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This study aimed to analyze the potential association between cognition reserve (CR) components, including education, working activity, and leisure time activity, and cognitive function in subjects with white matter hyperintensities (WMH). The study also explored the role of the frontoparietal control network (FPCN) in such association.White matter hyperintensities subjects with and without cognitive impairment (CI) were evaluated with multimodal magnetic resonance imaging, neuropsychological testing, and CR survey. FPCN patterns were assessed with dorsolateral prefrontal cortex seed-based functional connectivity analysis.Education was positively associated with cognitive function in WMH subjects with or without CI, whereas working activity and leisure time activity were positively associated with cognitive function only in those without CI. Similarly, education was associated with bilateral FPCN in both WMH groups, whereas working activity and leisure time activity were associated with bilateral FPCN mainly in the group without CI. Furthermore, FPCN partially mediated the association between education and cognitive function in both WMH groups.Education showed a positive impact on cognitive function in WMH subjects regardless of their cognitive status, whereas working activity and leisure time activity exhibited beneficial effects only in those without CI. The FPCN mediated the beneficial effect of education on cognitive function.

Metastasis contributes to treatment failure in nasopharyngeal carcinoma (NPC) patients. Our study aimed at elucidating the role of insulin‐like growth factor 2 mRNA binding protein 3 (IGF2BP3) in NPC metastasis and the underlying mechanism involved. IGF2BP3 expression in NPC was determined by bioinformatics, quantitative polymerase chain reaction and immunohistochemistry analyses. The biological function of IGF2BP3 was investigated by using in vitro and in vivo studies. In this study, IGF2BP3 mRNA and protein levels were elevated in NPC tissues. In addition, IGF2BP3 exerted an oncogenic role by promoting epithelial‐mesenchymal transition (EMT), thereby inducing NPC cell migration and invasion. Further studies revealed that IGF2BP3 regulated the expression of key regulators of EMT by activating AKT/mTOR signalling, thus stimulating NPC cell migration and invasion. Remarkably, targeting IGF2BP3 delayed NPC metastasis through attenuating p‐AKT and vimentin expression and inducing E‐cadherin expression in vivo. Moreover, IGF2BP3 protein levels positively correlated with distant metastasis after initial treatment. Importantly, IGF2BP3 expression served as an independent prognostic factor in predicting the overall survival and distant metastasis‐free survival of NPC patients. This work identifies IGF2BP3 as a novel prognostic marker and a new target for NPC treatment.

Background Dual antiplatelet therapy is considered beneficial in acute ischemic stroke (AIS) patients with intracranial artery stenosis (ICAS), with more bleeding events. Ginkgolide is shown to reduce platelet activation after infarction, which might be of benefit in AIS. We aimed to explore the effect of Ginkgolide in AIS patients with ICAS. Methods This was a randomized, double‐blinded, placebo‐controlled trial conducted at 61 centers in China. Within 72 h after onset, consecutive patients diagnosed as AIS with ICAS were randomized to either Ginkgolide or placebo treatment. The primary outcome was the composite of mortality and recurrent stroke (ischemic or hemorrhagic) during first 4 weeks in an intention‐to‐treat analysis. Secondary functional outcome was assessed by modified Rankin Scale and improvement of stroke severity was assessed by National Institution of Health Stroke Scale at day 28. Safety outcome was measured by the rate of severe adverse event (SAE). Results There were 936 patients randomized to either Ginkgolide or placebo treatment. Their average age was 64.2 ± 10.4 years old and 36.0% of the patients were female. The composite index event occurred in six patients in placebo group, and none occurred in Ginkgolide group (risk ratio 1.01; 95% CI 1.00–1.02). There were more patients who achieved favorable outcome in Ginkgolide group, compared with that of the placebo group (OR 2.16, 95%CI 1.37–3.41). SAE occurred in five (1.1%) patients in the Ginkgolide group and three (0.6%) in the placebo group (OR0.60, 95CI% 0.14–2.53). Intracranial hemorrhage occurred in 1/473 (0.2%) in the placebo group. Conclusions Ginkgolide, working as PAF antagonist, may reduce recurrent stroke in AIS with ICAS patients within 72 hours after onset. It might be an optional treatment in moderate‐to‐severe AIS patients with ICAS. (http://www.chictr.org.cn Number as ChiCTR‐IPR‐17012310)., Although dual antiplatelet therapy is considered benefit in acute ischemic stroke (AIS) patients with intracranial artery stenosis (ICAS), there are more bleeding events. Ginkgolide, works as PAF antagonist, may reduce recurrent and mortality in AIS with large artery stenosis within 72 hours atfer onset during 90 days follow‐up. It might play a role of neuroprotection in AIS patients with ICAS

It has been shown that PP2A is critical for apoptosis in neural progenitor cells. However, it remains unknown whether PP2A is required for neuronal survival. To address this question, we generated forebrain-specific Ppp2cα knockout (KO) mice. We show that Ppp2cα KO mice display robust neuronal apoptosis and inflammatory responses in the postnatal cortex. Previous evidence has revealed that PD98059 is a potent ERK inhibitor and may protect the brain against cell death after cardiac arrest. To study whether PD98059 may have any effects on Ppp2cα KO mice, the latter was treated with this inhibitor. We demonstrated that the total number of cleaved caspase3 positive (+) cells in the cortex was significantly reduced in Ppp2cα KO mice treated with PD98059 compared with those without PD98059 treatment. We observed that the total number of IBA1+ cells in the cortex was significantly decreased in Ppp2cα KO mice treated with PD98059. Mechanistic analysis reveals that deletion of PP2Aca causes DNA damage, which may be attenuated by PD98059. Together, this study suggests that inhibition of ERK may be an effective strategy to reduce cell death in brain diseases with abnormal neuronal apoptosis.

Aims We aimed to determine whether preprocedural renal function affects the outcome of acute ischemic stroke (AIS) patients with mechanical thrombectomy (MT) and whether this effect is modified by the onset‐to‐reperfusion time (OTR) and mediated by collateral status. Methods Eligible patients with anterior circulation large vessel occlusion (LVO) who underwent MT between August 2018 and August 2020 were reviewed. The main outcome was good functional outcome [defined as modified Rankin Scale (mRS) of 0–2] at 3 months. Multivariable logistic regression analyses were conducted to explore the relationship between renal function and good functional outcome. A moderation analysis and the Johnson‐Neyman technique were performed to assess the interaction between renal function and OTR to predict the outcome of AIS patients with MT. Results Among 100 enrolled patients, 36 (36%) exhibited good functional outcome. A decreased preprocedural estimated glomerular filtration rate (pre‐eGFR) was significantly associated with worse functional outcome [adjusted OR, 1.059 (1.012–1.108); p, 0.014], and this effect was partly mediated by collateral circulation. An interaction between OTR and pre‐eGFR on functional outcome was observed (P for interaction, 0.22), and pre‐eGFR only had a significant effect on functional outcome when OTR exceeded 455.8 min. Moreover, the adverse effect of OTR on functional outcome became no longer significant when the pre‐eGFR was higher than 89.0 mL/min/1.73 mL/min/1.73 m². Conclusions Renal function was related to functional outcome at 3 months, and this relationship could be modified by OTR. The results suggested that reducing OTR and improving collateral circulation may mitigate the adverse effect of reduced kidney function on functional outcome., The relationship between preoperative estimated glomerular filtration rate and functional outcome varies according to the onset‐to‐reperfusion time, reducing OTR may mitigate the negative effect of renal dysfunction.

BACKGROUND To evaluate the value of locoregional radiation therapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (mNPC) and identify suitable candidates for additional LRRT after palliative chemotherapy (PCT). METHODS Patients with de novo mNPC received platinum-based chemotherapy for a minimum of four cycles with or without definitive LRRT via intensity-modulated radiation therapy (IMRT) were all candidates for this study. RESULTS A total of 168 patients were included for this analysis. Additional LRRT was associated with significantly longer median OS (69.5 vs. 17.8 months, p

Among phosphorus-based nanomaterials, layered black phosphorus and violet phosphorus have been actively explored in the past decade. However, methods for the synthesis of red phosphorus nanosheets (RPNSs) is lacking, even though red phosphorus (RP) is commercially available at low cost and has excellent chemical stability at room temperature. We report an efficient strategy for fabrication of RPNSs and doped RPNSs using cysteine as a reducing reagent. Data from in vitro and in vivo studies suggested that RPNSs can trigger production of reactive oxygen species, DNA damage, and subsequent autophagy-mediated cell death in a shape-dependent manner. Our findings provide a method for construction of layered RP nanomaterials and they present a unique mechanism for the application of phosphorus-based materials in nanomedicines.

Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme and is involved in the progression of hepatocellular carcinoma (HCC). However, its specific function and the mechanism of modulation remain to be elucidated. In this study, we found that CYP2A6 is dramatically downregulated in HCC. CYP2A6 expression is closely associated with pathological grading, histologic grade, hepatitis, vascular metastasis, liver inflammation, and worse prognosis. Reduced expression of CYP2A6 contributes to alternative activation of macrophage polarization and impairs macrophage maturation and phagocytosis. Mechanistically, CYP2A6 participates in arachidonic acid metabolism, initiates 20‐hydroxyeicosatetraenoic acid (HETE) generation, and inhibits epoxyeicosatrienoic acid (EET) generation. Disruption of the equilibrium between 20‐HETE and EETs can induce macrophage polarization, thereby modulating antitumor immunity., Cytochrome P450 2A6 (CYP2A6) has an antitumor role and is dramatically downregulated in HCC. CYP2A6 participates in arachidonic acid metabolism, initiates 20‐hydroxyeicosatetraenoic acid (HETE) generation, and inhibits epoxyeicosatrienoic acid (EET) generation. Disruption of the equilibrium between 20‐HETE and EETs can induce macrophage polarization, thereby modulating antitumor immunity.

The present study describes an interesting and practical catalytic system that allows flexible conversion of lignin into aromatic or aliphatic hydrocarbons, depending on the hydrogen partial pressure. A combination of experiment and theory shows that the product distribution between aromatics and aliphatics can be simply tuned by controlling the availability of hydrogen on the catalyst surface. Noticeably, these pathways lead to almost complete oxygen removal from lignin biomass, yielding high‐quality hydrocarbons. Thus, hydrogen–lignin co‐refining by using this catalytic system provides high flexibility in hydrogen storage/consumption towards meeting different regional and temporal demands., Better together: A practical catalytic system is described that allows flexible conversion of lignin into aromatic or aliphatic hydrocarbons, depending on the hydrogen partial pressure. The hydrogen‐lignin co‐refining using this catalytic system provides high flexibility in hydrogen storage/consumption towards meeting different regional and temporal demands.

White matter injury (WMI), which reflects myelin loss, contributes to cognitive decline or dementia caused by cerebral vascular diseases. However, because pharmacological agents specifically for WMI are lacking, novel therapeutic strategies need to be explored. It is recently found that adaptive myelination is required for homeostatic control of brain functions. In this study, adaptive myelination-related strategies are applied to explore the treatment for ischemic WMI-related cognitive dysfunction. Here, bilateral carotid artery stenosis (BCAS) is used to model ischemic WMI-related cognitive impairment and uncover that optogenetic and chemogenetic activation of glutamatergic neurons in the medial prefrontal cortex (mPFC) promote the differentiation of oligodendrocyte precursor cells (OPCs) in the corpus callosum, leading to improvements in myelin repair and working memory. Mechanistically, these neuromodulatory techniques exert a therapeutic effect by inducing the secretion of Wnt2 from activated neuronal axons, which acts on oligodendrocyte precursor cells and drives oligodendrogenesis and myelination. Thus, this study suggests that neuromodulation is a promising strategy for directing myelin repair and cognitive recovery through adaptive myelination in the context of ischemic WMI.

Citrullinated histone H3 (H3Cit) is the product of the conversion of peptidylarginine to citrulline in histone H3. We evaluated the H3Cit level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues and assessed its association with Beclin1 messenger RNA (mRNA) (a key autophagic regulator). The level of H3Cit was detected by a capture enzyme-linked immunosorbent assay, while Beclin1 mRNA was determined by real-time polymerase chain reaction in 80 HBV-related patients with HCC. We found that the mean level of H3Cit was 72.25 ng/mg in HCC and 44.02 ng/mg in nontumor tissues. The mean HCC/nontumor ratio of Beclin1 mRNA was higher (0.096) in tumor samples than in nontumor specimens (0.056). Specifically, Beclin1 mRNA was elevated in 51 HCC cases (63.75%) and decreased in 29 cases (36.25%). Moreover, the levels of H3Cit and Beclin1 mRNA were significantly associated with vascular invasion and serum AFP levels. A shorter survival (19 months) was associated with a high H3Cit level. We also found increased levels of Beclin1 mRNA in the H3Cit (high) group compared with the H3Cit (low) group. The results implied that elevated histone H3 citrullination is associated with increased Beclin1 expression during the development of HBV-related HCC.

Aims White matter hyperintensity (WMH) is the most common neuroimaging manifestation of cerebral small vessel disease and is related to cognitive dysfunction or dementia. This study aimed to investigate the mechanism and effective indicators to predict WMH‐related cognitive impairment. Methods We recruited 22 healthy controls (HC), 25 cases of WMH with normal cognition (WMH‐NC), and 23 cases of WMH with mild cognitive impairment (WMH‐MCI). All individuals underwent diffusion tensor imaging (DTI) and a standardized neuropsychological assessment. Automated Fiber Quantification was used to extract altered DTI metrics between groups, and partial correlation was performed to assess the associations between WM integrity and cognitive performance. Furthermore, machine learning analyses were performed to determine underlying imaging markers of WMH‐related cognitive impairment. Results Our study found that mean diffusivity (MD) values of several fiber bundles including the bilateral anterior thalamic radiation (ATR), the left inferior fronto‐occipital fasciculus (IFOF), the right inferior longitudinal fasciculus (ILF), and the right superior longitudinal fasciculus (SLF) were negatively correlated with memory function, while that of the anterior component of the right IFOF and the posterior and intermediate component of the right ILF showed significant negative correlation with MMSE and episodic memory, respectively. Furthermore, machine learning analyses showed that the accuracy of recognizing WMH‐MCI patients from the WMH populations was up to 80.5% and the intermediate and posterior components of the right ILF and the anterior component of the right IFOF contribute the most. Conclusions Changes in the properties of DTI may be the potential mechanism of WMH‐related MCI, especially the right IFOF and the right ILF, which may become imaging markers for predicting WMH‐related cognitive dysfunction.

PURPOSE We set out to undertake a preliminary assessment of the left ventricular hemodynamic status with right ventricular double-chamber pacing by energy loss (EL), wall shear stress (WSS), and circulation intensity (CIR) of vector flow mapping (VFM). We also planned to evaluate the value of VFM technology by measuring cardiac function after pacemaker implantation. METHOD Data from 58 patients living with right ventricular double-chamber (right ventricular septal) pacemakers as well as 58 healthy volunteers matched in age and gender were collected. The EL, numbers of vortex cycles (n), area (A), CIR, and WSS of the left ventricle with different phases of the same cardiac cycle were obtained. RESULTS The EL of the left ventricle was significantly higher in the pacemaker group than the control group at partial section of atrial contraction (AC), isovolumetric contraction (IVC), and rapid ejection (RE) (P

BACKGROUND AND PURPOSE To investigate the prognostic value of retropharyngeal lymphadenopathy in nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy. MATERIALS AND METHODS Retrospective studies were performed in a total of 1197 patients. We evaluated the incidence of the retropharyngeal node (RPN) metastasis and the characteristics of the metastatic RPN including laterality, size, necrosis, and extranodal neoplastic spread. RESULTS RPN metastasis occured in 86.3% of patients. The RPN and level II metastasis shared similar survival outcomes. RPN metastasis was an independent prognostic factor for distant failure (hazard ratio = 1.615; 95% confidence interval, 1.063-2.452; P = 0.025), in which the laterality of RPN metastasis significantly influences both the distant failure (P = 0.006) and disease progression (P = 0.001). In N1 disease, the occurrence of unilateral and bilateral RPN metastasis resulted in significantly different outcomes of the disease-specific survival (P = 0.045) and progression-free survival (P = 0.049). The co-occurrence of bilateral RPN and cervical lymph nodes (CLN) metastasis was an independent adverse prognostic factor (P

Organic-inorganic halide perovskite solar cells (PSCs) have reached certified efficiencies of over 23 % with expensive organic hole-transporting materials. However, the use of an inorganic hole-transport layer (HTL) remains crucial as it would reduce cost combined with higher mobility and stability. In this direction, the application of Cu2 O as the top layer in PSCs is still complicated owing to the difficulty of solution processing. Herein, a solution-processing method is reported for preparing Cu2 O nanocubes as a p-type HTL in regular structure (n-i-p) PSCs. The controlled synthesis of Cu2 O nanocubes in a size range of 60-80 nm is achieved without using any surfactants, which are usually toxic and tricky to remove. The new structure of these Cu2 O nanocubes enhances the carrier mobility with preferable energy alignment to the perovskite layer and superb stability. The PSCs based on these Cu2 O nanocubes HTMs could achieve an efficiency exceeding 17 % with high stability, whereas organic P3HT-based PSCs display an efficiency of 15.59 % with a poorer running stability. This indicates that Cu2 O nanocubes are a promising HTM for efficient and stable PSCs.

The paracellular gap formed by endothelial cell (EC) contraction is fundamental for endothelium permeability, but the mechanism underlying EC contraction has yet to be determined. Here, we identified the zipper-interacting protein kinase (ZIPK) as the kinase for EC contraction and myosin light chain (MLC) phosphorylation. Inhibition of ZIPK activity by pharmacological inhibitors and small interfering RNAs led to a significant decrease in the mono- and diphosphorylation of MLCs along with a contractile response to thrombin, suggesting an essential role of ZIPK in EC paracellular permeability. To assess the role of ZIPK in vivo, we established mouse lines with conditional deletion of Zipk gene. The endothelium-specific deletion of Zipk led to embryonic lethality, whereas the UBC-Cre(ERT2)–mediated deletion of Zipk by tamoxifen induction at adulthood caused no apparent phenotype. The induced deletion of Zipk significantly inhibited ischemia-reperfusion–induced blood-brain barrier dysfunction and neuronal injuries from middle cerebral artery occlusion and reperfusion, as evidenced by reduced infarct and edema volume, attenuated Evans blue dye leakage, and improved neuronal behavior. We thus concluded that ZIPK and its phosphorylation of MLC were required for EC contraction and ischemic neuronal injuries. ZIPK may be a prospective therapeutic target for stroke.—Zhang, Y., Zhang, C., Zhang, H., Zeng, W., Li, S., Chen, C., Song, X., Sun, J., Sun, Z., Cui, C., Cao, X., Zheng, L., Wang, P., Zhao, W., Zhang, Z., Xu, Y., Zhu, M., Chen, H. ZIPK mediates endothelial cell contraction through myosin light chain phosphorylation and is required for ischemic-reperfusion injury.

The nature of muscle-bone crosstalk has been historically considered to be only mechanical, where the muscle is the load applier while bone provides the attachment sites. However, this dogma has been challenged with the emerging notion that bone and muscle act as secretory endocrine organs affect the function of each other. Biochemical crosstalk occurs through myokines such as myostatin, irisin, interleukin (IL)-6, IL-7, IL-15, insulin-like growth factor-1, fibroblast growth factor (FGF)-2, and β-aminoisobutyric acid and through bone-derived factors including FGF23, prostaglandin E(2), transforming growth factor β, osteocalcin, and sclerostin. Aside from the biochemical and mechanical interaction, additional factors including aging, circadian rhythm, nervous system network, nutrition intake, and exosomes also have effects on bone-muscle crosstalk. Here, we summarize the current research progress in the area, which may be conductive to identify potential novel therapies for the osteoporosis and sarcopenia, especially when they develop in parallel.

Different views appear in the literature on the extent of specific cytochrome P450 (CYP) involvement in methadone metabolism. The aim of this work is to leverage knowledge from drug-drug interaction (DDI) studies in new drug applications between methadone and antiviral medications to better understand methadone disposition and to inform design of future DDI studies with methadone. A database of DDI studies between all FDA-approved human immunodeficiency virus and hepatitis C virus medications and methadone was constructed. The database contains data from 29 DDI studies. Sixteen of the 29 studies had statistically significant changes in methadone area under the concentration-time curve. Methadone exposure was either decreased or unchanged when it was coadministered with weak to strong CYP3A inhibitors or a moderate CYP3A4 inducer. Methadone exposure was reduced when it was coadministered with CYP2B6 inducers. The role of other enzymes (CYP2C9, CYP2C19, and CYP2D6) cannot be fully elucidated from these studies. In conclusion, CYP2B6 plays a prominent role in methadone metabolism, although methadone exposure is not sensitive to CYP3A perturbation. In designing methadone DDI studies, (1) measuring R- and S-methadone is more informative than measuring total methadone, and (2) CYP2B6 genotyping of subjects enrolled in methadone DDI studies should be considered. Finally, there is a need for the development of predictive models to determine the influence of medications on methadone disposition.

Golgi phosphoprotein 73 (GP73) has been regarded as a novel serum biomarker for the diagnosis of hepatocellular carcinoma (HCC) in recent years. It has been reported that the upregulation of GP73 may promote the carcinogenesis and metastasis of HCC; however, the mechanisms remain poorly understood. In this study, GP73 correlates positively with matrix metalloproteinase‐2 (MMP‐2) in HCC‐related cells and tissues. Further studies indicate that the knockdown of GP73 blocks MMP‐2 trafficking and secretion, resulting in cell invasion inhibition. Additionally, the knockdown of GP73 induces the accumulation of intracellular MMP‐2, which inhibits the phosphorylation of Src at Y416 and triggers the inhibition of SAPK/JNK and p53‐p21 signalling pathways through a negative feedback loop. Finally, the transactivation of MMP2 was inhibited by the reduction in E2F1. This study reveals that GP73 plays functional roles in the trafficking and equilibrium of epithelial‐mesenchymal transition (EMT)‐related secretory proteins and that GP73 serves as a new potential target for combating the metastasis of HCC.

A simple, rapid, and selective ultra-performance liquid chromatography-tandem mass spectrometry method for determination of l-carnitine (LC) and acetyl-l-carnitine (ALC) in human serum was developed. Acetyl-l-carnitine-d3 (ALC-d3 ) was selected as internal standard (IS). After protein precipitation with acetonitrile-water (1 mL, 2:1, v/v), the analytes and IS were separated on a 2.5-μm XSelect HSS T3 C18 column by gradient elution with methanol-water (containing 0.01% ammonia water) as the mobile phase at a flow rate of 0.2 mL/min. Analytes were detected with multiple reaction monitoring using a positive scan mode with electrospray ionization. Good linearity (R2 > 0.999) was observed in the concentration range for LC and ALC. The inter- and intra-day values of relative error were -10.4% to 10.0% with CVs less than 9.84%. The average recoveries of the two analytes were 91.29%-98.23%. Blood samples containing LC and ALC were stable under various storage conditions. Normal, haemolytic, and hyperlipidaemic serum had no significant effect on the quantification of LC and ALC. This method was successfully applied to study the concentrations of endogenous LC and ALC in the serum of patients with first-episode depression.

Background Colorectal cancer (CRC) patients diagnosed with Lynch syndrome (LS) are recommended genetic testing. Increasing numbers of germline variants involved in homologous recombination have been identified in suspected LS patients. This study compared phenotypic the characteristics of suspected LS patients carrying BRCA and BRCA‐like variants with those of LS patients. Methods Forty‐two patients carrying pathogenic variants of DNA mismatch repair (MMR) genes (MMR group), 9 carrying BRCA variants, and 11 carrying BRCA‐like variants (BRCA/BRCA‐like group) who met LS clinical criteria were enrolled in this study. Clinical characteristics, pedigrees, and survival rates were compared and BRCA variants were analyzed. Results The earliest CRC‐onset age and tumor differentiation were higher in the BRCA/BRCA‐like group than in the MMR group. Metachronous CRCs were more numerous in the MMR group, resulting in a higher progression‐free survival rate in the BRCA/BRCA‐like group. Extra‐colorectal cancers were more frequently observed in the BRCA/BRCA‐like group. BRCA2 and BRCA1 variants were clustered in exons 11 and 4/7, respectively. Conclusion BRCA and BRCA‐like variants in CRC patients with LS showed moderate penetrance. BRCA/BRCA‐like variant carriers had a higher risk for extra‐colorectal cancers. Surveillance of susceptible organs other than the intestine should be performed for probands and affected family members., In order to figure out the phenotypic, pedigree and variant characteristics of BRCA and BRCA‐like carriers diagnosed as colorectal cancer (CRC) and Lynch syndrome (LS), we perform a comparison of BRCA and MMR mutation, meanwhile, refer to published literatures. As far as we know, our study is the first report concentrating on BRCA in LS. Furthermore, this is the first report introducing conception of “BRCA‐like” into LS and CRC, which may provide molecular evidence for developing individualized treatment and screening strategies for both CRC proband and affected family members.

A sensitive and selective high-performance liquid chromatography-tandam mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of sildenafil and its metabolite N-desmethyl sildenafil in human plasma. Sildenafil-d8 was used as an internal standard. The analytes were extracted by precipitation extraction and chromatographed on a C18 column using mobile phase A of water (containing 0.1% formic acid) and mobile phase B of acetonitrile (containing 0.1% formic acid) with gradient elution. Quantification was done using multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 475.4 → m/z 283.3 for sildenafil, m/z 461.4 → m/z 283.2 for N-desmethyl sildenafil and m/z 483.3 → m/z 108.1 for IS in positive ionization mode. The calibration curve was established over the range of 2.00-1,000 ng/ml and the correlation coefficient was >0.99. The intra-day and inter-day relative standard deviations were

Aim This study aimed to evaluate the efficacy of music therapy for reducing the anxiety and pain of patients who underwent a biopsy. Background Music can affect human anxiety and pain by triggering a neuroendocrine effect. Clinical study results indicated that music can influence the anxiety and pain caused by invasive procedures. There is no effective solution for anxiety and pain arising from a biopsy. Although researchers in this field have different views, music still holds promise in reducing the anxiety and pain in patients undergoing the biopsy. Design Systematic review and meta-analysis of randomized controlled trials. Data sources Systematic searches were conducted in PubMed, Embase, Medline and Cochrane databases for studies reported in the English language. The review period covered 2000 - December 2016. The outcome measure of interest was anxiety and pain. Methods This review followed Cochrane methods. Studies were selected according to the PICOS framework. The methodological quality of studies was assessed with the Cochrane risk of bias tool. A systematic review of effectiveness was conducted by using GRADE approach. Results Nine randomized controlled trials with a total of 326 participants in the music intervention group and 323 controls met the inclusion criteria. Music had a tendency towards decreasing systolic blood pressure before the biopsy, State-Trait Anxiety Inventory scores after the biopsy, diastolic blood pressure after the biopsy and heart rate after the biopsy. Similarly, music also tended to be more effective for controlling pain after the biopsy. There was moderate quality evidence for the outcome: State-Trait Anxiety Inventory scores after the biopsy; and low- or very low-quality evidence for other outcomes. Conclusion Music can be used for patients before and during the biopsy procedure. This approach may be performed by nurses to promote the recovery of patients after the biopsy.

Background Glycemic control is essential for managing acute stroke. This study evaluated the impact of a diabetes-specific formula (DSF) on glycemic control in severe acute ischemic stroke patients. Methods A randomized, prospective controlled trial was conducted in Nanjing Drum Tower Hospital. Acute ischemic stroke patients who scored > 10 on the National Institutes of Health Stroke Scale as well as had swallowing problems were randomized to group A, which received a diabetes-specific enteral formula, and group B, which received a standard formula. Glycemic parameters were assessed at baseline and 7 days after admission. Results One hundred four patients were enrolled in the study (group A, 53; group B, 51). Postprandial glucose parameters, including capillary glucose concentration from 8 hours to 16 hours after enteral nutrition (EN) consumption, incremental areas under the curve (iAUC0-16 h ), peak value, and mean glucose concentration, were significantly lower in group A than in group B following a 7-day intervention period. Moreover, changes in HOMAIR after the 7-day treatment were significantly higher in group A than in group B. No significant difference in the incidence of hypoglycemia, glycemic variability parameters, or nutrition parameters was found between the 2 groups, either at baseline or after treatment. There were no serious adverse events observed during the study. Conclusion A diabetes-specific formula may improve acute-term glycemic control in severe acute ischemic stroke patients.

Aims Depression is one of the most common nonmotor symptoms in Parkinson's disease (PD). But the pathogenesis is still unclear. Studies have shown that depression in PD is closely related to the white matter abnormalities, but the number of studies is still very small and lack of whole brain white matter lesions study. Methods In this study, we investigated whole brain white matter integrity in 31 depressed PD patients and 37 nondepressed PD patients by diffusion tensor imaging. Results There was no difference in age, gender, age of onset, disease duration, Hoehn-Yahr scale, Unified Parkinson's Disease Rating Scale scores-III, and Mini-Mental State Examination scores between the two groups. The only difference was the Hamilton Depression Rating Scale. Depressed PD patients showed reduced fractional anisotropy values in the left anterior corona radiata, left posterior thalamic radiation, left cingulum, left superior longitudinal fasciculus, left sagittal stratum (including inferior longitudinal fasciculus and inferior fronto-occipital fasciculus), and left uncinate fasciculus. In patients with depression, the Hamilton Depression Rating Scale (HDRS) was negatively correlated with the FA value in the left cingulum (r = -0.712, P = .032) and left superior longitudinal fasciculus (r = -0.699, P = .025). Conclusions This study suggested depression in PD was related to impaired white matter integrity especially the long contact fibers in the left hemisphere. These findings may be helpful for further understanding the potential mechanisms underlying depression in PD.

Boron (B) was introduced into the Ni/acid treated bentonite (Ni/A-Bn) catalysts to improve the anti-coking ability of nickel-based catalyst in the hydrogenation of nitrobenzene. The results showed the optimal B amount was 0.75 wt% on the Ni/A-Bn, which was more active than the catalyst without B. During a 105-hour reaction, Ni-B/acid treated bentonite (Ni-B/A-Bn) obtained a high nitrobenzene conversion (>99%) and a high aniline selectivity. The lifetime of Ni-B/A-Bn with B amount of 0.75 wt% extended 45 h compared to the Ni/A-Bn. The addition of B into Ni/A-Bn decreased the NiO particle size, improved the dispersion of the active components, and decreased the carbon deposition. The combination of B and Ni prevented the coke on the metallic Ni in the nitrobenzene hydrogenation, reducing the carbon deposition on the surface of Ni-B/A-Bn.

Summary The accumulation and deposition of beta‐amyloid (Aβ) is a key neuropathological hallmark of Alzheimer's disease (AD). Histone deacetylases (HDACs) are promising therapeutic targets for the treatment of AD, while the specific HDAC isoforms associated with cognitive improvement are poorly understood. In this study, we investigate the role of HDAC3 in the pathogenesis of AD. Nuclear HDAC3 is significantly increased in the hippocampus of 6‐ and 9‐month‐old APPswe/PS1dE9 (APP/PS1) mice compared with that in age‐matched wild‐type C57BL/6 (B6) mice. Lentivirus ‐mediated inhibition or overexpression of HDAC3 was used in the hippocampus of APP/PS1 mice to investigate the role of HDAC3 in spatial memory, amyloid burden, dendritic spine density, glial activation and tau phosphorylation. Inhibition of HDAC3 in the hippocampus attenuates spatial memory deficits, as indicated in the Morris water maze test, and decreases amyloid plaque load and Aβ levels in the brains of APP/PS1 mice. Dendritic spine density is increased, while microglial activation is alleviated after HDAC3 inhibition in the hippocampus of 9‐month‐old APP/PS1 mice. Furthermore, HDAC3 overexpression in the hippocampus increases Aβ levels, activates microglia, and decreases dendritic spine density in 6‐month‐old APP/PS1 mice. In conclusion, our results indicate that HDAC3 negatively regulates spatial memory in APP/PS1 mice and HDAC3 inhibition might represent a potential therapy for the treatment of AD.