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Acute alcohol exposure induces unconscious condition such as coma whose main physical manifestation is the loss of righting reflex (LORR). Xingnaojing Injection (XNJI), which came from Chinese classic formula An Gong Niu Huang Pill, is widely used for consciousness disorders in China, such as coma. Although XNJI efficiently shortened the duration of LORR induced by acute ethanol, it remains unknown how XNJI acts on ethanol-induced coma (EIC). We performed experiments to examine the effects of XNJI on orexin and adenosine (AD) signaling in the lateral hypothalamic area (LHA) in EIC rats. Results showed that XNJI reduced the duration of LORR, which implied that XNJI promotes recovery form coma. Microdialysis data indicated that acute ethanol significantly increased AD release in the LHA but had no effect on orexin A levels. The qPCR results displayed a significant reduction in the Orexin-1 receptors (OX1R) expression with a concomitant increase in the A1 receptor (A1R) and equilibrative nucleoside transporter type 1 (ENT1) expression in EIC rats. In contrast, XNJI reduced the extracellular AD levels but orexin A levels remained unaffected. XNJI also counteracted the downregulation of the OX1R expression and upregulation of A1R and ENT1 expression caused by EIC. As for ADK expression, XNJI but not ethanol, displayed an upregulation in the LHA in EIC rats. Based on these results, we suggest that XNJI promotes arousal by inhibiting adenosine neurotransmission via reducing AD level and the expression of A1R and ENT1.

Background and Objective Taohong Siwu Decoction (TSD) is a classic traditional Chinese medicine (TCM) compound with pharmacological effects such as vasodilation and hypolipidemia. Paeoniflorin (PF) is one of the active ingredients of TSD. The aim of this study was to evaluate the pharmacokinetics of PF in herbal extracts and their purified forms in rats. Method A sensitive and rapid high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS-MS) method for the determination of PF in rat plasma was developed. Rats were divided into three groups, and given PF solution, water extract of white peony root (WPR), or TSD by gavage. At different predetermined timepoints after gavage, blood was collected from the orbital vein. The pharmacokinetic parameters of PF in the plasma of rats in the three groups was determined. Results The pharmacokinetic studies showed that the time to reach maximum concentration ( T max ) of PF in the purified forms group was relatively high, while the half-lives ( T ½ ) of PF in the TSD and WPR groups were longer. Among the three groups, PF in the purified forms group had the maximum area under the concentration–time curve ( AUC 0- t  = 732.997 µg/L·h) and the largest maximum concentration ( C max  = 313.460 µg/L), which showed a significant difference compared with the TSD group ( P  < 0.05). Compared with the purified group, the clearance ( CL z /F = 86.004 L/h/kg) and the apparent volume of distribution ( V z /F = 254.787 L/kg) of PF in the TSD group increased significantly ( P  < 0.05). Conclusions A highly specific, sensitive, and rapid HPLC–MS-MS method was developed and applied for the determination of PF in rat plasma. It was found that TSD and WPR can prolong the action time of paeoniflorin in the body.

This study aims to report the trends and cross-national disparities in the burden of osteoarthritis (OA) by region, age, gender, and time from 1990 to 2021, and to further project changes through 2035. In this systematic analysis based on the Global Burden of Disease (GBD) study, population survey data on osteoarthritis from 21 countries/regions and U.S. insurance claims data were used to estimate the prevalence and incidence of OA in 204 countries and regions from 1990 to 2021. The reference case definition for OA was symptomatic and radiographically confirmed osteoarthritis. Studies using definitions other than the reference, such as self-reported OA, were adjusted through a regression model to align with the reference case. The distribution of OA severity was derived from a pooled meta-analysis using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Final prevalence estimates were multiplied by disability weights to calculate years lived with disability (YLD). An Autoregressive Integrated Moving Average (ARIMA) model was used to forecast the prevalence and incidence of OA through 2035. In 2021, approximately 607 million (95%UI 538-671) people worldwide were affected by osteoarthritis, accounting for 7.7% of the global population. Compared to 2020, the age-standardized prevalence of OA among males is projected to increase from 5,763 per 100,000-5,922 per 100,000 by 2036, while the age-standardized prevalence among females is expected to decline slightly from 8,034 per 100,000-7,925 per 100,000. In 2021, the global age-standardized YLD rate for osteoarthritis was 244.5 (95%UI 117.06-493.11), the global age-standardized prevalence rate was 6,967.29 (95%UI 6,180.7-7,686.06), and the global age-standardized incidence rate was 535 (95%UI 472.38-591.97). In 2021, the age-standardized prevalence rate exceeded 5.5% across all regions, ranging from 5,675.8 per 100,000 (95%UI 5,001.76-6,320.8) in Southeast Asia to 8,608.63 per 100,000 (95%UI 7,674.07-9,485.19) in high-income Asia Pacific regions. The knee was the most commonly affected joint. High BMI and metabolic risks are the only two GBD risk factors for osteoarthritis. From 1990 to 2021, the age-standardized prevalence, incidence, and YLD attributable to osteoarthritis have been on the rise, with substantial international variations across indicators. Countries with high socio-demographic index (SDI) bear a disproportionately high burden of OA, and inequalities in the burden of disease due to differences in SDI between countries have been increasing over time. As a major public health problem, the overall global burden of OA has shown an upward trend from 1990 to 2019, including an increase in the number of cases and inequalities in distribution across the globe, which has resulted in significant health losses and economic burdens. In addition, SDI-related inequalities between countries are increasing. In this regard, national public health authorities and the World Health Organization (WHO) should work together to improve diagnosis and early treatment rates by strengthening disease awareness and education, as well as strengthening international cooperation, providing necessary medical assistance to less developed regions, and actively exploring new strategies for the prevention and treatment of OA.

Drawing on the authors' extensive experimental work, this book provides an in-depth introduction to the crystal chemistry, synthesis, luminescence, and applications of phosphor materials for solid-state lighting, mainly focusing on new nitride phosphors. It collects the latest data and trends on LED phosphors and discusses the use of new white LED lamps for general illumination and LCD backlighting. Covering novel luminescent materials, the book brings readers up to date on the evolving field of solid-state lighting.

Macrophages play pivotal roles in development, homeostasis, tissue repair and immunity. Macrophage prolifera tion is promoted by macrophage colonystimulating factor （MCSF）induced Akt signaling; yet, how this process is terminated remains unclear. Here, we identify casein kinase 2interacting protein1 （CKIP1） as a novel inhibitor of macrophage proliferation. In resting macrophages, CKIP1 was phosphorylated at Serine 342 by constitutively active GSK3β, the downstream target of Akt. This phosphorylation triggers the polyubiquitination and proteasomal degra dation of CKIP1. Upon MCSF stimulation, Akt is activated by CSF1RPI3K and then inactivates GSIOp, leading to the stabilization of CKIP1 and β-catenin proteins, pcatenin promotes the expression of proliferation genes in cluding cyclin D and cMyc. CKIP1 interacts with TRAF6, a ubiquitin ligase required for K631inked ubiquitination and plasma membrane recruitment of Akt, and terminates TRAF6mediated Akt activation. By this means, CKIP1 inhibits macrophage proliferation specifically at the late stage after MCSF stimulation. Furthermore, CKIP1 defi ciency results in increased proliferation and decreased apoptosis of macrophages in vitro and CKIP-1/ mice sponta neously develop a macrophagedominated splenomegaly and myeloproliferation. Together, these data demonstrate that CKIP-1 plays a critical role in the regulation of macrophage homeostasis by inhibiting TRAF6-mediated Akt activation.

Background：Hyperglycemia is associated with poor clinical outcomes and mortality in several patients.However,studies evaluating hyperglycemia variation in tumor patients receiving total parenteral nutrition （TPN） are scarce.The aim of this study was to assess the relationship between glycemia and tumor kinds with TPN by monitoring glycemic variation in tumor patients.Methods：This retrospective clinical trial selected 312 patients with various cancer types,whose unique nutrition treatment was TPN during the monitoring period.All patients had blood glucose （BG） values assessed at least six times daily during the TPN infusion.The glycemic variation before and after TPN was set as the indicator to evaluate the factors influencing BG.Results：The clinical trial lasted 7.5 ± 3.0 days adjusted for age,gender,family cancer history and blood types.There were six cancer types：Hepatic carcinoma （HC,21.8%）,rectal carcinoma （17.3%）,colon carcinoma （CC,14.7%）,gastric carcinoma （29.8%）,pancreatic carcinoma （11.5%）,and duodenal carcinoma （DC,4.8%）.The patients were divided into diabetes and nondiabetes groups.No statistical differences in TPN glucose content between diabetes and nondiabetes groups were found;however,the tumor types affected by BG values were obvious.With increasing BG values,DC,HC and CC were more represented than other tumor types in this sequence in diabetic individuals,as well as in the nondiabetic group.BG was inclined to be more easily influenced in the nondiabetes group.Other factors did not impact BG values,includiug gender,body mass index,and TPN infusion duration time.Conclusions：When tumor patients are treated with TPN,BG levels should be monitored according to different types of tumors,besides differentiating diabetes or nondiabetes patients.Special BG control is needed for DC,HC and CC in both diabetic and nondiabetic patients.If BG overtly increases,positive measurements are needed to control BG values.The ClinicalTrials.gov ID is NCT02024321.

A reconstruction technology of finite element meshes based on reversal engineering was applied to solve mesh penetration and separation in the finite element simulation for the divergent extrusion. The 3D numerical simulation of the divergent extrusion process in- cluding the welding stage for complicated hollow sections was conducted. Based on the analysis of flowing behaviors, the flowing velocities of the alloy in portholes and near the welding planes were properly controlled through optimizing the expansion angle as well as porthole ar- eas and positions. After the die structure optimization, defects such as warp, wrist, and the wavelike are eliminated, which improves the sec- tion-forming quality. Meanwhile, the temperature distribution in the cross section is uniform. Especially, the temperature of the C-shape notch with a larger thickness is lower than that of other regions in the cross section, which is beneficial for balancing the alloy flowing velocity.

Background： The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy （IgAN） are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. Methods： It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan （80 mg/d） wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo （Group A）, 50 mg/d clopidogrel （Group B）, 20 mg/d leflunomide （Group C）, or 50 mg/d clopidogrel and 20 mg/d leflunomide （Group D）. The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry. Results： The effects oftelmisartan combined with leflunomide on changes in proteinuria （0.36 [95% confidence interval （CI） 0.18 0.55] g/d, P 〈 0.001）, in serum uric acid （76.96 [95% CI 57.44-96.49] μmol/L, P 〈 0.001）, in serum creatinine （9.49 [95% CI 6.54-12.44]μmol/L, P 〈 0.001）, and in estimated glomerular filtration rate （-6.72 [95% CI-9.46 to -3.98] ml.min -1. 1.73 m -2, p 〈 0.001） were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight （P 〉 0.05）.Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. Conclusions： Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.

Contrast echocardiography with left ventricular opacification （LVO） improves the definition of endocardium in two-dimensional echocardiography （2DE）. This study was aimed to determine whether LVO offered added diagnostic value in noncompaetion of left ventricular myocardium （NCVM）. A total of 85 patients （40± 20 years, 54 males） with suspected NCVM were subjected to transthoracic 2DE and LVO, and 40 healthy volunteers were examined with 2DE and assigned as control subjects. The location of NCVM, the thickness ratio of noncompacted to compacted myocardium （NCR）, and the cavity size and ejection fraction of LV were quantified. Results revealed that NCVM was mainly located in the LV medium （53.2%）, apical （46.2%） segments, and lateral wall （39.8%）. The NCR obtained through LVO was greater than that detected through 2DE （4.2 ±1.3 vs. 3.3 ±1.2, P 〈 0.001）, and higher inter-correlations and less intra- and inter-observer variabilities were determined in the former than in the latter. The NCVM detection rates were also increased from 63.5% via 2DE to 83.5% via LVO and 89.4% via 2DE combined with LVO （2DE ＋ LVO） （P = 0.0004）. The LV cavity size was greater and the LV ejection fraction （LVEF） was lower in the NCVM patients than in the control group （P 〈 0.01）. In the NCVM group, the LV cavity size was higher and the LVEF was lower in LVO than in 2DE （P 〈 0.01）. In conclusion, contrast echocardiography contributes significant sensitivity and reproducibility to routine transthoraeic echoeardiography in NCVM diagnosis. Therefore, this technique should be clinically performed to diagnose suspected NCVM.

Aim： To investigate whether fluvastatin is able to ameliorate the impaired cardiac function or baroreflex sensitivity （BRS） in rats with type I diabetes. Methods： Type I diabetic rats were induced by intraperitoneal injection of streptozotocin （STZ） and then administered fluvastatin （1.5, 3.0, and 6.0 mg·kg^-l·d^-1） for 30 d. Food and drink intake was recorded every day. Fasting blood glucose （FBG） level, blood lipid level, cardiac function and BRS were measured in diabetic rats after fluvastatin treatment for 30 d. Results： The polydipsia, polyphagia and abnormal biochemical indexes of blood were significantly ameliorated by the the 3.0- and 6.0- mg doses of fluvastatin in STZ-induced diabetic rats. FBG was decreased in diabetic rats after fluvastatin treatment for 30 d. The left ventricular systolic pressure （LVSP） and the maximum rate of change of left ventricular pressure in the isovolumic contraction and relaxation period （＋-dp/dtmax） were elevated, and left ventricular diastolic pressure （LVEDP） was decreased by fluvastatin. The attenu- ated heart rate responses to arterial blood pressure （ABP） increase induced by phenylephrine （PE） and ABP decrease induced by sodium nitroprusside （SNP） were reversed by the 3.0-mg dose of fluvastatin. Conclusion： Fluvastatin regulates blood lipid levels and decreases the FBG level in diabetic rats. These responses can protect the diabetic heart from complications by improving cardiac function and BRS.