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Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (Ctrough) was detected by ultra performance liquid chromatography tandem mass spectrometry. Results: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers' group (30 cases) and poor metabolizers' group (35 cases). The Ctrough of the 65 patients were detected for 169 times totally, and there was a significant difference of Ctrough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of Ctrough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ2=11.689, P=0.020). Conclusion: Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their Ctrough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.
Subject(s)
Humans , Antifungal Agents , Cytochrome P-450 CYP2C19/genetics , Genotype , Hematologic Diseases/genetics , Mycoses , Phenotype , Polymorphism, Genetic , VoriconazoleABSTRACT
<p><b>BACKGROUND</b>Transforming growth factor-beta 1 (TGF-β1) and gene variants have been extensively studied in various human diseases. For example, TGF-β1 polymorphisms were associated with fibrosis and pneumoconiosis, but the data remained controversial. The aim of this meta-analysis was to assess the association between TGF-β1 -509 C>T [rs1800469], +869 T>C [rs1800470], and +915 G>C [rs1800471] polymorphisms and pneumoconiosis.</p><p><b>METHODS</b>A comprehensive literature search was conducted through searching in PubMed, Embase, the Chinese Biomedical Database, and the Wei Pu (Chinese) Database by the end of April 2016. Eleven publications with 21 studies were included in this meta-analysis, covering a total of 4333 patients with pneumoconiosis and 3478 controls. Study quality was assessed, and heterogeneity and publication bias were measured. All statistical analyses were performed using STATA version 12.0 (StataCorp, College Station, TX, USA) software.</p><p><b>RESULTS</b>The data showed significant associations between TGF-β1 -509 C>T polymorphism and the risk of pneumoconiosis development (T vs. C, odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.00-1.81, P = 0.046); between TGF-β1 +915 G>C polymorphism and the pneumoconiosis risk (C vs. G, OR = 1.69, 95% CI: 1.19-2.40, P = 0.004; CG vs. GG, OR = 1.79, 95% CI: 1.23-2.60, P = 0.002; CC+CG vs. GG, OR = 1.80, 95% CI: 1.24-2.61, P = 0.002). In addition, the subgroup analysis of ethnicity versus pneumoconiosis types indicated a significant association of silicosis among Asian populations but not that of coal workers' pneumoconiosis in Caucasian populations. In contrast, no significant association was exhibited between TGF-β1 +869 T>C polymorphism and risk of pneumoconiosis.</p><p><b>CONCLUSION</b>The polymorphisms of both TGF-β1 -509 C>T and +915 G>C are associated with increased risk of pneumoconiosis.</p>
Subject(s)
Humans , Asian People , White People , Genetic Predisposition to Disease , Genetics , Genotype , Pneumoconiosis , Genetics , Polymorphism, Genetic , Genetics , Transforming Growth Factor beta1 , GeneticsABSTRACT
OBJECTIVE@#To study the effects of PDGF-Rb antagonists imatinib on endometrial injury repairing in the mouse model.@*METHODS@#The cultured MSCs cells from male mice were marked with BrdU in vitro, and then transplanted to the female mice which suffered from radiation injury through tail vein, PDGF-Rb antagonists imatinib was injected through abdominal cavity. Four groups were arranged, which were radiation transplantation group, normal control group, imatinib intervention group and radiation control group. BrdU incorporation, SRY expression and MVD status were detected in uterus of mice.@*RESULTS@#SRY gene was negative expressed in normal control group and radiation control group. SRY gene presented positive in radiation transplantation group and imatinib intervention group; BrdU incorporation showed negative in radiation control group and normal control group which died in the early stage in mice; the incorporation of BrdU was higher in radiation transplantation group compared with imatinib intervention group; CD34 was positive on the uterus of all the four groups, which showed highest in radiation control group and lowest in radiation control group; The MVD in imatinib intervention group was lower than radiation control group; the difference of MVD was significantly compared with normal control group (P < 0.05).@*CONCLUSIONS@#PDGF-Rb antagonists imatinib could inhibit the repairing function of MSCs in the endometrial lesions in mice.
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Objective: To study the effects of PDGF-Rb antagonists imatinib on endometrial injury repairing in the mouse model. Methods: The cultured MSCs cells from male mice were marked with BrdU in vitro, and then transplanted to the female mice which suffered from radiation injury through tail vein, PDGF-Rb antagonists imatinib was injected through abdominal cavity. Four groups were arranged, which were radiation transplantation group, normal control group, imatinib intervention group and radiation control group. BrdU incorporation, SRY expression and MVD status were detected in uterus of mice. Results: SRY gene was negative expressed in normal control group and radiation control group. SRY gene presented positive in radiation transplantation group and imatinib intervention group; BrdU incorporation showed negative in radiation control group and normal control group which died in the early stage in mice; the incorporation of BrdU was higher in radiation transplantation group compared with imatinib intervention group; CD34 was positive on the uterus of all the four groups, which showed highest in radiation control group and lowest in radiation control group; The MVD in imatinib intervention group was lower than radiation control group; the difference of MVD was significantly compared with normal control group (P < 0.05). Conclusions: PDGF-Rb antagonists imatinib could inhibit the repairing function of MSCs in the endometrial lesions in mice.
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Objective To explore the application of B-mode intra- and post-operative ultrasound in patients with traumatic brain injuries. Methods B-mode intra- and post-operative ultrasound were performed 35 times in 24 patients, including 7 times of intra-operation in 7 patients and 28 times of post-operation in 17 patients. Results During operation epidural hematomas in 3 cases as well as intracranial hematomas in 2 cases, subdural hematomas in 1 case, diffused brain swelling in 1 case were found. After operation epidural hematomas were examined in 4 cases as well as subdural hematomas in 1 case, delayed intracranial hematomas in 6 cases, scattered contusion and laceration of the brain in 12 cases, acute obstructive hydrocephalus in 1 case, and subdural hydroma in 4 cases. Six cases underwent operations again because of delayed hematomas, contusion and laceration of the brain. B-mode ultrasound was compared with CT scan and the total coincidence rate was 85.4%.Conclusions B-mode ultrasound is helpful to examine delayed hematomas and other emergent complications. It may save time and may improve rescue rate and has a good coincidence with CT scan. B-mode ultrasound may be widely used as a routine way in neurotrauma ICU.
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@# Objective To observe the effect of Chinese medicine Qingre Huoxue Xiaozhong Ⅰ/Ⅱ mixture on the knee joint function disorder after fracture.Methods 143 patients with knee joint function disorder after fracture were randomly divided into the treatment group(n=50),control Ⅰ group(n=48),control Ⅱ group(n=45).The cases of the treatment group were treated with Qingre Huoxue Xiaozhong Ⅰ mixture 150 ml three times per day orally,Qingre Huoxue Xiaozhong Ⅱ mixture exteral washing once every day,and combined with Honghua oil and TDP instrument therapy.The cases of the control Ⅰ group were treated with the prepared medicine Shenjin Dan 6 pieces,three times a day,combined with Honghua oil and TDP instrument therapy.The cases of the control Ⅱ group were treated only with Honghua oil and TDP instrument therapy.15 days were as a treatment course,and performed 1～2 treatment courses.The patients of the three groups also took the vitamins and calcitium simultaneously.The curative effect was evaluated according to the standard of Lysholm Joint Function.Results After treatment,the total excellent rates of the treatment group,control Ⅰ group and control Ⅱ group were 78%,39.58% and 24.44%,respectively,the result of the treatment group was significantly superior to that of the control Ⅰ group and control Ⅱgroup(P<001).The total effective rates of the treatment group,control Ⅰ group and control Ⅱ group were 98%,85.42% and 75.55%,respectively.The effect of the treatment group was also significantly superior that of the control Ⅰ group(P<0.05) and control Ⅱ group( P<0.01).Conclusion The Chinese native medicine Qingre Huoxue Xiaozhong Ⅰ/Ⅱ mixture has an obvious therapeutic effect in the multidisciplinary therapies on the knee joint function disorder after fracture.
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Objective To investigate the approach and effect of PDT and TTT therapeutic alliance for isolated choroidal angioma according to the lication. Methods After mydriasis,through 90D retinal mirror examination ,fluorescein fundus angiography (FFA) ,Indocyanine green angiography (ICGA) and ultrasound,the diagnosis of angiography choroidsal hemangioma was made. Position:peripapillary , six cases( tumors locating only in macula fovea were not included in this statistical area). OCT suggested that epithetlial tumors from the surface of nerve macular were affected. Period of the disease was between one week and two months . Preoperative best corrected vision acuity range was 1. 05 ～ 0.4. By ultrasonography, tumors thickenss was from 2.2mm to 4mm, and diameter was from 6.6mm to 11.2mm. OCT indicated that the height of neural epithetlium breaking away from macular area was between 156mm and 486mm. inferior retinas separated two months after morbidity. TTT was partly applied to cure tumor body ortside macdular area with IRIS Medical OculightSLX gallium arsenicde laser(810nm). Energy:per light spot shining diameter was 1 mm, and the power was between 150mw to 250mW, and time was 60s. Therapeutic standard was retinal surface changing to pale. Choroids shrunk back and retinal ptgment epithetlium prolixferated in TTT therapy area;recheck 2 weeks later. If FFA showed that active macula fovea pathological changes were not cured, PDT was performed as following :689nm laser was used , and veteporfin ( comm. ercial name : Visudyne) was injected by intravenous at a speed of 6mg/mm~2 , and 15 minutes later, the laser was irradiated for a period of 83 ～ 126s. For tumors with thicdness under 3mm,one light spot was irradiated for 83s;for rumors with thicdness above 3mm, acouple light apot was irradiated for 125s. A small quantity of hyperpigmintation occurred in the limbus,luteus retinae at the second week of follow up. All the cases were followed up for 3 months to 12 months. Results The final vision reached 0.1 ～ 1.0. OCT showed that the earliest complete recovery of limbus luteus retinae neural epithetlium was at the third week, and for another 3 cases,the recovery was at the 4th week. One case with detachment of retina partial recovered 3 months after treatment. OCT suggested that most of the macular detachment and epithetlial cystic degenerateion of neurons recovered to normal. type - B ultrasound was performed in the first three months of treatment. The tumors were difficult to be detected in two cases, and four cases had a thickness of 0. 8 ～2.2mm. At the 6th month,the detection of tumors for the six cases showed normal results. PDT was used only once in the included six cases. Conclusion PDT and TTT therapeutic alliance for isolated choroidsal angioma is safe and effective at special position of eye ground. Each treatment showed its unlque adventages in this combination with a reduction of frequentcy and cost of expensive cost of PDT, and satisfying results of the shrink of the rumors and improvement or preservation of vision.
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<p><b>OBJECTIVE</b>To study the influence of experimentally osteoporosis to osteogenic efficiency of bone matrix gelatin(BMG) implanted into the calvarial defects of rats.</p><p><b>METHODS</b>Sixty-eight female SD rats of 12 +/- 1 weeks were randomly divided into two groups with 34 rats in each group. The ovaries were excised in the ovariectomized group (VG). The control group underwent sham surgery. Ninety days after ovariectomy, 10 rats from each group were examined to ensure the formation of postmenopausal osteoporosis by measuring bone density of the femur with single photon absorptiometric measurements. A critical-sized (8 mm in diameter) calvarial defect was created on the rest of 48 rats. Bone matrix gelatin was implanted to the defect. The rats were scarified at the 21st and 56th day after surgery respectively. The new bone forming capability of BMG was evaluated with undecalcified histological observation, tetracycline fluorescence marker, quantitative bone histomorphometry, At 90th day after ovariectomy, bone density of scanning electron microscopy and X-ray spectrometry.</p><p><b>RESULTS</b>OVG showed very significant difference compared with the control group (0.315 +/-.015) g/cm2 vs [(0.347 +/- 0.017) g/cm2, P < 0.01 ]. At the 21st day following the implantation operation, new bone formed within the bone defects in both groups. The amount of new bone in OVG was lower than the control group. The tetracycline-labeled region in the bone defect was sparser in the OVG. At the 56th day, the bone defects healed mostly in the control group but fibrous tissue filled parts of bone defect in the OVG. The distance between two fluorescent lines of incorporated tetracycline and the mean mineralization deposition were significantly lower in the OVG than the control at the 21st day and 56th day. Mineralization of callus in OVG was inferior. Significant difference was found between the OVG and the control group in the calcium to phosphate ratio of callus in bone defects at the two time-points.</p><p><b>CONCLUSIONS</b>Experimentally induced osteoporosis depressed osteogenic efficiency of BMG, suggesting that estrogen could play an important role in bone remodeling with bone substitute participating.</p>