Ultralow Glassy Thermal Conductivity and Controllable, Promising Thermoelectric Properties in Crystalline o-CsCu5S3.

We thoroughly investigated the anharmonic lattice dynamics and microscopic mechanisms of the thermal and electronic transport characteristics in orthorhombic o-CsCu5S3 at the atomic level. Taking into account the phonon energy shifts and the wave-like tunneling phonon channel, we predict an ultralow κL of 0.42 w/mK at 300 K with an extremely weak temperature dependence following ∼T-0.33. These findings agree well with experimental values along with the parallel to the Bridgman growth direction. The κL in o-CsCu5S3 is suppressed down to the amorphous limit, primarily due to the unconventional Cu-S bonding induced by the p-d hybridization antibonding state coupled with the stochastic oscillation of Cs atoms. The nonstandard temperature dependence of κL can be traced back to the critical or dominant role of wave-like tunneling of phonon contributions in thermal transport. Moreover, the p-d hybridization of Cu(3)-S bonding results in the formation of a valence band with "pudding-mold" and high-degeneracy valleys, ensuring highly efficient electron transport characteristics. By properly adjusting the carrier concentration, excellent thermoelectric performance is achieved with a maximum thermoelectric conversion efficiency of 18.4% observed at 800 K in p-type o-CsCu5S3. Our work not only elucidates the anomalous electronic and thermal transport behavior in the copper-based chalcogenide o-CsCu5S3 but also provides insights for manipulating its thermal and electronic properties for potential thermoelectric applications.

Discovering Traditional Chinese Medicine (TCM) Formulas for Complex Diseases Based on a Combination of Reverse Systematic Pharmacology and TCM Meridian Tropism Theory: Taking COVID-19 as an Example.

OBJECTIVE: Infections and death have been a part of our daily lives since the COVID-2019 pandemic outbreak in 2019, and the societal and economic consequences have lingered for an unanticipated duration. Novel and effective treatments are still desperately needed around the world to combat the infection. Here, we discovered a novel traditional Chinese medicine formula (TCMF) to potentially combat COVID-19 through reverse systematic pharmacology (disease → targets → TCMF → disease). METHODS: Combining Integrative network pharmacology and the traditional Chinese medicine (TCM) theory, a TCMF for COVID-19 was identified. In silico physiological interactions between herbs and disease hub targets were validated by molecular docking and dynamics simulation. RESULTS: Based on disease-related gene/pathway targets and a combination of reverse pharmacology and TCM meridian tropism theory, a COVID-19-associated herb database was constructed. A new TCMF, including Gancao, Baitouweng, Congbai, and Diyu (GBCD), was discovered for anti-COVID-19 therapy. The KEGG and GO analyses of 49 intersecting genes suggested that GBCD could combat COVID-19 through antiviral, antiinflammation, immunoregulation, and cytoprotection activities. Moreover, these possible effects were validated through docking and MD simulation. CONCLUSIONS: To the best of our knowledge, this study is the first to combine reverse pharmacology and meridian tropism theories for TCMF development, and a novel herbal combination, GBCD, was discovered for anti-COVID-19 therapy.

Tumor cell membrane-coated continuous electrochemical sensor for GLUT1 inhibitor screening.

Glucose transporter 1 (GLUT1) overexpression in tumor cells is a potential target for drug therapy, but few studies have reported screening GLUT1 inhibitors from natural or synthetic compounds. With current analysis techniques, it is difficult to accurately monitor the GLUT1 inhibitory effect of drug molecules in real-time. We developed a cell membrane-based glucose sensor (CMGS) that integrated a hydrogel electrode with tumor cell membranes to monitor GLUT1 transmembrane transport and screen for GLUT1 inhibitors in traditional Chinese medicines (TCMs). CMGS is compatible with cell membranes of various origins, including different types of tumors and cell lines with GLUT1 expression knocked down by small interfering RNA or small molecules. Based on CMGS continuous monitoring technique, we investigated the glucose transport kinetics of cell membranes with varying levels of GLUT1 expression. We used CMGS to determine the GLUT1-inhibitory effects of drug monomers with similar structures from Scutellaria baicalensis and catechins families. Results were consistent with those of the cellular glucose uptake test and molecular-docking simulation. CMGS could accurately screen drug molecules in TCMs that inhibit GLUT1, providing a new strategy for studying transmembrane protein-receptor interactions.

Novel nanoparticles prepared from isothiocyanate derivatives for phototherapy of tumor.

Phototherapy is a new method to treat tumor, including photodynamic therapy (PDT) and photothermal therapy (PTT). However, the GSH in tumor cells could deplete ROS produced by photosensitizers, resulting in inadequate PDT. Isothiocyanate not only is a new type of anti-tumor drug, but also may combine with GSH, increasing the content of intracellular ROS and improving PDT effect. Here we synthesized a kind of water-soluble nanoparticles (BN NPs) parceling BODIPY-I-35 up with mPEG-ITC and lecithin. mPEG-ITC can react with GSH in tumor cells to reduce the consumption of ROS. BN NPs can be used as vectors to deliver drugs to tumor sites. Under 808 nm laser irradiation, BN NPs solution increased 13 °C within 10 min, indicating that BN NPs had superb photothermal performance. In vitro experiments, low dose BN NPs showed satisfactory PDT and PTT effects, and the cell viability of MCF-7 cell was only 13%. In vivo, BN NPs with excellent biocompatibility showed favorable phototherapy effect and tumor was effectively inhibited. Fluorescence imaging could present the long retention effect of BN NPs in tumor locations. In conclusion, the BN NPs showed the effect of enhancing phototherapy and provided a remarkable application prospect in the phototherapy of tumor cells.

δ-Opioid Receptor Activation Inhibits Ferroptosis by Activating the Nrf2 Pathway in MPTP-Induced Parkinson Disease Models.

Introduction: Recent studies suggest the involvement of ferroptosis in the pathogenesis of Parkinson disease (PD). δ-Opioid receptors (DORs) have neuroprotective effects in PD. It is not known whether the neuroprotective effects of DORs in PD are attributable to the inhibition of ferroptosis. Therefore, we aimed to investigate the role of DORs in ferroptosis in MPTP-induced PD models. Methods: To identify the influence of DORs on ferroptosis in MPTP-induced PD models, we measured the malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels, analyzed the levels of ferroptosis-related proteins (GXP4 and SLC7a11) and Nrf2 expression by using western blotting, and assessed mitochondrial dysfunction by using JC-1 staining and transmission electron microscopy. Results: DOR activation reduced the 4-HNE and MDA levels, increased the GXP4 and SLC7a11 levels, and ameliorated mitochondrial dysfunction in MPTP-induced PD models. These neuroprotective effects of DORs could be blocked by Nrf2-siRNA. Thus, the effects of DORs on ferroptosis in PD models were partially controlled by Nrf2, which regulated GXP4 and SLC7a11 synthesis. Conclusion: DORs exert neuroprotective effects in PD models by inhibiting ferroptosis partially via activating the Nrf2 pathway.

Photothermal and Concus Finn capillary assisted superhydrophobic fibrous network enabling instant viscous oil transport for crude oil cleanup.

Rapid and effective removal of highly viscous oil spills from the sea remains a great challenge globally. Superhydrophobic materials are attractive candidates for handling oil spills, but they are restrained to recover oils with low viscosity exclusively. Herein, we report a novel polypyrrole wrapped superhydrophobic fibrous network using cross-shaped polyester fibers as starting blocks. The polypyrrole coating enables the absorbent to convert light to heat, ensuring that the viscosity of heavy oils in the proximity can be easily controlled. In the meanwhile, the special structure of the starting fibers initiates Concus Finn (CFin) capillary allowing instant oil transport in the network. When the absorbent is exposed to light oils (0-500 mPa.s), the oils can be transported instantly via CFin capillary. Interestingly, under synergistic effect of light-to-heat conversion and CFin capillary, a drawing-sticking crude oil strip (105 mPa.s) is sucked instantly against gravity by the absorbent. The absorbent is successfully applied to efficiently separate both oil/water mixtures and oil/water emulsions (efficiency > 99%). Such absorbent can absorb 62.99-74.23 g/g light oils on average and up to 123.3 g/g crude oil under 0-2 sun illumination, holding a huge potential in managing oil spills.

Effectiveness of cognitive behavioral therapy on mood symptoms in patients with implantable cardioverter defibrillator: A systematic review and meta-analysis.

BACKGROUND: and purpose: Cognitive behavioral therapy (CBT) has gained increasing attention in the treatment of psychological disorders, but evidence is required to support practice. This systematic review was conducted to evaluate the current evidence for CBT's effectiveness in relieving symptoms of anxiety and depression experienced by patients with an implantable cardioverter-defibrillator (ICD). METHODS: PubMed, Cochrane Library, Web of Science, and Embase databases were systematically searched from inception to March 27, 2020. Both randomized controlled trials and cluster-randomized controlled trials were included in our review. Meta-analysis was conducted using RevMan 5.3 and Stata 15.1 software. RESULTS: A total of six trials, including 675 participants, were analyzed. The results demonstrated that CBT was superior to standard care in relieving symptoms of depression (standardized mean difference = -0.20; 95% confidence interval (CI): -0.39 to -0.01; P = 0.004). The effectiveness of CBT in relieving symptoms of anxiety experienced by patients with ICDs (standardized mean difference = -0.70; 95% CI: -1.10 to -0.30; P < 0.001) as well as the heterogeneity (I2 = 77%) were significant. CONCLUSION: This meta-analysis indicates that CBT effectively relieves symptoms of anxiety and depression experienced by patients with ICDs. Clinical personnel should pay close attention to the mental health of patients with ICDs and adopt CBT as a management strategy for such patients.

Efficacy of auricular acupressure in maintenance haemodialysis patients: A systematic review and meta-analysis.

OBJECTIVES: To systematically evaluate the efficacy of auricular acupressure on sleep disorders, depression, pruritus, xerostomia and daily net weight gain (%) in maintenance haemodialysis patients. BACKGROUND: Auricular acupressure has been used for various complications in maintenance haemodialysis patients, such as sleep disorders, depression, pruritus and xerostomia, but the efficacy has not yet been unified. DESIGN: Systematic review and meta-analysis. METHODS: Randomised controlled trials comparing auricular acupressure intervention with non-AA intervention in maintenance haemodialysis patients were included. We searched English databases (PubMed, Cochrane Library, Embase, Web of Science) and Chinese databases (CNKI, WanFang, CBM and VIP database) from the inception to 27 November 2020. The risk of bias was assessed by the Cochrane risk of bias tool. The RevMan 5.3 software was used to perform the meta-analysis. A descriptive analysis was conducted if the data were high of heterogeneity or could not be meta-analysed. The PRISMA statement was used to report systematic review and meta-analysis. RESULTS: A total of 12 RCTs with 805 MHD patients were included. Meta-analysis showed that auricular acupressure had a significant difference for improving sleep disorders (MD = -1.97 points, 95% CI: -2.62 to -1.32, p < .0001), pruritus (MD = -1.55 points, 95% CI: -2.01 to -1.08, p < .0001), and daily net weight gain (%) (MD = -0.29, 95% CI: -0.37 to -0.21, p < .0001). The efficacy of depression and xerostomia were analysed descriptively due to insufficient data. CONCLUSIONS: The meta-analysis results indicated that auricular acupressure had a positive efficacy in maintenance haemodialysis patients to improve sleep disorders, pruritus and daily net weight gain (%). But the results should be treated conservatively on account of the low quality of included studies. Future researchers need to conduct more high-quality, large sample, multi-centre randomised controlled studies to provide a solid basis to demonstrate of the efficacy of auricular acupressure in maintenance haemodialysis patients. RELEVANCE TO CLINICAL PRACTICE: Auricular acupressure has the advantages of low cost, non-invasive and easy to be accepted by patients. This review suggested that auricular acupressure could be considered a non-pharmacological intervention for maintenance haemodialysis patients. Medical staff could teach maintenance haemodialysis patients auricular acupressure to help them self-manage some complications at home.

Effectiveness of five-element music therapy in cancer patients: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the effectiveness of five-element music therapy on anxiety, depression, quality of life (QoL), sleep quality and Karnofsky performance score (KPS) in cancer patients. METHODS: We searched English databases (PubMed, Cochrane Library, Embase, Web of Science) and Chinese databases (CNKI, WanFang, CBM and VIP database) from the inception to December 25, 2020. Two investigators independently screened literature, extracted data, and assessed risk of bias according to the eligibility criteria. The RevMan 5.3 software was used to perform the meta-analysis. RESULTS: A total of 22 studies, 2053 people with cancer were included. Meta-analysis showed that five-element music therapy had a significant difference for relieving depression (SMD = -1.11, 95% CI: 1.41 to -0.82, P < 0.00001), QoL (SMD = 1.41, 95% CI:0.58 to 2.23, P = 0.0008), sleep quality (MD = -1.73, 95% CI: 2.34 to -1.12, P < 0.00001), and KPS (MD = 4.75, 95% CI:2.31 to 7.18, P = 0.0001). And five-element music therapy did not show a positive effect on anxiety (SMD = -0.60, 95% CI: 1.47 to 0.27, P = 0.17). CONCLUSIONS: Five-element music therapy had a positive effect on depression, QoL, sleep quality, and KPS in cancer patients, while did not show a positive effect on anxiety. Future researchers need to optimize the research program and conduct more high-quality, large sample, multi-center randomized controlled studies. Besides, it would be helpful for future researchers to explain the five-element music therapy being examined and how it is potentially useful in western contexts.

High prevalence of developmental venous anomaly in adult patients with midline thalamic diffuse gliomas.

OBJECTIVE: This study aimed to assess the prevalence of developmental venous anomaly (DVA) in patients with thalamic glioma. Furthermore, we explored the association between DVA and some important biomarkers, such as IDH1 mutation, and H3K27M mutation. PATIENTS AND METHODS: Patients who received tumor resection in West China Hospital between August 2009 and October 2017 were enrolled. Propensity score matching was conducted based on a logistic regression model and 1:1 matching for case and control was used to generate a new cohort from patients with meningioma. Chi-square test, t-test, univariate and multivariate analyses were employed to assess the prevalence of DVA in thalamic glioma and meningioma and to identify risk factors associated with DVA. RESULTS: Ninety-nine patients with thalamic glioma were enrolled in the current study (male, n = 54; female, n = 45). The mean age was 42.9 ± 15.3 years old. We identified a higher prevalence of DVA in 99 patients with thalamic glioma when compared with 99 patients with meningioma (18.18% vs. 7.07%), which was slightly lower than the prevalence of DVA in glioma reported in previous studies. Furthermore, the distribution of gender, age, and tumor grade in DVA did not reach statistical significance. Chi-square test, univariate and multivariate analyses showed that IDH1 mutation, ATRX mutation, MGMT promoter methylation, p53 mutation, MMP9, EGFR, and Top II positive expression, TERT mutation, and H3K27M mutation were not associated with the development of DVA in thalamic glioma. CONCLUSION: A higher prevalence of DVA was found in thalamic glioma compared with meningioma.

Effect of boiling and frying on the selenium content, speciation, and in vitro bioaccessibility of selenium-biofortified potato (Solanum tuberosum L.).

Selenium-enriched potato is a good supplement for selenium-deficient populations. This study evaluated the influence of two most common cooking methods, including boiling and frying, on selenium content, speciation, and in vitro bioaccessibility of selenium-biofortified potato tubers. After foliar application of 200 µg/mL sodium selenite, potato tubers with 1.33 µg Se/g were obtained. Peeling resulted in 53.4%-69.9% loss of selenium in tubers. The total selenium content decreased by approximately 43.3% after boiling, among which up to 38.5% of the lost selenium is found in the boiling water. Nearly 31.7% of selenium was lost via volatilization during frying. Both cooking methods significantly enhanced the bioaccessibility of Se(IV) in tubers. Whereas SeMeCys became less bioaccessible after boiling. SeMet and SeCys2 in fired tubers were not accessible after digestion. This study suggested that boiling is more appropriate for cooking selenium-enriched potatoes.

Novel Chinese Angelica Polysaccharide Biomimetic Nanomedicine to Curcumin Delivery for Hepatocellular Carcinoma Treatment and Immunomodulatory Effect.

BACKGROUND: Using natural polysaccharides from Traditional Chinese Medicine as nanodrug delivery systems have considerable potential for tumor diagnostics and therapeutics. PURPOSE: On the basis of targeted therapy and combining the advantages of natural polysaccharides (angelica polysaccharide, APS) and natural Chinese medicine (curcumin, Cur) to design functionalized nanoparticles to improve the therapeutic through cell membrane encapsulation and immunotherapy. STUDY DESIGN AND METHODS: Cur-loaded, glycyrrhetic acid (GA)-APS-disulfide bond (DTA)-Cur nanomicelle (GACS-Cur), which were prepared by the dialysis method. GACS-Cur was encapsulated with the membranes from red blood cells (RBCm) termed GACS-Cur@RBCm, which were prepared by the principle of extrusion using a miniature extruder. The developed formulations were subjected to various in vitro and in vivo evaluation tests. RESULTS: The resulting APS nanocarriers supported a favorable drug-loading capacity, biocompatibility, and enhanced synergistic anti-hepatoma effects both in vitro and in vivo. After administration in mice, in vivo imaging results showed that the GACS-Cur and RBCm-coated groups had an obvious stronger tumor tissue targeting ability than the control treatment groups. Additionally, the immunomodulatory effect increased IL-12, TNF-α and IFN-γ expression and CD8+ T cell infiltration (1.9-fold) than that of the saline group. Notably, in comparison with hyaluronic acid (HA) nanocarriers, APS nanocarriers possess higher anti-hepatoma efficiency and targeting capabilities and, thus, should be further studied for a wide range of anti-cancer applications. CONCLUSION: Our data demonstrated that APS nanocarriers encapsulated with erythrocyte membrane mighty be a promising clinical method in the development of efficacy, safety and targeting of liver cancer therapy.

Luteolin Protects Pheochromocytoma (PC-12) Cells against Aß 25-35-Induced Cell Apoptosis through the ER/ERK/MAPK Signalling Pathway.

The regulatory effect of luteolin on the progression of Alzheimer's disease (AD) remains unclear from the perspective of apoptosis. The present study aimed to investigate the protective effects of luteolin against Aß 25-35-induced cell apoptosis in pheochromocytoma (PC-12) cells. Aß 25-35 was used to induce an in vitro model of AD. Estradiol was used as a positive control. The PC-12 cells were incubated with luteolin alone or in combination with fulvestrant or U0126. The results showed that luteolin treatment significantly prevents Aß 25-35-induced decrease in cell viability and inhibits Aß 25-35-induced cell apoptosis. After the addition of fulvestrant and U0126, the apoptosis rate of PC-12 cells increased significantly. In addition, luteolin treatment significantly upregulated the expression of Bcl-2 and downregulated the expression of Bax and caspase-3, whereas fulvestrant and U0126 partially reversed the effects of luteolin. Moreover, luteolin treatment upregulated the expression of ERß and p-ERK1/2, whereas fulvestrant blocked the expression of p-ERK1/2. The study showed that luteolin could activate the ER/ERK/MAPK signalling pathway to protect PC-12 cells against Aß 25-35-induced cell apoptosis via selectively acting on ERß. Thus, luteolin may be considered as a potential novel therapeutic strategy for AD.

In Vitro and In Vivo Osteogenesis Induced by Icariin and Bone Morphogenetic Protein-2: A Dynamic Observation.

In the present study, we aimed to compare the effects of icariin (ICA) and bone morphogenetic protein-2 (BMP-2) on osteoblast proliferation and osteogenesis in bone defects. We found that in vitro ICA or BMP-2 treatment is able to increase osteoblast proliferation, which was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Specifically, ICA at a concentration of 30 µg/ml had the strongest ability to promote cell proliferation, which is equivalent with the effect of BMP-2 at a concentration of 50 µg/ml. Furthermore, Western blot and RT-qPCR analyses showed that treatment with ICA (20-30 µg/ml) had similar increase effect with BMP-2 (50 µg/ml) on the protein and mRNA levels of BMP-2, osteoprotegerin (OPG), and alkaline phosphatase (ALP) mRNAs. In addition, the animal model of bone defects was successfully prepared. The in vivo data showed that compared with the control group, highest osteogenesis in the ICA or BMP-2 groups was observed at different observational times. Four weeks after surgery, osteogenesis in the BMP-2 group was slightly higher than that in the ICA group, but there was no significant difference between the two groups until the eighth week. ICA promotes osteoblast proliferation by stimulating the expression of BMP-2 and OPG proteins and upregulating the expression of BMP-2, OPG, and ALP mRNAs. ICA at a certain concentration has the same osteogenic effect as BMP-2. ICA or BMP-2 composite nanomaterials can be used as a framework to guide bone regeneration and promote osteogenesis. In addition, the combined use of hematoxylin-eosin and Goldner's trichrome staining techniques contributes to acquiring better bone morphometric information about bone defects.

Hesperetin derivative-12 (HDND-12) regulates macrophage polarization by modulating JAK2/STAT3 signaling pathway.

Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin (HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12 (HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1 (Arg-1), interleukin-10 (IL-10), transforming growth factor ß (TGF-ß) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase (iNOS) was down-regulated in LPS- and IFN-γ-treated (M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490 (inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.

Efficacy of yoga training in chronic obstructive pulmonary disease patients: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the impact of yoga training in patients with chronic obstructive pulmonary disease (COPD). METHOD: A literature search was performed in PubMed, Cochrane Library, Embase, CINAHL, and Web of Science for relevant studies published before June 2017. Quality assessment, sensitivity analysis and heterogeneity were performed. Stata12.0 software was used for statistical analysis. RESULTS: Ten studies were eligible for this analysis. There were significantly greater improvements in 6MWD (p = 0.000), Borg scale scores (p = 0.018), FEV1 Value (p = 0. 013), PaCO2 (p = 0.037), SGRQ scores (p = 0. 000) and CAT scores (p = 0.009) in yoga training patients. No statistically significant difference was observed in the FEV1/FVC (p = 0.75), FEV1 predicted value (p = 0.057) and FVC (p = 0.05). CONCLUSIONS: This meta-analysis indicates that yoga training can be an acceptable and appropriated adjunctive rehabilitation program for COPD patients.

Prognostic Factors for the Survival Outcome of Bilateral Thalamic Glioma: An Integrated Survival Analysis.

OBJECTIVE: The aim of this study was to perform an integrated survival analysis of patients with bilateral thalamic glioma and to assess the influence of various prognostic factors on overall survival. METHODS: A literature search of PubMed, Web of Science, and Google Scholar was performed for literature in English published from 1964 to May 2017. Detailed information including demographics, clinical characteristics, treatments, critical events, and time to events for survival analysis were extracted from the included articles. In addition, 2 cases diagnosed in our institution were included. RESULTS: The study included 53 cases from 32 published articles and 2 cases from our institution that were selected for analysis. Univariate analysis showed the duration of symptoms (≥2 or <2 months), glioma type (astrocytoma or glioblastoma multiforme), and World Health Organization (WHO) grade (low or high) had a significant correlation with overall survival (log-rank P = 0.011, 0.001, and <0.001, respectively). Multivariate analysis showed that the duration of symptoms (hazard ratio [HR], 0.299; 95% confidence interval [CI], 0.121-0.736; P = 0.009), and WHO grade (HR, 4.639; 95% CI, 1.891-11.382; P = 0.001) were independent prognostic factors for bilateral thalamic glioma (BTG) survival. CONCLUSIONS: This comprehensive analysis of rare BTG patients revealed that a longer duration of symptoms (≥2 months) and low WHO grade were significantly associated with improved survival and were independent prognostic factors for overall survival.

IDH1 status is significantly different between high-grade thalamic and superficial gliomas.

BACKGROUND: While major progress has been made in diagnosis and treatment of gliomas based on molecules, molecular features of thalamic glioma have rarely been reported till now. OBJECTIVE: IDH1 mutation is important for prognosis of gliomas and represents a distinctive category of glioma. We intended to survey specific molecular abnormalities in high-grade thalamic gliomas (WHO III-IV). METHODS: We collected data of 50 and 93 newly diagnosed high-grade thalamic and superficial glioma patients respectively and conducted a comparative analysis of molecular characteristics between them. We analyzed expressions of molecules as follow: IDH1/2, P53, Ki-67, ATRX, PTEN, MMP9 and MGMT by Immunohistochemistry (IHC). Direct gene sequencing was performed to test the IDH1(R 132H) mutation. RESULTS: We found a significant difference of IDH1 mutation between those high-grade gliomas, with 92% (46/50) of the thalamic tumors and 71% (66/93) of the superficial gliomas showing IDH1 wild-type (p= 0.004). It also showed that IDH1 mutation in superficial glioblastomas 18.6% (13/70) occurred more than thalamic glioblastomas 2.6% (1/39) (p= 0.017). As to high-grade superficial gliomas, there were 26 patients with IDH1 mutation, which contained 7, 13, and 6 high, moderate and low Ki-67 expression gliomas, respectively. The IDH1 wild-type group (62 patients), was composed of 29, 30, and 3 high, moderate and low Ki-67 expression gliomas, respectively. There was a significant distinction between the IDH1 mutation and Ki-67 expressions (p= 0.024). We also noted that the occurrence of low Ki-67 expressions 23.1% (6/26) in IDH1 mutation group was outnumbered than IDH1 wild-type group 4.8% (3/62) (p= 0.018). In addition, we found PTEN negative correlated with MMP9 negative in thalamic high-grade gliomas, whereas no such difference was found in superficial gliomas (p= 0.016). CONCLUSION: The rare occurrence of IDH1 mutant high-grade thalamic gliomas strongly suggested that the high-grade thalamic glioma is another distinct tumor entity as compared to the high-grade superficial gliomas.

Optimal dosing regimen of biapenem in Chinese patients with lower respiratory tract infections based on population pharmacokinetic/pharmacodynamic modelling and Monte Carlo simulation.

In this study, a population pharmacokinetic (PPK) model of biapenem in Chinese patients with lower respiratory tract infections (LRTIs) was developed and optimal dosage regimens based on Monte Carlo simulation were proposed. A total of 297 plasma samples from 124 Chinese patients were assayed chromatographically in a prospective, single-centre, open-label study, and pharmacokinetic parameters were analysed using NONMEN. Creatinine clearance (CLCr) was found to be the most significant covariate affecting drug clearance. The final PPK model was: CL (L/h)=9.89+(CLCr-66.56)×0.049; Vc (L)=13; Q (L/h)=8.74; and Vp (L)=4.09. Monte Carlo simulation indicated that for a target of ≥40% T>MIC (duration that the plasma level exceeds the causative pathogen's MIC), the biapenem pharmacokinetic/pharmacodynamic (PK/PD) breakpoint was 4µg/mL for doses of 0.3g every 6h (3-h infusion) and 1.2g (24-h continuous infusion). For a target of ≥80% T>MIC, the PK/PD breakpoint was 4µg/mL for a dose of 1.2g (24-h continuous infusion). The probability of target attainment (PTA) could not achieve ≥90% at the usual biapenem dosage regimen (0.3g every 12h, 0.5-h infusion) when the MIC of the pathogenic bacteria was 4µg/mL, which most likely resulted in unsatisfactory clinical outcomes in Chinese patients with LRTIs. Higher doses and longer infusion time would be appropriate for empirical therapy. When the patient's symptoms indicated a strong suspicion of Pseudomonas aeruginosa or Acinetobacter baumannii infection, it may be more appropriate for combination therapy with other antibacterial agents.

Screening HIV-1 fusion inhibitors based on capillary electrophoresis head-end microreactor targeting to the core structure of gp41.

In this paper, we design a microreactor based on electrophoretically mediated microanalysis (EMMA) with capillary electrophoresis (CE) for screening HIV-1 inhibitors that bind to the N-terminal heptad repeat (NHR, N36) region. Initially, a test sample plug is loaded into a capillary filled with buffer solution followed by N36 peptide solution, and the two solutions simultaneously mix by diffusion. Then, voltage is applied, and the sample molecules pass through the N36 peptide zone. The active compounds combine with N36, leading to a loss in the peak height of the active compound. More than 100 traditional Chinese medicine extracts (TCME) were screened, and an extract of Pheretima aspergillum (E. Perrier) (L5) was identified as having potent inhibitory activity. The results showed that L5 could significantly inhibit the HIV-1JR-FL pseudotyped virus infection; the 50% effective concentration (EC50) of L5 was approximately 32.1±1.2µg/mL, and the 50% cytotoxicity concentration (CC50) value of L5 was 146.9±4.4µg/mL, suggesting that L5 had low in vitro cytotoxicity on U87-CD4-CCR5 cells. The new method is simple and rapid, is free of antibodies, and does not require tedious processes.