Calcium(II)-Mediated Three-Component Selenylation of gem-Difluoroalkenes: Access to α,α-Difluoroalkyl-ß-selenides.

A calcium-mediated three-component selenylation of gem-difluoroalkenes using alcohols as nucleophiles and N-(phenylseleno)phthalimide as the selenylation agent has been developed for the efficient synthesis of various α,α-difluoroalkyl-ß-selenides. This selenylation reaction exhibits broad substrate and functional group tolerance, along with high levels of chemo- and regioselectivity. Additionally, the synthetic utility of the developed transformation in the late-stage functionalization of drug molecules was demonstrated.

Association of Serum Vitamin D With Periodontal Disease.

OBJECTIVE: There are conflicting reports on the relationship between vitamin D and periodontal disease. Our research is intended to further analyse the association between serum 25(OH)D3, a vitamin D precursor and periodontal disease based on a large national survey sample in Japan. METHODS: We downloaded the 2009-2018 National Health and Nutrition Examination Survey (NHANES) cycle, which included a total of 23,324 samples. Logistic regression of factors influencing perioral disease including periodntal disease, and subgroup logistic regression were performed to analyse the relationship between serum vitamin D and perioral disease, using WTMEC2YR as weights for regression analysis. Then machine learning model-based prediction of perioral disease onset was performed, and the machine learning algorithms used included boost tree, artificial neural network, AdaBoost, and random forest. RESULTS: We evaluated the vitamin D, age, sex, race, education, marriage, body mass index, ratio of family income to poverty (PIR), smoking, alcohol consumption, diabetes, and hypertension as variables in the included samples. Vitamin D was negatively associated with perioral disease; compared with Q1, the odds ratios and 95% CI were 0.8 (0.67-0.96) for Q2, 0.84 (0.71-1.00) for Q3, and 0.74 (0.6-0.92) for Q4 (P for trend <.05), respectively. The results of the subgroup analysis showed that the effect of 25(OH)D3 on periodontal disease was more pronounced in women younger than 60 years. Based on the accuracy and receiver operating characteristic curve, we concluded that a boost tree was a relatively good model to predict periodontal disease. CONCLUSIONS: Vitamin D might be a protective factor for periodontal disease, and boost tree analysis we emplyed was a relatively good model to predict perioral disease.

Efficacy and safety of direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism: A systematic review and Bayesian network meta-analysis / Eficacia y seguridad de los anticoagulantes orales directos para el tratamiento de la tromboembolia venosa asociada al cáncer: una revisión sistemática y un metaanálisis en red bayesiana

Introduction: Direct oral anticoagulants (DOACs) could effectively prevent the occurrence of cancer-associated venous thromboembolism (CAVTE), which incidence rate was estimated to be 4–20%. But the efficacy and safety remain controversial between DOACs and low molecular weight heparin (LMWH).Materials and methodsPubMed, Cochrane Library, Embase, ClinicalTrials.gov databases for randomized controlled trials (RCTs) were systematically searched from inception to March 15, 2022. A random-effects model was used to report the odds ratio (OR) and 95% confidence interval (CI) for both direct and network meta-analyses.ResultsSeven studies were included totaling 3242 patients. A lower rate of recurrence VTE was noted in the DOACs compared with LMWH (OR 0.62, 95% CI 0.47–0.82, I2=0.0%). The aspect of major bleeding (MB) was similar (OR 1.30, 95% CI 0.77–2.18, I2=34.9%). When assessing clinically relevant nonmajor bleeding (CRNMB) (OR 1.61, 95% CI 1.17–2.22, I2=20.7%) and clinically relevant bleeding (CRB) (OR 1.39, 95% CI 1.11–1.74, I2=0.0%), a higher risk of events was observed in DOACs. In subgroup analyses, the MB of gastrointestinal and genitourinary malignancies had a higher rate in the DOACs. For ranking, apixaban ranked the first in prevention of VTE and reducing MB events. Edoxaban had the highest risk drug in MB. In terms of CRNMB and CRB, LMWH showed the lowest risk.ConclusionsCompared with LMWH, DOACs seemed to have a decreased risk of recurrence VTE while increasing CRNMB and CRB. DOACs and LMWH were equivalent to the aspect of MB, but DOACs had a higher MB risk in patients with gastrointestinal and genitourinary malignancies. Apixaban may be the lowest risk compared to the other DOACs in precaution of VTE and reducing bleeding events. (AU)

Introducción: Los anticoagulantes orales directos (ACOD) son eficaces en la prevención de la tromboembolia venosa (TEV) relacionada con el cáncer, cuya tasa de incidencia se estima en 4-20%. Sin embargo, la eficacia y seguridad de ACOD y heparina de bajo peso molecular (HBPM) siguen siendo controvertidas.Materiales y métodosDesde el inicio hasta el 15 de marzo de 2022 se realizaron búsquedas sistemáticas en las bases de datos de ensayos controlados aleatorios (ECA) en PubMed, The Cochrane Library, Embase, ClinicalTrials.gov. Se utilizó el modelo de efectos aleatorios para informar la razón de probabilidades (RP) y los intervalos de confianza (IC) de 95% para los metaanálisis directos y de red.ResultadosSe incluyeron siete estudios con un total de 3.242 pacientes. En comparación con HBPM, los ACOD tienen una tasa más baja de recurrencia de TEV (OR 0,62, IC 95%: 0,47 a 0,82, I2 = 0,0%). La frecuencia de hemorragias mayores fue similar (OR 1,30, IC 95% 0,77 a 2,18, I2 = 34,9%). Se observó un mayor riesgo de eventos en los ACOD. Cuando se evaluaron las hemorragias no mayores clínicamente relevantes (CRNMB) (OR 1,61, IC 95%: 1,17 a 2,22, I2 = 20,7%) y las hemorragias clínicamente relevantes (OR 1,39, IC 95%: 1,11 a 1,74, I2 = 0,0%), En los análisis de subgrupos, las hemorragias mayores en las neoplasias malignas gastrointestinales y genitourinarias fueron más frecuentes con los ACOD. Apixabán ocupó el primer lugar en la prevención de TEV y la reducción de eventos hemorrágicos mayores. Edoxabán tuvo el mayor riesgo de hemorragias mayores. Las HBPM demostraron tener menor riesgo de hemorragias mayores clínicamente relevantes y hemorragias clínicamente relevantes. (AU)

Efficacy and safety of direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism: A systematic review and Bayesian network meta-analysis.

INTRODUCTION: Direct oral anticoagulants (DOACs) could effectively prevent the occurrence of cancer-associated venous thromboembolism (CAVTE), which incidence rate was estimated to be 4-20%. But the efficacy and safety remain controversial between DOACs and low molecular weight heparin (LMWH). MATERIALS AND METHODS: PubMed, Cochrane Library, Embase, ClinicalTrials.gov databases for randomized controlled trials (RCTs) were systematically searched from inception to March 15, 2022. A random-effects model was used to report the odds ratio (OR) and 95% confidence interval (CI) for both direct and network meta-analyses. RESULTS: Seven studies were included totaling 3242 patients. A lower rate of recurrence VTE was noted in the DOACs compared with LMWH (OR 0.62, 95% CI 0.47-0.82, I2=0.0%). The aspect of major bleeding (MB) was similar (OR 1.30, 95% CI 0.77-2.18, I2=34.9%). When assessing clinically relevant nonmajor bleeding (CRNMB) (OR 1.61, 95% CI 1.17-2.22, I2=20.7%) and clinically relevant bleeding (CRB) (OR 1.39, 95% CI 1.11-1.74, I2=0.0%), a higher risk of events was observed in DOACs. In subgroup analyses, the MB of gastrointestinal and genitourinary malignancies had a higher rate in the DOACs. For ranking, apixaban ranked the first in prevention of VTE and reducing MB events. Edoxaban had the highest risk drug in MB. In terms of CRNMB and CRB, LMWH showed the lowest risk. CONCLUSIONS: Compared with LMWH, DOACs seemed to have a decreased risk of recurrence VTE while increasing CRNMB and CRB. DOACs and LMWH were equivalent to the aspect of MB, but DOACs had a higher MB risk in patients with gastrointestinal and genitourinary malignancies. Apixaban may be the lowest risk compared to the other DOACs in precaution of VTE and reducing bleeding events.

The association of non-vitamin K antagonist oral anticoagulants vs. warfarin and the risk of fractures for patients with atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: The fracture risks of non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin in patients with atrial fibrillation (AF) remain controversial. METHODS: PubMed, Cochrane Library, EMBASE, Clinical Trials.gov databases for RCTs, and cohort studies were systematically searched from inception to 10 June 2021. RESULTS: Twelve-two studies met the inclusion criteria and 477,821 patients were included. Warfarin increased the risk of fracture in AF patients compared with NOACs in overall any fracture (RR = 0.79; 95% CI = 0.70-10.88; p = 0.00), osteoporotic fracture (RR = 0.746; 95% CI = 0.630-0.883; p = 0.001). No significant difference was observed in the hip or pelvic fracture, vertebral fracture, extremity fracture, wrist fracture, femoral neck fracture, and ankle fracture. In subgroup analyses based on several aspects, NOACs were associated with a significant reduction in any fracture (standard dosage NOACs, cohort studies, elderly patients, rivaroxaban in RCTs, dabigatran, rivaroxaban, and apixaban in cohort studies), in the hip/pelvic fracture (follow-up time ≤1 year, cohort studies), and osteoporotic fracture (cohort studies). CONCLUSION: NOACs were associated with a significantly lower risk of any fracture and osteoporotic fracture compared to warfarin. This benefit was also observed in specific NOACs types of dabigatran, rivaroxaban, and apixaban. However, whether NOACs had a less fracture risk than warfarin on the other risk of fractures was still uncertain.

A Biological Insight into the Susceptibility to Influenza Infection in Junior Rats by Comprehensive Analysis of lncRNA Profiles.

Long noncoding RNAs (lncRNAs) have been reported to participate in regulating many biological processes, including immune response to influenza A virus (IAV). However, the association between lncRNA expression profiles and influenza infection susceptibility has not been well elucidated. Here, we analyzed the expression profiles of lncRNAs, miRNAs, and mRNAs among IAV-infected adult rat (IAR), normal adult rat (AR), IAV-infected junior rat (IJR), and normal junior rat (JR) by RNA sequencing. Compared with differently expressed lncRNAs (DElncRNAs) between AR and IAR, 24 specific DElncRNAs were found between IJR and JR. Then, based on the fold changes and P value, the top 5 DElncRNAs, including 3 upregulated and 2 downregulated lncRNAs, were chosen to establish a ceRNA network for further disclosing their regulatory mechanisms. To visualize the differentially expressed genes in the ceRNA network, GO and KEGG pathway analysis was performed to further explore their roles in influenza infection of junior rats. The results showed that the downregulated DElncRNA-target genes were mostly enriched in the IL-17 signaling pathway. It indicated that the downregulated lncRNAs conferred the susceptibility of junior rats to IAV via mediating the IL-17 signaling pathway.

The Role of Respiratory Flora in the Pathogenesis of Chronic Respiratory Diseases.

Large quantities of bacteria, including Firmicutes, Actinobacteria, and Bacteroidetes, colonize the surface of the respiratory mucosa of healthy people. They interact and coexist with the local mucosal immune system of the human airway, maintaining the immune stability and balance of the respiratory system. While suffering from chronic respiratory diseases, the microbial population in the airway changes and the proportion of Proteobacteria is increased in patients with asthma. The abundance of the microbial population in patients with chronic obstructive pulmonary disease (COPD) is decreased, and conversely, the proportion of Firmicutes and Proteobacteria increased. The diversity of airway microorganisms in cystic fibrosis (CF) patients is decreased, while pathogenic bacteria and conditional pathogenic bacteria are proliferated in large numbers. The proportion of Firmicutes and Proteobacteria is increased in patients with upper airway cough syndrome (UACS), which replaces the dominance of Streptococcus and Neisseria in the pharynx of a normal population. Therefore, a clear understanding of the immune process of the airway flora and the immune dysfunction of the flora on the pathogenesis of chronic respiratory diseases can provide new ideas for the prevention and treatment of human respiratory diseases.

Quinonoids: Therapeutic Potential for Lung Cancer Treatment.

Lung cancer is the leading cause of cancer-related deaths worldwide. Owing to its high incidence and mortality, the development and discovery of novel anticancer drugs is of great importance. In recent years, many breakthroughs have been achieved in the search for effective anticancer substances from natural products. Many anticancer drugs used clinically and proven to be effective are derived from natural products. Quinonoids, including naphthoquinones, phenanthrenequinones, benzoquinones, and anthraquinones, constitute a large group of natural bioactive compounds that widely exist in higher and lower plant species. Given that most of these compounds possess anticancer effects, they are applied in many cancer studies, especially in lung cancer research. They can promote apoptosis, induce autophagy, and inhibit proliferation, angiogenesis, and cell invasion and migration. Some drugs can enhance anticancer effects when combined with other drugs. Thus, quinonoids have broad application prospects in the treatment of lung cancer. Here, we summarize the previous studies on the antilung cancer activities of quinonoids together with their underlying mechanisms and analyze the common research targets with different effects so as to provide references for the discovery of quinonoids against lung cancer.

A quantification model for the structure of clay materials.

BACKGROUND: In this paper, the quantification for clay structure is explicitly explained, and the approach and goals of quantification are also discussed. The authors consider that the purpose of the quantification for clay structure is to determine some parameters that can be used to quantitatively characterize the impact of clay structure on the macro-mechanical behaviour. METHODS: According to the system theory and the law of energy conservation, a quantification model for the structure characteristics of clay materials is established and three quantitative parameters (i.e., deformation structure potential, strength structure potential and comprehensive structure potential) are proposed. And the corresponding tests are conducted. RESULTS: The experimental results show that these quantitative parameters can accurately reflect the influence of clay structure on the deformation behaviour, strength behaviour and the relative magnitude of structural influence on the above two quantitative parameters, respectively. CONCLUSIONS: These quantitative parameters have explicit mechanical meanings, and can be used to characterize the structural influences of clay on its mechanical behaviour.

[Study on effects of kurarinol combined with glycyrrhizic acid on cellular immunity of patients with chronic hepatitis B].

OBJECTIVE: To explore effects of kurarinol combined with Diammonium Glycyrrhizinate on specific cellular immunity of patients with chronic hepatitis B (CHB). METHODS: Sixty-three CHB patients were randomly divided into two groups, 32 cases in group of kurarinol combined with Diammonium Glycyrrhizinate group (combined therapy group) were treated with 600 mg kurarinol glucose injection intravenously, once a day for one month, then 200 mg kurarinol capsule was used orally, three times a day for two months. 150 mg Diammonium Glycyrrhizinate for Injection was added to 250 ml 10% glucose injection for intravenous drip, once a day for one month, then 150 mg Diammonium Glycyrrhizinate capsule was used orally, three times a day for two months; 31 case in kurarinol group (single drug group) only used kurarinol, methods and dosage were the same as those of treatment group. HBV specific CTL, T cell subgroups, change of Th1 and Th2 level, HBV-DNA and HBeAg negative rate of the two groups were compared. RESULTS: Three months after treatment, HBV specific CTL, CD4 + and Th1 of combined therapy group were higher than those before treatment, and higher than those of single drug group after treatment (P < 0.01). CONCLUSION: HBV-DNA and HBeAg negative rate between the two groups had no statistic significance (P > 0.05). CONCLUSION: Kurarinol combined with Diammonium Glycyrrhizinate can further increase HBV specific CTL, CD4+ and Th1 level of CHB patients.

Effect of oxymatrine on specific cytotoxic T lymphocyte surface programmed death receptor-1 expression in patients with chronic hepatitis B.

BACKGROUND: Oxymatrine has certain antiviral effects in the treatment of chronic hepatitis B (CHB), but its exact mechanism is unclear. The objective of the present study was to explore oxymatrine's antiviral mechanism by studying its effect on the hepatitis B virus (HBV) specific cytotoxic T lymphocyte (CTL) surface programmed death receptor-1 (PD-1) expression in CHB patients. METHODS: Sixty-five CHB patients who had HBV DNA(3)10(4) copies/ml, positive HBeAg, positive human leukocyte antigen (HLA)-A2, alanine aminotransferase (ALT) > 2 x upper limit of normal value (ULN) were randomly divided into two groups: treatment group (n = 33), treated with an intravenous infusion of 600 mg oxymatrine in glucose solution once a day for a month, then with a 200 mg oxymatrine oral capsule three times a day, and a 200 mg silibin meglumine tablet three times a day; control group (n = 32) patients were treated only with silibin meglumine tablet, method and dosage were the same as those of treatment group. Three months later, peripheral blood HBV-specific CTL surface PD-1 expression, HBV-specific CTL level, HBV DNA, HBeAg, and results of liver function tests were analyzed and compared. RESULTS: Three months post-treatment, in the treatment group, peripheral blood HBV-specific CTL surface PD-1 expression ((19.42 ± 15.94)%) decreased significantly compared to the pretreatment level ((31.30 ± 24.06)%; P < 0.05), and decreased significantly compared to that of control group three months after treatment ((29.45 ± 21.62)%; P < 0.05). HBV-specific CTL level ((0.42 ± 0.07)%) significantly increased compared with the pretreatment ((0.29 ± 0.15)%; P < 0.01), and the control group posttreatment level was (0.31 ± 0.15)% (P < 0.05). HBV DNA level in 11 cases became negative (HBV DNA < 500 copies/ml, 33.33%), which was higher than that of the control group after treatment (two cases, 6.25%; χ(2) = 7.45, P < 0.01), HBeAg of nine cases turned negative (27.27%), which was higher than that of the control group after treatment (one case, 3.13%; χ(2) = 7.27, P < 0.01). CONCLUSION: Oxymatrine could downregulate peripheral blood HBV-specific CTL surface PD-1 expression in CHB patients, increase HBV-specific CTL level, which may be one of the possible mechanisms by which oxymatrine clears or inhibits HBV in CHB patients.

[Effect of kurarinol on peripheral blood CTL surface PD-1 expression of patients with chronic hepatitis B].

OBJECTIVE: To explore the anti-viral mechanism of kurarinol through studying its influence on cytotoxic T lymphocyte (CTL) surface program death receptor-1 (PD-1) expression of patients with chronic hepatitis B (CHB). METHODS: 69 cases of CHB, HBV DNA > or = 10(4) copies/ml, HBeAg positive, human leukocyte antigen (HLA)-A2 positive, alanine aminotransferase (ALT) > 2 x upper limit of normal value(ULN).69 cases were randomly divided into two groups:34 cases in treatment group,600 mg of kurarinol glucose injection was used for intravenous dripping, once a day, one month later, 200 mg of kurarinol capsule was used orally,three times a day and 200 mg of silybin meglumine tablet was used orally, three times a day. 35 cases in control group, only silibin meglumine tablet was used, method and dosage were the same as those of treatment group. Three months later, their peripheral blood HBV specific CTL surface PD-1 expression, non-specific CTL surface PD-1 expression and level of HBV specific CTL,HBV DNA and HBeAg negative rate and liver functions were analyzed and compared. RESULTS: 3 months after treatment, peripheral blood HBV specific CTL surface PD-1 expression of the treatment group decreased compared with that before treatment (t = 2.39, P < 0.05), it also decreased compared with that of the control group 3 months after treatment (t = 2.26, P < 0.05), HBV specific CTL increased compared with that before treatment( t = 3.01, P < 0.01), it also increased compared with that of the control group after treatment (t = 2.65, P < 0.05). There was no significant difference of non-specific CTL surface PD-1 expression compared with that before treatment (P > 0.05), and there was no significant difference compared with that of the control group after treatment (P > 0.05). HBV DNA of 11 cases (32.5%) turned negative ( HBV DNA < 500 copies/ ml), higher than that of the control group after treatment (2 cases, 5.71%) chi2 = 7.99, P < 0.01, HBeAg of 9 cases (26.47%) turned negative, higher than that of the control group after treatment (1 case, 2.86%), chi2 = 7.75, P < 0.01. CONCLUSION: Kurarinol can increase level of HBV specific CTL by down-regulating peripheral blood HBV specific CTL surface PD-1 expression of CHB patients, which may be one of the possible mechanisms that kurarinol can remove or inhibit HBV of CHB patients.

Comparison and significance of specific and non-specific cellular immunity in patients with chronic hepatitis B caused by infection with genotypes B or C of hepatitis B virus.

The present study was designed to investigate possible relationships between the genotypes of hepatitis B virus (HBV) and the HBV-specific cytotoxic T lymphocyte (CTL) responses. HBV genotypes, HBV specific CTL HBV DNA and other markers of HBV infection were determined in 138 patients with chronic hepatitis B. The results showed that the patients infected with genotype C (n=62) had a significantly lower HBV-specific CTL response than those who were infected with HBV genotype B (P<0.01). HBV DNA titer was higher in patients infected with HBV genotype C than in those infected with HBV genotype B (P<0.01). Both alanine aminotransferase (ALT) and total bilirubin (TBIL) were higher in HBV genotype C infected patients than in those infected with genotype B (P<0.01 and <0.05, respectively). These results suggest that compared with CHB patients infected with HBV genotype B, the higher HBV DNA level and more severe liver damages in the patients infected with genotype C of HBV may be associated with genotype C of the virus.