ABSTRACT
Pulmonary fibrosis is a severe lung interstitial disease characterized by the destruction of lung tissue structure, excessive activation and proliferation of fibroblasts, secretion and accumulation of a large amount of extracellular matrix (ECM), and impaired lung function. Due to the complexity of the disease, a suitable animal model to mimic human pulmonary fibrosis has not yet been established. Precision-cut lung slice (PCLS) has been a widely used in vitro method to study lung physiology and pathogenesis in recent years. This method is an in vitro culture technology at the level between organs and cells, because it can preserve the lung tissue structure and various types of airway cells in the lung tissue, simulate the in vivo lung environment, and conduct the observation of various interactions between cells and ECM. Therefore, PCLS can compensate for the limitations of other models such as cell culture. In order to explore the role of discoidin domain receptor 2 (DDR2) in pulmonary fibrosis, Ddr2flox/flox mice were successfully constructed. The Cre-LoxP system and PCLS technology were used to verify the deletion or knockdown of DDR2 in mouse PCLS. Transforming growth factor β1 (TGF-β1) can induce fibrosis of mouse PCLS in vitro, which can simulate the in vivo environment of pulmonary fibrosis. In the DDR2 knock down-PCLS in vitro model, the expression of various fibrosis-related factors induced by TGF-β1 was significantly reduced, suggesting that knocking down DDR2 can inhibit the formation of pulmonary fibrosis. The results provide a new perspective for the clinical study of DDR2 as a therapeutic target in pulmonary fibrosis.
Subject(s)
Animals , Humans , Mice , Discoidin Domain Receptor 2/metabolism , Fibroblasts/pathology , Fibrosis , Lung/pathology , Pulmonary Fibrosis/metabolism , Transforming Growth Factor beta1/metabolismABSTRACT
OBJECTIVE@#To investigate the possibility and feasibility of one-stage cardiac and non-cardiac surgery.@*METHODS@#From July 1999 to August 2018, one hundred and eleven patients suffering from cardiac and non-cardiac diseases were treated by one-stage cardiac and non-cardiac operation in Department of Cardiac Surgery and Thoracic Surgery, General Surgery, Urinary Surgery, and Gynecology, Peking University First Hospital. There were 83 males (74.8%) and 28 females (25.2%), aged 41 to 84 years [mean age: (64.64±8.97) years]. The components of the cardiac disease included coronary heart disease, valvular heart disease, cardiac tumors, chronic constrictive pericarditis and congenital heart disease. The components of the non-cardiac diseases included lung benign and malignant diseases, thymoma and thymic cyst, breast cancer, chest wall giant hemangioma, digestive tract benign and malignant diseases, urinary system carcinoma and gynecological diseases.@*RESULTS@#Two patients died after operations in hospital; thus, the hospital mortality rate was 1.8%. One patient died of multiple organ failure on the 153th days after emergency coronary artery bypass grafting (CABG) combined with radical resection of bladder cancer. The other of pericardium stripping with lung cancer operation died of the multiple organ failure on the tenth day after surgery. The remaining 109 patients recovered and were discharged. There were 13 cases of complications during the days in hospital. The total operative morbidity was 11.7%: postoperative hemorrhage in 2 cases (1.8%), pulmonary infection and hypoxemia in 3 cases (2.7%), hemorrhage of upper digestive tract in 1 case (0.9%), incisional infection in 3 cases (2.7%), subphrenic abscess in 1 case (0.9%), and postoperative acute renal failure and hemofiltration in 3 case (2.7%). Of the 109 patients discharged, 108 patients were followed up. All the patients survived for 6 months, and 21 patients died due to tumor recurrence or metastasis within 1 to 5 years of follow-up, but no cardiogenic death. During the follow-up period, 1 patient developed cardiac dysfunction, 1 patient underwent percutaneous coronary intervention (PCI), 1 patient had cerebral hemorrhage due to excessive postoperative anticoagulation, and 1 patient suffered from incisional hernia.@*CONCLUSION@#One-stage surgeries in patients suffering from both cardiac and non-cardiac benign or malignant diseases are safe and possible with satisfactory short-term and long-term survival.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Coronary Artery Bypass , Heart Diseases , Neoplasm Recurrence, Local , Percutaneous Coronary Intervention , Retrospective Studies , Surgical Wound Infection , Treatment OutcomeABSTRACT
Objective To explore the methods of tobacco control through interactive sitcoms and evaluate its impact on audience in their empathy, knowledge acquisition and behavior, providing basis for health communication activities in relation to tobacco control. Methods Relevant knowledge and skills on tobacco control were integrated into the drama, which ran for 8 performances in Shanghai.Four of them were randomly selected for evaluation.All the audience were invited to complete a questionnaire. Results Over 90% of the audience gave affirmation to the design, performance and interaction of the drama.More than 70% smokers established their supportive attitude for smoke free environment.Audience who preferred interactive activities (OR=8.72, 95%CI:3.16-24.09) had higher education level (OR=2.10, 95%CI:1.06-4.14), and more empathy on roles (OR=6.63, 95%CI:2.38-18.51) thought psycho-scene drama had more effect than traditional ways on tobacco control.Smokers were curious to know the ending of the story (OR=3.90, 95%CI:1.73-8.79), wanted to learn more ways to discourage smoking (OR=4.00, 95%CI:1.88-8.49) and thought psycho-scene drama had more effect than traditional ways in this regard (OR=7.03, 95%CI:2.58-19.18).They came to have a stronger will to discourage smoking. Conclusion Psycho-scene drama proves to be a feasible way in tobacco control communication with a good effect on knowledge communication and behavior change.
ABSTRACT
Objective To explore the methods of tobacco control through interactive sitcoms and evaluate its impact on audience in their empathy, knowledge acquisition and behavior, providing basis for health communication activities in relation to tobacco control. Methods Relevant knowledge and skills on tobacco control were integrated into the drama, which ran for 8 performances in Shanghai.Four of them were randomly selected for evaluation.All the audience were invited to complete a questionnaire. Results Over 90% of the audience gave affirmation to the design, performance and interaction of the drama.More than 70% smokers established their supportive attitude for smoke free environment.Audience who preferred interactive activities (OR=8.72, 95%CI:3.16-24.09) had higher education level (OR=2.10, 95%CI:1.06-4.14), and more empathy on roles (OR=6.63, 95%CI:2.38-18.51) thought psycho-scene drama had more effect than traditional ways on tobacco control.Smokers were curious to know the ending of the story (OR=3.90, 95%CI:1.73-8.79), wanted to learn more ways to discourage smoking (OR=4.00, 95%CI:1.88-8.49) and thought psycho-scene drama had more effect than traditional ways in this regard (OR=7.03, 95%CI:2.58-19.18).They came to have a stronger will to discourage smoking. Conclusion Psycho-scene drama proves to be a feasible way in tobacco control communication with a good effect on knowledge communication and behavior change.
ABSTRACT
Objective@#To develop the ultra performance liquid chromatography tandem mass spectrometry ( UPLC-MS/MS ) for the determination of perfluorocarboxylic acids ( PFCAs ) in fish.@*Methods@#The fish samples were extracted with tert-butyl methyl ether and purified by WAX columns. The WAX cartridges were rinsed with methanol and 25 mmol/L ammonium acetate, and the target compound residues were eluted with 0.5% ammonia methanol and then redissolved with 50% methanol aqueous solution after nitrogen blowing to nearly dry. Nine kinds of PFCAs were simultaneously quantified by UPLC-MS/MS with 1 mmol/L ammonium acetate-methanol solution as the mobile phase.@*Results@#The extraction was separated well in UPLC BEH C18 column. There were good linear correlations of nine kinds of PFCAs in the range of 1.0-200.0 ng/mL, with the coefficients all more than 0.99. The limits of detection and quantification were 0.06-0.19 μg/kg and 0.19-0.62 μg/kg, respectively. The recovery rates were 70.08%-117.24% at different spiked levels ( 5.0, 25.0, 50.0 μg/kg ), and the relative standard deviations were 2.31%-19.68%. @*Conclusion@#Through optimizing the pretreatment conditions, the mobile phase of liquid chromatography and the detection conditions of mass spectrometry, the UPLC-MS/MS could meet the monitoring requirements of PFCAs in fish.
ABSTRACT
Objective:To discuss the clinical efficacy of modified Zuoguiwan on postmenopausal osteoarthritis of knee (KOA) with deficiency of liver and kidney based on theory of syndrome differentiation and treatment of kidney, and its effect on endocrine hormone and cartilage metabolism.Method:One hundred and forty patients of KOA were randomly divided into control group (70 cases) and observation group (70 cases) by random number table. Patients in two group got glucosamine hydrochloride capsule for 12 weeks, 1 capsule/time, 2 times/day, and those with obvious pain was added celecoxib capsules for 4 weeks, 0.2 g/time, 1 time/day. The control group took Kang Zengsheng pills orally. patients in observation group was also added with modified Zuoguiwan for 12 weeks, 1 dose/day. Before and after treatment, pain level during activity and rest by visual simulation of pain (VAS) were scored. And visual scale of osteoarthritis index (WOMAC) of Western Ontario and McMaster University, knee osteoarthritis severity index (ISOA), deficiency of liver and kidney, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were scored. And levels of serum estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), transforming growth factor-β (TGF-β), interleukin-1β (IL-1β), matrix metalloproteinase-3 (MMP-3) and tumor necrosis factor-α (TNF-α) were scored.Result:Scores of VAS during activity and rest in observation group were lower than those in control group (P<0.01). The total score of WOMAC, scores of pain, stiffness, joint function, deficiency of liver and kidney, SAS and SDS were all lower than those in control group (P<0.01). Total score of ISOA, symptoms and signs, maximum walking distance, daily life were lower than those in control group (P<0.01). Levels of E2, FSH, LH, TNF-α, IL-1β and MMP-3 were lower than those in control group (P<0.01). Level of TGF-β was higher than that in control group (P<0.01). And total clinical effective rate in observation group was 89.23%(58/65), which was higher than 74.60%(47/63) in control group (χ2=4.793, P<0.05).Conclusion:Modified Zuoguiwan can obviously alleviate symptoms, improve joint function, regulate the level of endocrine hormone, relieve anxiety and depression, regulate the environment of cartilage metabolism, inhibit inflammatory reaction, and improve the patients' ability of daily life and clinical efficacy.
ABSTRACT
OBJECTIVE@#To compare intranasal midazolam and intramuscular phenobarbital sodium for their sedative effect in neonates undergoing magnetic resonance imaging (MRI).@*METHODS@#A total of 70 neonates who underwent cranial MRI from September 2017 to March 2019 were randomized into an observation group and a control group, with 35 cases in each group. The observation group received intranasal drops of midazolam (0.3 mg/kg), and the control group received intramuscular injection of phenobarbital sodium (10 mg/kg). The sedation status of the neonates was evaluated using the Ramsay Sedation Scale. Meanwhile, the two groups were compared for the success rate of MRI procedure and incidence of adverse reactions.@*RESULTS@#In the observation group, the sedation score was the highest at 20 minutes post administration, then was gradually decreasing, and decreased to the lowest level at 70 minutes post administration. In the control group, the sedation score was the lowest at 10 minutes post administration, then was gradually increasing, and increased to the highest level at 40 minutes and 50 minutes post administration, followed by a gradual decrease. Comparison of the sedation score at each time period suggested that the sedation score was significantly higher in the observation group than in the control group within 40 minutes post administration (P0.05). The success rate of MRI procedure was significantly higher in the observation group than in the control group (89% vs 69%, P0.05).@*CONCLUSIONS@#Intranasal midazolam is superior to intramuscular phenobarbital sodium in the sedative effect in neonates undergoing MRI, with the benefits of being fast, convenient, safe, and effective.
Subject(s)
Humans , Infant, Newborn , Hypnotics and Sedatives , Pharmacology , Magnetic Resonance Spectroscopy , Midazolam , Prospective Studies , Single-Blind MethodABSTRACT
Andrographis Herba is a commonly used plant medicine, and has been recorded in pharmacopeias of different countries. However, there are some differences in the quality standards. Based on this, this paper compare the quality standards of Andrographis Herba between Chinese Pharmacopoeia, Hong Kong Chinese Materia Medica Standards, United States Pharmacopoeia, European Pharmacopoeia and Indian Pharmacopoeia, including origin, botanical characteristics, identification(microscopic identification and chromatographic identification), content determination, specific test(such as impurities, loss on drying, extractives, pesticides, heavy metals, mycotoxins, and other items) and storage requirements, so as to provide a reference for studying international quality standards of Andrographis.
Subject(s)
Andrographis , Drugs, Chinese Herbal , Materia Medica , Reference StandardsABSTRACT
Objective: To investigate the protective effect of compound Longmaining isoprenaline hydrochloride-induced myocardial infarction model and its effect on Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear transcription factor-kappa B (NF-κB) signaling pathway.Method: Forty-eight male SD rats were randomly divided into 6 groups:normal group,model group,compound salvia miltiorrhiza drop pill group (0.072 9 g·kg-1),and low,medium and high-dose compound Longmaining decoction groups (0.36,0.71,1.43 g·kg-1).The acute myocardial infarction model was induced through subcutaneous injection with isoproterenol.The pathological changes of myocardial tissue were examined by hematoxylin-eosin (HE) staining.The levels of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),monocyte chemotaxis protein-1(MCP-1) and nitrogen (NO) in serum were measured by enzyme linked immunosorbent assay (ELISA).The expression levels of inhibitors of NF-κB kinase subunit-β(IKKβ),NF-κB inhibitor α(IκBα),TLR4,MyD88 and NF-κB p65 were measured by immunohistochemical staining and Western blot.Result: Compared with normal group,the myocardial injury in model group was obvious.The levels of IL-1β,IL-6,TNF-α,MCP-1 and NO in serum increased significantly (PκBα decreased significantly (Pβ,TLR4,MyD88 and NF-κB p65 increased significantly in myocardial tissue (Pβ,IL-6,TNF-α,MCP-1 and NO levels in the serum (PκBα(Pβ,TLR4,MyD88 and NF-κB p65(PConclusion: Compound Longmaining plays a protective effect on acute myocardial infarction by regulatingthe expressions of TLR4/MyD88/NF-κB p65 signaling pathway and relevant inflammatory factors.
ABSTRACT
OBJECTIVE@#To investigate the clinical features and treatment of infective endocarditis (IE) patients with acute kidney injury (AKI), and to compare the adverse complications and outcome with IE patients without AKI.@*METHODS@#Clinical data of 100 IE cases in Peking University First Hospital from January 2002 to June 2018 were retrospectively reviewed. The patients were divided into AKI group (n=21) and non-AKI group (n=79) based on the AKI network (AKIN) definition. The clinical data and prognosis were compared between the two groups.@*RESULTS@#The incidence of AKI was 21%. The average age was (43.7±15.7) years, and the ratio of male to female was 3 ∶1. There was no significant difference in age and gender between the two groups. Compared with non-AKI group, the AKI group had more rash and lower limbs edema (P=0.017 and P=0.001), higher urine blood and protein positive rate (both P<0.001). Lower hemoglobin and serum albumin level (both P<0.001), worse clinical cardiac function (NYHA III-IV, P=0.033) were found in AKI group compared with non-AKI group. There was no significant difference in microbiologic positive rate and pathogenic bacteria sorts between the two groups. Nine patients refused surgery, and the other 91 cases underwent cardiac surgery with cardiopulmonary bypass under general anesthesia, including 19 cases of AKI group and 72 cases of non-AKI group. The ventilation time and intensive care unit (ICU) stay time were longer in AKI group than in non-AKI group (P=0.028 and P=0.003). AKI group needed more red blood cell transfusion (P=0.010). Using the last serum creatinine before surgery as basic level, there was more new-onset AKI cases in AKI group than in non-AKI group. During the median follow-up time 42 months, there was no significant difference in perioperative and follow-up mortality between the two groups (P=0.463 and P=0.581).@*CONCLUSION@#More perioperation complications occurred in IE patients with AKI, but no significant difference in in-hospital and follow-up mortality between the AKI and non-AKI groups was observed.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Acute Kidney Injury , Endocarditis , Incidence , Postoperative Complications , Prognosis , Retrospective Studies , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To study the influence of acute pancreatitis in pregnancy (APIP) on pregnancy outcomes and neonates.</p><p><b>METHODS</b>A retrospective analysis was performed for 33 APIP patients and 31 neonates born alive.</p><p><b>RESULTS</b>Of the 33 APIP patients, 26 (79%) developed APIP in the late pregnancy. Fourteen (45%) patients had hyperlipidemic APIP, 13 (42%) had biliary APIP, and 4 (13%) had other types of APIP. According to the severity, 22 (67%) were mild APIP, 5 (15%) were moderate APIP, and 6 were severe APIP. None of the 33 APIP patients died. Among the 20 patients with term delivery, 11 underwent termination of pregnancy; among the 10 patients with preterm delivery, 9 underwent termination of pregnancy; two patients experienced intrauterine fetal death, and one experienced abortion during the second trimester. Among the 31 neonates born alive (two of them were twins), 1 (3%) died, 12 (39%) experienced neonatal hyperbilirubinemia, 8 (26%) had neonatal hypoglycemia, 6 (19%) had neonatal respiratory distress syndrome, 5 (16%) experienced infectious diseases, and 2 (6%) experienced intracranial hemorrhage. The hyperlipidemic APIP group had a higher percentage of patients undergoing termination of pregnancy than the biliary APIP and other types of APIP groups (P<0.05). The incidence rate of preterm infants in the moderate APIP was higher than in the mild and severe APIP groups (P<0.05). The mean birth weights of neonates were the lowest in the moderate APIP group. The incidence rates of neonatal respiratory distress syndrome, intracranial hemorrhage, and infectious disease were the lowest in the mild APIP group (P<0.05).</p><p><b>CONCLUSIONS</b>APIP can lead to adverse pregnancy outcomes and neonatal diseases, which are associated with the severity of pancreatitis.</p>
Subject(s)
Female , Humans , Infant, Newborn , Male , Pregnancy , Acute Disease , Birth Weight , Infant, Premature , Pancreatitis , Pregnancy Complications , Retrospective StudiesABSTRACT
To study the effects of compound Longmaining(FFLMN) with different combinations on the intestinal absorption of puerarin. The rat single pass intestinal perfusion model was adopted, and the concentration of puerarin in intestinal samples was determined by HPLC. The effects of different combination groups on the absorption of puerarin in duodenum, jejunum, ileum and colon were investigated. The combined drugs were GG(Puerariae Lobatae Radix), GG-CSL (Puerariae Lobatae Radix compared with Dioscoreae Nipponicae Rhizoma), GG-CX(Puerariae Lobatae Radix compared with Chuanxiong Rhizoma) and FFLMN (compound Longmaining). We found that the absorption rate constant(Ka) and the apparent coefficient(Papp) of puerarin had no significant difference between GG-CSL and FFLMN groups, but significantly higher in GG and GG-CX groups(P<0.05) in the duodenum and ileum. In jejunum and colon, Ka and Papp of puerarin showed significant differences between GG and other groups(P<0.05). At the same time, FFLMN also had significant differences with GG-CSL and GG-CX groups(P<0.05). The results showed that in the whole intestine of rats, FFLMN could significantly promote the absorption of puerarin. In the duodenum and ileum, Dioscoreae Nipponicae Rhizoma played a significant role in promoting absorption of puerarin. In jejunum and colon, Dioscoreae Nipponicae Rhizoma and Chuanxiong Rhizoma have a synergistic effect in promoting absorption of puerarin.
ABSTRACT
<p><b>OBJECTIVE</b>To study the protocol of construction of the mutation E292V and M723I of hABCA3 gene associated with neonatal respiratory distress syndrome, as well as their eukaryotic green fluorescent protein expression rectors, and to examine the expression of mutation proteins in human lung carcinoma epithelial cells (A549).</p><p><b>METHODS</b>Site-directed mutagenesis method based on overlap extension PCR was used to introduce mutations in the two sites which were E292V and M723I in the ABCA3. The PCR fragments were subcloned to PEGFP-C2 vectors to construct the eukaryotic green fluorescent protein expression rectors. A549 cells were transiently transfected with the recombinants using Lipofectamine 2000 and the transfection efficiency was confirmed through GFP signal. The expression and location of recombinants were detected by FV1000 laser scanning microscope.</p><p><b>RESULTS</b>Direct sequence analysis confirmed an A to T transition at position 875 in E292V and a G to A transition at position 2169 in M723I. Recombinants were transfected to A549 cells and both wild type and mutant ABCA3 proteins were expressed in the cytoplasm.</p><p><b>CONCLUSIONS</b>The eukaryotic green fluorescent protein expression rectors of wild type and mutant ABCA3 gene were constructed and they were successfully expressed in A549 cells. This experiment provides a basis for subsequent research.</p>
Subject(s)
Humans , ATP-Binding Cassette Transporters , Genetics , Cell Line, Tumor , Green Fluorescent Proteins , Genetics , Mutagenesis, Site-Directed , TransfectionABSTRACT
<p><b>BACKGROUND</b>Mild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI).</p><p><b>METHODS</b>Totally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups.</p><p><b>RESULTS</b>The mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased.</p><p><b>CONCLUSIONS</b>The TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes among the different patterns of mild HIE.</p>
Subject(s)
Female , Humans , Infant, Newborn , Male , Brain , Pathology , Hypoxia-Ischemia, Brain , Diagnosis , Magnetic Resonance Imaging , MethodsABSTRACT
The contamination of extrinsic harmful contaminants including mycotoxins, heavy metals and pesticides, etc, brings serious risks to traditional Chinese medicines (TCMs), further to human health. Due to their unique photoluminescence, chemiluminescence, electrochemical and electrochemiluminescence properties, semiconductor quantum dots (QDs) nanoparticles are widely used to immobilize bioprobes and biosensors, etc. In this review, the luminescence characteristics and specific ligands of QDs probles which are used to determine contaminants were summed up. Then, the applications of QDs-coated novel probes in the determination of mycotoxins, heavy metals and pesticides were discussed in detail. In addition, the contamination levels and characteristics of extrinsic harmful residues in TCMs were investigated. Further, the maximum levels of those contaminants in TCMs were compared with those set by various countries. Finally, the future development trends and problems of QDs-coated probes in the determination of those extrinsic residues in TCMs were prospected.
Subject(s)
Humans , Drug Contamination , Medicine, Chinese Traditional , Methods , Nanotechnology , Methods , Quantum Dots , Safety , Time FactorsABSTRACT
The paper is to report the pharmacokinetics of furosemide in rats living at plain area and high altitude. After intragastric administration of furosemide (2.87 mg x kg(-1)), serial blood samples (0.5 mL) were collected by retro-orbital puncture at 0, 20 min, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h, samples were determined by LC-MS/MS, and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters. The main pharmacokinetic parameters: area under curve (AUC), mean residence time (MRT), the biological half-life (t1/2) and the peak concentration (C(max)) of furosemide, were significantly increased at high altitude, the time to reach peak concentration (t(max)) and clearance (CL) was significantly decreased. This study found significant changes on the pharmacokinetics of furosemide under the special environment of high altitude. This finding may provide some references for clinical rational application of furosemide at high altitude.
Subject(s)
Animals , Male , Rats , Administration, Oral , Altitude , Area Under Curve , Chromatography, Liquid , Furosemide , Metabolism , Pharmacokinetics , Half-Life , Rats, Wistar , Spectrometry, Mass, Electrospray Ionization , Tandem Mass SpectrometryABSTRACT
<p><b>OBJECTIVE</b>To evaluate the relationship between peroxisome proliferator-activated receptor-γ2 (PPARγ2) Pro12Ala polymorphism and type 2 diabetes mellitus (T2DM) in Chinese Han population.</p><p><b>METHODS</b>PubMed, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang database were searched for all relevant articles investigating the association between PPARγ2 Pro12Ala polymorphism and T2DM that were available from January, 1990 to June, 2011. A total of 29 relevant articles were selected. A Meta-analysis was performed to estimate heterogeneity and the pooled odds ratio (OR) to evaluate the relationship between PPARγ2 Pro12Ala polymorphism and T2DM. The sensitivity analysis was also assessed.</p><p><b>RESULTS</b>A total of 21 qualified articles including 3870 patients with T2DM and 3333 healthy controls were analyzed in the study. The frequencies of the allele Ala12 in T2DM and control groups were 4.13% (320/7740) and 4.56% (304/6666), respectively. There were not heterogeneity (χ(2) = 25.96, P = 0.17) among the 21 qualified articles. The pooled OR (95%CI) value of the frequencies of the PPARγ2 genotype (PA + AA)/PP calculated by fixed effects model was 0.96 (0.81 - 1.14) (P = 0.64). There was not heterogeneity among the remaining articles after excluding the article with the largest weight and the article with larger frequencies of the allele Ala12 respectively (χ(2) values were 24.23, 16.87 respectively, both P values > 0.05). The pooled OR (95%CI) value of the frequencies of the PPARγ2 genotype (PA + AA)/PP of the remaining articles were 1.01 (0.84 - 1.21) and 1.07 (0.89 - 1.28) after excluding the article with the largest weight and the article with larger frequencies of the allele Ala12 (both P values > 0.05).</p><p><b>CONCLUSION</b>PPARγ2 Pro12Ala polymorphism was not associated with type 2 diabetes mellitus in Chinese Han population.</p>
Subject(s)
Humans , Alleles , Asian People , Genetics , China , Diabetes Mellitus, Type 2 , Genetics , Gene Frequency , Genotype , PPAR gamma , Genetics , Polymorphism, Single NucleotideABSTRACT
<p><b>OBJECTIVE</b>To detect possible relationship between genetic defect within the gene encoding member A3 of the ATP Binding Cassette family (ABCA3) and neonatal respiratory distress syndrome (NRDS), thus to understand the genetic mechanisms of NRDS in Han ethnic group.</p><p><b>METHOD</b>The clinical data of 11 cases with NRDS hospitalized in neonatal intensive care unit was investigated. Blood samples were collected from 11 cases with NRDS and 97 unassociated normal individuals. Polymerase chain reaction (PCR) and DNA direct sequencing were performed to screen all exons and their flanking introns of ABCA3 gene for mutation analysis in 11 cases with NRDS. If a new missense variation was identified, single strand conformation polymorphism analysis was performed in 97 healthy controls. Lung tissue sample from a case who died 12 hours after birth was examined with light microscopy and electron microscopy.</p><p><b>RESULT</b>Three missense genetic variants in exons, which include c. 2169 G > A (p.M723I), c. 1010 T > G (p.V337G), c. 4972 A > G (p.S1658G), one splice junction site variation (Exon 30 + 2 T/G), several unreported polymorphism sites [213 C > T(p.F71F), exon 21 + 34C/T] and reported polymorphism site (p.F353F) were identified on ABCA3 gene coding region in 11 case. The homozygous variation (c.2169G > A), which was in exon 17 and causes an M723I amino acid change, was found in the case who died 13 hours after birth, but not detected in 97 controls, indicating that this variation is indeed a mutation and not a polymorphism. In the case carrying c.2169G > A, ultrastructural examination of the alveolar type II cells with electron microscopy demonstrated abnormally small and dense lamellar body with eccentrically distributed electron dense substance.</p><p><b>CONCLUSION</b>Genetic variants within ABCA3 may be the genetic cause of or a contributor to some unexplained refractory NRDS. Identification of ABCA3 genetic variant in NRDS infants is important to establish appropriate management and evaluation of treatment options, as well as to offer genetic counseling and prenatal diagnosis.</p>
Subject(s)
Humans , Infant, Newborn , ATP-Binding Cassette Transporters , Genetics , DNA Mutational Analysis , Exons , Polymorphism, Genetic , Respiratory Distress Syndrome, Newborn , GeneticsABSTRACT
Incidence rate of single root canal in maxillary second molar is very low. The emergence of curved single root canal in maxillary second molar with single root is especially rare. A case of curved single root canal in maxillary second molar with single root was successfully treated and reported in this article. This report also highlighted the role of cone beam computed tomography as an objective method to confirm the three-dimensional anatomy of teeth.
Subject(s)
Humans , Cone-Beam Computed Tomography , Dental Pulp Cavity , Maxilla , Molar , Root Canal Therapy , Tooth RootABSTRACT
<p><b>OBJECTIVE</b>To study the protocol of construction of a KCNQ2-c.812G>T mutant and it's eukaryotic expression vector, the c.812G>T (p.G271V) mutation which was detected in a Chinese pedigree of benign familial infantile convulsions, and to examine the expression of mutant protein in human embyonic kidney (HEK) 293 cells.</p><p><b>METHODS</b>A KCNQ2 mutation c.812G>T was engineered on KCNQ2 cDNAs cloned into pcDNA3.0 by sequence overlap extension PCR and restriction enzymes. HEK293 cells were co-transfected with pRK5-GFP and KCNQ2 plasmid (the wild type or mutant) using lipofectamine and then subjected to confocal microscopy. The transfected cells were immunostained to visualize the intracellular expression of the mutant molecules.</p><p><b>RESULTS</b>Direct sequence analysis revealed a G to T transition at position 812. The c.812G>T mutation was correctly combined to eukaryotic expressive vector pcDNA3.0 and expressed in HEK293 cells. Immunostaining of transfected cells showed the expression of both the wild type and mutant molecules on the plasma membrane, which suggested that the c.812G>T mutation at the pore forming region of KCNQ2 channel did not impair normal protein expression in HEK293 cells.</p><p><b>CONCLUSIONS</b>Successful construction of mutant KCNQ2 eukaryotic expression vector and expression of KCNQ2 protein in HEK293 cells provide a basis for further study on the functional effects of convulsion-causing KCNQ2 mutations and for understanding the molecular pathogenesis of epilepsy.</p>