Intermolecular Interactions, Morphology, and Photovoltaic Patterns in p-i-n Heterojunction Solar Cells With Fluorine-Substituted Organic Photovoltaic Materials.

During the layer-by-layer (LBL) processing of polymer solar cells (PSCs), the swelling and molecule interdiffusion are essential for achieving precise, controllable vertical morphology, and thus efficient PSCs. However, the influencing mechanism of material properties on morphology and correlated device performance has not been paid much attention. Herein, a series of fluorinated/non-fluorinated polymer donors (PBDB-T and PBDB-TF) and non-fullerene acceptors (ITIC, IT-2F, and IT-4F) are employed to investigate the performance of LBL devices. The impacts of fluorine substitution on the repulsion and miscibility between the donor and acceptor, as well as the molecular arrangement of the donor/acceptor and the vertical distribution of the LBL devices are systematically explored by the measurement of donor/acceptor Flory-Huggins interaction parameters, spectroscopic ellipsometry, and neutron reflectivity, respectively. With efficient charge transfer due to the ideal vertical and horizon morphology properties, devices based on PBDB-TF/IT-4F exhibit the highest fill factors (FFs) as well as champion power conversion efficiencies (PCEs). With this guidance, high-performance LBL devices with PCE of 17.2%, 18.5%, and 19.1% are obtained by the fluorinated blend of PBDB-TF/Y6, PBDB-TF/L8-BO, and D18/L8-BO respectively.

MiR-1281 is involved in depression disorder and the antidepressant effects of Kai-Xin-San by targeting ADCY1 and DVL1.

Kai-Xin-San (KXS) is a Chinese medicine formulation that is commonly used to treat depression caused by dual deficiencies in the heart and spleen. Recent studies indicated that miRNAs were involved in the pathophysiology of depression. However, there have been few studies on the mechanism underlying the miRNAs directly mediating antidepressant at clinical level, especially in nature drugs and TCM compound. In this study, we identified circulating miRNAs defferentially expressed among the depression patients (DPs), DPs who underwent 8weeks of KXS treatment and health controls (HCs). A total of 45 miRNAs (17 were up-regulated and 28 were down-regulated) were significantly differentially expressed among three groups. Subsequently, qRT-PCR was used to verify 10 differentially expressed candidate miRNAs in more serum samples, and the results showed that 6 miRNAs (miR-1281, miR-365a-3p, miR-2861, miR-16-5p, miR-1202 and miR-451a) were consistent with the results of microarray. Among them, miR-1281, was the novel dynamically altered and appeared to be specifically related to depression and antidepressant effects of KXS. MicroRNA-gene-pathway-net analysis showed that miR-1281-regulated genes are mostly key nodes in the classical signaling pathway related to depression. Additionally, our data suggest that ADCY1 and DVL1 were the targets of miR-1281. Thus, based on the discovery of miRNA expression profiles in vivo, our findings suggest a new role for miR-1281 related to depression and demonstrated in vitro that KXS may activate cAMP/PKA/ERK/CREB and Wnt/ß-catenin signal transduction pathways by down-regulating miR-1281 that targets ADCY1 and DVL1 to achieve its role in neuronal cell protection.

Efficient, Robust, and Flame-Retardant Electrothermal Coatings Based on a Polyhedral Oligomeric Silsesquioxane-Functionalized Graphene/Multiwalled Carbon Nanotube Hybrid with a Dually Cross-Linking Structure.

Graphene electrothermal coatings have attracted considerable attention in recent years due to their important application prospects in a broad range of areas. So far, lots of strategies have been explored for producing them. However, these strategies usually involve a complicated process with sophisticated conditions, limiting their scalable applications. Herein, we demonstrate a facile strategy for preparing efficient, robust, and flame-retardant electrothermal coatings from liquid-phase exfoliated graphene, by combining with multiwalled carbon nanotubes (MWCNTs) and polyhedral oligomeric silsesquioxane (POSS) nanoparticles. This relies on the use of a hyperbranched polyethylene copolymer that simultaneously bears UV-reactive moieties and POSS terminal groups. As a stabilizer, the copolymer can effectively promote the exfoliation of both graphite and MWCNTs in common organic solvents under sonication, rendering the POSS-functionalized graphene and MWCNTs well dispersible in the solvent. From their dispersions, POSS-functionalized graphene/MWCNT hybrid electrothermal coatings have been successfully prepared simply by vacuum filtration and UV irradiation under mild conditions. It has been confirmed that a dually cross-linking structure can be formed in the hybrid system. This significantly improves the thermal resistance of resultant coatings, which remain exhibiting a stable work state even at a temperature high as 280 °C without the occurrence of flammation. Meanwhile, this also endows them with excellent electrothermal performance and service stability. At a relatively low voltage, 15 V, the steady temperature can reach 188.4 °C, with a response time < 30 s; after being alternately folded for 2700 cycles or scraped 200 times, the coating still maintains a stable state. In particular, the process involved is relatively simple with mild conditions. With these features, the coatings obtained herein may find their important applications in the area of wearable devices and household heating systems.

Qiangjing tablets ameliorate asthenozoospermia via mitochondrial ubiquitination and mitophagy mediated by LKB1/AMPK/ULK1 signaling.

CONTEXT: Therapeutic effects of Qiangjing tablets (QJT) on sperm vitality and asthenozoospermia (AZS) have been confirmed. However, the mechanism of action remains unclear. OBJECTIVE: This study investigates the effects of QJT on AZS and the underlying mechanism of action. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were randomly divided into six groups: Control, ORN (ornidazole; 200 mg/kg), ORN + QJT-low (0.17 g/mL), ORN + QJT-middle (0.33 g/mL), ORN + QJT-high (0.67 g/mL), and ORN + QJT + Radicicol (0.67 g/mL QJT and 20 mg/kg radicicol) groups. Pathological evaluation and analysis of mitophagy were conducted by H&E staining and transmission electron microscopy, respectively. Reactive oxygen species were detected by flow cytometry. Protein expression was determined by Western blotting. RESULTS: QJT significantly improved ORN-treated sperm motility and kinematic parameters, as well as the pathological symptoms of testicular and epididymal tissues. In particular, QJT mitigated impaired mitochondrial morphology, and increased the PHB, Beclin-1, LC3-II protein, and ROS levels (p < 0.05), and reduced the protein expression levels of LC3-I and p62 (p < 0.05). Mechanistically, QJT antagonized the downregulation of SCF and Parkin protein levels (p < 0.05). Furthermore, QJT significantly increased the protein expressions levels of LKB1, AMPKα, p-AMPKα, ULK1 and p-ULK1 (p < 0.05). The ameliorative effect of QJT on pathological manifestations, mitochondrial morphology, and the expressions of mitophagy and mitochondrial ubiquitination-related proteins was counteracted by radicicol. DISCUSSION AND CONCLUSIONS: QJT improved AZS via mitochondrial ubiquitination and mitophagy mediated by the LKB1/AMPK/ULK1 signaling pathway. Our study provides a theoretical basis for the treatment of AZS and male infertility.

Functionalized zinc oxide microparticles for improving the antimicrobial effects of skin-care products and wound-care medicines.

ZnO is an important component in skin-protection products and wound-care medicines. However, ZnO's antibacterial activity is moderate. We developed two types of ZnO microparticles loading with phthalocyanine-type photosensitizers (ZnO/PSs) introducing the photodynamic effects. These photosensitive ZnO microparticles exhibited long-term while moderate antimicrobial effects by continuously releasing Zn2+ ions. The antimicrobial efficacies were remarkably enhanced by triggering the photodynamic antimicrobial effects. Compared to the sole ZnO which showed non-measurable antimicrobial activity at a concentration of 10 mg/L, both ZnO/PSs demonstrated antimicrobial rates ranged 99%-99.99% against Escherichia coli, normal and drug-resistant Staphylococcus aureus. In a dorsal wound infection mouse model, treatment with ZnO/PSs significantly accelerated the wound recovery rates. ZnO/PSs promoted wound healing by a dual effect: 1) the release of Zn2+ ions from ZnO facilitating tissue remodeling; 2) the photodynamic effect efficiently eliminates pathogens avoiding infection. Notably, ZnO/PSs inherited the high biosafety of ZnO without causing noticeable toxicity against erythrocyte and endothelial cells. This study not only provides a highly safe and efficient antimicrobial ZnO material for skin cares and wound modulations, but also proposes a strategy to functionalize ZnO materials.

Research on the Influence of Network Position on Corporate Social Responsibility: Moderating Effect Based on Ownership Concentration.

Based on the social network theory and the institutional theory, this study examines the influence of corporate network position on corporate social responsibility (CSR), and further explores the moderating role of ownership concentration. Given the characteristics of CSR in different aspects, this study explores the relationship between corporate network position and economic CSR, environmental CSR, and social CSR from the two aspects of the centrality and structural holes of interlocking directorate network based on the data of 1,034 Chinese A-share listed companies from 2010 to 2019. The results show that the centrality and structural holes of interlocking directorate network have positive effects on the overall level of CSR, and the impacts on economic CSR and environmental CSR are stronger than that on social CSR. In addition, ownership concentration has a positive moderating effect on the relationship between corporate network position and CSR. These findings enrich the depth of research on CSR, clarify the influence of the characteristics of interlocking directorate network on CSR in different dimensions, and supplement the knowledge of existing research.

Copper fumarate with high-bifunctional nanozyme activities at different pH values for glucose and epinephrine colorimetric detection in human serum.

Metal-organic frameworks (MOFs) have attracted extensive attention for the development of colorimetric detection methods due to their ease of modification and high density of active sites. However, most of the reported colorimetric sensors based on MOFs show only a single nanozyme activity. Herein, the bifunctional enzyme activities of a hexagonal prism Cu MOF with fumaric acid as the ligand (Cu FMA), namely laccase-like activity under alkaline conditions (pH = 8) and peroxidase-like activity under acidic conditions (pH = 4), were verified. The specificity of Cu FMA at different pH values may be due to the presence of the Cu+ active center introduced by the weak reducibility of FMA. At pH = 8, Cu+ active centers are beneficial for dissociating the H-O bonds of phenolic compounds for the laccase system. In contrast, the dissociation of H-O is weakened at pH = 4, which prompts the breaking of the O-O bonds of H2O2 as a Fenton-like reaction for the peroxidase system. Based on the dual enzyme activities, Cu FMA sensors exhibit outstanding detectability for epinephrine and glucose with linear ranges of 2.7-54.6 µM and 0.01-0.8 mM and detection limits of 1.1 µM and 2.28 × 10-7 M, respectively. The Cu FMA colorimetric sensor can be applied for detecting and measuring glucose and epinephrine in human serum samples. This work paves the way for Cu MOFs to be used as the basis for rational regulation of the activity of dual nanozymes and for multifunctional applications under completely independent conditions.

Effectiveness of psychological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: A protocol for systematic review and meta-analysis.

INTRODUCTION: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases in urology, which 50% of men are infected at some point in their lives. Type III CP/CPPS is the most complex and controversial of all types of prostatitis, the highest incidence rate, uncertain efficacy, the long-term treatment that affects the patient's psychopathic symptoms, increases the psychological burden of patients. Psychological intervention for patients with CP/CPPS, which is difficult to treat with drugs and physics, can effectively improve clinical efficacy and improve the psychological condition. The researchers found a high prevalence of psychosocial problems and catastrophic distress in CP/CPPS patients, such as serious mental disorders, especially depression, anxiety and stress, and the high incidence of pain-devastating illness. In this study, we will evaluate psychological interventions as an effective way to relieve chronic prostatitis. METHODS AND ANALYSIS: The databases of English databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, China Biology Medicine Database, Wanfang Database, VIP Database) will be retrieved. The search strategy that will be run in the PubMed and tailored to the other database when necessary is presented in this article. RevMan 5.3 and Stata 11.0 will be used for Systematic Review and Meta-analysis. This protocol reported under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement, and we will report the systematic review by following the PRISMA statement. RESULTS: The study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings in the third quarter of 2021. CONCLUSION: This systematic review will provide more evidence to assess whether psychological is an effective intervention for patients with chronic prostatitis/chronic pelvic pain syndrome. Besides, the results will be published in a public issue journal and offer the urologists help to make clinical decisions. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published research. Since this research does not involve patients, personal privacy will not be affected. The results of this review will be distributed to peer-reviewed journals or submitted to relevant conferences. PROTOCOL REGISTRATION NUMBER: INPLASY202080021.

The effect of varicocele repair for sperm DNA fragmentation: A protocol for systematic review and meta-analysis.

INTRODUCTION: Sperm DNA integrity has been considered as one of the important determinants of normal fertilization and embryonic development in natural and assisted pregnancy. It is difficult for men with high levels of sperm DNA fragmentation (SDF) in semen to conceive their partners naturally and assist in conception. The studies have found that the level of SDF in the semen of patients with varicocele (VC) was on the high side. In recent years, the effect of VC surgery on DNA fragmentation index has attracted the attention of researchers. In this study, we will evaluate the effectiveness of VC repair as a way to alleviate SDF and improve male fertility. METHODS AND ANALYSIS: Electronic databases including English databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, China Biology Medicine Database, Wanfang Database, VIP Database) will be searched from their inception to December 2020 to recognize related studies. All the randomized controlled trials of microsurgical varicocelectomy for the management of VC patients will be included. The potential outcome will include improvement in SDF, oxidative stress markers (reactive oxygen species, nitric oxide, and lipid peroxidation products), sperm chromatin compaction, other advanced sperm function characteristics, follow-up of fertility results. We will conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on April 5th of 2021. CONCLUSION: This systematic review will provide more evidence to assess whether varicocelectomy is an effective intervention for patients with SDF. The results will be published in a public issue journal and offer the urologists help to make clinical decisions. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published research. Since this research does not involve patients, personal privacy will not be affected. The results of this review will be distributed to peer-reviewed journals or submitted to relevant conferences. PROTOCOL REGISTRATION NUMBER: INPLASY202070119.

Development of a Computer-Assisted Adverse Drug Events Alarm and Assessment System for Hospital Inpatients in China.

BACKGROUND: Computerized detection is a promising method for monitoring adverse drug events (ADEs); however, this method is currently in its infancy and is a new area of exploration in China. This study aimed to develop a computerized ADE alarm and assessment system to help pharmacists effectively detect, assess, and analyze possible ADEs in patients in China. METHODS: Based on the clinical characteristics of these adverse drug events, we designed combined multiparameters as ADE alert rules to be assembled into detection configurations. We also developed system function modules by extracting data from the People's Liberation Army (PLA) general hospital information system (electronic medical records). Positive predictive values were calculated for the alert. RESULTS: Five function modules were created in this platform: automatic screening, assisted evaluation, risk characteristic analysis, report generation into SRS (spontaneous reporting system), and a dictionary database. Four ADE alert configurations were set in our ADE alarm and assessment system: drug-related thrombocytopenia, anemia, liver injury, and kidney injury. The positive predictive values of the 4 monitored ADEs were approximately 44.4% to 95.8%. CONCLUSIONS: An automatic ADE screening system was established for hospitalized patients in Chinese medical institutions. Compared with previous studies, combined drug-event alerts and a system-assisted assessment interface performed better than alerts based only on laboratory values. Furthermore, this platform's assisted-layered evaluation and risk factor analysis functions could save considerable time for professionals and improve early prevention of potentially serious ADEs. To date, this system has been applied in 10 large-scale medical institutions.

Comparison of Different Liver Test Thresholds for Drug-Induced Liver Injury: Updated RUCAM versus Other Methods.

According to the updated Roussel Uclaf Causality Assessment Method (RUCAM), drug-induced liver injury (DILI) is currently defined based on thresholds of alanine aminotransferase (ALT) levels above 5 × the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) levels greater than 2 × the ULN. However, many parameters with different thresholds are also currently used in the clinic. We therefore performed a comparative analysis to evaluate which set of criteria was the most appropriate to detect DILI. We enrolled hospitalized patients who received fluoroquinolones to treat or prevent infections. Three liver test criteria were used to diagnose DILI in these patients. RUCAM criteria were defined as the gold standard, and the other two criteria were as follows: 1) ALT or aspartate aminotransferase (AST) levels greater than 5 × the ULN on two consecutive occasions and/or ALP levels greater than 2 × the ULN on two consecutive occasions [issued by DILI Network (DILIN)]; 2) ALT levels greater than 1 × the ULN on two consecutive occasions or ALT levels greater than 2 × the ULN [issued by the National Medical Products Administration (NMPA) of China]. We found that the RUCAM criteria resulted in 657 warnings, DILIN criteria resulted in 358, NMPA criteria resulted in 1,377, and the positive predictive value (PPV) were 9.74%, 10.89%, and 9.73% (P = 0.80), respectively. The levels of agreement of the DILIN and NMPA criteria with the RUCAM criteria were moderate, but the agreement between the DILIN criteria and NMPA criteria was poor. In conclusion, the NMPA criteria with relatively lax thresholds for the parameters require much more labor to determine the diagnosis, making them unsuitable for clinical practice. Conversely, the DILIN criteria employing stricter thresholds for the parameters were more effective but would miss some positive cases, and the cases it identified were usually quite serious, which is not conductive to early intervention. Therefore, we still recommend the use of the RUCAM criteria in clinical practice.

Incidence, clinical features, and risk factors of fluoroquinolone-induced acute liver injury: a case-control study.

BACKGROUND: Fluoroquinolone-related hepatotoxicity is rare but serious and is attracting increasing attention. We explored the incidence, clinical features and risk factors of acute liver injury associated with fluoroquinolone use. MATERIALS AND METHODS: Based on the Adverse Drug Events Active Surveillance and Assessment System that we developed, we carried out a case-control study by enrolling patients who were hospitalized and received fluoroquinolones to treat or prevent infections at the Chinese People's Liberation Army General Hospital from Jan 2016 to Dec 2017. The incidence of fluoroquinolone-induced acute liver injury was estimated, and logistic regression was used to reveal the risk factors of this adverse reaction. RESULTS: We found that 17,822 patients received fluoroquinolones, and 13,678 of them met the inclusion criteria. A total of 91 patients developed acute liver injury after receiving the medication, and 369 controls were matched to these patients. The overall incidence of fluoroquinolone-induced acute liver injury in the Chinese population is approximately 6-7 cases per 1,000 individuals annually. Multivariate logistic regression analysis showed that older age slightly decreased the risk of hepatotoxicity (OR, 0.98; 95% CI, 0.96-0.99). The male sex (OR, 2.19; 95% CI, 1.07-4.48), alcohol abuse (OR, 2.91; 95% CI, 1.39-6.11) and hepatitis B carrier status (OR, 2.38; 95% CI, 1.04-5.48) increased the risk of liver injury. Concurrent use of cephalosporins or carbapenems was also associated with an increased risk. CONCLUSION: Increased risk of fluoroquinolone-related hepatotoxicity may be associated with youth, the male sex, alcohol abuse, hepatitis B carrier status and the concurrent use of cephalosporins or carbapenems.

MiR-539 Targets MMP-9 to Regulate the Permeability of Blood-Brain Barrier in Ischemia/Reperfusion Injury of Brain.

Cerebral ischemia/reperfusion (I/R) injury severely threatens human life, while the potential mechanism underlying it is still need further exploration. The rat model of cerebral I/R injury was established using middle cerebral artery occlusion (MCAO). The rat microvascular endothelial cell line bEND.3 was exposed to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic ischemic condition in vitro. Evans blue was performed to determine the blood-brain barrier (BBB) permeability. Real-time PCR and western blot were performed to determine gene expression in mRNA and protein level, individually. Luciferase reporter assay was conducted to determine the relationship between miR-539 and MMP-9. The infarct volume and BBB permeability of cerebral (I/R) rats were significantly greater than Sham group. The expression of miR-539 was decreased, while MMP-9 was increased in the brain tissues of I/R injury rats and OGD/R pretreated bEND.3. Up-regulated miR-539 in OGD/R pretreated bEND.3 significantly promoted the BBB permeability. MiR-539 targets MMP-9 to regulate its expression. OGD/R treatment significantly promoted the BBB permeability in bEND.3, miR-539 mimic transfection abolished the effects of OGD/R, while co-transfected with pcDNA-MMP-9 abolished the effects of miR-539 mimic. MiR-539 targets MMP-9 and further regulates the BBB permeability in cerebral I/R injury.

[Purification technology of puerarin by agar gel microspheres].

Puerarin is the main active component of flavonoids in Puerariae Lobatae Radix. In this study, agar gel microspheres bonded with ß-cyclodextrin (AG-ß-CD) were synthesized by using economical agar, and then high-purity puerarin was obtained with AB-8 through high-yield separation. With purity and yield of puerarin, and chromatographic purity of related impurities as indexes, four macroporous resins of different properties, namely ADS-7 (high polarity), ADS-17 (medium polarity), ADS-21 (polarity) and AB-8 (weak polarity), were selected for separation of puerarin and technological optimization. In addition, the AG-ß-CD purification process was optimized and verified. The results showed that, AB-8 resins showed the best effect and selected as the pre-treatment resins for crude puerarin, and puerarin with the purity of 87.68% showed a recovery rate of 89.66%. The optimized purification process parameters of AG-ß-CD included mobile phase (15% ethanol), loading capacity (the ratio of loading amount to column volume) (1.33 g•L⁻¹), sample concentration (8 g•L⁻¹) and flow rate (1 mL•min⁻¹), puerarin with the purity of 95% showed a recovery rate of more than 97%.

Effect of Intracoronary Plus Low-Dose Intravenous Tirofiban in Elderly Patients with Acute Myocardial Infarction.

BACKGROUND: To investigate the efficacy and safety of low-dose tirofiban in elderly patients undergoing primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (AMI). METHODS: One hundred and four patients aged 70 years and above undergoing PPCI for AMI were divided into control (n=52) and study (n=52) groups. All patients received bolus intracoronary injection of tirofiban (10µg/kg), which was followed by intravenous infusion at 0.15µg/kg/min in the control group and at 0.075µg/kg/min in the study group for 24h. RESULTS: There was no statistically significant difference between the study group and the control group in patients with complete ST segment resolution (84.2% vs. 85.7%, P=0.851), peak high-sensitive cardiac troponin T level (5.1±1.9 vs. 5.8±2.6µg/L, P=0.123), scores of thrombus in the infarct-related artery (0.98±0.51 vs. 1.12±0.59, P=0.214), and patients with TIMI grade 3 flow (86.0% vs. 88.2%, P=0.737) after PPCI. There were no statistically significant differences between the two groups in left ventricular ejection fraction (57.1±6.3 vs. 57.7±6.1, P=0.611) and composite major adverse cardiovascular events rate (P =0.778) at 90 days after PCI. The total bleeding rate in the study group was lower than in the control group (P=0.048). CONCLUSION: In elderly patients with AMI undergoing primary PCI, low and standard dose of tirofiban exerts similar effects on platelet aggregation, coronary flow, infarct size, left ventricular systolic function and short-term clinical outcomes. Low dose regimen is associated with a lower bleeding rate than the standard dose.

Inhibition of the JAK/STAT pathway with ruxolitinib overcomes cisplatin resistance in non-small-cell lung cancer NSCLC.

This study was aimed to elucidate the roles of inhibition of related JAK/STAT pathways in regulating cytotoxicity induced by cisplatin in non-small-cell lung cancer (NSCLC) cell. We treated five non-small-cell lung cancer cell lines with cisplatin alone or with cisplatin and Jak2 inhibitor (ruxolitinib) and assessed cell viability, expression of Jak2 and STAT3 and cell apoptosis. We also investigated the effect of combination treatment inhibited tumor xenograft growth in two human NSCLC xenograft models bearing the cisplatin resistant (H1299) and sensitive (A549) cells. Different cell lines with different genetic background showed half-maximal inhibitory concentrations (IC50) of cisplatin from 4.66 to 68.28 µmol/L. They could be divided into cisplatin intrinsic resistant and cisplatin sensitive cell lines. In cisplatin-resistant cells with higher Jak2 and STAT3 expression, cisplatin and ruxolitinib combination dramatically suppressed the cell growth, down-regulated the expression of phosphorylated STAT3 and induced cleaved caspase-3 expression. Moreover combination with cisplatin and ruxolitinib also significantly inhibited the growth of resistant cell H1299, A549/DDP and H2347 in soft agar model. Finally, combination group significant inhibited the tumor growth and induced the caspase-3 expression compared with either single agent alone (P < 0.05) on the resistant cell xenografts model. The present study indicates that further study is warranted to determine the effectiveness of combination treatment with cisplatin and Jak2/stat3 pathway inhibitor for platinum-resistant NSCLC.

Risk factors for thrombocytopenia in adult chinese patients receiving linezolid therapy.

BACKGROUND: Linezolid (LZD), an oxazolidinone antibiotic agent, has excellent activity and bioavailability against most methicillin-sensitive and methicillin-resistant gram-positive bacteria. Although LZD is generally well tolerated, several studies have found adverse hematologic effects, of which thrombocytopenia is of most concern. OBJECTIVE: To investigate the risk factors for thrombocytopenia in patients who received oral or parenteral LZD therapy between February 1 and November 30, 2010. METHODS: Data were extracted retrospectively from the electronic medical records in our hospital information system. Thrombocytopenia was defined as either a final platelet count of <100 × 10(9)/L (criterion 1) or a 25% reduction from the baseline platelet count (criterion 2). Risk factors were determined using logistic regression analysis, and clinical features were predicted using receiver operating characteristic curves. RESULTS: The study included 254 patients, with mean (SD) age of 59 (17.66) years. The duration of LZD therapy was 9.43 (5.63) days. Thrombocytopenia developed in 69 patients (27.2%), as defined by criterion 1, and in 127 patients (50%), as defined by criterion 2. At univariate analysis, age, weight, creatinine clearance, serum albumin concentration, baseline platelet count, daily dosage, and concomitant use of caspofungin, levofloxacin, and meropenem were significant risk factors for thrombocytopenia. At multivariate analysis and using ROC curves, daily dose ≥18.75 mg/kg, baseline platelet count ≤181 × 10(9)/L, duration of LZD therapy ≥10 days, and concomitant use of caspofungin and levofloxacin were independent risk factors for thrombocytopenia as defined by criterion 1, whereas creatinine clearance ≤88.39 mL/min/1.73 m(2), serum albumin concentration ≤33.5 g/L, daily dose ≥18.46 mg/kg, and caspofungin were independent risk factors for thrombocytopenia as defined by criterion 2. CONCLUSIONS: The incidence of LZD-related thrombocytopenia in the Chinese population is much higher than that suggested by the drug instructions. Low pretreatment platelet count, low body weight, low serum albumin concentration, long-term drug administration, advanced age, renal insufficiency, and concomitant use of caspofungin, levofloxacin, and meropenem have been identified as risk factors. Although predictors have been proposed for use in clinical practice to screen for patients at high risk who require intensified monitoring, further research on the dosage-based pharmacokinetics and pharmacodynamics of LZD are urgently needed.

Distribution pattern of plant species diversity in the mountainous region of Ili River Valley, Xinjiang.

In this paper, detrended canonical correspondence analysis was performed to analyze the relationships between diversity indices and environmental gradients, generalized additive model was employed to modal the response curves of diversity indices to the elevation, based on data from field investigation in the mountainous region of the Ili River Valley and a survey of 94 sample plots. Two hundred fifty-nine plant species were recorded in the 94 sample plots investigated, up to 235 species all appeared in the herb layer, and the species of woody plants were very limited. The communities with a complicated vertical structure presented higher values of indices. The distribution pattern of plant species diversity on the northern slope was affected by such factors as elevation, slope aspect, slope gradient, total nitrogen, total potassium, soil water content, organic matter, and that on the southern slope was mainly affected by such factors as slope gradient, elevation, available phosphorus, and soil water content. On the northern slope, Patrick index and Shannon-Wiener index of the plant communities presented a bimodality pattern along altitude; Simpson index and Pielou index showed a partially unimodal pattern. On the southern slope all the distribution pattern of species diversity indices showed two peaks, though Patrick index's bimodality pattern was not an obvious one. These altitudinal patterns were formed by the synthetic action of a variety of environmental factors with elevation playing an important role.

Rapid separation and identification of furocoumarins in Angelica dahurica by high-performance liquid chromatography with diode-array detection, time-of-flight mass spectrometry and quadrupole ion trap mass spectrometry.

High-performance liquid chromatography with diode-array detection (HPLC/DAD), time-of-flight mass spectrometry (HPLC/TOFMS) and quadrupole ion trap mass spectrometry (HPLC/QITMS) were used for separation, identification and structural analysis of furocoumarins in Angelica dahurica. Two furocoumarins (imperatorin and isoimperatorin) in Angelica dahurica extract were identified unambiguously by comparing their relative retention times, characteristic ultraviolet information and accurate mass measurement. A formula database of known furocoumarins in Angelica dahurica was established, against which the other 21 furocoumarins were identified effectively based on the accurate extract masses and formulae acquired by HPLC/TOFMS. In order to distinguish the isomers, multi-stage mass spectrometry (MSn, ion trap mass spectrometry) was used. General fragmentation behavior of the furocoumarins in the ion trap mass spectrometer was studied by the two furocoumarin standards, and their fragmentation rules in MS(n) spectra were summarized. These deduced fragmentation rules of furocoumarins were successfully implemented in distinguishing the three groups of isomers in Angelica dahurica by HPLC/QITMS. By using the three different analytical techniques, 23 furocoumarins in Angelica dahurica were tentatively identified within 30 min. Finally, HPLC/TOFMS fingerprints of Angelica dahurica were established by which it can be concluded that a rapid and effective method based on the three analytical techniques for identification of chemical components was established. This can provide help for further quality control of Angelica dahurica and pharmacology mechanism study of furocoumarins in Angelica dahurica.