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Influence of age and sex on pharmacodynamics of propofol in neurosurgical patients: model development

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Acta Pharmacologica Sinica 2006年第5期27卷 629-634页

作者： Yu-hong L1~(2,5) Fu-sheng WU~3 Jian-guo XU~4 ~2department of anesthesiology,~3department of Surgical Oncology,First Affiliated hospital,Zhejiang University College of Medicine,Hangzhou 310003,china ~4department of anesthesiology,nanjing jinling hospital,nanjing 210002,china departmentofanesthesiology departmentofSurgicalOncology 310003China departmentofanesthesiology NanjingJinlingFirstAffiliatedHospitalZhejiangUniversityCollegeofMedicineHangzhouHospitalNanjing210002China

Aim:To determine propofol concentration in the cerebral spinal fluid （CSF） ofneurosurgical patients and carry out a preliminary population ***:Twenty-seven elective neurosurgical patients （12 men and 15women） aged 17-74 years received propofol in a bolus dose of 2 mg/kg for 5 minand an infusion of 10 mg/kg per h for 5 *** CSF samples were drawn andassayed for propofol *** bispectral index （BIS） was used to mea-sure the drug *** data were analyzed first with the Excel software package,then pharmacodynamics modeling was performed using the NONMEM ***:The CSF concentration was related to the drug effect withlinear and sigmoid *** parameters for the linear addictive modelwere a= 1.11 and b=*** parameters for the linear exponential model were a=1.05 and b=*** parameters for the sigmoid Emaxmodel were Emax=119,EC50=53.6ng/mL,and N=*** the covariates of age,weight and sex wereconsidered,the parameters of models,objective function,the standard error of themean and the prediction error were not ***:Linear additive,linear exponential and sigmoid Emaxmodels can be used to describe the pharmaco-dynamics of propofol with respect to the concentration in *** this smallpopulation,age （17-74 years）,weight （47-98kg） and sex did not influence any ofthe pharmacodynamic parameters of *** verify these preliminary results,a larger study population is required.

关键词： propofol cerebrospinal fluid age factors sex factors pharmcodynamics

Pathogenesis and treatment of parenteral nutrition-associated liver disease

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Hepatobiliary & Pancreatic Diseases International 2012年第6期11卷 586-593页

作者： Zi-Wei Xu ,You-Sheng Li department of Surgery, jinling hospital, nanjing University School of Medicine, nanjing 210002, china department of Surgery Jinling Hospital Nanjing University School of Medicine Nanjing 210002 China

BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) has been common in patients who require long-term parenteral nutrition. PNALD develops in 40%-60% of infants on long-term parenteral nutrition compared with 15%-40% of adults on home parenteral nutrition for intestinal failure. The pathogenesis of PNALD is multifactorial and remains unclear There is no specific treatment. Management strategies for its prevention and treatment depend on an understanding of many risk factors. This review aims to provide an update on the pathogenesis and treatment of this disease. DATA SOURCES: A literature search was performed on the MEDLINE and Web of Science databases for articles published up to October 2011, using the keywords: parenteral nutrition associated liver disease, intestinal failure associated liver disease lipid emulsions and fish oil. The available data reported in the relevant literatures were analyzed. RESULTS: The literature search provided a huge amount of evidence about the pathogenesis and management strategies on PNALD. Currently, lack of enteral feeding, extended duration of parenteral nutrition, recurrent sepsis, and nutrient deficiency or excess may play important roles in the pathogenesis of PNALD. Recent studies found that phytosterols present as contaminants in soy-based lipid emulsions, are also an important factor in the pathogenesis. Moreover, the treatment of PNALD is discussed. CONCLUSIONS: The use of lipid emulsions, phytosterols in particular, is associated with PNALD. Management strategies for the prevention and treatment of PNALD include consideration of early enteral feeding, the use of specialized lipid emulsions such as fish oil emulsions, and isolated small bowel or combined liver and small bowel transplantation. A greater understanding of the pathogenesis of PNALD has led to promising interventions to prevent and treat this condition. Future work should aim to better understand the mechanisms of PNALD and the long-term outcomes

关键词： parenteral nutrition-associated liver disease phytosterol farnesoid X receptor fish oil

Influence of CYP2D610B genotype on pharmacokinetics of propafenone enantiomers in Chinese subjects

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Acta Pharmacologica Sinica 2003年第12期 103-106页

作者： CHEN Bing CAI Wei-Min department of Clinical Pharmacology, jinling hospital, nanjing 210002, china

AIM: To study the relationship between genotype of CYP2D6* 10B and pharmacokinetics of propafenone enantiomers. METHODS: Genotype of 17 healthy Chinese HAN subjects was determined by an allele specific amplification method. The blood samples (0-15 h) of the subjects were taken after oral administration of a single dose (400 mg) of propafenone hydrochloride. Concentrations of propafenone enantiomers in plasma were measured by a reverse-phase HPLC with precolumn derivatization. RESULTS: Seventeen subjects characterized for CYP2D6* 10B genotype included (*1/*1) (n=4), (*1/*10) (n=5) and (*10/*10) (n=8). The metabolic ratios (lg MR) of the three genotypes were-2.68±0.23, -2.2±0.7, and -1.1±0.5, respectively. The AUC of the three groups were (1534±334), (1891±793), (3171±1075) μg·h·L-1for S-enantiomer and (1136±345), (1467±817), (2277±745) μg·h·L-1for R-enantiomer, respectively. The AUC of propafenone enantiomers in *10/*10 is about 1.5-2 times of that of *1/*10 group or *1/*1 group, a

关键词： propafenone pharmacokinetics CYP2D6~* 10B genotype phenotype enantiomers

Role of toll-like receptor 4/mutant myeloid differentiation primary response 88/nuclear factor kappa-B mediated inflammation in diabetes mellitus with Northwest dryness syndrome

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Journal of Traditional Chinese Medicine 2024年第5期44卷 963-973页

作者： DENG Deqiang XIAO Yan MA Dan QIU jinling HAO Congli WANG Di ZHANG Miao State Key Laboratory of Pathogenesis Prevention and Treatment of High Incidence Diseases in Central AsiaXinjiang Medical University department of Endocrinology Traditional Chinese Medicine Hospital of Urumqi

OBJECTIVE: To investigate the role of toll-like receptor 4(TLR4)/mutant myeloid differentiation primary response 88(MyD88)/nuclear factor kappa-B(NF-κB) signaling pathway-mediated inflammation in diabetes mellitus with Northwest dryness ***: Rats were randomly divided into the normal control, type 2 diabetes(T2DM) model, Northwest dryness syndrome + T2DM(Northwest dryness), and simple internal dampness + T2DM(internal dampness)groups. Enzyme-linked immunosorbent assay was used to detect biochemical indexes and inflammatory *** histopathological observation was *** real-time polymerase chain reaction and Western blot analysis were used to detect the mRNA and protein expression levels, ***: Compared with the T2DM group, the glycosylated hemoglobin A1c, insulin, glucose tolerance,the homeostasis model assessment of insulin resistance,tumor necrosis factor-α, interleukin 1β, interleukin 16,malondialdehyde, blood lipid, alanine aminotransferase,and aspartate aminotransferase were significantly elevated in the internal dampness group. Their levels were significantly elevated in the Northwest dryness group than in the T2DM and internal dampness *** superoxide dismutase, glutathione peroxidase, liver glycogen, and organ-to-weight ratio were significantly declined in the internal dampness group and the Northwest dryness group than in the T2DM ***, these levels were elevated in the Northwest dryness group than in the internal dampness ***, the mRNA expression levels of interferon regulatory factor 5 and NF-κB p65, and the protein expression levels of TLR4, MyD88, and NF-κB were significantly higher in the internal dampness and the Northwest dryness groups than the T2DM ***, the mRNA and protein levels were significantly higher in the Northwest dryness group than in the internal dampness ***: Northwest dryness syndrome-mediated TLR4/MyD88/NF-κB pathway and chronic i

关键词： NF-kappa B Northwest dryness syndrome diabetes mellitus inflammation myeloid differentiation factor 88 toll-like receptor 4

Human papillomavirus and p53 protein immunoreactivity in condylomata acuminatum and squamous cell carcinoma of penis

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Asian Journal of Andrology 2001年第1期3卷 75-77页

作者： Xin-Hua ZHANG Gui-Qin SUN Yu YANG Tai-He ZHANG department of Pathology, General hospital of nanjing Command, PLA, nanjing 210002, china department of Pathology General Hospital of Nanjing Command China

Aim: To determine the immunoreactive pattern of human papillomavirus (HPV) antigen and p53 protein in condylo-mata acuminatum (CA) and squamous cell carcinoma (SCC) of penis. Methods: Immunohistochemistry for HPVand p53 were performed in 40 specimens of formalin fixed, paraffin embedded tissues using a polyclonal (rabbit) anti-body against HPV and a monoclonal (mouse) antibody against human p53 protein. Twenty one cases of CA and nine-teen cases of SCC were examined. Results: HPV antigen was detected in all 21 CA and 2 penile SCC. p53 proteinoverexpression was observed in 12 of 19 (63%) SCC in which 6 cases were strong positive. Five of 21 CA (24%)showed low-grade p53 protein overexpression. Conclusion; CA is related to HPV infection and some cases showp53 protein low-grade overexpression. In contrast, p53 protein overexpression is common in penile SCC, which is sel-dom related to HPV infection. (Asian J Androl 2001 Mar; 3: 75-77)

关键词： condylomata acuminata penile diseases carcinoma HPV protein p53

Lipopolysaccharide decreasing albumin expression in rat hepatocytes

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Hepatobiliary & Pancreatic Diseases International 2005年第3期4卷 410-415页

作者： Research Institute of General Surgery, jinling hospital, nanjing 210002, china (Wang XY, Li WQ, Li N and Li JS) and department of Orthopaedics, Zhongda hospital, nanjing 210009, china (Lu J) Research Institute of General Surgery Jinling Hospital Nanjing 210002 China. wxinying@***

The relations of the severity of hypoalbu-minemia to morbidity and mortality of patients with critical illness illustrate the need for better understanding of molecular mechanism of hypoalbuminemia. This study was undertaken to investigate the response of albumin synthesis to lipopolysaccharide(LPS)in rat hepatocytes in vitro in early acute phase of sepsis. METHODS:Hepatocytes were cultured at an initial cell density of 1.5×106 cells/well in 3 ml culture medium. There were two groups of samples which received either normal saline or 1 μg/L LPS randomly. Albumin mRNA in hepatocytes was assessed by reverse transcription-poly-merase chain reaction(RT-PCR) and albumin level in the supernatant was measured by ELISA at 0,2,8,12,24 hours after exposure. Meanwhile, the albumin precursor was evaluated at the same time points by flow cytometry. RESULTS:The quantitative changes of mRNA, albumin precursor and its protein were analogous. All of them tended to decline at 12 hours post-treatment and did not decrease significantly until 24 hours after LPS exposure. Meanwhile, albumin mRNA decreased about 30% and the levels of albumin precursor and albumin reduced approximately 50%. CONCLUSIONS: LPS can inhibit albumin synthesis in rat hepatocytes by prevention of albumin transcription. Moreover, the response of hepatic albumin synthesis to LPS changes with the stage of sepsis process. The results show that albumin metabolism in sepsis is a complicated process and further studies are required to understand the molecular mechanism of LPS-induced hypoalbuminemia in sepsis.

关键词： lipopolysaccharide hepatocyte albumin hypoalbuminemia signal transduction sepsis

Color Doppler Imaging in the Study of Retrobulbar Hemodynamic Changes of Primary Angle-closure Glaucoma

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眼科学报 1997年第3期13卷 113-115页

作者： Nong Tian, Ninghua Fudepartment of Ophthalmology, department of Ultrasonic Diagnosis General hospital of nanjing Military Area, nanjing 210002, china department of Ophthalmology General Hospital of Nanjing Military Area Nanjing 210002 China

Purpose: To investigate the hemodynamic changes of ophthalmic and central retinal artery (OA,CRA) in Primary Angle-closure Glaucoma (PACG) and the effects of intraocular pressure (TOP) on the retrobulbar ***: The hemodynamic changes of OA, CRA in PACG were explored with color Doppler imaging (CDI) technique. Peak systolic blood flow velocity (PSV), end-diastolic blood flow velocity (EDV),pulsatile and resistive indices (PI,RI) were recorded and compared with those of the normal subjects. There were 20 patients (40 eyes) with PACG who were divided into two groups according to their IOP levels; ocular hypertension (15 eyes) and normal tension (25 eyes) .Results : Compared with the normal subjects, the hypertension group of PACG showed significant reduction in the EDV and increases in PI, RI of CRA; normal tension group of PACG also showed remarkable increase in RI of CRA. The ocular hypertension was significantly correlated with the RI and not with the EDV by the analysis of multiple

关键词：眼球血液动脉闭角型青光眼彩色多普勒成像 PACG

Tissue-resident macrophages exacerbate lung injury after remote sterile damage

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Cellular & Molecular Immunology 2024年第4期21卷 332-348页

作者： Hanhui Zhong Jingjing Ji jinling Zhuang Ziying Xiong Pengyun Xie Xiaolei Liu Jundi Zheng Wangli Tian Xiaoyang Hong Jing Tang The department of anesthesiology Affiliated Hospital of Guangdong Medical UniversityZhanjiangGuangdongChina The department of Critical Care Medicine General Hospital of Southern Theater Command of PLAGuangzhouChina The department of Respiratory Medicine Guangdong Provincial Hospital of Integrated Chinese and Western MedicineFoshanChina Pediatric Intensive Care Unit Senior Department of Pediatricsthe Seventh Medical Center of PLA General HospitalBeijingChina

Remote organ injury,which is a common secondary complication of sterile tissue damage,is a major cause of poor prognosis and is difficult to ***,we report the critical role of tissue-resident macrophages in lung injury after trauma or stroke through the inflammatory *** found that depleting tissue-resident macrophages rather than disrupting the recruitment of monocyte-derived macrophages attenuated lung injury after trauma or *** findings revealed that the release of circulating alarmins from sites of distant sterile tissue damage triggered an inflammatory response in lung-resident macrophages by binding to receptor for advanced glycation end products(RAGE)on the membrane,which activated epidermal growth factor receptor(EGFR).Mechanistically,ligand-activated RAGE triggered EGFR activation through an interaction,leading to Rab5-mediated RAGE internalization and EGFR phosphorylation,which subsequently recruited and activated P38;this,in turn,promoted RAGE translation and trafficking to the plasma membrane to increase the cellular response to RAGE ligands,consequently exacerbating *** study also showed that the loss of RAGE or EGFR expression by adoptive transfer of macrophages,blocking the function of RAGE with a neutralizing antibody,or pharmacological inhibition of EGFR activation in macrophages could protect against trauma-or stroke-induced remote lung ***,our study revealed that targeting the RAGE-EGFR signaling pathway in tissue-resident macrophages is a potential therapeutic approach for treating secondary complications of sterile damage.

关键词： tissue-resident macrophage RAGE remote sterile damage

Mechanism of reduction of albumin expression induced by lipopolysaccharide in rat hepatocytes

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中华医学杂志(英文版) 2005年第20期000卷 25-32页

作者： WANG Xin-ying, LI Wei-qin, LU Jun, LI Ning and LI Jie-shou Research Institute of General Surgery, jinling hospital, nanjing 210002, china department of Orthopaedics, Zhongda hospital, nanjing 210009, china Research Institute of General Surgery Jinling Hospital Nanjing 210002 China department of Orthopaedics Zhongda Hospital Nanjing 210009 China

Background The severity of hypoalbuminemia has been sho wn to be related to morbidity and mortality in some critical illnesses, illustra ting the need for better understanding of molecular mechanism of hypoalbuminemia . Lipopolysaccharide (LPS) is a key mediator inducing hypoalbuminemia in sepsis and septic shock. The present study was designed to identify if the reduction of albumin expression is directly induced by LPS and modulated by activated extr acellular signal-regulated protein kinase (ERK) and p38 mitogen-activated prot ein kinase (MAPK) in rat hepatocytes. Methods Primary rat hepatocytes were divided into five groups. In two of them, hepatocytes were treated with normal saline or 1 μg/ml LPS, th en albumin mRNA expression was observed at 0, 2, 8, 12 and 24 hours after treatm ent. In another group, hepatocytes were pretreated with 100, 40 or 20 μmol/L o f cycloheximide (CHX, an inhibitor of protein synthesis) for 30 minutes followed by 1 μg/ml LPS for 24 hours. Then the RNA was extracted from the cells for RT -PCR to detect the expression of albumin. The other two groups were administer ed 1 μmol/L, 10 μmol/L and 50 μmol/L of SB203580 (p38 MAPK inhibitor) or PD98 059 (ERK inhibitor) 30 minutes prior to 1 μg/ml LPS treatment. After 24 hours of LPS treatment, the supernatant was collected and assayed for albumin concentr ations. Data were analyzed by one-way analysis of variance, followed by the Ne wman-Keul test; a P<0.05 was considered significant. Results There was no marked change in albumin mRNA expression i n the control group during 24-hours treatment with normal saline. The reductio n did not occur until 24 hours after LPS treatment, and albumin mRNA decreased b y 30% approximately compared to the control group at 24 hours (0.587 vs 0.832, P=0.007). CHX could inhibit the decline of albumin mRNA induced by LPS an d the effect was correlated with the dose of CHX. The ERK inhibitor PD98059 cau sed a significant increase in LPS-induced albumin production

关键词： lipopolysaccharide · hepatocytes · albumin · hypoalbuminemia · signal transduction