Current status and prospect of virtual reality technique's application in wound repair / 中华烧伤杂志

As a new technology of drug-free treatment, virtual reality technique has been used in various medical fields, and is being increasingly applied in the field of wound repair. Virtual reality technology can alleviate the pain caused by acute and chronic wounds, relieve the psychological anxiety of patients with wounds, and then facilitate the recovery of patients. This paper reviews the research progress of virtual reality technique's application as a clinical adjuvant therapy in wound repair in three aspects: pain treatment, psychological treatment, and functional rehabilitation, analyzes the advantages and disadvantages of this technique, and discusses the prospects of its further application in the field of wound repair.

Analysis of metabolites of doxorubicin in breast cancer cell line MCF-7 / 中国药理学通报

Aim To investigate the intracellular disposition process of doxorubicin (DOX) in human breast cancer MCF-7, providing reference for explaining the pharmacology and their side effects of anti-tumor drugs. Methods The drug-resistant cell line MCF-7/DOX of breast cancer with DOX indication was selected as the material, and ultra-high performance liquid chromatography quadrupole tandem time-of-flight high-resolution mass spectrometry (UPLC-Q-TOF-MS/MS) method was established to analyze the disposal of DOX by target cells. Results Two unreported trace a-mounts of new metabolites of doxorubicin were found, and their structures were deduced by high-resolution multistage mass spectrometry. Molecular docking showed that its affinity for DNA was lower than that of DOX. Conclusion Target cells have unique and diverse drug metabolism pathways for DOX, which may be related to drug resistance mechanisms.

Analysis of treating syndrome by I-Ching navel acupuncture / 中国针灸

Based on the theories of I-Ching and umbilicus-hologram, the navel acupuncture is considered as a new acupuncture therapy that only acupuncture at Shenque (CV 8). It has a good effect on the treatment of syndrome and provides a new treatment idea for syndrome. This article presents the definition, etiology and treatment of syndrome, and introduces the application of umbilical-holographic, the principle and method of positioning and needle-inserting, the adjustment of therapies and the analysis of cases, in order to introduce the idea of treating syndrome by I-Ching navel acupuncture.

Development of a novel method for UPLC-QTOF-MS analysis of anti-schis-tosomiasis heterocyclic compounds / 中国血吸虫病防治杂志

Objective To develop an ultra-performance liquid chromatography/quadrupole-time of flight mass spectrometry(UPLC-QTOF-MS)method for the determination of an oxadiazole-2-oxide heterocyclic compound F-2015-14.Methods Mouse plasma and liver homogenate specimens were extracted with ethyl acetate and chromatographed on a Waters CORTECS column(C18,1.6μm,2.1 mm×150 mm)by using a mobile phase of 10％acetonitrile-0.1％formic acid with by a volume fractionation by gradient elution.Then,UPLC-QTOF-MS was performed to determine F-2015-14 in mouse plasma and liver homogenate speci-mens.Results The linearity of F-2015-14 in plasma ranged from 12.5 to 250 μg/mL with a correlation coefficient of 0.990 and a detection limit of 8.8 μg/mL.F-2015-14 in liver homogenates ranged from 12.5 to 250 μg/mL.The linearity was good with a cor-relation coefficient of 0.992 and a limit of detection of 5.6 μg/mL.If the concentration of plasma and liver homogenate specimens was 12.5 μg/mL,the accuracy and the matrix effect were 80％to 120％,and the inter-day and intra-day precision was within 20％.If the concentrations of plasma and liver homogenate specimens were 100 μg/mL and 200 μg/mL,the accuracy and the ma-trix effect were 85％to 115％,and the inter-day and intra-day precision was within 15％.Conclusion The UPLC-QTOF-MS es-tablished in this study has a high sensitivity and good reproducibility for the determination of F-2015-14,which provides bases for the development of novel anti-schistosomiasis drugs.

Study on the change of retinal thickness and choroidal thickness and correlative factors for macular edema after Ranibizumab injection / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the change of retinal thickness and choroidal thickness in patients with diabetic macular edema or retinal vein occlusion- macular edema after intravitreal Ranibizumab injection using spectral domain-optical coherence tomography(SD-OCT),and to identify determinants for the change of different types of macular edema. METHODS: Patients were recruited from March 2016 to July 2017 diagnosed with diabetic macular edema or retinal vein occlusion - macular edema. Subfoveal choroidal thickness (SFCT) and central retinal thickness (CRT) of all eyes were measured by SD - OCT preoperatively and at 1, 3, 6mo after operation. The change of retinal thickness and choroidal thickness after intravitreal ranibizumab injection for macular edema caused by different diseases were evaluated. Moreover, the potential determinants were studied about the change of retinal thickness and choroidal thickness. RESULTS: Thirty-six eyes of 36 patents with macular edema were treated with intravitreal ranibizumab injection. After the intravitreal ranibizumab injection, the CRT and SFCT decreased, when compared with the CRT and SFCT preoperative. There was a significant difference in the change of CRT and SFCT in different time points of following-up (FCRT=40.876, PCRT<0.001; FSFCT=46.319, PSFCT< 0. 001). In diabetic macular edema group, the change of SFCT was associated with the preoperative SFCT, and the change of CRT was correlated with preoperative CRT and the fast blood glucose level. In retinal vein occlusion-macular edema group, the change of SFCT was associated with the preoperative SFCT, the change of CRT was associated with preoperative CRT,the obstructive positions and the onset time of disease. CONCLUSION: Reduction of choroidal thickness and retinal thickness in macular edema caused by different diseases can be detected with SD-OCT after intravitreal injections of ranibizumab. The reduction of choroidal thickness was correlated with the preoperative choroidal thickness. In diabetic macular edema eyes, the reduction of retinal thickness was correlated with preoperative CRT and the fast blood glucose level. Whereas,in retinal vein occlusion-macular edema eyes, the reduction of retinal thickness was correlated with the preoperative CRT, the obstructive positions and the onset time.

Yinzhihuang supplementary illumination analysis of humanized nursing in the treatment of neonatal jaundice / 中国生化药物杂志

Objective To investigate the effect of Yinzhihuang auxiliary light clinical effect of the treatment of neonatal jaundice, and analyze the treatment process right humanized nursing service measures. Methods 1100 children with jaundice from October 2015 to October 2016 were selected and randomly divided into the study group (n=550) and the control group (n=550). The control group with jaundice in conventional treatment combined with blue light irradiation, the study group jaundice in the control group treated with Yinzhihuang oral liquid. The clinical efficacy of two groups of jaundice children was recorded, and the data were analyzed by statistical test (SPSS). Results The total effective rate of clinical treatment in children with jaundice in the study group (94.91%) was significantly better than that in the control group the total effective rate of clinical treatment was 70.36% (P<0.05). Conclusion In the blue light plus can rise to the ideal effect of adjuvant therapy of neonatal jaundice with Yinzhihuang oral liquid, can improve the patients clinical curative effect, combined with humanized nursing service or the prognosis and quality of life of children with strong support.

Effect of FSD-C10 on modulation of inflammatory microenvironment in an Alzheimer disease double transgenic mouse model / 中国病理生理杂志

AIM:To explore the therapeutic effect of a novel Rho kinase inhibitor FSD-C10 onβ-amyloid pro-tein precursor (APP)/presenilin-1 (PS1) double transgenic mice.METHODS: The transgenic mice overexpressing hu-man APP with the Swedish mutation (695) and human PS1 with ΔE9 mutation at the age of 8 months were used in this study.The mice were randomly divided into model group and FSD-C10 intervention group, and wild-type mice at the same age served as normal controls .The mice in FSD-C10 intervention group were treated with FSD-C10 (25 mg· kg-1 · d-1 ) for 2 months by intraperitoneal injection .The mice in model group and the wild-type mice were injected with saline in the similar manner.Morris water maze (MWM) test was applied to examine the capacity of learning and memory .The Aβ1-42 deposition, Tau protein phosphorylation , and the expression of β-site APP-cleaving enzyme ( BACE) as well as inflammato-ry molecules, such as TLR-4 and NF-Κb, and M1/M2 microglial markers, such as Inos and Arg-1, were determined by the methods of immunohistochemistry and Western blot .RESULTS: Compared with model group , FSD-C10 significantly improved the learning and memory abilities of APP/PS1 double transgenic mice , accompanied by reduced Aβ1-42 deposi-tion, Tau protein phosphorylation and BACE expression in the hippocampus .The intervention of FSD-C10 decreased the protein levels of TLR-4 and p-NF-Κb, reduced the expression of Inos and increased the expression of Arg-1 in the brain tissues.CONCLUSION:The novel Rho kinase inhibitor FSD-C10 improves the capacity of spatial learning and memory in APP/PS1 double transgenic mice , which may be related to the inhibition of TLRs/NF-Κb signaling pathway , the reduction of the secretion of inflammatory molecules and the polarization of anti-inflammatory M2 microglia, thus improving the in-flammatory microenvironment of the brain in APP/PS1 double transgenic mice .

1α,25( OH) 2 D3 regulates expression of lubricin of chondrocytes in rat articular cartilage / 中国比较医学杂志

Objective To investigate the effects of vitamin D on synthesis and secretion of lubricin in chondrocytes at the cellular level. Methods Rat articular chondrocytes were stimulated by TNF-α. Normal and inflammatory chondrocytes were treated by different doses of vitamin D respectively. ELISA and Western Blot were used to detect the secretion of lubricin in the supernatant and the synthesis level in the cells. Results TNF-α significantly reduced the activity of both normal chondrocytes and chondrocytes in inflammatory state. TNF-α also significantly reduced the expression of lubricin in the cells and supernatant. 1α,25(OH)2D3 increased the activity of both normal chondrocytes and chondrocytes in inflammatory state. 1α,25(OH)2D3 significantly elevated the secretion and expression of supernatant and intracellular lubricin only in chondrocytes stimulated by TNF-α in a dose-dependent manner, but not in normal chondrocytes. Conclusions Vitamin D can promote the secretion and expression of lubricin in inflammatory state chondrocytes, which may act as one of the mechanisms of vitamin D protecting the cartilage surface in osteoarthritis.

Yinzhihuang supplementary illumination analysis of humanized nursing in the treatment of neonatal jaundice / 中国生化药物杂志

Objective To investigate the effect of Yinzhihuang auxiliary light clinical effect of the treatment of neonatal jaundice, and analyze the treatment process right humanized nursing service measures. Methods 1100 children with jaundice from October 2015 to October 2016 were selected and randomly divided into the study group (n=550) and the control group (n=550). The control group with jaundice in conventional treatment combined with blue light irradiation, the study group jaundice in the control group treated with Yinzhihuang oral liquid. The clinical efficacy of two groups of jaundice children was recorded, and the data were analyzed by statistical test (SPSS). Results The total effective rate of clinical treatment in children with jaundice in the study group (94.91%) was significantly better than that in the control group the total effective rate of clinical treatment was 70.36% (P<0.05). Conclusion In the blue light plus can rise to the ideal effect of adjuvant therapy of neonatal jaundice with Yinzhihuang oral liquid, can improve the patients clinical curative effect, combined with humanized nursing service or the prognosis and quality of life of children with strong support.

Effect of FSD-C10 on modulation of inflammatory microenvironment in an Alzheimer disease double transgenic mouse model / 中国病理生理杂志

AIM:To explore the therapeutic effect of a novel Rho kinase inhibitor FSD-C10 onβ-amyloid pro-tein precursor (APP)/presenilin-1 (PS1) double transgenic mice.METHODS: The transgenic mice overexpressing hu-man APP with the Swedish mutation (695) and human PS1 with ΔE9 mutation at the age of 8 months were used in this study.The mice were randomly divided into model group and FSD-C10 intervention group, and wild-type mice at the same age served as normal controls .The mice in FSD-C10 intervention group were treated with FSD-C10 (25 mg· kg-1 · d-1 ) for 2 months by intraperitoneal injection .The mice in model group and the wild-type mice were injected with saline in the similar manner.Morris water maze (MWM) test was applied to examine the capacity of learning and memory .The Aβ1-42 deposition, Tau protein phosphorylation , and the expression of β-site APP-cleaving enzyme ( BACE) as well as inflammato-ry molecules, such as TLR-4 and NF-Κb, and M1/M2 microglial markers, such as Inos and Arg-1, were determined by the methods of immunohistochemistry and Western blot .RESULTS: Compared with model group , FSD-C10 significantly improved the learning and memory abilities of APP/PS1 double transgenic mice , accompanied by reduced Aβ1-42 deposi-tion, Tau protein phosphorylation and BACE expression in the hippocampus .The intervention of FSD-C10 decreased the protein levels of TLR-4 and p-NF-Κb, reduced the expression of Inos and increased the expression of Arg-1 in the brain tissues.CONCLUSION:The novel Rho kinase inhibitor FSD-C10 improves the capacity of spatial learning and memory in APP/PS1 double transgenic mice , which may be related to the inhibition of TLRs/NF-Κb signaling pathway , the reduction of the secretion of inflammatory molecules and the polarization of anti-inflammatory M2 microglia, thus improving the in-flammatory microenvironment of the brain in APP/PS1 double transgenic mice .

1α,25( OH) 2 D3 regulates expression of lubricin of chondrocytes in rat articular cartilage / 中国比较医学杂志

Objective To investigate the effects of vitamin D on synthesis and secretion of lubricin in chondrocytes at the cellular level. Methods Rat articular chondrocytes were stimulated by TNF-α. Normal and inflammatory chondrocytes were treated by different doses of vitamin D respectively. ELISA and Western Blot were used to detect the secretion of lubricin in the supernatant and the synthesis level in the cells. Results TNF-α significantly reduced the activity of both normal chondrocytes and chondrocytes in inflammatory state. TNF-α also significantly reduced the expression of lubricin in the cells and supernatant. 1α,25(OH)2D3 increased the activity of both normal chondrocytes and chondrocytes in inflammatory state. 1α,25(OH)2D3 significantly elevated the secretion and expression of supernatant and intracellular lubricin only in chondrocytes stimulated by TNF-α in a dose-dependent manner, but not in normal chondrocytes. Conclusions Vitamin D can promote the secretion and expression of lubricin in inflammatory state chondrocytes, which may act as one of the mechanisms of vitamin D protecting the cartilage surface in osteoarthritis.

Effects of Acupuncture-rehabilitation Therapy on Apoptosis and Expression of X-linked Inhibitor of Apoptosis Protein and Cleaved-caspase-9 in Ischemic Penumbra of Rats with Cerebral Ischemia / 中国康复理论与实践

Objective To explore the effect of acupuncture-rehabilitation therapy on apoptosis and the expression of X-linked inhibitor of apoptosis protein (XIAP) and cleaved-caspase-9 in ischemic penumbra of rats with cerebral ischemia. Methods A total of 180 male Sprague-Dawley rats were randomly divided into sham operation group,model group,acupuncture group,rehabilitation group and acupunc-ture-rehabilitation therapy group.Each group was divided into three days,seven days and 14 days subgroups(n=12).The model was estab-lished with the modified Longa suture method. The model group and the sham operation group received no treatment. The acupuncture group received cluster needling of scalp acupuncture,the rehabilitation group received treadmill training,and the acupuncture-rehabilitation therapy group received both acupuncture and treadmill training.On the third,seventh and 14th days after modeling,the neurological func-tion was assessed with modified Neurological Severity Score(mNSS).The apoptosis was observed by TUNEL staining and the expression of XIAP and cleaved-caspase-9 protein was determined by Western blotting in cerebral ischemic penumbra,respectively.Results Compared with the model group,the mNSS scores decreased,the rate of apoptosis decreased,the expression of XIAP protein increased,and the expres-sion of cleaved-caspase-9 decreased in each treatment group at each time point(P<0.05).Compared with the other two treatment groups,the rate of apoptosis further decreased at each time points(P<0.05),the expression of XIAP protein further increased at each time points(P<0.05),the mNSS score further decreased(P<0.05)and the expression of cleaved-caspase-9 protein further decreased(P<0.05)seven days and 14 days after modeling in the acupuncture-rehabilitation therapy group.Conclusion Acupuncture and rehabilitation therapy could re-duce the neurological deficit in rats with cerebral ischemia,which was superior to the simple acupuncture treatment and rehabilitation train-ing.The mechanism may be related to th reduction of apoptosis by promoting XIAP protein expression and inhibiting caspase-9 protein acti-vation.

Reliability and validity of Chinese version of Atrial Fibrillation-Quality of Life-18 / 中国实用护理杂志

Objective To translate and revise the Atrial Fibrillation-Quality of Life -18 (AF-QoL-18),and to test its reliability and validity. Methods The Chinese version of AF-QoL-18 was developed through the process of translation, back- translation, cultural adaptation, and preliminary experiment. A total of 187 atrial fibrillation (AF) patients in eight hospitals in Jiangsu province were investigated using the Chinese version to test the reliability and validity. Results Exploratory factor analysis identified three factors, including physiological, psychological and sexual dimensions, which could explain 65.055%of the total variance. The content validity index was 0.969. The Cronbach α coefficient was 0.915 and the retest reliability was 0.948 for the total scale. Conclusions The Chinese version AF-QoL-18 has proved to be reliable and valid.It can be used to measure the quality of life of AF patients in China.

Pharmacokinetics of once daily prolonged-release formulation of tacrolimus in children with primary nephrotic syndrome / 北京大学学报(医学版)

Objective:Tacrolimus prolonged-release(PR) formulation is a new once-daily formulation of the calcineurin inhibitor tacrolimus,which is currently used in adult liver or kidney transplant patients,and is also gradually widely used in children with nephrotic syndrome.The present study was undertaken to preliminarily investigate the pharmacokinetic characteristics of tacrolimus PR in pediatric nephrotic syndrome recipients.Methods:This single-center open-label prospective study was performed in pediatric nephrotic syndrome recipients.Pharmacokinetic samples were collected from eight pediatric subjects with nephrotic syndrome from Department of Pediatric Nephrology in Peking University First Hospital between June and August 2011.They followed administration of single oral doses of tacrolimus PR formulation at 0.02 mg/kg (n =2),0.05 mg/kg (n =2) and 0.10 mg/kg (n =4).Blood samples were taken before the dose and 1,2,4,6,8,10,12 and 24 h after drug intake.No other medicines or interacting food or drinks were taken during the study period.Blood concentrations were measured using an enzyme multiplied immunoassay technique.Pharmacokinetic analysis was performed using WinNolin Phoenix software Version 6.0 (Pharsight,Cary,NC,USA).Results:The pharmacokinetic data were best described by a non-compartment model.Pharmacokinetic parameters of tacrolimus PR formulation in the 3 ascending doses groups (0.02 mg/kg,0.05 mg/kg and 0.10 mg/kg) were as follows:the maxi mum drug concentrations (Cm=/D) were (1.7 ± 1.0) μg/L,(3.1 ± 1.9) μg/L,(8.0 ± 3.5) μg/L,respectively;Areas under the drug concentration-time curve (AUCo-∞/D) were (47.2 ± 47.1) h · μg/ L,(84.0 ± 13.1) h · μg/L,(175.6 ± 107.1) h · μg/L,respectively;Oral clearance rates were (0.8±0.9) L/(h·kg),(0.4±0.1) L/(h · kg),(1.9 ±1.3) L/(h · kg),respectively;Body weight normalized distribution volumes were (7.0 ± 3.4) L/kg,(12.4 ± 8.4) L/kg and (73.6 ± 68.6) L/kg,respectively.Both mean Cmax normalized level for the administered dose (Cmax/D) and mean AUC0-∞ normalized level for the administered dose (AUC0-∞/D) were higher in the 0.05 mg/kg dosage group than in the 0.02 and 0.10 mg/kg dosage group.There were two peaks in the drug concentrations in every dose group;a primary peak appeared at the end of about 2 h followed by a small secondary peak at h 12,which was more noticeable in the 0.10 mg/kg dose group than in the two lower dosages.Conclusion:The pharmacokinetic characteristics of tacrolimus PR formulation were initially explored in pediatric patients with nephritic syndrome.The data presented form a basis for subsequent larger scale studies on pharmacokinetics of tacrolimus PR formulation in nephritic syndrome children.

Clinical characteristics of glucocorticoid-induced eye adverse reactions in children with primary nephrotic syndrome / 北京大学学报(医学版)

Objective:To investigate the clinical features and side effects,with regard to glucocorticoid-induced ocular hypertension,glaucoma or cataract in children with primary nephrotic syndrome.Methods:Clinical data were collected and analyzed from 71 cases of primary nephrotic syndrome with glucocorticoid-induced ocular hypertension,glaucoma or cataract from Jun.2014 to Jun.2016.These children were hospitalized in Peking University First Hospital.Results:Totally 1 580 children with primary nephrotic syndrome were collected,glucocorticoid-induced complications in eyes were found in 71 cases,and the incidence was 4.5％.There were 66 cases with ocular hypertension,2 cases with glucocorticoid glaucoma,2 cases with glucocorticoid glaucoma combined with cataract,1 case with high intraocular pressure combined with cataract.There were 41 boys and 30 girls with eye-related side effects caused by glucocorticoid.The average age of onset of glucocorticoid-induced eye adverse reactions in children with primary nephrotic syndrome in our research were 8 (2,16) years.The average duration or interval time from glucocorticoid medication use to eye adverse effects was 157 (6,420) days.No statistical significance was found in intraocular pressure between different genders,types of glucocorticoid,different route of glucocorticoid and whether methylprednisolone pulse treatment (P ＞ 0.05).There was no significant correlation between age,body mass index,blood pressure,cumulative dosage,duration time of glucocorticoid,mean daily dosage and glucocorticoid-induced ocular hypertension (P ＞ 0.05).The ocular hypertension was controlled after treatment.Conclusion:Children with nephrotic syndrome after treatment of glucocorticoid are susceptible to ocular complications,and the occurrence of ocular hypertension is closely related to glucocorticoid susceptibility of the nephrotic children.Regular eye monitor is indispensable for the children suffering from primary nephrotic syndrome.

Comparison between continuous noninvasive hemoglobin monitoring and venous blood hemoglobin monitoring in children with kidney disease / 北京大学学报(医学版)

Objective:To assess the correlation and consistency between continuous noninvasive hemo globin detection and venous blood hemoglobin detection in children with kidney disease,and try to analyze the affecting factors.Try to provide a reference for the monitoring of hemoglobin in children with kid ney disease by continuous noninvasive hemoglobin detection technique.Methods:Eighty-five inpatient children with kidney disease,50 boys (58.8％) and 35 girls (41.2％),aged from 3 years old to 18 years old (9.35 ± 4.29) were included finally.Noninvasive hemoglobin monitoring by spectrophotometry (SpHb) was stably read by PRONTO-7,selecting the ring finger of the non handedness as the detection site.And then the venous blood hemoglobin of the same patient was collected in 5 minutes as the true hemoglobin (tHb) by Beckman coulter DXH-800.The data of SpHb and tHb were compared and analyzed using SPSS 17.0 and MedCalc.Results:Correlation analysis showed data of SpHb and tHb were with significant correlation,the correlation coefficient between SpHb and tHb was 0.85 (P ＜ 0.05).BlandAltman plot points suggested that the mean of differences between SpHb and tHb was-1.3 g/dL.The 95％ CI of agreement of SpHb-tHb was-4.2-1.5 g/dL,suggesting that the average measurement re sult of SpHb was lower than that of tHb.The mean of differences as percent between SpHb and tHb was -9.8％,95％ CI of agreement was (-35.9％,16.2％) exceeding the acceptable range of true value ± 6％.The consistent rate of non-invasive hemoglobin detection and venous blood hemoglobin detection was 31.8％,the 95％ CI of consistent rate was (21.7％,41.9％).The chi square test of the fourfold table showed that the diagnosis of anemia with SpHb was of high sensitivity,but the specificity was low,the false positive rate was high,and the difference was statistically significant (P =0.000).Conclusion:There was a significant correlation between SpHb and tHb in the children with kidney disease.Noninvasive hemoglobin measurement can be used for monitoring of changes of hemoglobin in children with kidney diseases.But the consistency between SpHb and tHb needs to be improved.Noninvasive hemoglobin measurement could not replace the venous hemoglobin measurement.It could not be used for the diagnosis of anemia,and the accuracy of hemoglobin concentration measurement in children with kidney disease should be further explored.

Pulmonary arterial hypertension as leading manifestation of methylmalonic aciduria: clinical characteristics and gene testing in 15 cases / 北京大学学报(医学版)

Objective:To deepen our understanding of Methylmalonic aciduria (MMA) associated pulmonary hypertension (PH) by analyzing the characteristics of clinical presentation,pulmonary high resolusion CT(HRCT),treatment response and gene mutation.Methods:This study includes 15 cases of pediatric patients with MMA associated PH diagnosed and treated in Peking University First Hospital pediatric department between May 2012 and May 2016 with symptoms of PH as their leading presentation.Clinical symptoms and signs were recorded,Routine blood laboratory examinations was done including arterial blood gas analysis.Plasma total homocysteine (Hcy) and brain natriuretic peptide (BNP) level were measured.MMA gene mutation was analyzed.Chest HRCT was done in most of the patients.Standard treatment strategy to MMA and PH was given and follow up study was done,and the related literature was reviewed.Statistical analysis was done.The diagnosis of MMA was made by methylmalonic acid level ＞ 100 times the normal value in the urine.The diagnosis of PH was made by pulmonary arterial systolic pressure (PASP) ＞ 40 mmHg,which was estimated by the measurement of tricuspid regurgitation velocity through Doppler Echocardiography.Results:(1) Patient characteristics:There were 10 male and 5 female patients diagnosed as MMA associated PH,aged 0.5 to 13.8 years,with an average of (5.0 ± 4.3) years.The age of onset of PH was (3.7 ± 3.5) years,with an early onset type MMA in 5 cases and late-onset type in 10 cases.(2) Clinical presentation:Among the 15 cases of MMA,the first symptoms were associated with PH in 10 cases,so PH and MMA were diagnosed at the same time,and PH was diagnosed 3 to 72 months post MMA presentation in the other 5 cases.The main presentations of PH were techypnea/dyspnea and cyanosis in 11 cases each,weakness and fatigue on exertion in 6 cases,and edema in 4 cases.PH WHO functional classification (WHO FC) was Class Ⅱ in 4,Class Ⅲ in 5 and Class Ⅵ in 6 cases,with an average of Class 3.1 ± 0.8.Multi-system involvements were common with the highest frequency in the kidney (14 cases).Macrocytic anemia was present in 8 cases and subclinical hypothyroidism in 5 cases,and mild to moderate mental retardation in 4 cases.(3) Laboratory examination:PASP of the 15 patients was from 49 to 135 mmHg,with an average of (90.3 ±23.9) mm Hg.Total blood Hcy level was severely elevated to (121.2 ± 48.2) μmol/L (range:35.0-221.0 μmol/L),and Hcy ＞ 100 μmoL/L within 11 cases.Plasma BNP level was also elevated,median 794 ng/ L (range:21.0-4 995.0 ng/L) with 12 cases ＞ 300 ng/L.Blood gas analysis showed low arterial blood oxygen saturation between 70％ and 94％,with an average of 81.4％ ±8.4％.(4) Chest HRCT:chest HRCT showed a diffuse ground-glass centrilobular nodular opacities with septal line thickening in the lungs in 9 cases,and with associated mediastinal lymph node enlargement in 1 case,which indicated pulmonary veno-occlusive disease (PVOD),a rare type of pulmonary arterial hypertension (PAH).There was lung infection or edema in 3 cases,and interstitial infiltration and mesh-like feature in other 3 cases,which was inferred to interstitial lung disease.(5) Gene mutation:Genetic testing was done in 10 cases,totally 5 reported disease-causing mutations were found.There were 100％ presence of MMACHC c.80A ＞ G mutation in all the 10 patients tested,with the allelic genes of c.609G ＞ A mutation in 6 patients,including a sister and a brother from the same parents.(6).Treatment and follow up:Intramus cular hydroxocobalamin or vitamin B12 was given to all of the patients,together with betaine,levocarnidtine,folinic acid and vitamin B6.According to the severity of PH,single or combined PAH targeted drugs was given to 11 cases.By an average of (20.0 ± 13.5) days of in-hospital treatment in 13 patients (excepting 1 case treated as outpatient),symptoms remarkably resolved,WHO FC reduced to an average of Class 2.4 ±0.9,PASP dropped to (69.4 ±21.3) mmHg,and plasma Hcy and BNP level were decreased to (74.9 ± 25.9) μmol/L and (341.6 ± 180.2) ng/L,respectively.The above values all reached statistical significance (P ＜ 0.05) compared with each related value before treatment.Therewere 2 patients who expired during hospitalization despite of treatment.At the end of 3 months' follow up,all of the 13 patients disposed oxygen,and PASP significantly dropped to 38.7 ± 7.9 mmHg,and plasma BNP returned to normal,but plasma Hcy level showed no further decline.At the last follow up of 27.5 ± 19.0 (range:11-64) months,all the patients' PASP remained normal except for the 13.8-year-old boy with 6 years-long history of MMA and almost 3.6 years' history of PH still having PASP 58 mmHg.Conclusion:PH is a severe complication of MMA combined type,especially cblC type,it is more often happens in late-onset type of male patients and can be the first and leading manifestations of MMA.Its clinical symptoms are urgent and severe,characterized by tachypnea/dyspnea and cyanosis,and sometimes right heart failure,hypoxemia is usually present,chest HRCT is often indicative of PVOD,lung edema and interstitial lung disease may occur.Rapid diagnosis and targeted treatment of MMA with appropriate anti-PAH mcdication can reverse PH and save life.MMACHC gene c.80A ＞ G mutation may be the hot point of MMA cblC type associated PH.

LC-MS/MS method for determination of tripterine in plasma： pharmacokinetic study in Beagles / 中国中药杂志

To establish a LC-MS/MS method for determination of tripterine in Beagle plasma and study its pharmacokinetics after oral administration of tripterygium tablet. Plasma samples were extracted with dichloromethane and separated on a Phenomenex Luna C₈ (2.0 mm×50 mm, 3 μm) column with methanol-acetonitrile isopropanol(1∶1)-1‰formic acid (15∶55 ∶30) as the mobile phase. Tripterine ([M+H] ⁺, m/z 451.3/201.1) and internal standard prednisolone ([M+H] ⁺, m/z 361.1/147.1) were monitored in multiple reaction monitoring (MRM). The concentration-time curves were simulated by drug and statistic software 1.0 and the pharmacokinetic parameters were calculated. There was a good linear relationship between peak area ratio and concentration of tripterine and internal standard prednisolone within range of 0.680 0-136.0 μg•L⁻¹. The limit of quantitation was 0.680 0 μg•L⁻¹ and the intra- and inter-day precision was within 6.15%. The absolute recovery rate was between 50.42% to 51.65%. The concentration-time curves were consistent with the one-compartment model(w=1/cc). The main pharmacokinetic parameters after a single dose were as follows： Cmax (35.64±9.540) μg •L⁻¹,Tmax(2.62±0.69) h,T1/2(2.93±0.29) h, CL (0.308±0.056) L•kg⁻¹•h⁻¹, AUC0-12 (131.16±31.94) μg•L•h⁻¹, AUC0-∞ (142.83±37.57) μg•L•h⁻¹. The established LC-MS/MS method was proved to be sensitive, accurate and convenient, suitable for the pharmacokinetic study of Tripterygium tablet in Beagle dogs.