Sublingual administration of atropine eye drops for treating sialorrhea after stroke: A randomized controlled trial.

BACKGROUND: Sialorrhea is a common concern in patients with swallowing disorders after stroke. Atropine sulfate blocks the muscarinic receptors in the salivary glands and leads to reduced saliva production. OBJECTIVE: The present study aimed to assess the safety, efficacy, and tolerability of sublingual administration of atropine eye drops for treating sialorrhea after stroke. DESIGN: This was a prospective cohort study. SETTING: This study was conducted at Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Hubei Province, China. POPULATION: Stroke patients with sialorrhea were analyzed. METHODS: One hundred stroke patients with sialorrhea were randomly assigned to the control group and the test group (n = 50 per group). The control group received routine swallowing rehabilitation training and neuromuscular electrical stimulation. The test group received therapy with 1% atropine eye drops, wherein one drop was administered sublingually 3 times per day. The Sialorrhea Scoring Scale and the incidence of adverse events were used to compare the severity of sialorrhea in the two groups. RESULTS: The mean (standard deviation) sialorrhea score improved from 5.12 for the control group with routine rehabilitation training to 3.94 for the test group with atropine eye drop administration (P < 0.01). No significant differences in the incidence of adverse events were observed between the two groups. CONCLUSIONS: The sublingual administration of 1% atropine eye drops three times per day can reduce the degree of sialorrhea to an extent more than that achieved with routine rehabilitation training; thus, this approach is effective, safe, and minimally invasive for treating sialorrhea after stroke.

Novel deoxyvasicinone and tetrahydro-beta-carboline hybrids as inhibitors of acetylcholinesterase and amyloid beta aggregation.

A novel series of deoxyvasicinone-tetrahydro-beta-carboline hybrids were synthesized and evaluated as acetylcholinesterase (AChE) and ß-amyloid peptide (Aß) aggregation inhibitors for the treatment of Alzheimer's disease. The results revealed that the derivatives had multifunctional profiles, including AChE inhibition, Aß1-42 aggregation inhibition, and neuroprotective properties. Inspiringly, hybrids 8b and 8d displayed excellent inhibitory activities against hAChE (IC50 = 0.93 and 1.08 nM, respectively) and Aß1-42 self-aggregation (IC50 = 19.71 and 2.05 µM, respectively). In addition, 8b and 8d showed low cytotoxicity and good neuroprotective activity against Aß1-42-induced damage in SH-SY5Y cells.

The pomegranate (Punica granatum L.) genome provides insights into fruit quality and ovule developmental biology.

Pomegranate (Punica granatum L.) has an ancient cultivation history and has become an emerging profitable fruit crop due to its attractive features such as the bright red appearance and the high abundance of medicinally valuable ellagitannin-based compounds in its peel and aril. However, the limited genomic resources have restricted further elucidation of genetics and evolution of these interesting traits. Here, we report a 274-Mb high-quality draft pomegranate genome sequence, which covers approximately 81.5% of the estimated 336-Mb genome, consists of 2177 scaffolds with an N50 size of 1.7 Mb and contains 30 903 genes. Phylogenomic analysis supported that pomegranate belongs to the Lythraceae family rather than the monogeneric Punicaceae family, and comparative analyses showed that pomegranate and Eucalyptus grandis share the paleotetraploidy event. Integrated genomic and transcriptomic analyses provided insights into the molecular mechanisms underlying the biosynthesis of ellagitannin-based compounds, the colour formation in both peels and arils during pomegranate fruit development, and the unique ovule development processes that are characteristic of pomegranate. This genome sequence provides an important resource to expand our understanding of some unique biological processes and to facilitate both comparative biology studies and crop breeding.

Effect of Magnesium Bond on the Competition Between Hydrogen and Halogen Bonds and the Induction of Proton and Halogen Transfer.

HOX (X=Cl, Br, I, and At) can engage in either a H-bond (HB) or halogen bond (XB) with a base-like HCN, NH3 , and imidazole. Although the former is energetically preferred for X=Cl and Br, it is the XB that is more stable for At, with I showing little preference. MgY2 forms a Mg-bond with the O atom of HOX, which grows stronger in the order X=Cl

Brief cognitive-behavioural therapy for patients in the community with schizophrenia: randomised controlled trial in Beijing, China.

BackgroundBrief cognitive-behavioural therapy (CBT) is an emerging treatment for schizophrenia in community settings; however, further trials are needed, especially in non-Western countries.AimsTo test the effects of brief CBT for Chinese patients with schizophrenia in the community (trial registration: ChiCTR-TRC-13003709).MethodA total of 220 patients with schizophrenia from four districts of Beijing were randomly assigned to either brief CBT plus treatment as usual (TAU) or TAU alone. Patients were assessed at baseline, post-treatment and at 6- and 12-month follow-ups by raters masked to group allocation.ResultsAt the post-treatment assessment and the 12-month follow-up, patients who received brief CBT showed greater improvement in overall symptoms, general psychopathology, insight and social functioning. In total, 37.3% of those in the brief CBT plus TAU group experienced a clinically significant response, compared with only 19.1% of those in the TAU alone group (P = 0.003).ConclusionsBrief CBT has a positive effect on Chinese patients with schizophrenia in the community.

Comparison of σ-Hole and π-Hole Tetrel Bonds Formed by Pyrazine and 1,4-Dicyanobenzene: The Interplay between Anion-π and Tetrel Bonds.

The σ-hole tetrel bond in pyrazine/1,4-dicyanobenzene⋅⋅⋅TH3 F (T=C and Si) and the π-hole tetrel bond in pyrazine/1,4-dicyanobenzene⋅⋅⋅F2 TO have been compared. The π-hole tetrel bond is stronger than the corresponding σ-hole tetrel bond, with a larger interaction energy, shorter binding contact, greater electron density, and bigger charge transfer. Pyrazine forms a more stable tetrel-bonded complex than 1,4-dicyanobenzene even though the nitrogen atom in the former has a smaller negative electrostatic potential than the latter. An interesting cooperative effect was found when anion-π and tetrel-bond interactions coexisted in the same multicomponent complex of X- ⋅⋅⋅pyrazine/1,4-dicyanobenzene⋅⋅⋅TH3 F/F2 TO (X=F, Cl, and Br). Both interactions displayed a positive cooperative effect, as shown by the larger interaction energies, shorter binding separations, and greater electron densities. The enhancement in the tetrel bond is dependent on the strength of the anion-π interaction and it becomes larger in the order Br-

Validity and reliability of the toxic leadership behaviors of nurse managers scale among Chinese nurses.

Objectives: Toxic leadership is increasingly becoming common in the nursing field, but the measurement tools are lacking. Therefore, this study aimed to translate the toxic leadership behaviors of nurse managers (ToxBH-NM) scale into Chinese and test its psychometric properties among Chinese nurses. Methods: The data for this study were obtained from a cross-sectional survey of 1,195 nurses. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to examine the structural validity of the ToxBH-NM. The following psychometric properties of the scale were assessed: content validity, criterion validity, internal consistency reliability, and test-retest reliability. Results: The Chinese version of the ToxBH-NM (C-ToxBH-NM) scale had two dimensions and 30 items. The correlation coefficients between the scores of each item and the total scores were 0762-0.922 (p < 0.001), and the range of the CR determination values of all the items were 8.610-18.998, with statistical significance (p < 0.001). The total content validity index (CVI) was 0.996, the average CVI was 0.996, and the item-level CVI was 0.875-1.000. Two common factors were identified in the EFA, and 81.074% of the variation was explained cumulatively. The CFA showed that all the fitting indexes reached the standard, and the model fit degree was good. When the Chinese version of the Destructive Leadership Scale was used as calibration, the correlation coefficient was 0.378 (p < 0.001). The Cronbach's alpha coefficients of the overall scale were 0.989 and of the two dimensions were 0.969 and 0.987, respectively, with a split-half reliability of 0.966 and test-retest reliability of 0.978. Conclusion: The research results show that the C-ToxBH-NM scale has good reliability and validity and can be used to evaluate the severity of toxic leadership behavior among nursing managers.

Targeting cell death in NAFLD: mechanisms and targeted therapies.

Nonalcoholic fatty liver disease (NAFLD) is a group of chronic liver disease which ranges from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and is characterized by lipid accumulation, inflammation activation, fibrosis, and cell death. To date, a number of preclinical studies or clinical trials associated with therapies targeting fatty acid metabolism, inflammatory factors and liver fibrosis are performed to develop effective drugs for NAFLD/NASH. However, few therapies are cell death signaling-targeted even though the various cell death modes are present throughout the progression of NAFLD/NASH. Here we summarize the four types of cell death including apoptosis, necroptosis, pyroptosis, and ferroptosis in the NAFLD and the underlying molecular mechanisms by which the pathogenic factors such as free fatty acid and LPS induce cell death in the pathogenesis of NAFLD. In addition, we also review the effects of cell death-targeted therapies on NAFLD. In summary, our review provides comprehensive insight into the roles of various cell death modes in the progression of NAFLD, which we hope will open new avenues for therapeutic intervention.

[Clinical Characteristics and Prognosis of Patients with Primary Testicular Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To analyze the clinical manifestations, therapeutic response and prognosis of patients with primary testicular diffuse large B-cell lymphoma (PT-DLBCL). METHODS: Thirty-eight patients with PT-DLBCL were enrolled, who hospitalized from January 2010 to April 2021, and their clinical characteristics, treatment regimen and efficacy were collected and analyzed retrospectively. RESULTS: The median age of the patients was 56 years old (ranged from 38 to 79 years). There were 4 cases (10.5%) with bilateral lesions, 13 cases (34.2%) with left lesions, and 21 cases (55.3%) right lesions. There were 2 cases(5.3%) with B symptoms, 6 cases (15.8%) of germinal center B-cell-like(GCB) subtype and 32 cases(84.2%) of non-GCB subtype. Efficacy was evaluated in 36 cases, including 10 cases with CHOP regimen, 21 cases with R-CHOP regimen (7 cases were treated with rituximab combined with high-dose methotrexate injection chemotherapy at intervals of R-CHOP regimen), and 5 cases with other regimens. In 36 patients, the efficacy evaluation of initial chemotherapy showed that the overall response rate (ORR) was 86.1%, 29 cases (80.6%) reached complete response (CR), and 2 cases (5.5%) reached partial response (PR). The R-CHOP group was superior to CHOP group in ORR (95.2% vs 60.0%, P=0.027) and CR (90.4% vs 50.0%, P=0.022). Of the 36 patients, 7 cases had central nervous system(CNS) recurrence and 4 cases had contralateral testicular recurrence. Compared with the CHOP group, the CNS recurrence rate in the R-CHOP group was significantly lower (4.8% vs 50.0%, P=0.007), and the testicular recurrence rate in the R-CHOP group was also lower than the CHOP group, but the difference was not statistically significant (4.8% vs 30.0%, P=0.087). The median follow-up time was 27(3-135) months, and the 5-year PFS and OS were 71% and 74%, respectively. Kaplan-Meier univariate analysis showed that the R-CHOP regimen significantly improved the patients' PFS (P=0.024) and OS (P=0.025) compared with the CHOP regimen. CONCLUSION: PT-DLBCL is mainly treated with comprehensive treatment. Compared with CHOP regimen, R-CHOP regimen can improve the CR rate and ORR, reduce CNS recurrence and contralateral testicular recurrence, and improve the patients' survival. Patients may benefit from high-dose methotrexate combined with rituximab interlaced with R-CHOP regimen.

[Clinical Characteristics and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm].

OBJECTIVE: To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN). METHODS: The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively. RESULTS: 4 patients had bone marrow， spleen and lymph nodes involvement， 2 patients had skin lesions， and 3 patients had central nervous system infiltration． Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients， and CD304 in 3 patients． One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again． One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine. CONCLUSION: The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.

A Mendelian randomization study of the effect of tea intake on breast cancer.

Background: The relationship between tea consumption and the risk of breast cancer is inconsistent in previous observational studies and is still in dispute. We intended to detect the causal association between tea consumption and breast cancer risk using two-sample Mendelian randomization (MR) analysis. Materials and methods: The summary statistics of tea consumption was obtained from the UK Biobank Consortium with 349,376 individuals and breast cancer information was obtained from the Breast Cancer Association Consortium (BCAC) (122,977 cases and 105,974 non-cases). Sensitivity analyses of evaluating the influence of outliers and pleiotropy effects were performed by a variety of MR methods under different model assumptions. Results: After potentially excluding pleiotropic single nucleotide polymorphisms (SNPs) using the MR Pleiotropy RESidual Sum and Outlier method, the odds ratio (OR) for per extra daily cup of tea intake for overall, estrogen receptor (ER)-positive, and ER-negative breast cancer risk was 1.029 [95% confidence interval (CI) = 0.983-1.077, P = 0.2086], 1.050 (95% CI = 0.994-1.109, P = 0.078), and 1.081 (95% CI = 0.990-1.103, P = 0.6513), respectively. The results were consistent with a sensitivity analysis that excluded SNPs associated with other phenotypes, manifesting that the findings were convincing and robust. Moreover, in the multivariable MR analysis, the null associations for breast cancer risk remained after adjusting for smoking and alcohol consumption separately or together. Conclusion: Our MR results based on genetic data did not support a causal relationship between tea consumption and breast cancer risk.

A Droplet Digital PCR Based Approach for Identification and Quantification of Porcine and Chicken Derivatives in Beef.

Adulteration of high-value beef with lower-priced alternatives is a world-wide problem resulting in consumers' distrust and market chaos. Therefore, effective methods for the identification and quantification of adulterated beef products are urgently needed. In this study, we developed a reliable droplet digital PCR (ddPCR) method targeting the single-copy nuclear genes for qualitative and quantitative detection of the presence of porcine and chicken derivatives in beef. A fixed constant (transfer coefficient) was introduced to directly transform the ratio of DNA copy number to the mass proportion of targeted meats. Results revealed that the linearity range of quantification for pork and chicken were both from 1% (w/w) to 90% (w/w). The limit of detection (LOD) and limit of quantification (LOQ) of the developed ddPCR method were the same for pork and chicken in beef, with LOD 0.1% (w/w) and LOQ 1% (w/w). The accuracy and applicability of the method was tested and verified using mixed samples with the known proportions and commercially available beef products. We conclude that our developed ddPCR method was accurate and reliable in identifying and quantifying porcine and chicken derivatives in beef and therefore has great potential to be applied in routine analyses and quality control of beef products.

The Prevalence of Mental Problems for Chinese Children and Adolescents During COVID-19 in China: A Systematic Review and Meta-Analysis.

The outbreak of coronavirus disease 2019 (COVID-19) has caused mental problems among the public and medical staff in China, especially for children and adolescents, a vulnerable group that might present with more mental problems. It seems that there is a rapid growth in the mental problems (such as depression or anxiety) of Chinese children and adolescents during the outbreak of COVID-19. Although several studies reported the prevalence of depression or anxiety problems for children and adolescents, the results are different across different age groups and sex groups. Moreover, the sample size of these studies was small. In the present study, we aim to perform a meta-analysis to identify the confirmed prevalence of depression and anxiety problems for Chinese children and adolescents during home confinement. Five databases were searched including PubMed, Web of Science, PsycINFO, Google Scholar, and the China National Knowledge Infrastructure (CNKI), and both inclusion and exclusion criteria were developed. Finally, a total of 12 studies were included in this meta-analysis. The protocol of this systematic review was registered with INPLASY (protocol ID: INPLASY202150032). It found that the pooled prevalence of mental problems was 28% (95% confidence interval, CI: 0.22-0.34), and the depression and anxiety problem for children and adolescents in China was 22% (95% CI: 0.16-0.30) and 25% (95% CI: 0.20-0.32) based on a random effect model, separately. Subgroup analysis was used to identify that there are no differences between different age groups (primary and middle school vs. high school) (p = 0.26). Meta-regression analysis was performed and the results showed that the moderator of boy percentage was a significant factor (p = 0.04). It indicated that there was an increasing number of children and adolescents with mental problems during the home confinement. It suggested that we should pay more attention to this vulnerable population during a public health crisis in the future, especially for the girls groups, and more detailed implements for mental health management were needed and should be prepared. Systematic Review: The protocol of this systematic review was registered with INPLASY. The protocol ID was INPLASY202150032.

MiR-103a promotes tumour growth and influences glucose metabolism in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common and high-mortality cancer worldwide. Numerous microRNAs have crucial roles in the progression of different cancers. However, identifying the important microRNAs and the target biological function of the microRNA in HCC progression is difficult. In this study, we selected highly expressed microRNAs with different read counts as candidate microRNAs and then tested whether the microRNAs were differentially expressed in HCC tumour tissues, and we found that their expression was related to the HCC prognosis. Then, we investigated the effects of microRNAs on the cell growth and mobility of HCC using a real-time cell analyser (RTCA), colony formation assay and subcutaneous xenograft models. We further used deep-sequencing technology and bioinformatic analyses to evaluate the main functions of the microRNAs. We found that miR-103a was one of the most highly expressed microRNAs in HCC tissues and that it was upregulated in HCC tissue compared with the controls. In addition, high miR-103a expression was associated with poor patient prognosis, and its overexpression promoted HCC cell growth and mobility. A functional enrichment analysis showed that miR-103a mainly promoted glucose metabolism and inhibited cell death. We validated this analysis, and the data showed that miR-103a promoted glucose metabolism-likely function and directly inhibited cell death via ATP11A and EIF5. Therefore, our study revealed that miR-103a may act as a key mediator in HCC progression.

Impact of the Gut Microbiome on the Progression of Hepatitis B Virus Related Acute-on-Chronic Liver Failure.

The relationship between the progression of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and the gut microbiota is poorly understood, and an HBV-ACLF-related microbiome has yet to be identified. In this study alterations in the fecal microbiome of 91 patients with HBV-ACLF (109 stool samples), including a cohort of nine patients at different stages of HBV-ACLF, were determined by high-throughput 16S rDNA sequencing. The operational taxonomic units and Shannon indexes indicated that the diversity and abundance of the gut microbiome significantly decreased with the progression of HBV-ACLF (p <0.05). The relative abundance of the Bacteroidetes phylum in the microbiome was significantly reduced, whereas the abundance of potentially pathogenic bacteria, such as Veilonella, Streptococcus, Enterococcus, and Klebsiella, was highly enriched in the HBV-ACLF group compared with the healthy control group. The abundance of Bacteroidetes was negatively correlated with the level of serum alpha fetoprotein, and the abundance of Veilonella was positively correlated with serum total bilirubin (TBIL). Furthermore, the abundance of Coprococcus was significantly negatively correlated with the level of serum TBIL and the international normalized ratio and positively correlated with prothrombin time activity. Our findings suggest that the gut microbiota plays an important role in the development of HBV-ACLF.

The expression of stem cell-related indicators as a prognostic factor in human lung adenocarcinoma.

INTRODUCTION: The purpose of the present study was to detect the presence of BASC-like stem cell-related indicators, such as clara cell secretory protein (CCSP), Octamer-4 (OCT4) and Bmi-1, and evaluate their implications in the prognosis of patients with lung adenocarcinoma. METHODS: Specimens of 134 cases of lung adenocarcinoma were collected after radical surgery from January 1999 to June 2004. RESULTS: One hundred and twenty-six cases showed cells that were positive for CCSP, 99 cases positive for OCT4, 91 cases simultaneous expression of CCSP and OCT4 and 74 cases positive for Bmi-1. Bmi-1 was significantly higher in patients at stage III compared to patients at stages I and II. The pattern of survival curves showed that Bmi-1 was a significant prognostic factor of poor overall survival in lung adenocarcinoma patients (P = 0.0000), and the patients with OCT4(+) expression showed a greater increase in mortality than OCT4(-) patients (P = 0.0103). The results of univariate and multivariate Cox analysis revealed that the pathological stages of tumor node metastases (P = 0.037), OCT4 (P = 0.046) and Bmi-1 expression (P = 0.001) were independent prognostic factors. CONCLUSIONS: OCT4 and Bmi-1 may be good biomarkers to predict the prognosis of patients with completely resected lung adenocarcinoma.

Physiological Characteristics and Environment Adaptability of Reef-Building Corals at the Wuzhizhou Island of South China Sea.

The health of coral reef has declined significantly around the world due to the impact of human activities and natural environment changes, and corals have to develop effective resistance mechanisms to survive. In this study, we examined the physiological characteristics and Symbiodiniaceae types of four dominant scleractinian corals in the reefs at the Wuzhizhou Island (WZZ) in South China Sea. The water environmental conditions are complex on the north side of WZZ due to regional geography and tourism development, and all corals had their unique physiological conditions and Symbiodiniaceae types. For all corals of this study, the rETRm ax and protein content were significantly lower and the SOD enzyme activity was significantly higher in the north than in the south. Interestingly, ITS2 genotyping showed that Galaxea fascicularis contained dominant Symbiodiniaceae either genotype C21 or D1a depending on the regional environmental stress, and had stronger heterotrophy than the other three coral species. In addition, the light use efficiency of the dominant Symbiodiniaceae type C1 for Pocillopora verrucosa was significantly lower in the north and the half saturating irradiance was stable. Besides, Montipora truncata and P. verrucosa increased their density of the symbiotic zooxanthella C1 in the north to offset the decline of photosynthetic efficiency and thus supply energy. For Porites lutea and G. fascicularis, their half saturating irradiance declined sharply in the north, where P. lutea resorted to heterotrophic feeding to balance the energy budget when the number of zooxanthellas fell short and G. fascicularis reduced its energy reserve significantly when the energy source was limited. We thus demonstrated the differences in the physiological responses and energy metabolism strategies between the zooxanthella and the host coral of the four reef-building coral species under the stress of complex water environment on the north side of WZZ. The corals were found to cope with natural and anthropogenic stressors by adjusting the nutrient input sources and the energy structure metabolism of coral hosts or adapting to more sustainable relationship with Symbiodiniaceae clades. The corals exhibited their capacity against long-term disturbances by developing their own successful resistance mechanisms at symbiotic relationship and energy metabolism level.

Cyclodextrin-mediated formation of porous RNA nanospheres and their application in synergistic targeted therapeutics of hepatocellular carcinoma.

Spherical and porous nanoparticles are ideal nanostructures for drug delivery. But currently they are mainly composed of non-degradable inorganic materials, which hinder clinical applications. Here, biological porous nanospheres using RNA as the building blocks and cyclodextrin as the adhesive were synthesized. The RNA contained the aptamer of EpCAM for targeting delivery and siRNA for gene silencing of EpCAM, while cyclodextrin could load insoluble sorafenib, the core drug of targeted therapy for hepatocellular carcinoma (HCC), through its hydrophobic cavity. After being internalized into targeted HCC cells under the assistance of the aptamer, the porous nanospheres could be degraded by the cytoplasmic Dicer enzymes, releasing siRNA and sorafenib for synergistic therapy. The synergistic efficacy of the porous RNA nanospheres has been validated at in vitro function assay, subcutaneous tumor bearing mice, and orthotopic tumor bearing mice in vivo models. In view of the broad prospects of synergy of gene therapy with chemotherapy, and the fact that RNA and cyclodextrin of the porous nanospheres can be extended to load various types of siRNA and small molecule drugs, respectively, this form of biological porous nanospheres offers opportunities for targeted delivery of suitable drugs for treatment of specific tumors.