightforward. The stata 15.0 software (Cambridge, UK) was used for statistical analysis of data collected for analysis. RESULTS: Finally, we included seven articles and investigated 592 patients, including 362 patients with IDFU and 230 patients without diabetic foot ulcer infection (NIDFU). Seven studies assessed the results of CRP, with significant heterogeneity among included studies (χ2 = 18.93, P = 0.004; I2 = 68.3%). Therefore, the combined effect adopts the random effect model, and the combined impact of standardized mean difference is 0.81 (95% CI 0.49-1.12; z = 4.99, p = 0.000). The funnel plot showed no significant asymmetry, and Egger's Test (z = 0.30, P = 0.764) and Begg's Test (t = -0.50, p = 0.637) showed no publication bias. Sensitivity analysis shows that the results are robust. Through subgroup analysis, we find that regional and CRP types are both sources of high heterogeneity. Meanwhile, the meta-regression results of the random effect model showed that HbA1c (P = 0.021), BMI (P = 0.029), and creatinine levels (P = 0.003) had significant effects on the heterogeneity of the relationship between IDFU, and serum CRP levels. DISCUSSION: Meta-analysis showed a clear association between C-reactive protein and IDFU. Understanding the pathophysiology of IDFU and rapid identification of risk factors for reducing patient burdens, amputation, and mortality are essential.

Incidence of Death Anxiety in Palliative Care: A Systematic Review and Meta-Analysis.

Objective: To explore the incidence of death anxiety in palliative care patients, find some existing and potential causes, and put forward suggestions. Methods: Publication bias, sensitivity analysis, subgroup analysis, and regression analysis were also conducted to explore the sources of the heterogeneity in our analysis. Results: The 607 studies were obtained, and 20 studies were included after reading the articles and quality evaluation. The incidence of death anxiety in patients was 0.44 (95%CI:0.38,0.51, p < 0.001). and heterogeneity was significant (I2 = 98.2%, p < 0.001). In the test of regression analysis, the average age (I2 = 98.15%, R2 = - 6.99%, p < 0.001); in gender (I2 = 97.84%, R2 = 1.14%, p < 0.001), its heterogeneity was also significant. Conclusion: The incidence of death anxiety is relatively high. More often occur in elderly female patients. This requires more attention to life itself rather than death.

Improving biomedical named entity recognition with syntactic information.

BACKGROUND: Biomedical named entity recognition (BioNER) is an important task for understanding biomedical texts, which can be challenging due to the lack of large-scale labeled training data and domain knowledge. To address the challenge, in addition to using powerful encoders (e.g., biLSTM and BioBERT), one possible method is to leverage extra knowledge that is easy to obtain. Previous studies have shown that auto-processed syntactic information can be a useful resource to improve model performance, but their approaches are limited to directly concatenating the embeddings of syntactic information to the input word embeddings. Therefore, such syntactic information is leveraged in an inflexible way, where inaccurate one may hurt model performance. RESULTS: In this paper, we propose BIOKMNER, a BioNER model for biomedical texts with key-value memory networks (KVMN) to incorporate auto-processed syntactic information. We evaluate BIOKMNER on six English biomedical datasets, where our method with KVMN outperforms the strong baseline method, namely, BioBERT, from the previous study on all datasets. Specifically, the F1 scores of our best performing model are 85.29% on BC2GM, 77.83% on JNLPBA, 94.22% on BC5CDR-chemical, 90.08% on NCBI-disease, 89.24% on LINNAEUS, and 76.33% on Species-800, where state-of-the-art performance is obtained on four of them (i.e., BC2GM, BC5CDR-chemical, NCBI-disease, and Species-800). CONCLUSION: The experimental results on six English benchmark datasets demonstrate that auto-processed syntactic information can be a useful resource for BioNER and our method with KVMN can appropriately leverage such information to improve model performance.

Isolation and Crystallographic Characterization of Lu3 N@C2n (2n=80-88): Cage Selection by Cluster Size.

The small Sc3 N cluster has only been found in such small cages as C2n (2n=68, 78, 80, 82), whereas the large M3 N (M=Y, Gd, Tb, Tm) clusters choose those larger cages C2n (2n=82-88). Herein, concrete experimental evidence is presented to establish the size effect of the internal metallic cluster on selecting the outer cage of endohedral metallofullerenes (EMFs) by using a medium-sized metal, lutetium, which possesses an ionic radius between Sc and Gd. A series of lutetium-containing EMFs have been obtained and their structures are unambiguously determined as Lu3 N@Ih (7)-C80 , Lu3 N@D5h (6)-C80 , Lu3 N@C2v (9)-C82 , Lu3 N@Cs (51365)-C84 , Lu3 N@D3 (17)-C86 , and Lu3 N@D2 (35)-C88 by single-crystal X-ray diffraction crystallography. It was confirmed that the encaged Lu3 N cluster always adopts a planar geometry in Lu3 N@C80-88 isomers to ensure substantial metal-cage/metal-nitrogen interactions. As a result, the Lu3 N cluster selects the C2v (9)-C82 cage, which also encapsulates Sc3 N, instead of the Cs (39663)-C82 cage which is more suitable for M3 N (M=Y, Gd, Tb, Tm). However, different from Sc3 N, Lu3 N can also template the C84-88 cages which are absent for Sc3 N-containing EMFs, confirming clearly the size effect of the internal cluster on selecting the outer cage.

[Changes in C-reactive protein and procalcitonin levels in neonates with necrotizing enterocolitis and their clinical significance].

OBJECTIVE: To study the changes in C-reactive protein (CRP) and procalcitonin (PCT) levels in neonates with necrotizing enterocolitis (NEC) and their clinical significance. METHODS: According to the modified Bell's staging criteria, 142 neonates with NEC were divided into stage I group (n=40), stage II group (n=72), and stage III group (n=30). All the 18 neonates who underwent surgical treatment had stage III NEC, and among the 124 neonates who underwent conservative treatment, 12 had stage III NEC and the others had stage I or II NEC. CRP and PCT were measured before treatment, on the next day after treatment, and during the recovery stage. RESULTS: Before treatment, on the next day after treatment, and during the recovery stage, the stage III group had a higher level of CRP than the stage I and stage II groups (P<0.05). On the next day after treatment, the stage II and stage III groups had an increase in CRP (P<0.05), and the stage III group had an increase in PCT (P<0.05). The stage II and stage III groups had lower CRP and PCT in the recovery stage than before treatment and on the next day after treatment (P<0.05). The stage III group had higher incidence rate of respiratory failure and rate of mechanical ventilation than the stage I and stage II groups (P<0.05), and the stage III group had a higher incidence rate of sepsis than the stage II group (P=0.010). Gastrointestinal perforation and intestinal stenosis were observed in 10 and 8 neonates respectively in the stage III group. CRP on the next day after treatment had a value in predicting stage III NEC (P<0.05), and CRP before treatment and on the next day after treatment had a value in predicting the need for surgery (P<0.05). CONCLUSIONS: Levels of CRP and PCT and their changes can help with the early diagnosis of Bell stage II/III NEC, and CRP can be used to predict the development of stage III NEC and the need for surgery.

Discovery of acylguanidine oseltamivir carboxylate derivatives as potent neuraminidase inhibitors.

In search of novel anti-influenza agents with higher potency, a series of acylguanidine oseltamivir carboxylate analogues were synthesized and evaluated against influenza viruses (H1N1 and H3N2) in vitro. The representative compounds with strong inhibitory activities (IC50 <40nM) against neuraminidase (NA) were further tested against the NA from oseltamivir-resistant strain (H259Y). Among them, compounds 9 and 17 were potent NA inhibitors that exhibited a 5 and 11-fold increase in activity comparing with oseltamivir carboxylate (2, OC) against the H259Y mutant, respectively. Furthermore, the effect against influenza virus H259Y mutant (H1N1) replication and cytotoxicity assays indicated that compounds 9 and 17 exhibited a 20 and 6-fold increase than the parent compound 2, and had no obvious cytotoxicity in vitro. Moreover, the molecular docking studies revealed that the docking modes of compounds 9 and 17 were different from that of oseltamivir, and the new hydrogen bonds and hydrophobic interaction were formed in this case. This work provided unique insights in the discovery of potent inhibitors against NAs from wild-type and oseltamivir-resistant strains.

Radioactive self-expanding stents for palliative management of unresectable esophageal cancer: a systematic review and meta-analysis.

Stent insertion is a feasible and safe palliative management for advanced unresectable esophageal cancer. The aim of this study is to assess the efficacy of radioactive stent for unresectable esophageal cancer compared with conventional stent. Systematic searches of the PubMed and Web of science are dated from their beginning to January 25, 2016. Studies that compared radioactive stent with conventional stent for unresectable esophageal cancer were included. The outcomes were postimplantation survival, relief of dysphagia, and complications related to stent implant. Six studies with 539 patients were included. All of them used stent equipped with radioactive iodine beads as a radioactive stent. The pooled weighted mean difference for median survival was 2.734 months (95% CI 1.710-3.775; Z = 5.21, P = 0.000) between two groups. The 1,3,6 month survival rates were higher in radioactive stents than conventional stent, with the pooled ORs 3.216 (95% CI 1.293-7.999; Z = 2.51, P = 0.012), 3.095 (95% CI 1.908-5.020; Z = 4.58, P = 0.000), and 7.503 (95% CI 2.206- 25.516; Z = 3.23, P = 0.001, respectively). The pooled hazard ratio was 0.464 (95% CI 0.328-0.655; Z = 4.35, P = 0.000) between two groups. For relief of dysphagia, two stents all have good relief of the dysphagia effect, but radioactive stent showed a better effect at 3, 6 months follow-up after implantation. For complications related to stent implant, no significant differences were found between two stents in terms of severe chest pain (30.0% vs. 35.7%, OR 0.765, 95% CI 0.490-1.196), gastroesophageal reflux (18.6% vs. 16.1%, OR 1.188, 95% CI 0.453-3.115), fever (12.1% vs. 12.1%, OR 1.014, 95% CI 0.332-3.097), bleeding (16.7% vs. 14.2%, OR 1.201, 95% CI 0.645-2.236), perforation or fistula (6.1% vs. 9.0%, OR 0.658, 95% CI 0.291-1.486), pneumonia (10.7% vs. 14.1%, OR 0.724, 95% CI 0.343-1.526), stent migration (7.0% vs. 10.2%, OR 0.651, 95% CI 0.220-1.924), and restenosis (24.2% vs. 20.6%, OR 1.228, 95% CI 0.674-2.239). Radioactive stent insertion had potential benefits for palliative management for patients with unresectable esophageal cancer. This method prolonged survival and dysphagia relief period without more complications. However, this conclusion should be confirmed by more trials.

Length of surgery and pressure ulcers risk in cardiovascular surgical patients: a dose-response meta-analysis.

The aim of this study was to assess the relationship between length of surgery (LOS) and pressure ulcer (PU) risk in cardiovascular surgery patients. PubMed and Web of Science were systematically searched. We compared LOS difference between PU (+) group and PU (-) group. We also examined the dose-response effect of this relationship. The mean LOS in the PU(+) groups ranged from 252·5 to 335·7 minutes, compared with 233·0 to 298·3 minutes in PU(-) groups. The LOS was higher in PU(+) groups compared with PU(-) groups [weighted mean difference (WMD) = 36·081 minutes; 95% CI: 21·640-50·522 minutes; Z = 4·90, P = 0·000]. The funnel plot showed no publication bias. A significant dose-response association was also found between the LOS and the risk of surgery-related pressure ulcers (SRPU, model χ2 = 9·29, P = 0·000). In the linear model, the PU OR was 1·296 (95% CI 1·097-1·531) for a 60-minute increase in the LOS intervals and 13·344 (95% CI 2·521-70·636) for a 600-minute increase. In a spline model, the OR of PU increased almost linearly along with the LOS. Our meta-analysis indicated that LOS was an important risk factor for pressure ulcers in cardiovascular surgical patients.

A new nomogram score for predicting surgery-related pressure ulcers in cardiovascular surgical patients.

The aim of this study was to build a new nomogram score for predicting surgery-related pressure ulcers (SRPU) in cardiovascular surgical patients. We performed a prospective cohort study among consecutive patients with cardiovascular surgery between January 2015 and December 2015. Univariate and multivariate logistic regression was used to analyse the risk factors for SRPU. A nomogram-predicting model was built based on the logistic regression model. Then, calibration and discrimination were tested. A total of 149 patients with cardiovascular surgery were included in the study. Thirty-seven patients developed SRPUs, with an incidence rate of 24·8% (95%CI: 18·1-32·6%). The logistic regression model for predicting SRPU with four risk factors was Logit(P) = (1·861 × VDH, OR 2·174 × CAD, OR 1·747 × TAA) - 0·029 × weight + 0·005 × surgery duration + 1·241 × perioperative corticosteroids administration (P = 0·003, R2 = 0·1181). The goodness-of-fit test (Pearson χ2 = 150·69, P = 0·217) indicated acceptable calibration, and the C-index (0·725) indicated moderate discrimination. When the probability cut-off is 0·25 (total score 12), the nomogram model has the best sensitivity and specificity in predicting SRPU. We established a new nomogram model that can provide an individual prediction of SRPU in cardiovascular surgical patients. When the probability is more than 0·25 (total score 12), the cardiovascular surgery patients should be considered at high-risk.