Elevated Preoperative NMPR Predicts an Unfavorable Chance of Survival in Resectable Esophageal Squamous Cell Carcinoma.

Background and objectives: Combined peripheral neutrophil−platelet indexes reflecting the systemic inflammatory status have been reported to predict the clinical outcome in patients with various types of cancer. However, the prognostic value of combined neutrophil−platelet indexes in operable esophageal squamous cell carcinoma (ESCC) remains unclear. The study introduced a novel combined neutrophil−meanplateletvolume−platelet ratio (NMPR) index and investigated its clinical and prognostic value in patients with operable ESCC receiving curative surgery. Materials and Methods: A retrospective analysis of the clinicopathologic data of 277 consecutive ESCC patients who received curative resection at Zhejiang Cancer Hospital in China between January 2007 and December 2010 was conducted (the training cohort). In addition, the clinicopathologic data of 101 resectable ESCC patients at Renmin Hospital of Hubei University of Medicine between December 2018 and June 2021 were collected (the external validation cohort). The optimal cutoff value of NMPR concerning overall survival (OS) in the training cohort was determined by X-tile software. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of NMPR along with other variables in the training cohort, which was further validated with the same cutoff value in the external validation cohort. Significant predictors of OS were used to construct the nomogram, of which the discrimination and calibration was evaluated by concordance index (C-index) and calibration plots. Results: With a cutoff value of 16.62, the results from both the training and external validation cohorts supported the association of high NMPR (>16.62) with increased tumor length and advanced T stage but not with other variables. In the training cohort, a significant association between shorter OS and high NMPR (p = 0.04) as well as high CRP (p < 0.001), poor tumor differentiation (p = 0.008), advanced T stage (p = 0.006), advanced N stage (p < 0.001) and high CEA (p = 0.007) was revealed. Additionally, the high NMPR was verified to independently predict unfavorable OS (p = 0.049) in the external validation cohort. The C-index of the OS nomogram cooperating significant predictors in the training cohort was 0.71 and the calibration plots of the OS nomogram fitted well. Conclusions: The present study demonstrates that high NMPR is an independent predictor of unfavorable OS in resectable ESCC patients without neoadjuvant therapy.

Efficacy of different drugs in the treatment of minimal hepatic encephalopathy: A network meta-analysis involving 826 patients based on 10 randomized controlled trials.

Minimal hepatic encephalopathy (MHE), a complex neuropsychological complication of cirrhosis, is characterized by delayed reaction time and the inhibition of abnormal response. This network meta-analysis (NMA) was adopted to compare the efficacy of five drugs including lactulose, probiotics, rifaximin, acetyl-L-carnitine (ALC), and L-Ornithine L-aspartate (LOLA) in the treatment of MHE. The Cochrane Library, PubMed, and Embase databases were searched for any existing entail on these five drugs from the inception to February 2018, including Randomized controlled trials (RCTs). The NMA of the five drugs, accounting for both direct and indirect comparisons to assess WMD (weighted mean difference) and SUCRA (surface under the cumulative ranking curves) was conducted. In total, 10 RTCS with 826 MHE patients met the inclusion criteria and were included in the NMA. The meta-analysis revealed that compared with placebo, lactulose, and probiotics had better efficacy in reducing ammonia serum levels and total SIP (Sickness Impact Profil) score; ALC had better efficacy in lowering serum level of ammonia and increasing the serum level of albumin; rifaximin and LOLA had better efficacy in reducing total SIP score. The results from SUCRA revealed that in terms of ammonia and albumin serums, ALC presented with the highest rankings when it comes to efficacy (serum ammonia: 87.2%; serum albumin: 92.25%). Hence, the key findings from the present study highly suggested that ALC had the best efficacy in the treatment of MHE patients.

Vitrectomy with internal limiting membrane peeling versus inverted internal limiting membrane flap technique for macular hole-induced retinal detachment: a systematic review of literature and meta-analysis.

BACKGROUND: To evaluate the effects on vitrectomy with internal limiting membrane (ILM) peeling versus vitrectomy with inverted internal limiting membrane flap technique for macular hole-induced retinal detachment (MHRD). METHODS: Pubmed, Cochrane Library, and Embase were systematically searched for studies that compared ILM peeling with inverted ILM flap technique for macular hole-induced retinal detachment. The primary outcomes are the rate of retinal reattachment and the rate of macular hole closure 6 months later after initial surgery, the secondary outcome is the postoperative best-corrected visual acuity (BCVA) 6 months later after initial surgery. RESULTS: Four studies that included 98 eyes were selected. All the included studies were retrospective comparative studies. The preoperative best-corrected visual acuity was equal between ILM peeling and inverted ILM flap technique groups. It was indicated that the rate of retinal reattachment (odds ratio (OR) = 0.14, 95% confidence interval (CI):0.03 to 0.69; P = 0.02) and macular hole closure (OR = 0.06, 95% CI:0.02 to 0.19; P < 0.00001) after initial surgery was higher in the group of vitrectomy with inverted ILM flap technique than that in the group of vitrectomy with ILM peeling. However, there was no statistically significant difference in postoperative best-corrected visual acuity (mean difference (MD) 0.18 logarithm of the minimum angle of resolution; 95% CI -0.06 to 0.43 ; P = 0.14) between the two surgery groups. CONCLUSION: Compared with ILM peeling, vitrectomy with inverted ILM flap technique resulted significantly higher of the rate of retinal reattachment and macular hole closure, but seemed does not improve postoperative best-corrected visual acuity.

Number of parity and the risk of rheumatoid arthritis in women: A dose-response meta-analysis of observational studies.

AIM: The association between parity and rheumatoid arthritis (RA) risk has been investigated, but results are controversial. Thus, our aim was to systematically analyze the effect of number of parity on the risk of RA in women. METHODS: Relevant published studies were identified using PubMed and embase databases through 1 April 2016. We pooled the relative risks (RR) and 95% confidence intervals (CI) using random-effects models. RESULTS: In all, 12 studies with a total of 2 497 580 participants and 11 521 RA cases were included. A borderline significant inverse association was observed when we compared parity with nulliparity for RA, with summarized RR = 0.90 (95%CI: 0.79-1.02; I2  = 58.5%, Pheterogeneity  = 0.010). In dose-response analysis, we observed a significant nonlinear (Pnonlinearity  = 0.000) relation between parity number and the risk of RA. Compared with null parity, the pooled RR of RA were 0.89 (95%CI: 0.86-0.93), 0.84 (95%CI: 0.79-0.89), 0.85 (95%CI: 0.79-0.90), 0.88 (95%CI: 0.81-0.95), 0.90 (95%CI: 0.83-0.97), 0.92 (95%CI: 0.84-1.02), and 0.94 (95%CI: 0.83-1.07) for 1, 2, 3, 4, 5, 6, and 7 live births, respectively. Subgroup and sensitivity analyses showed similar associations. No publication bias was found. CONCLUSION: The findings from the current meta-analysis indicate that parity was related to decreased risk of RA. The greatest risk reduction appeared when the parity number reached two. Further studies are warranted to confirm our findings.

The Clinical Significance of MiR-429 as a Predictive Biomarker in Colorectal Cancer Patients Receiving 5-Fluorouracil Treatment.

BACKGROUND 5-Fluorouracil (5-FU) based treatment is the standard therapy for metastatic colorectal cancer (CRC), but the development of chemoresistance is inevitable. Increasing evidence shows that dysregulation of microRNAs (miRNAs) is involved in malignant transformation. Thus, it is imperative that we find new diagnostic and prognostic marker for chemotherapy in CRC. MATERIAL AND METHODS For clinical parameter analysis, 78 CRC tissues and adjacent normal tissues and 45 serum specimens from CRC patients were included in this study. For chemo-response analysis, 116 primary tissues were collected from the patients receiving first-line 5-FU treatment. Quantitative Real-Time PCR (qRT-PCR) was used to detect microRNAs expression. RESULTS The expression of miR-429 was significantly increased in both serum and primary tissues from CRC patients, and enhanced miR-429 level was associated with tumor size, lymph node metastasis, and TNM stage. The diagnostic and prognostic values were also confirmed in CRC by using primary tissues. For patients receiving 5-FU-based treatment, miR-429 levels were significantly lower in responding group. The proportions of patients that did not experience response to therapy were higher in primary tumors with high miR-429 expression levels as compared with primary tumors with low miR-429 expression levels. Finally, Kaplan-Meier survival analysis showed that miR-429 is an independent prognostic indicator for chemo-response to 5-FU therapy among CRC patients. CONCLUSIONS High level of miR-429 expression was correlated with enhanced malignant potential and poor prognosis of CRC patients. Furthermore, miR-429 could affect the chemo-sensitivity of CRC patients to 5-FU therapy and was associated with poor response to 5-FU-based chemotherapy in patients with CRC.

The classification of recurrent spinal epidural hematoma: a review of the literature and a comparison with the cases.

Symptomatic postoperative spinal epidural hematoma (SEH) and spontaneous spinal epidural hematoma (SSEH) are both rare conditions, and recurrent SEH occurs even less frequently. Therefore, we describe a case of symptomatic postoperative SEH after surgical evacuation of SSEH, which was diagnosed using magnetic resonance imaging (MRI) and managed with negative pressure wound therapy (NPWT). The authors classified the reported recurrent SEHs into two types based on the cause of their previous hematoma, which can be classified as spontaneous or postoperative. The characteristics, diagnosis, managements, and results of recurrent SEHs were analyzed. The authors suggest that the postoperative SEH in the Type II will be treated with NPWT, and the new classification will be helpful for prognosis, diagnosis, and management of the recurrent SEHs.

Outcomes of different surgical procedures in the treatment of spinal tuberculosis in adults.

OBJECTIVE: To investigate surgical methods and outcomes in the treatment of spinal tuberculosis (TB) in adults. SUBJECTS AND METHODS: One hundred and eighty-one patients (average age 39 years) without multiple-level noncontiguous spinal TB were followed up for 22-72 months. The patients were divided into four groups according to surgical procedure on the basis of the position and extension of the foci: group A (74 cases): anterior radical debridement and strut grafting with instrumentation; group B (83 cases): posterior instrumentation and bone grafting with anterior radical debridement and strut grafting in a single- or two-stage procedure; group C (10 cases): extrapleural anterolateral decompression and strut grafting with posterior instrumentation in thoracic or thoracolumbar spine, and group D (27 cases): single-stage transforaminal decompression and posterior instrumentation and fusion. RESULTS: There was a significant decrease (p < 0.05) in mean preoperative (81%) Oswestry's Disability Index. Except for 24 patients with lumbosacral TB who were only instrumented posteriorly, kyphosis degrees were corrected by a mean of 11.5° in the anterior instrumentation group and 12.6° in the posterior instrumentation group (p < 0.01). The correction loss was 6.8° in the anterior instrumentation group and 6.1° in the posterior instrumentation group at the last follow-up (p < 0.01). CONCLUSION: The four surgical procedures obtained good results for correction and maintenance of the correction, clearance of the foci, decompression of the spinal cord and pain relief in the treatment of spinal TB in adults, providing that the operative indication is accurately identified. However, the posterior approach was superior to anterior instrumentation for correcting deformity and maintaining the correction.

Interleukin 6 destabilizes atherosclerotic plaques by downregulating prolyl-4-hydroxylase α1 via a mitogen-activated protein kinase and c-Jun pathway.

Interleukin 6 (IL-6) is a pivotal cytokine that regulates extracellular matrix metabolism by ameliorating the modification of collagen content, important in fibrous caps of atherosclerotic plaque. Prolyl-4-hydroxylase α1 (P4Hα1) is a key intracellular enzyme required for synthesis of collagen in animals. We investigated the relationship of IL-6 and P4Hα1 in atherosclerosis-prone mice and human aortic smooth muscle cells (HASMCs). Apolipoprotein E (ApoE)-/- mice were fed a high-fat diet and a perivascular constrictive silica collar was placed on the right common carotid artery to induce atherosclerotic lesions, then mice were divided into two groups for transfection with empty lentivirus or IL-6 lentivirus. HASMCs were transfected with small interfering RNA or treated with recombinant human IL-6. IL-6 significantly downregulated collagen, P4Hα1 and smooth muscle cell contents in atherosclerotic mouse arteries. Macrophage and lipid contents in the atherosclerotic area were significantly increased with IL-6 treatment. IL-6 significantly downregulated P4Hα1 expression in HASMCs through an RAF-MEK1/2-ERK1/2 mitogen-activated protein kinase (MAPK) pathway, and c-Jun was involved in the process. Our findings highlight IL-6 destabilize atherosclerotic plaques in mice by downregulating P4Hα1 via an RAF-MEK1/2-ERK1/2 MAPK and c-Jun pathway.

Outcomes of anterior and posterior instrumentation under different surgical procedures for treating thoracic and lumbar spinal tuberculosis in adults.

PURPOSE: There are few articles in the literature comparing outcomes between anterior and posterior instrumentation in the management of thoracic and lumbar spinal tuberculosis (TB). METHODS: Between January 2004 and December 2009, 217 adult patients, average age 39 (range 16-67) years with thoracic and lumbar spinal TB were treated by anterior radical debridement and fusion plus instrumentation, anterior radical debridement with fusion and posterior fusion with instrumentation, posterolateral debridement and fusion plus posterior instrumentation or transpedicular debridement and posterior fusion with instrumentation in a single- or two-stage procedure. We followed up 165 patients for 22-72 (mean 37) months. Of these, 138 underwent more than three weeks chemotherapy with isoniazid, rifampin, pyrazinamide and ethambutol, and the remaining 27 underwent operation for neurological impairment within six to 18 hours of the same chemotherapy regimen. In no case did relapse occur. Apart from eight patients with skip lesions treated by hybrid anterior and posterior instrumentation, anterior instrumentation was used in 74 patients (group A) and 83 patients (group B) were fixed posteriorly. RESULTS: In both groups, local symptoms were relieved significantly one to three weeks postoperatively; ten of 14 patients (71%) in group A and 14 of 19 (74%) in group B with neurological deficit had excellent or good clinical results (P > 0.05). Erythrocyte sedimentation rates (ESR) returned from 43.6 mm/h and 42.7 mm/h, respectively, preoperatively to normal levels eight to 12 weeks postoperatively. Kyphosis degree was corrected by a mean of 11.5° in group A and 12.6° in group B, respectively (P < 0.01). Correction loss was 6.8° in group A and 6.1° in group B at the last follow-up (P < 0.01). Fusion rates of the grafting bone were 92.5% and 91.8%, respectively, at final follow-up (P > 0.05). Severe complications did not occur. CONCLUSION: These results suggest that both anterior and posterior instrumentation attain good results for correction of the deformity and maintaining correction, foci clearance, spinal-cord decompression and pain relief in the treatment of thoracic and lumbar spinal TB providing that the operative indication is accurately identified. However, the posterior approach may be superior to anterior instrumentation to correct deformity and maintain that correction.

[Thoughts and exploration on pharmacokinetic study of herbal medicines based on metabonomics and complex network].

The change of drug development pattern pushes the innovation of drug valuation methods. The pharmacokinetic research of traditional Chinese medicines (TCM) is an important part of TCM modernization and plays a key role in novel drug development of TCM. However, the research methods and techniques are in consistent with the specific characteristics of TCM, i.e., multiple-components is still in the infant. This review makes a brief summary of current pharmacokinetic exploration of TCM, metabonomics and complex network, and puts forward a new strategy based on complex network and metabonomics to study TCM pharmacokinetic in order to disclose the active components and mechanism of TCM.

[Outcomes of anterior versus posterior instrumentation under different surgical procedures in the treatment of thoracolumbar spinal tuberculosis in adults].

OBJECTIVE: To compare the outcomes of anterior verus posterior instrumentation under different surgical procedures in the surgical management of thoracolumbar spinal tuberculosis (TB). METHODS: Between January 2004 and December 2009, 241 adult patients with thoracolumbar spinal TB underwent radical debridement and strut grafting plus anterior or posterior instrumentation in single-stage or two-stages. The mean age was 39 years (range: 16 - 67). The mean follow-up period for 189 patients was 37 months (range: 22 - 72). Among them, 157 cases underwent > 3 weeks of chemotherapeutic regimen of isoniazid, rifampin, pyrazinamide and ethambutol and the remaining 32 were operated for neurological impairment after 6-18 h with the same chemotherapeutic regimen. Except for 8 patients with skip lesions undergoing hybrid anteroposterior instrumentation, anterior instrumentation was utilized in 74 patients (Group A) and posterior instrumentation in 107 patients (Group B). RESULTS: In both groups, local symptoms of all patients were relieved significantly 1-3 weeks postoperatively. And 10/14 cases (71%) in Group A and 14/19 cases (74%) in Group B with neurological deficits had excellent or good clinical outcomes (P > 0.05). The levels of erythrocyte sedimentation rates (ESR) returned from 43.6 mm/h and 42.4 mm/h preoperatively to normal at 8-12 weeks postoperatively. Kyphosis degrees were corrected by a mean of 11.5° in Group A and 12.6° in Group B (P < 0.01). The correction loss was 6.8° in Group A and 6.1° in Group B at the last follow-up (P < 0.01). Fusion rates of the grafting bone were 92.5% and 91.8% respectively at the final follow-up (P > 0.05). Severe complications did not occur. CONCLUSION: Either anterior or posterior instrumentation can obtain good results in correction and maintenance of deformity, clearance of foci, decompression of spinal cord and pain relief in the treatment of thoracolumbar spinal TB as long as the surgical indications are properly selected. Posterior instrumentation may be superior to anterior instrumentation in the correction and maintenance of deformity.

[Expression of osteonectin in lens epithelium cells in age-related cataract].

OBJECTIVE: To study the expression of osteonectin (also called secreted protein acidic and rich in cysteine, SPARC) in the lens epithelium cells in cortex cataract and nucleus cataract. METHOD: This is an experimental research. Forty-five capsulotomy specimens were obtained from 33 patients suffered form pure cortex or/and nucleus cataracts and classified as nucleus group and cortex group, between May to July of 2010. Immunohistochemistry was used to detect the SPARC, which was analyzed by gray value. TUNEL was used to examine the apoptosis of lens epithelium cell. The difference of SPARC expression and apoptosis rate between these two groups was analyzed by LSD-t. RESULTS: Twenty specimens were studied with immunohistochemistry (C/N = 8/12), and 25 specimens studied by TUNEL test (C/N = 9/16). Expression of SPARC in the cortex group was significantly less than that in the nucleus group (peripheral region: t = 2.827, P < 0.05; central region: t = 2.264, P < 0.05). Expression of SPARC in the central region was significantly less than that in the peripheral region (peripheral region: t = 3.473, P < 0.05; central region: t = 2.771, P < 0.05). Apoptosis rate in the nucleus group was significantly lower than the cortex group (nucleus group: t = 2.364, P < 0.05; cortex group: t = 2.723, P < 0.05). Apoptosis rate in peripheral region was significantly less than that in central region (nucleus group: t = 2.771, P < 0.05; cortex group: t = 2.473, P < 0.05). CONCLUSIONS: The expression of SPARC is different between nucleus cataract and cortex cataract and also different between central and peripheral regions. The expression of SPARC is related with apoptosis of lens capsule epithelium cells.

Dexmedetomidine inhibits the growth and metastasis of esophageal cancer cells by down-regulation of lncRNA MALAT1.

This study aims to evaluate the effect of dexmedetomidine (DEX)-on esophageal cancer (EC) via regulating long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). The effect of DEX on MALAT1 expression and EC cell viability was detected. EC cells were divided into Blank, DEX, scrambled/MALAT1 siRNA, and DEX + control/MALAT1 groups, followed by a series of experiments including quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blotting, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), Annexin V-FITC/PI staining, wound healing, and Transwell assays. Additionally, mice were subjected to the subcutaneous injection of Eca109 cells transfected by control/MALAT1 activation lentiviral vector to construct EC models with the DEX treatment, and then the tumor volume and the expression of Ki-67 and active caspase-3 were determined. DEX reduced the expression of MALAT1 in EC cells in a dose-dependent manner. DEX inhibited the viability of EC cells, but increased the cell apoptosis, which, however, was reversed by MALAT1 overexpression. Moreover, MALAT1 overexpression abolished the inhibitory effect of DEX on the epithelial-mesenchymal transition (EMT) of EC cells, with enhanced migration and invasion. Furthermore, DEX succeeded in decreasing the tumor volume with the down-regulation of MALAT1. In comparison with the DEX group, mice in the DEX + MALAT1 group had larger tumors, with the up-regulation of Ki-67 and the down-regulation of active caspase-3. DEX can reduce the expression of MALAT1 in EC cells, thereby inhibiting the proliferation, invasion and migration, as well as EMT, and promoting the apoptosis of EC cells.

Prospective population pharmacokinetic study of tacrolimus in adult recipients early after liver transplantation: A comparison of Michaelis-Menten and theory-based pharmacokinetic models.

Background and Objective: Tacrolimus, a calcineurin inhibitor widely used as a potent immunosuppressant to prevent graft rejection, exhibits nonlinear kinetics in patients with kidney transplantation and nephrotic syndrome. However, whether nonlinear drug metabolism occurs in adult patients undergoing liver transplantation remains unclear, as do the main underlying mechanisms. Therefore, here we aimed to further confirm the characteristics of nonlinearity through a large sample size, and determine the potential influence of nonlinearity and its possible mechanisms. Methods: In total, 906 trough concentrations from 176 adult patients (150 men/26 women; average age: 50.68 ± 9.71 years, average weight: 64.54 ± 11.85 kg after first liver transplantation) were included in this study. Population pharmacokinetic analysis was performed using NONMEM®. Two modeling strategies, theory-based linear compartmental and nonlinear Michaelis-Menten (MM) models, were evaluated and compared. Potential covariates were screened using a stepwise approach. Bootstrap, prediction-, and simulation-based diagnostics (prediction-corrected visual predictive checks) were performed to determine model stability and predictive performance. Finally, Monte Carlo simulations based on the superior model were conducted to design dosing regimens. Results: Postoperative days (POD), Aspartate aminotransferase (AST), daily tacrolimus dose, triazole antifungal agent (TAF) co-therapy, and recipient CYP3A5*3 genotype constituted the main factors in the theory-based compartmental final model, whereas POD, Total serum bilirubin (TBIL), Haematocrit (HCT), TAF co-therapy, and recipient CYP3A5*3 genotype were important in the nonlinear MM model. The theory-based final model exhibited 234 L h-1 apparent plasma clearance and 11,000 L plasma distribution volume. The maximum dose rate (V max ) of the nonlinear MM model was 6.62 mg day-1; the average concentration at steady state at half-V max (K m ) was 6.46 ng ml-1. The nonlinear MM final model was superior to the theory-based final model and used to propose dosing regimens based on simulations. Conclusion: Our findings demonstrate that saturated tacrolimus concentration-dependent binding to erythrocytes and the influence of daily tacrolimus dose on metabolism may partly contribute to nonlinearity. Further investigation is needed is need to explore the causes of nonlinear pharmacokinetic of tacrolimus. The nonlinear MM model can provide reliable support for tacrolimus dosing optimization and adjustment in adult patients undergoing liver transplantation.

Population pharmacokinetic analysis, renal safety, and dosing optimization of polymyxin B in lung transplant recipients with pneumonia: A prospective study.

Objectives: This study aims to characterize the population pharmacokinetics of polymyxin B in lung transplant recipients and optimize its dosage regimens. Patients and methods: This prospective study involved carbapenem-resistant organisms-infected patients treated with polymyxin B. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological efficacy, nephrotoxicity, and hyperpigmentation were assessed. Monte Carlo simulation was performed to calculate the probability of target attainment in patients with normal or decreased renal function. Results: A total of 34 hospitalized adult patients were included. 29 (85.29%) patients were considered of clinical cure or improvement; 14 (41.18%) patients had successful bacteria elimination at the end of the treatment. Meanwhile, 5 (14.71%) patients developed polymyxin B-induced nephrotoxicity; 19 (55.88%) patients developed skin hyperpigmentation. A total of 164 concentrations with a range of 0.56-11.66 mg/L were obtained for pharmacokinetic modeling. The pharmacokinetic characteristic of polymyxin B was well described by a 1-compartment model with linear elimination, and only creatinine clearance was identified as a covariate on the clearance of polymyxin B. Monte Carlo simulations indicated an adjusted dosage regimen might be needed in patients with renal insufficiency and the currently recommended dose regimens by the label sheet of polymyxin B may likely generate a subtherapeutic exposure for MIC = 2 mg/L. Conclusion: Renal function has a significant effect on the clearance of polymyxin B in lung transplant recipients, and an adjustment of dosage was needed in patients with renal impairments.

Salvianolic acid B alleviates neurological injury by upregulating stanniocalcin 1 expression.

Background: Salvianolic acid B (Sal B) is a representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which promotes angiogenesis in myocardial infarction and diabetic cardiomyopathy. However, whether Sal B has a neuroprotective function in ischemic stroke by promoting angiogenesis is still unclear. Methods: In the present study, ischemic stroke models were induced in rats by middle cerebral artery occlusion (MCAO), and Sal B (10 or 20 mg/kg/d) was intraperitoneally injected according to a previous study. Neurological deficits were evaluated by the modified Longa five-point scale, modified Bederson scores and cerebral infarction sizes by triphenyltetrazolium chloride (TTC) staining. Apoptotic cells were tested by cleaved-caspase3 immunofluorescence staining and an in situ cell death (TUNEL) detection kit. Human umbilical vein endothelial cells (HUVECs) exposed to hypoxia were used to investigate the effects of Sal B on angiogenesis and tube formation in vitro. Results: Sal B ameliorated the neurological deficits, decreased the cerebral infarction volumes in rats with ischemic stroke, significantly increased the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and VEGFA and promoted angiogenesis both in vivo and in vitro. Furthermore, Sal B increased stanniocalcin 1 (STC1) expression, induced the phosphorylation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR) activity, enhanced cell migration, and activated VEGFR2/VEGFA signaling in endothelial cells. Conclusions: This study showed that Sal B promoted angiogenesis and alleviated neurological apoptosis in rats with ischemic stroke by promoting STC1.

Metabolomics study on quality control and discrimination of three curcuma species based on gas chromatograph-mass spectrometry.

INTRODUCTION: Metabonomic analysis is an important molecular phenotyping method for characterising plant ecotypic variations; hence, it may become a powerful tool for quality control and discrimination of traditional Chinese medicine (TCM). OBJECTIVE: To discriminate and assess the quality of Curcuma phaeocaulis, C. kwangsiensis and C. wenyujin from different ecotypes. The identification of the compositions of essential oils from the three Curcuma species was included in this study. METHODOLOGY: Metabolomics analysis was carried out on all samples by gas chromatography-mass spectrometry (GC-MS) coupled with multivariate statistical analysis. Characterisation of phytochemicals in essential oils was performed by automated matching to the MS library and comparison of their mass spectra (NIST05 database). RESULTS: Principal component analysis (PCA) effectively distinguished the samples from different species and ecotypes. Partial least squares discrimination analysis (PLS-DA) was successfully employed in classifying the GC-MS data of authentic, commercial and introduction cultivation samples. Furthermore, the components contributing significantly to the discrimination, namely curzerenone, germacrone, curdione and epicurzerenone, were screened by PCA and PLS-DA loading plots and further can be used as chemical markers for discrimination and quality control among different groups of samples.

C-peptide and diabetic encephalopathy.

With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic encephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cognitive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glucose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronal loss and damaged cognitive functions. Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor (IGF) system, hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide deficiency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients. Those findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.

[Protective effects of erythromycin on human bronchial epithelial cells impaired by interleukin-4].

OBJECTIVE: To study the protective effects and mechanisms of erythromycin on human bronchial epithelial (HBE) cells damaged by interleukin-4. METHODS: The growth curve of HBE cells was recorded by MTT. The cells were divided into the following groups: control (incubation for 24, 48 h); IL-4 (0.01 mg/L, incubation for 24, 48 h); erythromycin intervention group 1 (4 mg/L erythromycin co-incubation for 24, 48 h after adding IL-4) and erythromycin intervention group 2 (40 mg/L erythromycin co-incubation for 24, 48 h after adding IL-4). The mitotic cycle of HBE cell was determined by flow cytometry and its apoptosis examined by Hoechst dyeing. RESULTS: The viability of HBE cells was significantly enhanced after a 24/48-hour treatment of erythromycin as compared with IL-4 group (P < 0.05, P < 0.01). In erythromycin intervention group 1, the cell ratios of G(0)/G(1) and S phases were (55.9 ± 2.5)% and (34.7 ± 3.4)% respectively while the rate of cell apoptosis was (9.5 ± 0.9)%. There were significant differences as compared with IL-4 group (P < 0.05). In erythromycin intervention group 2, the cell ratios of G(0)/G(1) and S phases were (55.1 ± 0.5)% and (36.2 ± 2.7)% respectively while the rate of cell apoptosis was (4.0 ± 0.6)%. There were significant differences as compared with IL-4 group (P < 0.05). CONCLUSION: Erythromycin has protective effects on HBE cells damaged by IL-4. The mechanism is probably through influencing the mitotic cycle and inhibiting the apoptosis.

Effect of adiponectin overexpression on stability of preexisting plaques by inducing prolyl-4-hydroxylase expression.

BACKGROUND: Although adiponectin has been implicated as an antiinflammatory factor in atherosclerotic lesion development, little is known about its role in advanced atherosclerotic plaque. This study assessed the effect and mechanism of adiponectin on the expression of prolyl 4-hydroxylase (P4H) alpha1 and its role in the stability of preexisting plaque. METHODS AND RESULTS: Atherosclerotic lesions in the carotid arteries of apolipoprotein E-deficient mice were induced by the placement of a perivascular collar. Six weeks after surgery, 120 mice were divided into phosphate-buffered saline (PBS) (n=40), empty adenovirus (Ad.Empty) (n=40) and adiponectin adenovirus (Ad.Adipo) groups (n=40). The number of vulnerable lesions were lower with Ad.Adipo than with Ad.Empty transfection. Mean cap thickness, cap area, cap-to-core ratio and intimal collagen content were all greater with Ad.Adipo than with Ad.Empty transfection; however, the groups did not differ in plaque area or intima-media thickness. Plasma adiponectin level positively correlated with intimal collagen content. Adiponectin transfection conferred enhanced expression of P4H, with no changes in the PBS and Ad.Empty groups. CONCLUSIONS: Adiponectin increases collagen production by inducing the expression of P4H, which may play a major role in the development of the thick fibrous cap of advanced atherosclerotic plaque.