Predictive value of prognostic nutritional index as prognostic biomarkers in patients with lymphoma: a systematic review and meta-analysis.

BACKGROUND: Several research have indicated the significant potential of the Prognostic Nutritional Index (PNI) as a prognostic biomarker in lymphoma patients. However, there is some inconsistency in the findings of a few studies. Hence, to offer a thorough evaluation of the predictive significance of PNI in lymphoma patients, we performed a meta-analysis to examine the prognostic value of PNI for survival outcomes in lymphoma patients. METHODS: We conducted a comprehensive search for pertinent works published up until December 2023 in databases such as PubMed, EMBASE, Cochrane Library, and Web of Science. We obtained hazard ratio (HR) data related to survival outcomes and computed aggregated HRs with their corresponding 95% confidence intervals (CIs) to evaluate the correlation between PNI and both overall survival (OS) and progression-free survival (PFS) in lymphoma patients. RESULTS: By analyzing data from 1260 patients in 28 studies, we found that PNI levels were associated with prognosis in lymphoma patients. High PNI levels predicted that patients had longer OS (HR: 0.46, 95% CI 0.37-0.58, P < 0.05) and better PFS (HR: 0.56, 95% CI 0.45-0.70, P < 0.05). Subgroup analyses showed that the predictive ability of PNI for patient prognosis may differ depending on the type of lymphoma. In addition, we found that the critical PNI value had greater predictive potential at 40-45 and above 45. CONCLUSION: Our study suggests a strong association between PNI and prognostic outcomes in lymphoma patients, indicating that PNI holds substantial prognostic value in this population.

Sonographic characteristics and clinical characteristics combined with nomogram for predicting the aggressiveness of papillary thyroid carcinoma coexisted with Hashimoto's thyroiditis.

OBJECTIVE: The association between Papillary Thyroid Carcinoma (PTC) and coexistent Hashimoto's Thyroiditis (HT) was controversial. The purpose of this study was to evaluate the presence of HT exerts any influence on the aggressiveness of PTC, and to establish a nomogram for predicting the possibility of aggressiveness in PTC. METHODS: 373 consecutive PTC patients with/without coexistent HT from January 2017 to December 2020 were retrospective reviewed. Patients' clinicopathologic and sonographic characteristics were collected for univariate and multivariate analyses. A nomogram was established based on the risk factors for aggressiveness in PTC. RESULTS: Male (p = 0.001), tumor size >1.0 cm (p = 0.046) and lymph node metastasis (p = 0.018) were negatively associated with PTC coexisted with HT, while it was significantly positively associated with the frequence of multifocality (p = 0.010). Univariate and multivariate analyses suggested that age ≥55 years (p = 0.000), male (p = 0.027), HT (p = 0.017), tumor size >1.0 cm (p = 0.015), multifocality (p = 0.041), distance to capsular ≤0 cm (p = 0.050) and blood flow (Grade I: p = 0.044) were independent risk factors for predicting the aggressiveness in PTC. A nomogram according to these predictors was further developed and validated. The receiver operating characteristic curve (AUC = 0.734 and 0.809 for training and validation cohorts, respectively) and decision curve analyses indicated that the nomogram model was clinically useful. The calibration curve revealed that the nomogram exhibited an excellent consistency. CONCLUSIONS: In this study, the coexistent HT might play a protective role in preventing the proliferation of PTC. Dispensable aggressive treatment may be reduced in PTC by pre-operative identification of sonographic and clinical characteristics and incorporating with the predicted nomogram model.

Albumin corrected anion gap for predicting in-hospital death among patients with acute myocardial infarction: A retrospective cohort study.

OBJECTIVE: To explore the relationship between Anion Gap (AG), Albumin Corrected AG (ACAG), and in-hospital mortality of Acute Myocardial Infarction (AMI) patients and develop a prediction model for predicting the mortality in AMI patients. METHODS: This was a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC)-Ⅲ, MIMIC-IV, and eICU Collaborative Study Database (eICU). A total of 9767 AMI patients who were admitted to the intensive care unit were included. The authors employed univariate and multivariable cox proportional hazards analyses to investigate the association between AG, ACAG, and in-hospital mortality; p < 0.05 was considered statistically significant. A nomogram incorporating ACAG and clinical indicators was developed and validated for predicting mortality among AMI patients. RESULTS: Both ACAG and AG exhibited a significant association with an elevated risk of in-hospital mortality in AMI patients. The C-index of ACAG (C-index = 0.606) was significantly higher than AG (C-index = 0.589). A nomogram (ACAG combined model) was developed to predict the in-hospital mortality for AMI patients. The nomogram demonstrated a good predictive performance by Area Under the Curve (AUC) of 0.763 in the training set, 0.744 and 0.681 in the external validation cohort. The C-index of the nomogram was 0.759 in the training set, 0.756 and 0.762 in the validation cohorts. Additionally, the C-index of the nomogram was obviously higher than the ACAG and age shock index in three databases. CONCLUSION: ACAG was related to in-hospital mortality among AMI patients. The authors developed a nomogram incorporating ACAG and clinical indicators, demonstrating good performance for predicting in-hospital mortality of AMI patients.

Value of circulating tumor cell assisting low-dose computed tomography in screening pulmonary nodules based on existing liquid biopsy techniques: a systematic review with meta-analysis and trial sequential analysis.

OBJECTIVE: This study aims to assess the diagnostic utility of circulating tumor cells (CTCs) in conjunction with low-dose computed tomography (LDCT) for differentiating between benign and malignant pulmonary nodules and to substantiate the foundation for their integration into clinical practice. METHODS: A systematic literature review was performed independently by two researchers utilizing databases including PubMed, Web of Science, The Cochrane Library, Embase, and Medline, to collate studies up to September 15, 2023, that investigated the application of CTCs in diagnosing pulmonary nodules. A meta-analysis was executed employing Stata 15.0 and Revman 5.4 to calculate the pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curve (AUC). Additionally, trial sequential analysis was conducted using dedicated TSA software. RESULTS: The selection criteria identified 16 studies, encompassing a total of 3409 patients. The meta-analysis revealed that CTCs achieved a pooled sensitivity of 0.84 (95% CI 0.80 to 0.87), specificity of 0.80 (95% CI 0.73 to 0.86), PLR of 4.23 (95% CI 3.12 to 5.72), NLR of 0.20 (95% CI 0.16 to 0.25), DOR of 20.92 (95% CI 13.52 to 32.36), and AUC of 0.89 (95% CI 0.86 to 0.93). CONCLUSIONS: Circulating tumor cells demonstrate substantial diagnostic accuracy in distinguishing benign from malignant pulmonary nodules. The incorporation of CTCs into the diagnostic protocol can significantly augment the diagnostic efficacy of LDCT in screening for malignant lung diseases.

COMPARISON OF DYNESYS AND HYBRID SYSTEM FOR MULTI-SEGMENTAL LDD.

Objective: To compare effectiveness of Dynesys and hybrid system in treating patients with multi-segmental lumbar degenerative disease (LDD). Methods: Patients involved in this retrospective study were divided into Dynesys (n = 22) and Hybrid (n = 13) groups. Clinical outcomes were evaluated using Oswestry Disability Index (ODI), and Visual Analogue Scale (VAS). Radiologic evaluations included X-ray, MRI, and CT. Furthermore, different complications were analyzed. Results: At the last follow-up, ODI and VAS of each group were improved (p < 0.05), and the range of motion (ROM) of operating segments decreased. However, Dynesys group preserved a larger extent of ROM at the final follow-up (p < 0.05). ROM of the upper adjacent segment was increased in both groups (p < 0.05), while the disc heights were decreased at the final follow-up (p < 0.05). Besides, Dynesys group had a more obvious decrease in the disc height of dynamic segments (p < 0.05). No significant difference existed in complications between both groups (p > 0. 05). Conclusion: In our study, similar satisfactory results were obtained in both groups. Both surgical procedures can be employed as effective treatments for middle-aged and physically active patients with multi-segmental LDD. Level of Evidence III; Retrospective Comparative Study.

Objetivo: Comparar a eficácia do Dynesys e do sistema híbrido no tratamento de pacientes com doença degenerativa lombar multissegmentar (DLD). Métodos: Os pacientes envolvidos neste estudo retrospectivo foram divididos em grupos Dynesys (n = 22) e Híbrido (n = 13). Os desfechos clínicos foram avaliados por meio do Oswestry Disability Index (ODI) e da Escala Visual Analógica (EVA). As avaliações radiológicas incluíram radiografia, ressonância nuclear magnética (RNM) e tomografia computadorizada. Ademais, diferentes complicações foram analisadas. Resultados: No acompanhamento final, o ODI e a EVA de todos os grupos melhoraram (p < 0,05), e houve diminuição da amplitude de movimento (ADM) dos segmentos operacionais. No entanto, o grupo Dynesys preservou uma maior extensão da ADM no acompanhamento final (p < 0,05). A ADM do segmento superior adjacente foi ampliada em ambos os grupos (p < 0,05), enquanto as alturas dos discos foram reduzidas no acompanhamento final (p < 0,05). No entanto, o grupo Dynesys apresentou uma redução mais evidente na altura do disco dos segmentos dinâmicos (p < 0,05). Não houve diferença significativa nas complicações entre esses dois grupos (p > 0,05). Conclusão: Neste estudo, resultados satisfatórios semelhantes foram obtidos em ambos os grupos. Ambos os procedimentos cirúrgicos podem ser empregados como tratamentos eficazes para pacientes de meia-idade e fisicamente ativos com LDD multissegmentar. Nível de Evidência III; Estudo Retrospectivo Comparativo.

NLRP1 restricts porcine deltacoronavirus infection via IL-11 inhibiting the phosphorylation of the ERK signaling pathway.

Continuously emerging highly pathogenic coronaviruses remain a major threat to human and animal health. Porcine deltacoronavirus (PDCoV) is a newly emerging enterotropic swine coronavirus that causes large-scale outbreaks of severe diarrhea disease in piglets. Unlike other porcine coronaviruses, PDCoV has a wide range of species tissue tropism, including primary human cells, which poses a significant risk of cross-species transmission. Nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) has a key role in linking host innate immunity to microbes and the regulation of inflammatory pathways. We now report a role for NLRP1 in the control of PDCoV infection. Overexpression of NLRP1 remarkably suppressed PDCoV infection, whereas knockout of NLRP1 led to a significant increase in PDCoV replication. A mechanistic study revealed that NLRP1 suppressed PDCoV replication in cells by upregulating IL-11 expression, which in turn inhibited the phosphorylation of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor U0126 effectively hindered PDCoV replication in pigs. Together, our results demonstrated that NLRP1 exerted an anti-PDCoV effect by IL-11-mediated inhibition of the phosphorylation of the ERK signaling pathway, providing a novel antiviral signal axis of NLRP1-IL-11-ERK. This study expands our understanding of the regulatory network of NLRP1 in the host defense against virus infection and provides a new insight into the treatment of coronaviruses and the development of corresponding drugs.IMPORTANCECoronavirus, which mainly infects gastrointestinal and respiratory epithelial cells in vivo, poses a huge threat to both humans and animals. Although porcine deltacoronavirus (PDCoV) is known to primarily cause fatal diarrhea in piglets, reports detected in plasma samples from Haitian children emphasize the potential risk of animal-to-human spillover. Finding effective therapeutics against coronaviruses is crucial for controlling viral infection. Nucleotide-binding oligomerization-like receptor (NLR) family pyrin domain-containing 1 (NLRP1), a key regulatory factor in the innate immune system, is highly expressed in epithelial cells and associated with the pathogenesis of viruses. We demonstrate here that NLRP1 inhibits the infection of the intestinal coronavirus PDCoV through IL-11-mediated phosphorylation inhibition of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor can control the infection of PDCoV in pigs. Our study emphasizes the importance of NLRP1 as an immune regulatory factor and may open up new avenues for the treatment of coronavirus infection.

Albumin corrected anion gap for predicting in-hospital death among patients with acute myocardial infarction: A retrospective cohort study

Abstract Objective: To explore the relationship between Anion Gap (AG), Albumin Corrected AG (ACAG), and in-hospital mortality of Acute Myocardial Infarction (AMI) patients and develop a prediction model for predicting the mortality in AMI patients. Methods: This was a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC)-III, MIMIC-IV, and eICU Collaborative Study Database (eICU). A total of 9767 AMI patients who were admitted to the intensive care unit were included. The authors employed univariate and multivariable cox proportional hazards analyses to investigate the association between AG, ACAG, and in-hospital mortality; p < 0.05 was considered statistically significant. A nomogram incorporating ACAG and clinical indicators was developed and validated for predicting mortality among AMI patients. Results: Both ACAG and AG exhibited a significant association with an elevated risk of in-hospital mortality in AMI patients. The C-index of ACAG (C-index = 0.606) was significantly higher than AG (C-index = 0.589). A nomo-gram (ACAG combined model) was developed to predict the in-hospital mortality for AMI patients. The nomo-gram demonstrated a good predictive performance by Area Under the Curve (AUC) of 0.763 in the training set, 0.744 and 0.681 in the external validation cohort. The C-index of the nomogram was 0.759 in the training set, 0.756 and 0.762 in the validation cohorts. Additionally, the C-index of the nomogram was obviously higher than the ACAG and age shock index in three databases. Conclusion: ACAG was related to in-hospital mortality among AMI patients. The authors developed a nomogram incorporating ACAG and clinical indicators, demonstrating good performance for predicting in-hospital mortality of AMI patients.

Comparison of dynesys and hybrid system for multi-segmental ldd / Comparação entre dynesys e sistema híbrido para ldd multissegmental

ABSTRACT Objective: To compare effectiveness of Dynesys and hybrid system in treating patients with multi-segmental lumbar degenerative disease (LDD). Methods: Patients involved in this retrospective study were divided into Dynesys (n = 22) and Hybrid (n = 13) groups. Clinical outcomes were evaluated using Oswestry Disability Index (ODI), and Visual Analogue Scale (VAS). Radiologic evaluations included X-ray, MRI, and CT. Furthermore, different complications were analyzed. Results: At the last follow-up, ODI and VAS of each group were improved (p < 0.05), and the range of motion (ROM) of operating segments decreased. However, Dynesys group preserved a larger extent of ROM at the final follow-up (p < 0.05). ROM of the upper adjacent segment was increased in both groups (p < 0.05), while the disc heights were decreased at the final follow-up (p < 0.05). Besides, Dynesys group had a more obvious decrease in the disc height of dynamic segments (p < 0.05). No significant difference existed in complications between both groups (p > 0. 05). Conclusion: In our study, similar satisfactory results were obtained in both groups. Both surgical procedures can be employed as effective treatments for middle-aged and physically active patients with multi-segmental LDD. Level of Evidence III; Retrospective Comparative Study.

RESUMO Objetivo: Comparar a eficácia do Dynesys e do sistema híbrido no tratamento de pacientes com doença degenerativa lombar multissegmentar (DLD). Métodos: Os pacientes envolvidos neste estudo retrospectivo foram divididos em grupos Dynesys (n = 22) e Híbrido (n = 13). Os desfechos clínicos foram avaliados por meio do Oswestry Disability Index (ODI) e da Escala Visual Analógica (EVA). As avaliações radiológicas incluíram radiografia, ressonância nuclear magnética (RNM) e tomografia computadorizada. Ademais, diferentes complicações foram analisadas. Resultados: No acompanhamento final, o ODI e a EVA de todos os grupos melhoraram (p < 0,05), e houve diminuição da amplitude de movimento (ADM) dos segmentos operacionais. No entanto, o grupo Dynesys preservou uma maior extensão da ADM no acompanhamento final (p < 0,05). A ADM do segmento superior adjacente foi ampliada em ambos os grupos (p < 0,05), enquanto as alturas dos discos foram reduzidas no acompanhamento final (p < 0,05). No entanto, o grupo Dynesys apresentou uma redução mais evidente na altura do disco dos segmentos dinâmicos (p < 0,05). Não houve diferença significativa nas complicações entre esses dois grupos (p > 0,05). Conclusão: Neste estudo, resultados satisfatórios semelhantes foram obtidos em ambos os grupos. Ambos os procedimentos cirúrgicos podem ser empregados como tratamentos eficazes para pacientes de meia-idade e fisicamente ativos com LDD multissegmentar. Nível de Evidência III; Estudo Retrospectivo Comparativo.

Effect of Survivin Down-Regulation by Egr1-Survivin shRNA Combined with Radiotherapy on Radiosensitivity of Esophageal Squamous Carcinoma / Efecto de la Regulación Negativa de Survivina por shRNA de Egr1-Survivina Combinado con Radioterapia sobre la Radiosensibilidad del Carcinoma Escamoso de Esófago

SUMMARY: This study is to investigate the effect of survivin down-regulation by Egr1-survivin shRNA combined with radiotherapy on the apoptosis and radiosensitivity of esophageal squamous cell carcinoma ECA109 and KYSE150 cells. ECA109 and KYSE150 cells were transfected with Egr1-survivin shRNA, and then treated with radiotherapy. After 24 h, the mRNA and protein levels of Egr1-survivin were detected by qPCR and Western-Blot. Cell cycle and apoptosis were detected by flow cytometry. Western blot also detected levels of cleavaged Caspase 3 and Caspase 9. YM155 was used as a positive control to inhibit survivin expression. The levels of survivin mRNA and protein in ECA109 and KYSE150 cells treated with Egr1-survivin shRNA combined with radiotherapy were significantly lower than those of the blank control group, the empty vector control group, and, the YM155 + radiotherapy group (P<0.05). Meanwhile, after survivin down-regulation, the ratio of G2 to S phase of ECA109 and KYSE150 cells increased significantly, leading to significant G2 and S phase arrest. Additionally, apoptosis of ECA109 and KYSE150 cells increased significantly (P <0.01). Further, protein levels of cleavaged Caspase 3 and Caspase 9 significantly increased in Egr1-survivin shRNA combined with radiotherapy group. Egr1-survivin shRNA combined with radiotherapy can down-regulate survivin expression, which further increases the apoptosis, and enhances the radiosensitivity of ECA109 and KYSE150 cells.

Este estudio tuvo como objetivo investigar el efecto de la regulación negativa de survivina por el shRNA de Egr1-survivina combinado con radioterapia sobre la apoptosis y la radiosensibilidad del carcinoma de células escamosas de esófago Células ECA109 y KYSE150. Las células ECA109 y KYSE150 se transfectaron con shRNA de survivina Egr1 y luego se trataron con radioterapia. Después de 24 h, los niveles de ARNm y proteína de Egr1-survivina se detectaron mediante qPCR y Western-Blot. El ciclo celular y la apoptosis se detectaron mediante citometría de flujo. La transferencia Western también detectó niveles de Caspasa 3 y Caspasa 9 escindidas. Se usó YM155 como control positivo para inhibir la expresión de survivina. Los niveles de ARNm y proteína de survivina en células ECA109 y KYSE150 tratadas con shRNA de survivina Egr1 combinado con radioterapia fueron significativamente más bajos que los del grupo control en blanco, el grupo control de vector vacío y el grupo de radioterapia YM155 + (P <0,05). Mientras tanto, después de la regulación negativa de survivina, la proporción entre las fases G2 y S de las células ECA109 y KYSE150 aumentó significativamente, lo que llevó a una detención significativa de las fases G2 y S. Además, la apoptosis de las células ECA109 y KYSE150 aumentó significativamente (P <0,01). Además, los niveles de proteína de Caspasa 3 y Caspasa 9 escindidas aumentaron significativamente en el shRNA de Egr1- survivina combinado con el grupo de radioterapia. El shRNA de survivina de Egr1 combinado con radioterapia puede regular negativamente la expresión de survivina, lo que aumenta aún más la apoptosis y mejora la radiosensibilidad de las células ECA109 y KYSE150.

Tumor mutational burden and efficacy of chemotherapy in lung cancer.

PURPOSE: TMB is one of the potent biomarkers of response to immune checkpoint blockade. The association between TMB and efficacy of chemotherapy in advanced lung cancer has not been comprehensively explored. METHODS: Ninety lung cancer patients receiving first-line chemotherapy with large panel next-generation sequencing data of pre-treatment tumor tissue were identified. The effect of TMB on PFS of chemotherapy were evaluated in univariate and multivariate analyses. RESULTS: The median TMB level of lung cancer patients enrolled in this study was 9.4 mutations/Mb, with TMB levels in smokers significantly higher than those in non-smokers. All patients were divided into high TMB and low TMB groups with the cutoff of the median TMB. The patients with low TMB had longer PFS of first-line chemotherapy (median PFS 9.77 vs 6.33 months, HR = 0.523, 95% CI 0.32-0.852, log-rank P = 0.009). Subgroup analysis showed that PFS of chemotherapy favored low TMB than high TMB among subgroups of male, age < 60, NSCLC, adenocarcinoma, stage IV, ECOG PS 0, driver mutation positive, TP53 wild type and patients not receiving bevacizumab. In multivariate analysis, PFS of chemotherapy remained significantly longer in low TMB group (HR = 0.554, p = 0.036). In those patients received immunotherapy upon unsatisfactory chemotherapy, PFS of immunotherapy was much longer in high TMB group (median PFS 32.88 vs 6.62 months, HR = 0.2426, 95% CI 0.06-0.977, log-rank P = 0.04). CONCLUSIONS: TMB level of tumor tissue is a potent biomarker for efficacy of chemotherapy and immunotherapy in lung cancer. It may provide some clues for the decision of treatment strategy.

Breast cancer-associated SNP rs72755295 is a cis-regulatory variation for human EXO1.

Breast cancer is the most common malignant tumor in women. A previous genome-wide association study reports that rs72755295, a SNP locating at intron of EXO1 (exonuclease 1), is associated with breast cancer. Due to the complete linkage disequilibrium between rs72755295 and rs4149909, a nonsynonymous mutation for EXO1, rs4149909 is supposed to be the causal SNP. Since EXO1 is overexpressed in breast carcinoma samples, we hypothesized that the genetic variations in this locus might confer breast cancer risk by regulating EXO1 expression. To substantiate this, a functional genomics study was performed. The dual luciferase assay indicated that G of rs72755295 presents significantly higher relative enhancer activity than A, thus verifying that this SNP can influence gene expression in breast cell. Through chromosome conformation capture it was disclosed that the enhancer containing rs72755295 can interact with the EXO1 promoter. RNA-seq analysis indicated that EXO1 expression is dependent on the rs72755295 genotype. By chromatin immunoprecipitation, the transcription factor PAX6 (paired box 6) was recognized to bind the region spanning rs72755295. In electrophoretic mobility shift assay, G of rs72755295 displays obviously higher binding affinity with nuclear protein than A. Our results indicated that rs72755295 is a cis-regulatory variation for EXO1 and might confer breast cancer risk besides rs4149909.

Clinical relevance of miR-423-5p levels in chronic obstructive pulmonary disease patients.

OBJECTIVE: This study aimed to examine changes in miRNAs expression profile of COPD patients. METHODS: Thirty-six COPD patients as well as thirty-three healthy volunteers were recruited. Total RNAs were collected from the plasma of each participant. The differentially expressed miRNAs in COPD were screened from the GEO database. RT-qPCR was carried out to detect miRNA expression. RESULTS: In total, 9 out of 55 miRNAs were expressed differentially in COPD patients. Confirmed by RT-qPCR validation, 6 miRNAs increased while 3 miRNAs decreased. Further analysis of miR-423-5p, which has not been reported in COPD, showed that AUC for the diagnosis of COPD was 0.9651, and miR-423-5p levels was inversely correlated with the duration of smoking. CONCLUSION: The present study demonstrates that miR-423-5p is a potential marker for identifying COPD patients.

Combination of Paraconiothyrium brasiliense fabricated titanium dioxide nanoparticle and antibiotics enhanced antibacterial and antibiofilm properties: A toxicity evaluation.

Antimicrobial resistance (AMR) causes global consequences through increased mortality and economic loss. Antimicrobial drugs including nanomaterials are an emerging environmental impact. Hence, this work aimed to synthesize and characterize the titanium dioxide nanoparticles (TiO2 NPs) using the aqueous extract of endophytic fungus Paraconiothyrium brasiliense (Pb) for enhancing the antibacterial efficiency of existing standard antibiotics at minimum concentration. The FTIR and XRD results confirmed the capping of functional molecules and the crystalline nature of Pb-TiO2 NPs. The spherical-shaped TiO2 NPs with the size of 57.39 ± 13.65 nm were found in TEM analysis. The average hydrodynamic size (68.43 ± 1.49 d. nm) and the zeta potential (-19.6 ± 1.49 mV) was confirmed the stability of Pb-TiO2 NPs. Antibacterial studies revealed that bare Pb-TiO2 NPs (20 µg/mL) did not exhibit significant antibacterial activity while combination of TCH + Pb-TiO2 NPs considerably increased the inhibition of E. coli biofilm evidenced by CLSM and SEM analysis. Further, Pb-TiO2 NPs (100 µg/mL) were found to be moderately toxic to cell line (NIH3T3), red blood cells (RBC), and egg embryos. Hence, this study concluded that <50 µg/mL of TiO2 NPs can be mixed with antibiotics for enhanced antibacterial application thereby minimizing the AMR and the environmental toxicity.

Clinical relevance of miR-423-5p levels in chronic obstructive pulmonary disease patients

Abstract Objective: This study aimed to examine changes in miRNAs expression profile of COPD patients. Methods: Thirty-six COPD patients as well as thirty-three healthy volunteers were recruited. Total RNAs were collected from the plasma of each participant. The differentially expressed miRNAs in COPD were screened from the GEO database. RT-qPCR was carried out to detect miRNA expression. Results: In total, 9 out of 55 miRNAs were expressed differentially in COPD patients. Confirmed by RT-qPCR validation, 6 miRNAs increased while 3 miRNAs decreased. Further analysis of miR-423-5p, which has not been reported in COPD, showed that AUC for the diagnosis of COPD was 0.9651, and miR-423-5p levels was inversely correlated with the duration of smoking. Conclusion: The present study demonstrates that miR-423-5p is a potential marker for identifying COPD patients.

Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial.

BACKGROUND: Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19. METHODS: In this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT04421027. FINDINGS: Between June 11, 2020, and Jan 15, 2021, 1525 participants were randomly assigned to the baricitinib group (n=764) or the placebo group (n=761). 1204 (79·3%) of 1518 participants with available data were receiving systemic corticosteroids at baseline, of whom 1099 (91·3%) were on dexamethasone; 287 (18·9%) participants were receiving remdesivir. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint (odds ratio 0·85 [95% CI 0·67 to 1·08], p=0·18), with an absolute risk difference of -2·7 percentage points (95% CI -7·3 to 1·9). The 28-day all-cause mortality was 8% (n=62) for baricitinib and 13% (n=100) for placebo (hazard ratio [HR] 0·57 [95% CI 0·41-0·78]; nominal p=0·0018), a 38·2% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants. The 60-day all-cause mortality was 10% (n=79) for baricitinib and 15% (n=116) for placebo (HR 0·62 [95% CI 0·47-0·83]; p=0·0050). The frequencies of serious adverse events (110 [15%] of 750 in the baricitinib group vs 135 [18%] of 752 in the placebo group), serious infections (64 [9%] vs 74 [10%]), and venous thromboembolic events (20 [3%] vs 19 [3%]) were similar between the two groups. INTERPRETATION: Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone, and was associated with reduced mortality in hospitalised adults with COVID-19. FUNDING: Eli Lilly and Company. TRANSLATIONS: For the French, Japanese, Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

Fine-Scale Space-Time Cluster Detection of COVID-19 in Mainland China Using Retrospective Analysis.

Exploring spatio-temporal patterns of disease incidence can help to identify areas of significantly elevated or decreased risk, providing potential etiologic clues. The study uses the retrospective analysis of space-time scan statistic to detect the clusters of COVID-19 in mainland China with a different maximum clustering radius at the family-level based on case dates of onset. The results show that the detected clusters vary with the clustering radius. Forty-three space-time clusters were detected with a maximum clustering radius of 100 km and 88 clusters with a maximum clustering radius of 10 km from 2 December 2019 to 20 June 2020. Using a smaller clustering radius may identify finer clusters. Hubei has the most clusters regardless of scale. In addition, most of the clusters were generated in February. That indicates China's COVID-19 epidemic prevention and control strategy is effective, and they have successfully prevented the virus from spreading from Hubei to other provinces over time. Well-developed provinces or cities, which have larger populations and developed transportation networks, are more likely to generate space-time clusters. The analysis based on the data of cases from onset may detect the start times of clusters seven days earlier than similar research based on diagnosis dates. Our analysis of space-time clustering based on the data of cases on the family-level can be reproduced in other countries that are still seriously affected by the epidemic such as the USA, India, and Brazil, thus providing them with more precise signals of clustering.

Anti-inflammatory and neuroprotective effects of natural cordycepin in rotenone-induced PD models through inhibiting Drp1-mediated mitochondrial fission.

Accumulating evidences suggest that inflammation-mediated neurons dysfunction participates in the initial and development of Parkinson's disease (PD), whereas mitochondria have been recently recognized as crucial regulators in NLRP3 inflammasome activation. Cordycepin, a major component of cordyceps militaris, has been shown to possess neuroprotective and anti-inflammatory activity. However, the effects of cordycepin in rotenone-induced PD models and the possible mechanisms are still not fully understood. Here, we observed that motor dysfunction and dopaminergic neurons loss induced by rotenone exposure were ameliorated by cordycepin. Cordycepin also reversed Drp1-mediated aberrant mitochondrial fragmentation through increasing AMPK phosphorylation and maintained normal mitochondrial morphology. Additionally, cordycepin effectively increased adenosine 5'-triphosphate (ATP) content, mitochondrial membrane potential (MMP), and reduced mitochondrial ROS levels, as well as inhibited complex 1 activity. More importantly, cordycepin administration inhibited the expression of NLRP3 inflammasome components and the release of pro-inflammatory cytokine in rotenone-induced rats and cultured neuronal PC12 cells. Moreover, we demonstrated that the activation of NLRP3 inflammasome within neurons could be suppressed by the mitochondrial division inhibitor (Mdivi-1). Collectively, the present study provides evidence that cordycepin exerts neuroprotective effects partially through preventing neural NLRP3 inflammasome activation induced by Drp1-dependent mitochondrial fragmentation in rotenone-injected PD models.

Chamado à ação de São Paulo para prevenção e controle da hipertensão arterial, 2020

[RESUMO]. • Cerca de ¼ dos adultos têm hipertensão arterial, que é o fator de risco isolado mais importante para morte (incluídas as mortes por cardiopatia e acidente vascular cerebral). • Existem políticas eficazes que poderiam facilitar escolhas pessoais saudáveis para evitar a elevação da pressão arterial e, se plenamente implementadas, podem prevenir a ocorrência da hipertensão arterial. • É fácil rastrear e tratar a hipertensão, MAS somente cerca de 50% dos adultos hipertensos estão cientes de sua condição, e apenas cerca de 1 em cada 7 é tratado adequadamente. • A prevenção e controle da hipertensão é o principal mecanismo de prevenção e controle das doenças não transmissíveis e um modelo para outros riscos de doenças não transmissíveis. • Tratamentos eficazes com mudanças de estilo de vida e medicamentos poderiam prevenir e controlar a hipertensão arterial na maioria das pessoas se aplicados sistematicamente à população; as intervenções simples são viáveis em todos os ambientes e podem melhorar a atenção primária. • É necessária a ação continuada e urgente a fim de obter mudanças efetivas nas políticas públicas e no sistema de saúde para prevenir e controlar a hipertensão arterial.

[ABSTRACT]. • About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke). • There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring. • Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated. • Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks. • Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care. • Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.

[RESUMEN]. • Cerca de una cuarta parte de los adultos tienen hipertensión, el principal factor de riesgo de muerte (inclusive la causada por cardiopatía y accidente cerebrovascular). • Existen políticas eficaces que podrían ayudar a las personas a elegir opciones saludables para prevenir el aumento de la presión arterial; si se las aplicara plenamente, se podría evitar en gran medida el desarrollo de hipertensión. • La hipertensión es fácil de detectar y tratar, PERO solo alrededor de 50% de los adultos que presentan dicha afección son conscientes de su situación y solamente 1 de cada 7 de ellos recibe el tratamiento adecuado. • La prevención y el control de la hipertensión es el mecanismo principal para prevenir y controlar las enfermedades no transmisibles y un modelo para evitar otros riesgos de presentar dichas enfermedades. • La adopción de un modo de vida saludable y el tratamiento farmacológico efectivo podrían prevenir y controlar la hipertensión en la mayoría de las personas si se implementaran de manera sistemática en la población; en todos los entornos es posible aplicar intervenciones sencillas, que pueden usarse para mejorar la atención primaria. • Es urgente adoptar medidas sostenidas para introducir cambios eficaces en las políticas públicas y los sistemas de salud pública con miras a prevenir y controlar la hipertensión.

Llamado a la acción de San Pablo para la prevención y el control de la hipertensión arterial, 2020

[RESUMEN]. • Cerca de una cuarta parte de los adultos tienen hipertensión, el principal factor de riesgo de muerte (inclusive la causada por cardiopatía y accidente cerebrovascular). • Existen políticas eficaces que podrían ayudar a las personas a elegir opciones saludables para prevenir el aumento de la presión arterial; si se las aplicara plenamente, se podría evitar en gran medida el desarrollo de hipertensión. • La hipertensión es fácil de detectar y tratar, PERO solo alrededor de 50% de los adultos que presentan dicha afección son conscientes de su situación y solamente 1 de cada 7 de ellos recibe el tratamiento adecuado. • La prevención y el control de la hipertensión es el mecanismo principal para prevenir y controlar las enfermedades no transmisibles y un modelo para evitar otros riesgos de presentar dichas enfermedades. • La adopción de un modo de vida saludable y el tratamiento farmacológico efectivo podrían prevenir y controlar la hipertensión en la mayoría de las personas si se implementaran de manera sistemática en la población; en todos los entornos es posible aplicar intervenciones sencillas, que pueden usarse para mejorar la atención primaria. • Es urgente adoptar medidas sostenidas para introducir cambios eficaces en las políticas públicas y los sistemas de salud pública con miras a prevenir y controlar la hipertensión.

[ABSTRACT]. • About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke). • There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring. • Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated. • Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks. • Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care. • Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.

[RESUMO]. • Cerca de ¼ dos adultos têm hipertensão arterial, que é o fator de risco isolado mais importante para morte (incluídas as mortes por cardiopatia e acidente vascular cerebral). • Existem políticas eficazes que poderiam facilitar escolhas pessoais saudáveis para evitar a elevação da pressão arterial e, se plenamente implementadas, podem prevenir a ocorrência da hipertensão arterial. • É fácil rastrear e tratar a hipertensão, MAS somente cerca de 50% dos adultos hipertensos estão cientes de sua condição, e apenas cerca de 1 em cada 7 é tratado adequadamente. • A prevenção e controle da hipertensão é o principal mecanismo de prevenção e controle das doenças não transmissíveis e um modelo para outros riscos de doenças não transmissíveis. • Tratamentos eficazes com mudanças de estilo de vida e medicamentos poderiam prevenir e controlar a hipertensão arterial na maioria das pessoas se aplicados sistematicamente à população; as intervenções simples são viáveis em todos os ambientes e podem melhorar a atenção primária. • É necessária a ação continuada e urgente a fim de obter mudanças efetivas nas políticas públicas e no sistema de saúde para prevenir e controlar a hipertensão arterial.

Llamado a la acción de San Pablo para la prevención y el control de la hipertensión arterial, 2020 / São Paulo call to action for the prevention and control of high blood pressure: 2020 / Chamado à ação de São Paulo para prevenção e controle da hipertensão arterial, 2020

RESUMEN Cerca de una cuarta parte de los adultos tienen hipertensión, el principal factor de riesgo de muerte (inclusive la causada por cardiopatía y accidente cerebrovascular). Existen políticas eficaces que podrían ayudar a las personas a elegir opciones saludables para prevenir el aumento de la presión arterial; si se las aplicara plenamente, se podría evitar en gran medida el desarrollo de hipertensión. La hipertensión es fácil de detectar y tratar, PERO solo alrededor de 50% de los adultos que presentan dicha afección son conscientes de su situación y solamente 1 de cada 7 de ellos recibe el tratamiento adecuado. La prevención y el control de la hipertensión es el mecanismo principal para prevenir y controlar las enfermedades no transmisibles y un modelo para evitar otros riesgos de presentar dichas enfermedades. La adopción de un modo de vida saludable y el tratamiento farmacológico efectivo podrían prevenir y controlar la hipertensión en la mayoría de las personas si se implementaran de manera sistemática en la población; en todos los entornos es posible aplicar intervenciones sencillas, que pueden usarse para mejorar la atención primaria. Es urgente adoptar medidas sostenidas para introducir cambios eficaces en las políticas públicas y los sistemas de salud pública con miras a prevenir y controlar la hipertensión.

ABSTRACT About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke). There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring. Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated. Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks. Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care. Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.

RESUMO Cerca de » dos adultos têm hipertensão arterial, que é o fator de risco isolado mais importante para morte (incluídas as mortes por cardiopatia e acidente vascular cerebral). Existem políticas eficazes que poderiam facilitar escolhas pessoais saudáveis para evitar a elevação da pressão arterial e, se plenamente implementadas, podem prevenir a ocorrência da hipertensão arterial. É fácil rastrear e tratar a hipertensão, MAS somente cerca de 50% dos adultos hipertensos estão cientes de sua condição, e apenas cerca de 1 em cada 7 é tratado adequadamente. A prevenção e controle da hipertensão é o principal mecanismo de prevenção e controle das doenças não transmissíveis e um modelo para outros riscos de doenças não transmissíveis. Tratamentos eficazes com mudanças de estilo de vida e medicamentos poderiam prevenir e controlar a hipertensão arterial na maioria das pessoas se aplicados sistematicamente à população; as intervenções simples são viáveis em todos os ambientes e podem melhorar a atenção primária. É necessária a ação continuada e urgente a fim de obter mudanças efetivas nas políticas públicas e no sistema de saúde para prevenir e controlar a hipertensão arterial.