Search

This study investigates the factors influencing the willingness of older cancer patients to receive palliative care, considering the 'person-centered' approach to advance care planning in Taiwan. Autonomy challenges are prevalent among these patients. The retrospective study, conducted at a tertiary teaching hospital in southern Taiwan from June 2020 to December 2022, included 195 eligible older cancer patients. Logistic regression was utilized to analyze factors influencing their willingness for palliative care. The optimal logistic regression analysis identified five key factors associated with receiving palliative care: age (OR, 0.42; 95% CI, 0.20–0.92), educational level (OR, 2.82; 95% CI, 1.27–6.25), metastatic disease (OR, 4.62; 95% CI, 2.08–10.27), hospice and palliative care knowledge (OR, 1.32; 95% CI, 1.11–1.57), and attitude (OR, 1.22; 95% CI, 1.12–1.33). The findings suggest that younger, more educated patients with metastatic disease, higher knowledge of hospice and palliative care, and positive attitudes toward these services were more likely to receive palliative care. Patients' awareness of hospice and palliative care, attitudes shaped by such awareness, and disease status significantly influenced their willingness to undergo palliative care. This highlights the increasing vulnerability of older cancer patients to decision-making challenges as their illness progresses, emphasizing the importance of initiating conversations about advance care planning early on. Healthcare practitioners are urged to actively advocate for these discussions, particularly considering the decline in decision-making capacity as the disease advances. Future research should focus on empowering individuals in making end-of-life care choices. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is acknowledged as an immunosuppressive neoplasm, whereby the inactive microenvironment facilitates immune tolerance and evasion of HCC. Post‐surgical resected liver cancer exhibits a proclivity for relapse, rendering prevention of recurrence challenging as it may transpire at any point subsequent to surgery. Among the various anti‐recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab (A+T) is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. Therefore, the objective is to utilize a recently developed block copolymer as a protective carrier for two specific monoclonal antibody drugs. Subsequently, a modified hemostatic hydrogel will be synthesized for application during hepatic surgery. The immunotherapy impact of this approach is significantly prolonged and intensified due to the combined hemostasis properties and controlled release of the constituents within the synthesized nanocomposite hydrogel. Furthermore, these nanocomposite hydrogels exhibit remarkable efficacy in preventing postoperative wound bleeding and substantially enhancing the safety of liver cancer resection. This research on the anti‐recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future. [ABSTRACT FROM AUTHOR]

Proteins play an important role in life activities and are the basic units for performing functions. Accurately annotating functions to proteins is crucial for understanding the intricate mechanisms of life and developing effective treatments for complex diseases. Traditional biological experiments struggle to keep pace with the growing number of known proteins. With the development of high-throughput sequencing technology, a wide variety of biological data provides the possibility to accurately predict protein functions by computational methods. Consequently, many computational methods have been proposed. Due to the diversity of application scenarios, it is necessary to conduct a comprehensive evaluation of these computational methods to determine the suitability of each algorithm for specific cases. In this study, we present a comprehensive benchmark, BeProf, to process data and evaluate representative computational methods. We first collect the latest datasets and analyze the data characteristics. Then, we investigate and summarize 17 state-of-the-art computational methods. Finally, we propose a novel comprehensive evaluation metric, design eight application scenarios and evaluate the performance of existing methods on these scenarios. Based on the evaluation, we provide practical recommendations for different scenarios, enabling users to select the most suitable method for their specific needs. All of these servers can be obtained from https://csuligroup.com/BEPROF and https://github.com/CSUBioGroup/BEPROF. [ABSTRACT FROM AUTHOR]

Bacterial Extracellular Vesicles (BEVs) possess the capability of intracellular interactions with other cells, and, hence, can be utilized as an efficient cargo for worldwide delivery of therapeutic substances such as monoclonal antibodies, proteins, plasmids, siRNA, and small molecules for the treatment of neurodegenerative diseases (NDs). BEVs additionally possess a remarkable capacity for delivering these therapeutics across the blood–brain barrier to treat Alzheimer's disease (AD). This review summarizes the role and advancement of BEVs for NDs, AD, and their treatment. Additionally, it investigates the critical BEV networks in the microbiome–gut–brain axis, their defensive and offensive roles in NDs, and their interaction with NDs. Furthermore, the part of BEVs in the neuroimmune system and their interference with ND, as well as the risk factors made by BEVs in the autophagy–lysosomal pathway and their potential outcomes on ND, are all discussed. To conclude, this review aims to gain a better understanding of the credentials of BEVs in NDs and possibly discover new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: The frequently occurred chemotherapy-induced diarrhea (CID) caused by irinotecan (CPT-11) administration has been the most representative side-effects of CPT-11, resulting in the chemotherapy suspension or failure. Our previous studies indicated that Gegen Qinlian formula exhibited a significant alleviation effect on CPT-11-induced diarrhea. However, referencing to Japanese Kampo medicine, the TCM standard decoction would supply the gap between ancient preparation application and modern industrial production. Methods: The LC–MS technology combined with network pharmacology was employed to identify the active ingredients and mechanisms of GQD standard decoction for CPT-11-induced diarrhea. The anti-inflammatory activities associated with intestinal barrier function of GQD standard decoction were studied by SN-38 activated NCM460 cells in vitro and CPT-11-induced diarrhea in vivo. Proteins involved in inflammation, mRNA levels, disease severity scores, and histology involved in intestinal inflammation were analysed. Results: There were 37 active compounds were identified in GQD standard decoction. Network pharmacology analyses indicated that PI3K-AKT signaling pathway were probably the main pathway of GQD standard decoction in CPT-11-induced diarrhea treatment, and PIK3R1, AKT1, NF-κB1 were the core proteins. Moreover, we found that the key proteins and pathway predicted above was verified in vivo and in vitro experiments, and the GQD standard decoction could protect the cellular proliferation in vitro and ameliorate CPT-11-induced diarrhea in mice model. Conclusions: This study demonstrated the molecular mechanism of 37 active ingredients in GQD standard decoction against CPT-11-induced diarrhea. And the core proteins and pathway were validated by experiment. This data establishes the groundwork for particular molecular mechanism of GQD standard decoction active components, and this research can provide a scientific reference for the TCM therapy of CID. [ABSTRACT FROM AUTHOR]

Motivation Biomarkers with prognostic ability and biological interpretability can be used to support decision-making in the survival analysis. Genes usually form functional modules to play synergistic roles, such as pathways. Predicting significant features from the functional level can effectively reduce the adverse effects of heterogeneity and obtain more reproducible and interpretable biomarkers. Personalized pathway activation inference can quantify the dysregulation of essential pathways involved in the initiation and progression of cancers, and can contribute to the development of personalized medical treatments. Results In this study, we propose a novel method to evaluate personalized pathway activation based on signaling entropy for survival analysis (SEPA), which is a new attempt to introduce the information-theoretic entropy in generating pathway representation for each patient. SEPA effectively integrates pathway-level information into gene expression data, converting the high-dimensional gene expression data into the low-dimensional biological pathway activation scores. SEPA shows its classification power on the prognostic pan-cancer genomic data, and the potential pathway markers identified based on SEPA have statistical significance in the discrimination of high- and low-risk cohorts and are likely to be associated with the initiation and progress of cancers. The results show that SEPA scores can be used as an indicator to precisely distinguish cancer patients with different clinical outcomes, and identify important pathway features with strong discriminative power and biological interpretability. Availability and implementation The MATLAB-package for SEPA is freely available from https://github.com/xingyili/SEPA. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Selective inhibition of targeted protein kinases is an effective therapeutic approach for treatment of human malignancies, which interferes phosphorylation of cellular substrates. However, a drug‐imposed selection creates pressures for tumor cells to acquire chemoresistance‐conferring mutations or activating alternative pathways, which can bypass the inhibitory effects of kinase inhibitors. Thus, identifying downstream phospho‐substrates conferring drug resistance is of great importance for developing poly‐pharmacological and targeted therapies. To identify functional phosphorylation sites involved in 5‐fluorouracil (5‐FU) resistance during its treatment of colorectal cancer cells, CRISPR‐mediated cytosine base editor (CBE) and adenine base editor (ABE) are utilized for functional screens by mutating phosphorylated amino acids with two libraries specifically targeting 7779 and 10 149 phosphorylation sites. Among the top enriched gRNAs‐induced gain‐of‐function mutants, the target genes are involved in cell cycle and post‐translational covalent modifications. Moreover, several substrates of RSK2 and PAK4 kinases are discovered as main effectors in responding to 5‐FU chemotherapy, and combinational treatment of colorectal cancer cells with 5‐FU and RSK2 inhibitor or PAK4 inhibitor can largely inhibit cell growth and enhance cell apoptosis through a RSK2/TP53BP1/γ‐H2AX phosphorylation signaling axis. It is proposed that this screen approach can be used for functional phosphoproteomics in chemotherapy of various human diseases. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of deep vein thrombosis (DVT) prevention among real-world surgical inpatients who received panax notoginseng saponins (PNS) combined with low-molecular-weight heparin (LMWH). Methods: A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital, Capital Medical University, Beijing, China. Participants received LMWH alone or PNS combined with LMWH for preventing DVT. The primary outcome was incidence of lower extremity DVT, which was screened once a week. Participants in the LMWH group were given LMWH (enoxaparin) via hypodermic injection, 4000–8000 AxalU once daily. Participants in the exposure group received PNS (Xuesaitong oral tablets, 100 mg, 3 times daily) combined with LMWH given the same as LMWH group. Results: Of the 325 patients screened for the study, 281 participants were included in the final analysis. The cohort was divided into PNS + LMWH group and LMWH group with 134 and 147 participants, respectively. There was a significant difference of DVT incidence between two groups (P=0.01), with 21 (15.7%) incident DVT in the PNS + LMWH group, and 41 (27.9%) incident DVT in the LMWH group. Compared with participants without DVT, the participants diagnosed with DVT were older and had higher D-dimer level. The multivariate logistic regression model showed a significant lower risk of incident DVT among participants in the PNS + LMWH group compared with the LMWH group (odds ratio 0.46, 95% confidence interval, 0.25–0.86). There were no significant differences in thromboelaslography values (including R, K, Angle, and MA) and differences in severe bleeding between two groups. No symptomatic pulmonary embolism occurred during the study. Conclusion: Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy, without increased risk of bleeding. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the predominant cause of cancer-related death worldwide, because of the lack of effective therapeutic targets. Estrogen-related receptor gamma (ESRRG), which belongs to the family of nuclear receptors, functions as an important element regulating gene transcription. In our report, we identified ESRRG as a potential tumor suppressor. The decreased level of ESRRG was initially observed in CRC and was highly associated with a poor prognosis. ESRRG overexpression abrogated cell growth and metastasis in vitro and in vivo. Mechanistically, ESRRG repressed the epithelial-to-mesenchymal transition process and antagonized Wnt signaling by regulating β-catenin degradation. In addition, significant ESRRG hypermethylation was found in CRC and inversely correlated with its expression. Consistently, the expression of ESRRG was induced after treatment with DNA demethylating agent 5-aza-2ʹ-deoxycytidine. Taken together, these findings define a tumor-suppressive role of ESRRG in CRC, providing a potential novel therapeutic approach for this cancer. [ABSTRACT FROM AUTHOR]

With the epidemic of betacoronavirus increasing frequently, it poses a great threat to human public health. Therefore, the research on the pathogenic mechanism of betacoronavirus is becoming greatly important. Murine hepatitis virus strain-3 (MHV-3) is a strain of betacoronavirus which cause tissue damage especially fulminant hepatic failure (FHF) in mice, and is commonly used to establish models of acute liver injury. Recently, MHV-3-infected mice have also been introduced to a mouse model of COVID-19 that does not require a Biosafety Level 3 (BSL-3) facility. FHF induced by MHV-3 is a type of severe liver damage imbalanced by regenerative hepatocellular activity, which is related to numerous factors. The complement system plays an important role in host defense and inflammation and is involved in first-line immunity and/or pathogenesis of severe organ disorders. In this study, we investigated the role of aberrant complement activation in MHV-3 infection-induced FHF by strategies that use C3-deficient mice and intervene in the complement system. Our results showed that mice deficient in C3 had more severe liver damage, a higher viral load in the liver and higher serum concentrations of inflammatory cytokines than wild-type controls. Treatment of C57BL/6 mice with C3aR antagonist or anti-C5aR antibody reduced liver damage, viral load, and serum IFN-γ concentration compared with the control group. These findings indicated that complement system acts as a double-edged sword during acute MHV-3 infection. However, its dysregulated activation leads to sustained inflammatory responses and induces extensive liver damage. Collectively, by investigating the role of complement activation in MHV-3 infection, we can further understand the pathogenic mechanism of betacoronavirus, and appropriate regulation of immune responses by fine-tuning complement activation may be an intervention for the treatment of diseases induced by betacoronavirus infection. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the mechanisms of 4 effective components from a Chinese medicine formula, namely Qingre Huoxue Jiedu Formula (QHJ heat- and toxin-clearing and blood-activating formula), in the treatment of nerve growth factor (NGF)-induced psoriasis. Methods: Keratinocyte proliferation and T cell proliferation models were developed using NGF. An NGF solution (NGF+DMEM, 100 ng/mL) was added to all induced groups and treated groups and were cultured for 24 h, while a solution with NTRK1 antagonist (K252a+DEME, 300 nmol/L) was added and cultured for 1 h. The models were used to evaluate the effects of the treatment with each of the 4 components of QHJ, namely shikonin, paeonol, astilbin and ursolic acid. Cell apoptosis and proliferation were measured by flow cytometry analysis and CCK8 assay, respectively. The mRNA expression levels of Bax, Bcl-xl, and NGF receptor (NGFR) were assessed by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. Results: (1) All QHJ-treated groups showed significantly increased cell apoptosis and inhibition of cell proliferation compared with the NGF-induced groups (P<0.05). In addition, treatment with QHJ plus NTRK1 significantly enhanced cell apoptosis and inhibition of cell proliferation compared with cells treated with QHJ only (P<0.05), particularly in cells treated with ursolic acid. (2) QHJ-treated groups showed higher protein expression levels of Bax, Bcl-xl compared with other groups (P<0.05). Additionally, treatment with QHJ plus NTRK1 significantly increased the protein expression levels of Bax, Bcl-xl and NGFR compared with those treated with QHJ only (all P<0.05), especially in those treated with shikonin. Conclusion: The action mechanism of QHJ on psoriasis might be through enhancing cell apoptosis and inhibition of cell proliferation, and upregulating the expression level of Bax, Bcl-xl and NGFR. [ABSTRACT FROM AUTHOR]

In recent decades, exploring potential relationships between diseases has been an active research field. With the rapid accumulation of disease-related biomedical data, a lot of computational methods and tools/platforms have been developed to reveal intrinsic relationship between diseases, which can provide useful insights to the study of complex diseases, e.g. understanding molecular mechanisms of diseases and discovering new treatment of diseases. Human complex diseases involve both external phenotypic abnormalities and complex internal molecular mechanisms in organisms. Computational methods with different types of biomedical data from phenotype to genotype can evaluate disease–disease associations at different levels, providing a comprehensive perspective for understanding diseases. In this review, available biomedical data and databases for evaluating disease–disease associations are first summarized. Then, existing computational methods for disease–disease associations are reviewed and classified into five groups in terms of the usages of biomedical data, including disease semantic–based, phenotype-based, function-based, representation learning–based and text mining–based methods. Further, we summarize software tools/platforms for computation and analysis of disease-disease associations. Finally, we give a discussion and summary on the research of disease–disease associations. This review provides a systematic overview for current disease association research, which could promote the development and applications of computational methods and tools/platforms for disease–disease associations. [ABSTRACT FROM AUTHOR]

Dianthi herba (called "Qumai" in Chinese) is the dried aerial part of Dianthus superbus L. and Dianthus chinensis L. The species are mainly distributed in the temperate and warm temperate regions in the northern hemisphere, and some regions in Africa and Oceania, as well as South America. However, the distribution pattern of Dianthi herba has not been reviewed. In this review, we summarize the research progress on the botany, traditional use, phytochemistry, pharmacology, toxicology, and clinical applications of Dianthi herba. Approximately 194 chemical compounds have been identified and isolated from Dianthi herba, the most important being triterpenoid saponins, flavonoids, and volatile oil compounds. These compounds possess antiviral, anticancer, antioxidant, and antimicrobial properties, inter alia. Further studies should be carried out on Dianthi herba to elucidate more of its active principles and their mechanisms of action. [ABSTRACT FROM AUTHOR]

Background: Shanzhuyu (the dried mature sarcocarp of Cornus officinalis Sieb. et Zucc., DMSCO) is a Chinese herb that can be used for the treatment of Alzheimer's disease (AD), but its mechanism remains unknown. The present study aimed to investigate the active ingredients and effective mechanisms of DMSCO for the treatment of AD based on a network pharmacology approach. Methods: The active components of DMSCO were collected from the TCMSP and ETCM databases and the target proteins of these compounds were predicted using TCMSP, SwissTargetPrediction and the STITCH database. The AD-related target proteins were identified from the OMIM, DisGeNet, GEO and GeneCards databases. The network interaction model of the compound-target-disease was established and was used to obtain the key targets of DMSCO on AD through network topology analysis. Subsequently, gene enrichment in Gene Ontology (GO) and KEGG pathways were conducted using the David 6.8 online tool. Results: A total of 30 DMSCO effective compounds and 209 effective drug targets were obtained. A total of 172 AD-related genes and 37 shared targets of DMSCO and AD were identified. A total of 43 key targets for the treatment of AD were obtained from the topological analysis of the DMSCO-AD target network. These key targets were involved in a variety of biological processes, including amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress and pathways, such as the PI3K-AKT, MAPK and TNF pathways. Three key compounds, namely ursolic acid, anethole and ß-sitosterol were obtained from the analysis of the key targets. Conclusions: Ursolic acid, anethole and ß-sitosterol may be the main active components of DMSCO in the treatment of AD. DMSCO can treat AD by regulating amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress via the PI3K-AKT, MAPK and other signaling pathways. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) remains an incurable hematological malignancy characterized by proliferation and accumulation of plasma cells in the bone marrow. Innovative and effective therapeutic approaches that are able to improve the outcome and the survival of MM sufferers, especially the identification of novel natural compounds and investigation of their anti-MM mechanisms, are needed. Here, we investigated the effects and the potential mechanisms against MM of forskolin, a diterpene derived from the medicinal plant Coleus forskohlii, in MM cell line MM.1S. CCK-8 assay showed that forskolin significantly inhibited MM.1S cells viability in a time- and dose-dependent manner. Furthermore, we demonstrated that forskolin induced G2/M phase arrest with a remarkable increase of p-cdc25c, p-cdc2, and a decrease of cyclin B1, indicating the suppression of cdc25C/cdc2/cyclin B pathway. Moreover, we found that forskolin induced mitochondrion-dependent apoptosis which was accompanied by the increase of pro-apoptotic proteins Bax, Bad, Bim and Bid, the decrease of anti-apoptotic proteins Bcl-2 and Bcl-xl, the changes of the mitochondrial membrane potential (MMP) and increase of cleaved caspase-9, cleaved caspase-3 and cleaved PARP. Of note, we demonstrated that forskolin induced a decrease of p-C-Raf, p-MEK, p-ERK1/2 and p-p90Rsk, and an increase of p-PERK, p-eIF2α and CHOP, which indicated that the inhibition of Raf/MEK/ERK pathway and activation of PERK/eIF2α/CHOP pathway were involved, at least partially, in forskolin-induced MM.1S cells apoptosis. These findings confirm the anti-MM action of forskolin and extend the understanding of its anti-MM mechanism in MM.1S cells, as well as reinforcing the evidence for forskolin as a natural chemotherapeutic compound against MM. [ABSTRACT FROM AUTHOR]

Background: Long-term chemotherapy reduces the sensitivity of colon cancer cells to chemotherapeutics like vincristine (VCR) and lead to drug resistance, which has become a major barrier for colon cancer treatment. Calcium antagonists are used as clinical tumor multidrug resistance reversal agents to regulate the P-glycoprotein (P-gp) level and block efflux pump function now, but they have significant side effects. Hyperin as active component with low toxicity in traditional Chinese medicine has calcium antagonistic effect. Thus, the purpose of this study was to evaluate the in hibitory effect of hyperin on the growth of HCT8/VCR colon cancer cell line (vincristine-resistant) and analyze the enhancing effect of hyperin on the sensitivity of cancer cells to VCR and its relationship to the expression and function of P-gp. Methods: Using the MTT method, we investigated the influence of hyperin, VCR alone, and hyperin plus VCR on the growth of HCT8/VCR cells. Western blot analysis was employed to detect the expression of P-gp, and flow cytometry was used to evaluate P-gp function by detecting the fluorescence intensity of intracellular Rho123. Results: The inhibitory effect of hyperin at the dose of 12.5 µM on HCT8/VCR cell growth was not enhanced as time progressed and no significant inhibitory effect was found for VCR-treated cells at the dose of 2 µM. But the inhibition of cell growth was observed aft er the combined treatment of hyperin (12.5 µM) and VCR (2 µM). P-gp expression levels in HCT8/VCR cells treated with hyperin plus VCR were markedly lower than the levels in control cells and those treated with VCR. In addition, the intensity of Rho123 fluorescence of HCT8/VCR cells treated with hyperin plus VCR or hyperin alone was significantly higher than intensity observed in control cells and those treated with VCR alone. Conclusions: Hyperin synergistically augments the growth inhibitory effect of vincristine. The underlying mechanism most probably involves down-regulation of P-gp expression and inhibiting the function of the P-gp pump in HCT8/VCR cells. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese medicine (TCM) has gained widespread application in treating chronic heart failure (CHF) secondary to coronary heart disease (CHD). However, the sound clinical evidence is still lacking. Corresponding clinical trials vary considerably in the outcome measures assessing the efficacy of TCM, some that showed the improvement of clinical symptoms are not universally acknowledged. Rational outcome measures are the key to evaluate efficacy and safety of each treatment and significant elements of a convincing clinical trial. We aimed to summarize and analyze outcome measures in randomized controlled trials (RCTs) of TCM in treating CHF caused by CHD, subsequently identify the present problems and try to put forward solutions. Methods: We systematically searched databases including Embase, PubMed, Cochrane Library, CBM, CNKI, VIP and Wanfang from inception to October 8, 2018, to identify eligible RCTs using TCM interventions for treating CHF patients caused by CHD. Cochrane Database of Systematic Reviews (CDSR) was searched to include Cochrane systematic reviews (CSRs) of CHF. Two authors independently assessed the risk of bias of the included RCTs according to the Cochrane Handbook. Outcome measures of each trial were extracted and analyzed those compared with the CSRs. We also evaluated the reporting quality of the outcome measures. Results: A total of 31 RCTs were included and the methodology quality of the studies was generally low. Outcome measures in these RCTs were mortality, rehospitalization, efficacy of cardiac function, left ventricular ejection fraction (LVEF), 6 min' walk distance (6MWD) and Brain natriuretic peptide (BNP), of which mortality and rehospitalization are clinical end points while the others are surrogate outcomes. The reporting rate of mortality and rehospitalization was 12.90% (4/31), the other included studies reported surrogate outcomes. As safety measure, 54.84% of the studies reported adverse drug reactions. Two trials were evaluated as high in reporting quality of outcomes and that of the other 29 studies was poor due to lack of necessary information for reporting. Conclusions: The present RCTs of TCM in treating CHF secondary to CHD did not concentrate on the clinical end points of heart failure, which were generally small in size and short in duration. Moreover, these trials lacked adequate safety evaluation, had low quality in reporting outcomes and certain risk of bias in methodology. For objective assessment of the efficacy and safety of TCM in treating CHF secondary to CHD, future research should be rigorous designed, set end points as primary outcome measures and pay more attention to safety evaluation throughout the trial. [ABSTRACT FROM AUTHOR]

Keywords: stroke; epilepsy; multiple sclerosis; dementia; neurodegenerative diseases EN stroke epilepsy multiple sclerosis dementia neurodegenerative diseases 1 3 3 05/02/22 20220427 NES 220427 Neurological disorders affect the central and peripheral nervous systems by impairing the function of brain, spinal cord and peripheral nerves. Stroke, epilepsy, multiple sclerosis, dementia, neurodegenerative diseases. [Extracted from the article]

The COronaVIrus Disease 2019 (COVID-19), which developed into a pandemic in 2020, has become a major healthcare challenge for governments and healthcare workers worldwide. Despite several medical treatment protocols having been established, a comprehensive rehabilitation program that can promote functional recovery is still frequently ignored. An online consensus meeting of an expert panel comprising members of the Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation was held to provide recommendations for rehabilitation protocols in each of the five COVID-19 stages, namely (1) outpatients with mild disease and no risk factors, (2) outpatients with mild disease and epidemiological risk factors, (3) hospitalized patients with moderate to severe disease, (4) ventilator-supported patients with clear cognitive function, and (5) ventilator-supported patients with impaired cognitive function. Apart from medications and life support care, a proper rehabilitation protocol that facilitates recovery from COVID-19 needs to be established and emphasized in clinical practice. [ABSTRACT FROM AUTHOR]

Liver plays a critical role in metabolism, nutrient storage and detoxification. Emergency signals or appropriate immune response leads to pathological inflammation and breaks the steady state when liver dysfunction appears, which makes body more susceptible to chronic liver infection, autoimmune diseases and tumour. Compelling proof has illustrated the non‐redundant importance of C‐C chemokine receptor type 2 (CCR2), one of G‐protein‐coupled receptors, in different diseases. Selectively expressed on the surface of cells, CCR2 is involved in various signalling pathways and regulates the migration of cells. Especially, a peculiar role of CCR2 has been identified within decades in the onset and progression of hepatic diseases, which led to particular focusing on CCR2 as a new therapeutic and diagnostic target for non‐alcoholic fatty liver disease and hepatocellular carcinoma. In this review, we discuss the effect of CCR2 in monocytes/macrophages on liver diseases. The application and translation of the decades of discoveries into therapies promise novel approaches in the treatment of liver disease. [ABSTRACT FROM AUTHOR]

Saposhnikovia divaricata (Turcz.) Schischk., a perennial herb belonging to the family Umbelliferae, is widely distributed in Northeast Asia. Its dried root (Radix Saposhnikoviae) is used as a Chinese herbal medicine for the treatment of immune system, nervous system, and respiratory diseases. Phytochemical and pharmacological studies have shown that the main constituents of S. divaricata are chromones, coumarins, acid esters, and polyacetylenes, and these compounds exhibited significant anti-inflammatory, analgesic, antioxidant, antiproliferative, antitumor, and immunoregulatory activities. The purpose of this review is to provide comprehensive information on the botanical characterization and distribution, traditional use and ethnopharmacology, phytochemistry, and pharmacology of S. divaricata for further study concerning its mechanism of action and development of better therapeutic agents and health products from S. divaricata. [ABSTRACT FROM AUTHOR]

With improved standards of living, the incidence of multiple metabolic disorders has increased year by year, especially major risk factors for cardiovascular disease such as hyperglycemia and hyperlipidemia, continues to increase. Emerging epidemiological data and clinical trials have shown the additional protective effects of some metabolic therapy drugs against cardiovascular diseases. A series of studies have found that these drugs may work by modulating the composition of gut microbiota. In this review, we provide a brief overview of the contribution of the gut microbiota to both metabolic disorders and cardiovascular diseases, as well as the response of gut microbiota to metabolic therapy drugs with cardiovascular benefits. In this manner, we link the recent advances in microbiome studies on metabolic treatment drugs with their cardiovascular protective effects, suggesting that intestinal microorganisms may play a potential role in reducing cardiovascular risk factors. We also discuss the potential of microorganism-targeted therapeutics as treatment strategies for preventing and/or treating cardiovascular disease and highlight the need to establish causal links between therapeutics for metabolic diseases, gut microbiota modulation, and cardiovascular protection. [ABSTRACT FROM AUTHOR]

Objective. To systematically evaluate the effectiveness of Shenqi Jiangtang granule (SQJT) in the treatment of type 2 diabetes. Methods. We searched CNKI, Wanfang Data, VIP, and PubMed databases to collect randomized controlled trials (RCT) of Shenqi Jiangtang granules in the treatment of type 2 diabetes. The search time was from January 2014 to the present. Data were extracted, and quality was evaluated. Metadata analysis of the extracted data was carried out using RevMa5.2 software. The final results are expressed in relative risk (RR), mean difference (MD), and 95% CI. Results. This study included a total of 13 studies, 1160 subjects. Meta-analysis results showed that the test group was better than the control group (RR = 1.26, 95% CI 1.18–1.34, P < 0.00001). The fasting blood glucose, postprandial blood glucose, and glycated hemoglobin of the test group were also significantly better than those of the control group. Conclusion. Shenqi Jiangtang granules have a certain clinical effect and low adverse reaction rate for the treatment or adjuvant treatment of type 2 diabetes. At present, the drug has been widely used in clinical practice, but a large number of large-sample clinical trials are needed to further verify its specific efficacy and safety. [ABSTRACT FROM AUTHOR]

Hydrogen, one of the most well-known natural molecules, has been used in numerous medical applications owing to its ability to selectively neutralize cytotoxic reactive oxygen species and ameliorate hazardous inflammations. Hydrogen can exert protective effects on various reactive oxygen species-related diseases, including the transplantation-induced intestinal graft injury, chronic inflammation, ischemia-reperfusion injuries, and so on. Especially in the eye, hydrogen has been used to counteract multiple ocular pathologies in the ophthalmological models. Herein, the ophthalmological utilizations of hydrogen are systematically reviewed and the underlying mechanisms of hydrogen-induced beneficial effects are discussed. It is our hope that the protective effects of hydrogen, as evidenced by these pioneering studies, would enrich our pharmacological knowledge about this natural element and cast light into the discovery of a novel therapeutic strategy against ocular diseases. [ABSTRACT FROM AUTHOR]

Internal jugular vein stenosis (IJVS) results in poor venous outflow and can result in intracranial hypertension. Venous stenting has become a debated topic for correction of this pathology. A 49-year-old male merchant with bilateral IJVS presented with headache, dizziness, and pulsatile tinnitus. He was found to have intracranial hypertension and left IJVS caused by styloid process compression and right IJVS caused by damage of the venous intima. His symptoms improved after undergoing styloidectomy followed by left intra–internal jugular vein (IJV) balloon. However, 1 year later, the prior symptoms reoccurred. At this time, the patient underwent right intra-IJV stenting. After treatment of the contralateral side, the symptoms resolved during the following 3 months. The clinical practice in this case indicated that in patients with bilateral IJVS, a 2-side intervention may be necessary when unilateral correction fails. We advise a staged approach to correction of bilateral IJVS. Styloid compression–induced IJVS should be corrected by styloidectomy in combination with balloon and/or stenting, whereas IJVS induced by venous wall issues needs only stenting. [ABSTRACT FROM AUTHOR]

Heat shock protein 90α (HSP90α) maintains cell stabilization and regulates cell death, respectively. Recent studies have shown that HSP90α is involved in receptor interacting protein 3 (RIP3)‐mediated necroptosis in HT29 cells. It is known that oxygen and glucose deprivation (OGD) can induce necroptosis, which is regulated by RIP3 in neurons. However, it is still unclear whether HSP90α participates in the process of OGD‐induced necroptosis in cultured neurons via the regulation of RIP3. Our study found that necroptosis occurs in primary cultured cortical neurons and PC‐12 cells following exposure to OGD insult. Additionally, the expression of RIP3/p‐RIP3, MLKL/p‐MLKL, and the RIP1/RIP3 complex (necrosome) significantly increased following OGD, as measured through immunofluorescence (IF) staining, Western blotting (WB), and immunoprecipitation (IP) assay. Additionally, data from computer simulations and IP assays showed that HSP90α interacts with RIP3. In addition, HSP90α was overexpressed following OGD in cultured neurons, as measured through WB and IF staining. Inhibition of HSP90α in cultured neurons, using the specific inhibitor, geldanamycin (GA), and siRNA/shRNA of HSP90α, protected cultured neurons from necrosis. Our study showed that the inhibitor of HSP90α, GA, rescued cultured neurons not only by decreasing the expression of total RIP3/MLKL, but also by decreasing the expression of p‐RIP3/p‐MLKL and the RIP1/RIP3 necrosome. In this study, we reveal that inhibition of HSP90α protects primary cultured cortical neurons and PC‐12 cells from OGD‐induced necroptosis through the modulation of RIP3 expression. [ABSTRACT FROM AUTHOR]

Objective: There is still no consensus on the treatment for periodic limb movement in sleep (PLMS). This study aimed to determine the efficacy and tolerability of rotigotine in patients suffering from PLMS. Methods: Publications listed in PubMed, ScienceDirect, The Cochrane Library, and ClinicalTrials.gov were reviewed to assess the efficacy of rotigotine on PLMS. Analyses of PLMS frequency before and after rotigotine treatments (pre- and post-intervention studies) and PLMS frequency between placebo and rotigotine treatments (placebo-controlled trial studies) were included in our study. A systematic review and meta-analysis was conducted. Results: Five publications involving 197 participants were included in this study. Among these articles, pre- and post-intervention data involving 55 participants were available from three articles, while placebo-controlled trial data from 107 participants receiving rotigotine and 70 participants receiving a placebo were available from an additional three articles. In the pre- and post-intervention studies, the periodic limb movement index was significantly decreased after therapy with rotigotine with a difference in means of −5.866/h (95% CI, −10.570 to −1.162, p = 0.015). In comparison with the placebo, the use of rotigotine significantly lowered the periodic limb movement index, with a difference in means of −32.105/h (95% CI, −42.539 to −21.671, p < 0.001), reduced the PLMS with arousal index, with a difference in means of −7.160/h (95% CI, −9.310 to −5.010, p < 0.001), and increased the withdrawal rate, with an odds ratio of 3.421 (95% CI, 1.230 to 9.512, p = 0.018). Conclusions: This meta-analysis revealed the considerable efficacy of rotigotine in alleviating the frequency of PLMS. However, the high withdrawal rate should be taken into account. [ABSTRACT FROM AUTHOR]

Background: The metastasis of breast cancer is the leading cause of death, while lung metastasis is a major clinical phenomenon in patients with invasive breast cancer. The current treatment option comprising surgery, radiation, and standard chemotherapy cannot achieve a satisfactory effect on the treatment of lung metastasis of breast cancer. In this study, we report the potential of preventing lung metastasis of invasive breast cancer using the newly developed functional vincristine plus dasatinib liposomes. Methods: The investigations were performed on invasive breast cancer MDA-MB-231 cells in vitro and in lung metastatic model of invasive breast cancer MDA-MB-231 cells in nude mice. Results: The functional drug liposomes were able to induce cell cycle arrest at G2 /M phase, induce apoptosis, inhibit adhesion, migration, and invasion of breast cancer cells in vitro, and prevent lung metastasis of breast cancer in nude mice. Conclusion: These findings indicate a potential clinical use of functional vincristine plus dasatinib liposomes for treating metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Low-grade central osteosarcoma is a rare subtype of tumor with low-grade malignancy. Currently, wide resection with negative resection margin is the standard treatment for this disease. The role of neoadjuvant chemotherapy in low-grade central osteosarcoma was controversial and was mostly considered for tumors containing high-grade focal areas. Local tumor recurrences often exhibited a tumor with higher histologic grade or differentiation with the potential for metastases. In low-grade central osteosarcoma, timely wide resection after definite diagnosis can result in 5-year survival for almost 90%. However, the relatively nonspecific radiological and pathological findings make diagnosis very difficult. MDM2 and CDK4 are specific and provide sensitive markers for the diagnosis of low-grade central osteosarcoma, helping to differentiate low-grade central osteosarcoma from some benign lesions, including fibrous dysplasia, bone giant cell tumor, and chondrosarcoma. Here, we report the case of a 19-year-old woman with low-grade central osteosarcoma located at the proximal humerus. The affected site was rare, but the sensitive biomarkers CDK4 and MDM2 were positive. The patient recovered well after wide tumor resection following a proximal humerus endoprosthesis replacement. Our case highlighted the management strategies in low-grade central osteosarcoma. Being familiar with radiographic features, understanding the biological characteristics, and mastering diagnostic biomarkers can help oncologists avoid embarrassing situations in treatment when this rare tumor is highly suspected, even when located at an uncommon site. The discussion in this report focuses on radiographic and pathological features, advances of biomarkers that help in differential diagnosis, and current treatment options in low-grade central osteosarcoma. [ABSTRACT FROM AUTHOR]

Recent studies suggest an anti-inflammatory activity of oxyresveratrol, a stilbene extracted from Cortex mori root used in traditional Chinese medicine that also presents estrogen-like activity. We herein tested the hypothesis that oxyreservatrol exerts an anti-inflammatory effect through its estrogenic-like function. In MCF-7 cells, oxyresveratrol significantly induced proliferation, which was accompanied with estrogen receptor (ER)-mediated transcriptional activation, increased estrogen-targeted gene expression ( e.g., pS2, PGR, and CTSD), and increased ERα/β proteins. The estrogen-like effect of oxyresveratrol was reversed by the ER inhibitor ICI 182780. Strong ER-binding activities of oxyresveratrol were revealed by negative docking scores. The LPS-induced inflammatory response ( e.g., upregulated IκB-α phosphorylation, NF-κB nuclear translocation, and cytokine messenger RNA expression) was significantly suppressed in an ER-dependent manner by oxyresveratrol in RAW264.7 cells. These results suggest that oxyresveratrol may function as an ER agonist and modulate NF-κB signaling. [ABSTRACT FROM AUTHOR]

Cadmium (Cd), a highly ubiquitous heavy metal, induces neurotoxicity. Melatonin, a major secretory product of the pineal gland, protects against Cd-induced neurotoxicity. However, the mechanism that accounts for this protection remains to be elucidated. Herein, we exposed mouse neuroblastoma cells (Neuro-2a cells) to different concentrations of cadmium chloride (CdCl2) (12.5, 25, and 50 μ mol L−1) for 24 hours. We showed that Cd inhibits autophagosome-lysosome fusion and impairs lysosomal function, subsequently leading to nerve cell death. In addition, Cd decreases the level of transcription factor EB ( TFEB) but induces the nuclear translocation of TFEB, associated with compromised lysosomal function or a compensatory effect after the impairment of the autophagic flux. Moreover, compared to the 50-μ mol L−1 Cd group, administration of 1 μ mol L−1 melatonin increased ' TFEB-responsive genes' ( P<.05) and the levels of lysosomal-associated membrane protein (0.57±0.06 vs 1.00±0.11, P<.05), preserved lysosomal protease activity (0.52±0.01 vs 0.90±0.02, P<.05), maintained the lysosomal pH level (0.50±0.01 vs 0.87±0.05, P<.01), and enhanced autophagosome-lysosome fusion (0.05±0.00 vs 0.21±0.01, P<.01). Notably, melatonin enhanced TFEB expression (0.37±0.04 vs 0.72±0.07, P<.05) and nuclear translocation (2.81±0.08 vs 3.82±0.05, P<.05). Tfeb si RNA blocked the melatonin-mediated elevation in autophagy-lysosome machinery in Cd-induced neurotoxicity ( P<.01). Taken together, these results uncover a potent role for TFEB-mediated autophagy in the pathogenesis of Cd-induced neurotoxicity, suggesting that control of the autophagic pathway by melatonin might provide an important clue for exploring potential targets for novel therapeutics of Cd-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Formaldehyde (FA), a well-known carbonyl species, plays a crucial role in physiological function and is produced endogenously via enzymatic pathways. However, an abnormal concentration of FA is closely related with various types of diseases, including Alzheimer's disease, cancer and diabetes. Thus, it is significant to real-time visualize the changes in FA in organisms. In this study, we engineered a unique two-photon probe for sensing FA based on a coumarin derivative as a two-photon reporter and a homoallylamino group as the responsive site. In the presence of FA, the probe showed good selectivity, a low detection limit and high stability. Significantly, its successful application in living cells and zebrafish showed that this probe has the ability to sense FA with the desirable two-photon mode. Moreover, with its feature of high resolution, the three-dimensional imaging of living tissues exhibited remarkable fluorescence signal changes with/without the treatment of FA with this probe in the two-photon mode. Therefore, this probe is a powerful molecular tool for sensing FA in living systems. [ABSTRACT FROM AUTHOR]

Background and objectives: An invasive approach is recommended as the treatment of patients with non-ST elevated acute coronary syndromes (NSTE-ACS). However, it remains unclear that the optimal time of angiography and intervention for patients with NSTE-ACS at present. This study was designed to compare the effect of early and delayed invasive strategies on short-medium term prognosis in patients with those. Methods: Pubmed, Cochrane Library and Embase were searched up to Dec-30-2018. Randomized clinical trials comparing an early versus a delayed invasive strategy in patients with NSTE-ACS were included. The primary endpoint (all-cause death and recurrent myocardial infarction) and secondary endpoint (major bleeding and recurrent revascularization), as well as composite endpoint were assessed by random or fixed effected meta-analysis with software RevMan 5.3 version after short-medium term follow up. Result: A total of six randomized clinical trials involving 4,277 early or delayed invasive strategies patients with NSTE-ACS were included in the meta-analysis. Time to coronary angiography varied from 0.5 to 24 h in the early invasive strategy and from 18.6 to 72 h in the delayed invasive strategy. There was a statistical difference in the primary endpoint of all-cause death among patients with NSTE-ACS between early and delayed invasive strategies (4.6% vs 6%; OR:0.76; 95% CI:0.58 to 1.00; P = 0.05; I2 = 0%), but not for recurrent myocardial infarction (6.0% vs 6.3%; OR: 0.94; 95% CI: 0.55 to 1.61; P = 0.82; I2 = 60%). The major bleeding in patients with NSTE-ACS was similar between both invasive strategies (2.7% vs 3.1%; OR:0.88; 95% CI:0.59 to 1.31; P = 0.54; I2 = 0%). However, the composite endpoint in the early invasive strategy patients with NSTE-ACS was significantly lower than that of the delayed invasive strategy (10.9% vs 13.9%; OR:0.76; 95% CI:0.63 to 0.92; P = 0.006; I2 = 0%), and the recurrent revascularization between both strategies was just the opposite (8.7% vs 5.9%; OR:1.5; 95%CI:1.15 to 1.97; P = 0.003; I2 = 0%). Conclusion: The systematic review and meta-analysis demonstrated that the early invasive strategy had a beneficial trend on all-cause death and significantly reduced the composite endpoint in patients with NSTE-ACS, but increased the rate of revascularization. These data could provide a solution for patients with those. [ABSTRACT FROM AUTHOR]

We aimed to compare the clinical efficacy of titanium mesh cage with that of allogeneic bone graft to reconstruct the anterior column through posterior approach for the surgical management of patients with thoracolumbar spinal tuberculosis with kyphosis. From January 2011 to March 2013, 57 patients with single-segment or two-segments thoracolumbar spinal tuberculosis with kyphosis were treated by debridement, interbody graft, posterior instrumentation, and fusion via a posterior-only procedure. Twenty-four patients in group A were treated with allogeneic bone graft to reconstruct the anterior column, whereas 33 patients in group B were treated with titanium mesh cage. The clinical efficacy was evaluated by visual analog scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neurologic function recovery, kyphotic Cobb angle, and postoperative complications. The mean follow-up was 72.4 months. Neurologic function was significantly improved after surgery in all cases. There were significant differences of VAS, ESR, and CRP between preoperation and postoperation at the final follow-up, with no significant difference between the two groups. The kyphotic Cobb correction was significantly improved when compared with those in preoperation, but there was no significant difference between the two groups. One patient in group A with two segments involved experienced graft fracture. He had anterior bone graft with titanium mesh cage. Minimum 5-year follow-up outcomes showed that one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation, and fusion is an effective treatment for patients with thoracolumbar spinal tuberculosis accompanied by kyphosis. It may obtain better clinical efficacy than allogeneic bone graft for treating two-segments thoracolumbar spinal tuberculosis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and safety of Chinese herbs in the treatment of sub-health systematically. Methods: Nine databases were systematically and extensively searched to collect randomized controlled trials (RCTs) about Chinese herbs in the treatment of sub-health. The outcomes included overall effective rate, main symptoms, quality of life, etc. Literature screening, data extraction and quality assessment were conducted according to Cochrane Handbook 5.1. Meta-analysis was conducted to the included literature with Review Manager Software. Results: Seventy-two studies involving 9,296 patients with sub-health were included with 4,908 patients in experimental groups and 4,387 patients in control groups. The overall quality of included clinical research was not high. In the aspect of improving overall effective rate, relieving main symptoms, Pittsburgh sleep quality index (PSQI) score, Athens Insomnia Scale (AIS) score, Fatigue Scale-14 (FS-14), Cornell Medical Index (CMI) score and discontinuation rate, the effects of experimental groups were better than that of control groups. According to available research reports, adverse reactions in Chinese herb groups were mainly mild gastrointestinal symptoms, which did not affect the treatment. Conclusion: Chinese herbs have a curative effect in the treatment of sub-health. However, there are no clear criteria for diagnosis and curative effectiveness judgment globally, which would affect the accuracy of curative effect evaluation. [ABSTRACT FROM AUTHOR]

OBJECTIVE. We investigated the effects on motor and daily function of robot-assisted therapies in people with chronic stroke using the Bi-Manu-Track (BMT) and InMotion 3.0 (IMT) compared with control treatment (CT). METHOD. In this comparative efficacy trial, 30 participants were randomized to receive BMT, IMT, or CT. Outcome measures included the Fugl-Meyer Assessment (FMA), Modified Ashworth Scale (MAS), Motor Activity Log (MAL), and Medical Research Council (MRC) scale. RESULTS. The IMT group improved more in FMA and proximal MAS scores than the BMT group (both ps < .01) and the CT group (p < .01 and p = .03, respectively). The IMT and BMT groups showed clinically relevant improvements after treatment on the MRC rather than the MAL. CONCLUSION. The results indicate that the IMT might improve motor function. The IMT and BMT groups showed similar benefits for muscle power but limited improvements in self-perceived use of the affected arm. [ABSTRACT FROM AUTHOR]

To investigate the clinical characteristics of acute myeloid leukemia (AML) with biliary obstruction as the first manifestation and explore the treatment options. A retrospective analysis was performed on a case of AML with biliary obstruction as the first manifestation admitted to the First Affiliated Hospital of Jishou University (Jishou, China). The relevant laboratory examination, imaging, pathological results and treatment strategies were analyzed. The patient was a 44-year-old male with an initial manifestation of biliary obstruction. Combined with the results of laboratory tests and bone marrow aspiration, the patient was diagnosed with AML and was treated with an IA regimen (idarubicin 8 mg d1-3, cytarabine 0.2 d1-5). After 2 courses of treatment, complete response was achieved, the liver function returned to normal and the biliary obstruction disappeared. The initial symptoms of AML are varied, and always combine with multi-system organ damage. Early diagnosis and active treatment of primary diseases are the keys to improving the prognosis of these patients. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the five year clinical and radiographic outcome of unilateral open-door laminoplasty with alternative levels centerpiece mini-plate fixation for cervical compressive myelopathy.Methods: From August 2009 to June 2010, 56 patients with cervical compressive myelopathy underwent unilateral open-door laminoplasty with alternative levels centerpiece mini-plate fixation with a mean age of 64.8 years. Clinical results were investigated including Japanese Orthopedic Association (JOA) scores, Neck Dysfunction Index (NDI), occurrences of complications and neurological deterioration. Radiographic results including cervical alignments, cervical range of motion (ROM), spinal canal enlargement and spinal cord decompression were assessed on X-ray, three-dimensional CT and MRI.Results: The mean follow-up period was 59.2 months (range 53∼64 months), and all patients achieved osseous fusion at hinge side at an average of 6.8 months after operation. The average cost from admission to discharge is $9817.9. Compared to previous all-level fixation, the cost decreased nearly 40 %. During the follow-up, all patients showed a significant improvement in the JOA score and NDI score. A 23.2 % incidence of axial neck pain were also observed; Significant enlargement of the spinal canal and spinal cord drift was achieved and well maintained, overall cervical ROM decreased by 27.1 % (mean 12.9° loss) at the final follow-up and cervical lordosis decreased slightly in all patients without statistic difference. No instrumentation failure or lamina reclosure was observed in our study. Comparing mini-plate segments and suture segments, the mean AP diameter and Pavlov's ratio at the final follow-up showed no statistic difference, only open angle at the final follow-up showed significant decrease.Conclusions: Unilateral open-door laminoplasty with alternative levels centerpiece mini-plate fixation is a safe, effective and economical surgical method for cervical compressive myelopathy and the five year result is satisfactory. [ABSTRACT FROM AUTHOR]

Purinergic P2X3 receptors (P2X3Rs) play extensive roles in nerve cells in the central nervous system, particularly in hyperexcitability and calcium (Ca) influx. However, the role of P2X3Rs in epilepsy has not been previously investigated. To determine the relationship between P2X3Rs and epilepsy, the expression and cellular location of P2X3Rs in patients with intractable temporal lobe epilepsy (TLE) and in a lithium chloride-pilocarpine-induced chronic rat model of epilepsy were assessed. Furthermore, the function of P2X3Rs was assessed in vitro. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used to evaluate the expression levels of P2X3Rs in brain tissues from TLE patients and an epileptic rat model, whereas immunofluorescence labeling was applied to determine the distribution of target proteins. Whole-cell recording was subsequently performed to identify the influence of P2X3Rs on seizure-like discharges. P2X3Rs were located at the cell bodies and dendrites of neurons with significantly increased expression in the TLE patients and epileptic rat model. In vitro, P2X3R activation accelerated sustained repetitive firing, whereas P2X3R inhibition led to relatively low-frequency discharges. To the best of our knowledge, this is the first study provide evidence that upregulated P2X3R expression exists in both epileptic humans and rats and may aggravate the epileptic state in vitro. Thus, P2X3Rs may represent a novel therapeutic target for antiepileptic drugs. [ABSTRACT FROM AUTHOR]

Objective To investigate the six degrees of freedom (6 DOF) kinematics of anterior cruciate ligament ( ACL) deficient knees during gait and to explore the clinical significance of a novel knee joint stability assessment system (Opti_Knee, Innomotion, Shanghai, China) in comparison with imaging and arthroscopic examination. Methods Three subjects diagnosed with ACL deficient knees on the basis of preoperative MRI and CT findings were subjected to treadmill gait analysis. Motion of both knees in 6 DOF was measured and analyzed with an optical joint kinematics measurement system. Arthroscopic examination, the gold standard, was performed to confirm the final diagnosis and the clinical diagnosis of ACL deficiency by imaging and motion marker techniques compared with this gold standard. Results Only two of the three subjects diagnosed with ACL deficiency by imaging techniques were later confirmed to have this condition by arthroscopic examination; the third was found to have an intact ACL. When the kinematics of their injured and contralateral knees were compared, abnormalities were found in the two subjects confirmed by arthroscopy to be ACL deficient However, no kinematic difference between the two knees was found in the ACL intact subject. Conclusions Opti_Knee (Innomotion) can detect abnormal kinematics in ACL deficient knees and thus provides an effective way of assisting the diagnosis of this condition and has potential for clinical application. [ABSTRACT FROM AUTHOR]

Highlights • Silencing RGMa expression improved infarct volume, brain edema and neurological scores by ameliorating BBB dysfunction. • RGMa plays an important role in BBB recovery after I/R injury. • RGMa is involved in BBB recovery accompanied by up-regulation of CDC-42 and PAK-1 after I/R injury. Abstract Background Repulsive guidance molecule A (RGMa) is implicated in focal cerebral ischemia-reperfusion (I/R) injury, but its mechanisms are still largely unknown. This work focused on the effects of RGMa on the blood-brain barrier (BBB) after focal cerebral I/R injury. Methods Sprague-Dawley (SD) rats were randomly divided into four groups: sham, middle cerebral artery occlusion (MCAO)/reperfusion (I/R), MCAO/reperfusion administered recombinant adenovirus expressing sh-con (I/R + sh-con) and MCAO/reperfusion administered recombinant adenovirus expressing sh-RGMa (I/R + sh-RGMa) groups. Infarct volume, brain edema and neurological scores were evaluated at 3 day after reperfusion. Evens blue leakage and transmission electron microscopy was performed. And the expression level of claudin-5 and ZO-1, CDC-42 and PAK-1, RGMa were detected by western blot. Results Compared with I/R or I/R + sh-con groups, I/R + sh-RGMa group showed smaller infarction volume, attenuated brain edema, improved neurological scores and better BBB integrity, such as reduced Evans blue leakage and ultra-structural change. We also observed improved BBB function followed by down-regulation of MMP-9 and up-regulation of claudin-5 and ZO-1 in the I/R + sh-RGMa group. In addition, up-regulation of the CDC-42 and PAK-1 in the I/R + sh-RGMa group was obtained. Conclusions RGMa may be involved in I/R injury associated with BBB dysfunction via the CDC-42/PAK-1 signal pathway and may be a promising therapeutic target for I/R injury. [ABSTRACT FROM AUTHOR]

The aim of the present study was to observe the efficacy and safety of long-course treatment with tacrolimus combined with low-dose corticosteroids for idiopathic membranous nephropathy (IMN). A total of 76 patients with IMN diagnosed by renal biopsy between March 2012 and January 2016 form The First People's Hospital of Changzhou (Changzhou, China) were selected and randomly divided into a short-course group and a long-course group (each, n=38). Patients in the short-course group were treated with hormone combined with tacrolimus for 12 months, whereas those in the long-course group received the same treatment for 24 months. The efficacy, safety and recurrence of the two groups of patients were observed, and serum ALB, urine protein, Scr and blood glucose were assessed once a month for 24 months by measuring blood biochemistry. A total of 11 patients exhibited adverse effects, 6 of whom were serious and as such were excluded from the study. In the short-course group, 8 of 35 patients demonstrated complete remission (CR), 17 patients exhibited partial remission (PR) and the remaining 10 patients had no remission (NR); however the disease recurred in 8 patients following treatment. In the long-course group, 16 of 35 patients exhibited CR, 14 patients demonstrated PR and the remaining 5 patients had NR. Furthermore, the disease recurred in 4 patients following treatment. Significant differences were observed in urine protein and serum ALB at 18 and 24 months following treatment between the two groups while Scr and blood glucose had no significant differences at any time point. It was concluded that long-course tacrolimus combined with low-dose hormone effectively treats idiopathic membranous nephropathy and that therapy demonstrated a relatively high remission rate, and the recurrence rate of the disease is low. [ABSTRACT FROM AUTHOR]

Antibody dependent enhancement (ADE) has most often been associated with dengue virus (DENV). Studies using leukemia cell lines suggest that DENV specific antibodies can enhance Zika virus (ZIKV) infectivity, and vice versa. To examine the mechanisms of ADE of ZIKV infection in primary human cells, we assessed 40 serum samples obtained from convalescent DENV-1 or DENV-3 infected subjects. All sera tested exhibited high binding potency, while modest or none neutralization activities against ZIKV. Primary CD14+ monocytes, rather than B and T cells in peripheral blood mononuclear cells (PBMCs), were found to be the mediators of the enhancement of ZIKV infectivity by DENV immune sera. Monocyte-derived immature dendritic cells (DCs), but not mature DCs were highly permissive to ZIKV infection, whereas neither immature nor mature DCs could mediate enhanced ZIKV infection in the presence of DENV immune sera. In addition, antibody blocking of either FcγRI (CD64), or FcγRII (CD32), or FcγRIII (CD16) resulted in diminished ADE of ZIKV infection. Our findings provide an improved understanding of the pathogenesis of ZIKV infection, and inform rational vaccine design. [ABSTRACT FROM AUTHOR]

Objective. Up to 62% of perimenopausal women have depression symptoms. However, there is no efficacy treatment. The aim of this study is to compare the clinical efficacy and safety of EA therapy and escitalopram on perimenopause women with mild-moderate depressive symptom. Method. A multicenter, randomized, positive-controlled clinical trial was conducted at 6 hospitals in China. 242 perimenopause women with mild-moderate depressive symptom were recruited and randomly assigned to receive 36 sessions of EA treatment or escitalopram treatment. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HAMD-17). The secondary outcome measures include menopause-specific quality of life (MENQOL) and serum sexual hormones which include estrogen, follicle-stimulating hormone, and luteinizing hormone. Results. 221 (91.3%) completed the study, including 116 in the EA group and 105 in the escitalopram group. The baseline levels of demographic and outcome measurements were similar in the two groups. In the intervention period, there was no difference between two groups. However, in the follow-up, both HAMD-17 and MENQOL were significantly decreased, and at week 24 the mean differences were −2.23 and −8.97, respectively. There were no significant differences in the change of serum sexual hormones between the two groups. No serious adverse events occurred. Conclusion. EA treatment is effective and safe in relieving depression symptom and improving the quality of life in the perimenopausal depression. Further research is needed to understand long-term efficacy and explore the mechanism of this intervention. This study is registered with ClinicalTrials.gov NCT02423694. [ABSTRACT FROM AUTHOR]

Purpose: The development of next-generation sequencing (NGS) has revolutionized the understanding of oncogenesis of multiple types of cancer, including non-small cell lung cancer (NSCLC). However, there has been some debate over the utility of NGS for predicting patient prognosis and determining molecular targeted therapy. Therefore, we sought to demonstrate the numerous applications of NGS in the prognostic predictions and treatment of NSCLC patients.Materials and methods: We performed NGS on either liquid or tissue tumor biopsies obtained from 53 NSCLC patients. The sequences were analyzed for oncogenic mutations, which were then correlated to clinical prognosis and smoking history.Results: NGS of tumor biopsies detected both well-known driver mutations as well as rare or novel mutations. EGFR was the most frequently mutated gene, accounting for 32.4% (33/102) of the somatic mutations in this study. The EGFR mutations detected included rare variants such as EGFR exon 19 insertion (K745_E746insIPVAIK) and in cis H835L+L833V. Additionally, novel RET fusion mutations PCM1–RET and ADD3-RET were detected in two adenocarcinoma patients. To demonstrate the functional applications of NGS, we correlated mutations with patient characteristics, outcomes of matched targeted therapy, and outcomes based on allelic frequency of the EGFR-T790M mutation. Finally, we demonstrated that circulating tumor DNA can be used both to measure response to targeted therapy and as a predictor of clinical outcome, by presenting a case study of a single patient.Conclusion: We demonstrated that NGS can be used in multiple applications to effectively identify potential oncogenic driver mutations, guide mutation-targeted therapy decisions, and predict clinical outcomes in Chinese NSCLC patients. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance against colistin has emerged worldwide threatening the efficacy of one of the last-resort antimicrobials used for the treatment of Enterobacteriaceae. To investigate the presence of the recently identified colistin resistance genes (mcr-4, mcr-5) in China, we established PCRs to detect mcr-4 and mcr-5 on 213 anal and 1,339 nasal swabs from apparently healthy pigs (n = 1,454) in nine provinces, and 1,696 cloacal and 1,647 oropharyngeal samples from poultry (n = 1,836) at live-bird markets in 24 provinces of China. The prevalence of the mcr-4 in swine swabs (41.4%; 642/1,552) was significantly higher than in swabs from poultry (11.5%; 384/3,343). The mcr-4 gene was found in geese (49.5%, 54/109), chickens (17.2%, 257/1,498), pigeons (17.2%, 17/99) and ducks (15.4%, 20/130). In a similar trend, the prevalence of the mcr-5 in swine swabs (33.1%; 514/1552) was significantly higher than in swabs from poultry (5.6%; 187/3,343). The mcr-5 was identified in geese (17.4%, 19/109), chickens (9.9%, 148/1,498), ducks (7.7%, 10/130) and pigeons (3%, 3/99). The mcr-4 prevalence in the nasal swabs from pigs (59.2%, 58/98) was significantly higher than that in anal swabs (29.6%, 29/98) (P<0.001). Similarly, the mcr-5 prevalence in the nasal swabs from pigs (61.2%, 60/98) was significantly higher than in anal swabs (44.9%, 44/98) (P = 0.02), and significantly higher in oropharyngeal swabs (7.2%, 109/1,507) than in the cloacal swabs (3.7%, 56/1,507) (P<0.001). This study further confirms the presence of the mcr-4 and mcr-5 in animals and indicates these genes are prevalent and widespread in food producing animals (pig and poultry) in China. Future studies are needed to characterize the bacteria carrying the mcr-4 and mcr-5 and their locations on plasmids and/or the bacterial chromosomes, and determine co-resistances in the mcr-4 and mcr-5 positive strains. [ABSTRACT FROM AUTHOR]

The XOD inhibitory effects of Plantaginis Semen, that is, the seeds of P. asiatisca, and its representative four single compounds, acteoside, 1H-indolo-3-carbaldehyde, isoacteoside, and myristic acid, were evaluated by electron transfer signal blocking activities (ETSBA), which is based on the electron transfer signal of XOD enzymatic reaction. The blocking activities were detected using an electrochemical biosensing method. Compared with control, significant effects were observed after the addition of P. asiatica extract, acteoside, and 1H-indolo-3-carbaldehyde (all p<0.05). The IC50 values of the extract and acteoside are 89.14 and 7.55 μg·mL−1, respectively. The IC20 values of the extract, acteoside, and 1H-indolo-3-carbaldehyde are 24.28, 3.88, and 16.16 μg·mL−1, respectively. Due to the relatively lower inhibitory potential of 1H-indolo-3-carbaldehyde, its IC50 was not obtained. In addition, isoacteoside and myristic acid did not show any XOD inhibitory effects. Our data demonstrated that the XOD inhibitory effects of the extract, acteoside, and 1H-indolo-3-carbaldehyde can be accurately evaluated by the ETSBA method. The results from this study indicated that Plantaginis Semen significantly inhibited XOD activities to reduce hyperuricemia and treat gout. The study also proves that measuring the electron transfer signal blocking activities is a simple, sensitive, and accurate method to evaluate the XOD inhibitory effects. [ABSTRACT FROM AUTHOR]