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BACKGROUND:The clinical manifestation of acute radiation skin injury is recurrent necrotic ulcers,and its pathogenesis is still not fully understood.The establishment of a suitable animal model will have important clinical implications for the study of its pathogenesis,prevention and treatment. OBJECTIVE:To establish a model of acute β-ray radiation skin injury and to investigate the mechanism of injury. METHODS:Sixty-nine Sprague-Dawley rats were randomly divided into 30,45,60 Gy 32P-β-ray groups(n=21 per group)and control group(n=6).A single local irradiation of the back of the rats was performed using 32P radionuclide.The control group was operated in the same way as the irradiated groups except that it was not irradiated.The body mass and skin appearance of the rats were measured at 7,15,30,45,and 60 days after irradiation.Three rats from each group were selected at each observation time point.The skin injury was observed by hematoxylin-eosin staining,Masson staining,transmission electron microscopy,and TUNEL assay.P53,Bcl-2 and Bax protein levels in the skin were measured by immunohistochemistry and western blot assay. RESULTS AND CONCLUSION:There was no accidental death after irradiation,and the body mass of rats showed a gradual increase.The rats showed different degrees of epidermal necrosis,inflammatory cell infiltration,reduction of hair follicles and appendages,and collagen fibrillation,which were evident at 60 and 45 Gy.The levels of serum inflammatory factors,interleukin-6 and tumor necrosis factor-α,were significantly increased in a dose-dependent manner.Under the electron microscope,there are varying degrees of mitochondrial reduction,vacuolization and nuclear pyknosis in the cells.The degree of cell apoptosis showed a certain dose-dependence.Immunohistochemistry and western blot results showed an increase in the expression of P53 and Bax proteins and a decrease in the expression of Bcl-2 protein in the skin after irradiation.There were significant differences between the 60 Gy group and the 45 Gy and 30 Gy groups(P<0.05).To conclude,irradiation with 60 Gy and 45 Gy 32P radionuclide on the back of rats could successfully establish a practically pre-clinical animal model,and the mechanism is related to the up-regulation of P53 and Bax and the down-regulation of Bcl-2.This model can provide a reference for the establishment of animal models for the study of the mechanism of radiation skin injury and its prevention and treatment.
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Objective:To discuss the classification and treatment of ureteroileal anastomotic stricture (UAS) after radical cystectomy.Methods:The clinical data of 34 patients with UAS after radical cystectomy in the Department of Urology of Tongji Hospital from January 2017 to January 2022 were reviewed and analyzed. There were 25 males and 9 females. The average age was (66.3±7.7)years, including 2 cases of bilateral hydronephrosis and 32 cases of unilateral hydronephrosis. The average time of UAS was detected (14.7±6.5)months after radical cystectomy. There were 32 patients of unilateral hydronephrosis and 2 patients of bilateral hydronephrosis. Two patients had undergone nephrostomy in an external hospital. Three patients had elevated leukocytes in blood routine. Among them, two patients had fever. First, nephrostomy on the hydronephrosis side and anti-infection treatment were performed. After routine blood tests showed that the white blood cells were normal and antibiotics were stopped for 24 hours without fever, the operation was performed. 34 patients had preoperative hydronephrosis of (2.7±0.6) cm. Of the 34 cases in this group, 5 cases were injected with methylene blue through a preoperative nephrostomy tube, and 29 were injected with methylene blue through the renal pelvis using an 18G puncture needle under ultrasound guidance. Using a ureteroscope to observe in the ileal bladder, methylene blue was seen in 4 cases. Methylene blue was used to guide the search for the stenosis and a super smooth guide wire was inserted. Among them, 3 cases were dilated with a 5 mm ureteral dilation balloon catheter, 1 case was dilated with a F14 ureteral access sheath, and then a F6 single J stent was inserted. Methylene blue was not seen in the ileal conduit in 30 cases, of which 16 cases were treated with a flexible ureteroscope through the nephrostomy to locate the stenosis, incised with a 30 W holmium laser. 9 cases were treated with 5 mm ureteral dilation balloon catheter, and 7 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 14 cases were unable to find the stenosis by antegrade method. According to the operation time and patient's condition, it was decided to perform immediate or second stage dual endoscope surgery. Through the nephrostomy, a flexible ureteroscope was used to enter the stenosis along the super slide guide wire. A rigid ureteroscope was used to observe the stenosis through the ileal conduit, and the stenosis was found. The stenosis was found in 10 cases and incised with a 30 W holmium laser. 8 cases were treated with 5 mm ureteral dilation balloon catheter, and 2 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 4 cases were still unable to accurately locate the stenosis using the dual endoscope surgery(one case was bilateral stenosis, and one side was relieved), and continued indwelling nephrostomy. The definition of successful removal of stricture in this study is that an F6 single J stent can be inserted into the ureter.Results:UAS were classified into four types based on the severity of the intraoperative findings: Type Ⅰ, the narrow ureteral lumen is more than 50% narrower than the normal ureteral lumen, but methylene blue can pass through in strands; Type Ⅱ, needle like stricture of the ureteral lumen, allowing only methylene blue filaments to pass through; Type Ⅲ, membranous atresia of the ureter, with a narrow segment of 1 to 3 mm in length, and methylene blue cannot pass through; Type Ⅳ, long segment stenosis. Of the 34 cases in this group, 4 cases were type Ⅰ, and the stenosis was dredged by retrograde method; 16 cases were type Ⅱ, and the stenotic segments were dredged by antegrade method; 10 cases were type Ⅲ, and the stenosis was dredged by the dual endoscope surgery; Four cases were of type Ⅳ (one case was of bilateral UAS, one side was of type Ⅲ, and the other side was of type Ⅳ, which was classified as type Ⅳ). The stenotic segment could not be solved through the above methods. Among the 34 patients, 30 patients were successfully relieved of anastomotic obstruction, and 1 patient with bilateral obstruction was unilaterally relieved of anastomotic obstruction. In the other 3 cases, because the stenosis segment was too long, 2 cases were changed to nephrostomy, and 1 case was changed to open surgery, with a success rate of 88.2%. UAS was classified into 4 types based on the severity of UAS seen during surgery. No serious complications occurred during and after the operation. During the follow-up of 6-24 months, the imaging evaluation of 4 patients showed that hydronephrosis was aggravated, with an average increase in creatinine of (32.5±10.9)μmol/L, requiring replacement of a single J tube. The imaging evaluation of the remaining 26 patients showed that the postoperative hydronephrosis was 0.9 ± 0.6 cm less than the preoperative hydronephrosis 2.6 ± 0.6 cm, with a statistically significant difference ( P<0.01). The quality of life score at 3 months after surgery was (1.9±0.6), which was significantly improved compared to the preoperative indwelling nephrostomy period (5.2±0.7), with a statistically significant difference ( P<0.01) Conclusions:The treatment of UAS after radical cystectomy with retrograde, antegrade, and dual endoscope surgery has a high success rate, which can help some patients avoid the inconvenience of indwelling external drainage tubes and the risk of open surgery. Choosing an appropriate surgical method can achieve the goal of treating UAS with minimal trauma.
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ObjectiveTo investigate the value of reduced field-of-view DWI (r-FOV DWI) in quantitative assessment of axial spondyloarthritis. MethodsA total of 112 patients with chronic back pain or suspected axial spondyloarthritis receiving full field-of-view DWI (f-FOV DWI) and reduced field-of-view DWI (r-FOV DWI) from December 2019 to December 2021 were enrolled. Next, subjective image quality assessment (anatomical detail, artifacts, distortion, overall image quality) and objective image quality assessment including (signal to noise ratio and contrast to noise ratio) were conducted by two experienced radiologists. In addition, the Apparent Diffusion Coefficient (ADC) values of three groups (active group, inactive group, and control group) on the two DWI sequences were measured by the two radiologists, respectively. Finally, the consistency of measurement between the two researchers was evaluated and the differences in ADC values was compared. Results102 patients were included and were divided into three groups, including the active group (n=32), inactive group (n=29), and control group (n=41) according to ASAS diagnostic criteria. All subjective and objective image quality metrics were rated in favor of r-FOV DWI images compared with f-FOV DWI images [overall image quality: DWI 4(3~4) vs. 3(3~3) and SNR: 6.58(5.05~10.38) vs. 4.46(2.37~10.04), CNR: 2.04(-1.14~8.29) vs. 0.97(-8.19~7.12);P<0.05]. Inter-rater consistency of the two researchers were 0.60~0.74. According to the AUC curve, group inactive vs. control showed r-FOV DWI was better than f-FOV DWI. In other groups (lesion vs. control, active vs. inactive), there were no differences between both sequences(P<0.05). ConclusionThe subjective image quality score and signal to noise ratio of r-FOV DWI were higher than those of f-FOV DWI, which could be used for quantitative assessment of axial spondyloarthritis.
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Since the emergence of the term "materia medica", scholars have proposed different opinions on its concept. This term has been used to refer to traditional Chinese medicines, or medical books, or traditional pharmacology. Due to the differences in the concept of materia medica, scholars also have controversies about the concept of herbalism. Herbalism is usually understood as traditional Chinese pharmacology. After years of evolution, the term "herbalism" has now possessed the characteristics of an independent discipline, which can be defined as an applied basic discipline that comprehensively utilizes traditional and modern technological methods to study the formation, development, and changes of traditional pharmacology and reveal the basic theories and application laws of traditional medicine. At present, the research content of herbalism mainly includes three aspects: materia medica history, materia medica literature, and traditional pharmacology. This study explores the disciplinary concepts and main research content of herbalism based on a systematic review of the literature about the concepts of materia medica and herbalism, with the aim of attracting more attention to promote the establishment and development of the discipline of herbalism.
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China , Drugs, Chinese Herbal , Herbal Medicine , Materia Medica , Medicine, Chinese Traditional , TechnologyABSTRACT
Objective:To explore the trans-membrane signaling mechanism of interleukin-6 (IL-6)-induced osteogenic differentiation and calcification of human umbilical artery smooth muscle cells (HUASMCs).Methods:HUASMCs were primarily cultured in vitro and were stimulated with IL-6, IL-6+solutable IL-6 receptor (sIL-6R), IL-6+sIL-6R+solutable gp130 (sgp130), or vehicle (blank control). Alizarin red and Von Kossa staining were used for detecting cell calcification, Western blot was used to test the protein expression of tissue-nonspecific alkaline phosphatase (TNAP), osteopontin (OPN), bone morphogenetic protein-2 (BMP-2) and Runt related transcription factor 2 (Runx2), and immunofluorescence was used to examine the mIL-6R expression of HUASMCs. The comparison of measurement date between the two groups was conducted by t-test. The comparison of measurement date between multiple groups was conducted by one-way analysis of variance (ANOVA). Results:The intensity severity of calcification stain was IL-6+sIL-6R group >IL-6+sIL-6R+sgp130 group>IL-6 group=blank control. After stimulated for 12 hours, the TNAP expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.44±0.08), (0.52±0.14), (0.84±0.16) and (0.55±0.10) respectively ( F=290.96, P<0.001). After stimulated for 3 days, the OPN expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.61±0.84), (0.95±0.16), (1.65±0.24) and (0.99±0.10) respectively ( F=507.72, P<0.001). After stimulated for 12 hours, the BMP-2 expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.77±0.05), (1.69±0.16), (2.81±0.26) and (0.57±0.12) respectively ( F=959.09, P<0.001). After stimulated for 3 days, the Runx2 expression in blank control, IL-6 group, IL-6+sIL-6R group,IL-6+sIL-6R+sgp130 group were (0.57±0.03) , (0.92±0.10), (1.31±0.13) and (0.66±0.06) respectively ( F=1141.27, P<0.001). Comparing with Jurkat cells (positive control) and CEM cells (negative control), HUASMCs limited expressed mIL-6R. Conclusion:IL-6 may induce HUASMCs osteogenic differentiation and calcification mainly via the sIL-6R-mediated trans-signaling pathway.
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Objective:To analyze the difference and clinical significance of reflux related parameters between patients with reflux asthma (RA) and typical gastroesophageal reflux disease (TGERD).Methods:From June 2017 to June 2020, at PLA Rocket Force Characteristic Medical Center, the clinical data of 120 patients with gastroesophageal reflux disease (GERD) who underwent gastroscopy, high-resolution esophageal manometry (HREM) and 24 h pH-impedance monitoring contemporaneously were retrospectively analyzed. The GERD patients were divided into RA group and TGERD group according to the symptom correlated indexes, 60 cases in each group. The reflux related indexes of two groups were compared, which included reflux esophagitis (RE) score, esophageal hiatal hernia, Hill grade score of gastroesophageal flap valve, upper esophageal sphincter (UES) pressure, DeMeester score, and reflux episodes. Mann-Whitney U test and chi-square test were used for statistical analysis. Results:There were no significant differences in RE score and Hill grade score between TGERD group and RA group (0.0, 0.0 to 1.0 vs. 0.0, 0.0 to 1.8; 3.0, 2.0 to 3.0 vs. 3.0, 2.0 to 3.0) (both P>0.05). The detection rate of UES pressure less than 34 mmHg (1 mmHg=0.133 kPa) of RA group was higher than that of TGERD group (41.7%, 25/60 vs. 23.3%, 14/60), and the difference was statistically significant ( χ2=4.596, P=0.032). The UES pressure of RA group was lower than that of TGERD group (51.7 mmHg, 23.6 mmHg to 70.1 mmHg vs. 62.0 mmHg, 37.4 mmHg to 77.4 mmHg), and the difference was statistically significant ( Z=-2.105, P=0.035). There were no significant differences in other parameters of HREM between TGERD group and RA group (all P>0.05). The detection rates of DeMeester score more than 14.7, acid exposure time more than 4.5% and total reflux episodes more than 73 episodes of RA group were all higher than those of TGERD group (41.7%, 25/60 vs. 23.3%, 14/60; 40.0%, 24/60 vs. 21.7%, 13/60; 38.3%, 23/60 vs. 20.0%, 12/60, respectively), and the differences were all statistically significant ( χ2=5.546, 4.728 and 4.881, all P<0.05). The total reflux episodes and weak acid gas reflux episodes of RA group were both higher than those of TGERD group (60 episodes, 43 episodes to 98 episodes vs. 52 episodes, 34 episodes to 69 episodes; 12 episodes, 6 episodes to 21 episodes vs. 9 episodes, 3 episodes to 14 episodes), and the differences were statistically significant ( Z=-2.323 and -2.053, both P<0.05). There were no significant differences in other parameters of 24 h pH-impedance monitoring between TGERD group and RA group (all P>0.05). Conclusion:Low UES pressure, abnormal esophageal acid exposure and increased reflux episodes, especially weak acid gas reflux episodes, may be more likely to induce RA.
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Sudden sensorineural hearing loss (SSNHL) refers to the sudden and unexplained sensorineural hearing loss within 72 h and a decrease in hearing of ≥30 dB affecting at least 3 consecutive frequencies. It is one of the common emergencies in neurology and otolaryngology. Early etiological evaluation and systematic and targeted treatment are very important for delaying the progression of SSNHL and restoring hearing. Recent studies have shown that SSNHL overlaps with vascular risk factors of ischemic stroke, and may predict the risk of ischemic stroke. SSNHL may be one of the clinical manifestation and even the prodromal symptoms of ischemic stroke, especially the infarction of the blood supply area of the anterior inferior cerebellar artery or its branch internal auditory artery. Although these factors can not fully reveal the relationship between SSNHL and ischemic stroke, they are enough to warn clinicians that they should consider the possibility of ischemic stroke when receiving patients with SSNHL. Screening of vascular risk factors for patients with SSNHL as early as possible is helpful to avoid the risk of recurrence of ischemic stroke.
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In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol- containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.
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Objective: To evaluate the effect of nordihydroguaiaretic acid (NDGA) on ceftazidime resistance of Pseudomonas aeruginosa mediated by efflux pump system MexCD-OprJ and explore its mechanism. Methods: The bacterial solution with a concentration of 0.5 mcburney was diluted and inoculated in a 96-well plate, and NDGA and ceftazidime were added by the checkerboard dilution method. At the same time, the untreated control group, NDGA control group and ceftazidime control group were set; After being cultured for 24 h, the absorbance was measured by an enzyme micro-plate reader, the minimum inhibitory concentration (MIC) of each drug was recorded and the bacteriostatic rate and fractional inhibitory concentration (FIC) index were calculated. Bacteria were inoculated with the bacterial liquid coating method in the 96-well plates, and the bacterial colony number was counted after 24 h of culture. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the gene expressions of efflux pump membrane protein MexC, MexD, OprJ and nfxB. Results: Compared with ceftazidime or NDGA alone, combination of ceftazidime and NDGA significantly inhibited the growth of efflux pump system MexCD-OprJ-mediated ceftazidime-resistant P. aeruginosa (P < 0.05); The pharmacological effects of ceftazidime and NDGA showed synergistic or additive effects; After combined administration, the MIC values of ceftazidime and NDGA were significantly decreased, and the MIC value of some ceftazidime had no significant difference from that of ceftazidime-sensitive P. aeruginosa; Compared with ceftazidime alone, the gene expressions of efflux pump membrane proteins MexC, MexD and OprJ were significantly decreased after combined application of ceftazidime and NDGA (P < 0.05), while the expression of nfxB was significantly increased (P < 0.05). Conclusion: The mechanism of NDGA on ceftazidime resistance of P. aeruginosa mediated by efflux pump system MexCD-OprJ is related to its ability to down-regulate the gene expression of efflux pump membrane proteins MexC, MexD and OprJ, and up-regulate the gene expression of the negative regulatory gene nfxB of the above three proteins.
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OBJECTIVE@#The current difficulties in the treatment of tumor include repeated administration and high recurrence rate after tumor resection. In order to reduce the number of doses, avoid side effects of chemotherapeutic drugs, suppress tumor growth and delay tumor recurrence after surgery, a temperature-sensitive in situ gel with paclitaxel microspheres (PTX/M gel) was prepared. PTX/M gel was administered by intratumoral injection once a month.@*METHODS@#First of all, paclitaxel microspheres (PTX/M) were prepared by emulsion solvent evaporation method. A laser particle size distribution analyzer was used to investigate the size, distribution, specific surface area of microspheres. Paclitaxel content was determined by high performance liquid chromatography (HPLC). Then encapsulation efficiency of paclitaxel was calculated and in vitro release characteristics were studied. Secondly, PTX/M gel was prepared by cold dissolution method. The phase transition temperature, elastic modulus, dissolution curve, correlation between dissolution and release were measured. Finally, U87 MG and 4T1 subcutaneous tumor models were established respectively to study the efficacy of PTX/M gel in suppressing tumor growth and delaying tumor recurrence after surgery.@*RESULTS@#The median diameter of the selected PTX/M was (32.24±1.09) μm, the specific surface area was (206.61±10.23) m2/kg, the encapsulation efficiency was 85.29%±1.34%, and the cumulative release percentage of paclitaxel from PTX/M was 33.56%±3.33% in one month. Phase transition temperature of PTX/M gel was 33 °C. The elastic modulus of PTX/M gel at 25 °C and 37 °C were 4.2×103 Pa and 18×103 Pa, respectively. The gel could stay in the body for up to 48 hours. It could be seen from the results of animal experiments that were compared with the saline group and the Taxol group, and the tumor-bearing mice of the PTX/M gel group had the slowest tumor growth (P<0.05). Similarly, in the tumor recurrence experiments, the mice of PTX/M gel group had the latest tumor recurrence after surgery.@*CONCLUSION@#As a local sustained-release preparation, PTX/M gel can effectively suppress tumor growth and delay postoperative recurrence of tumors. It has potential advantages in tumor treatment.
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Animals , Mice , Antineoplastic Agents, Phytogenic , Cell Line, Tumor , Delayed-Action Preparations , Microspheres , PaclitaxelABSTRACT
Objective To rapidly establish a mouse model for optical imaging of the dynamical process of pseudotyped Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Methods In vitro expression in HeLa cells and functions of hDPP4 encoded by recombinant adenovirus Ad5 and pseudo-typed MERS-CoV were verified. The recombinant adenovirus expressing hDPP4 (Ad5-hDPP4) was injected into BALB/ c mice, which were then injected with pseudotyped MERS-CoV expressing firefly luciferase at a titer of 3×107 TCID50(50% tissue culture infective dose) via intrathoracic (I. T. ) or intraperitoneal (I. P. ) injection. MERS-CoV infection and tissue distribution were observed using optical imaging techniques. Re-sults hDPP4 and firefly luciferase were efficiently expressed in HeLa cells. In BALB/ c mice injected with Ad5-hDPP4 via I. P. , firefly luciferase expression were detected in abdomen between 48-96 h after pseudo-typed MERS-CoV infection. The expression of firely luciferase was also detected in chests of BALB/ c mice injected with Ad5-hDPP4 via I. T. around 48 h after pseudotyped MERS-CoV infection. Conclusions This study reported a simple and rapid method for establishing a mouse model for conveniently and dynamically monitoring pseudotyped MERS-CoV infection, which might provide an effective means for in vivo evaluation of neutralizing antibodies or entry inhibitors by visualization with optical imaging techniques.
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To study and analyze prevalence condition of hypertension and complicated cardiovascular risk factors in north Fujian rural area .Methods : By cluster sampling , an epidemiological questionnaire and physical ex‐amination were performed among 1784 residents using standardized survey method , who were ≥35 years from six towns and eight villages in north Fujian rural area from Jun 2013 to Mar 2014. Hypertension was diagnosed accord‐ing to The 2010 Chinese Guideline for the Prevention and Treatment of Hypertension , multivariate Logistic regres‐sion was used to analyze independent risk factors for hypertension in these subjects .Results : Prevalence rate of hy‐ pertension was 17.43% (31/1784 ) in north Fujian rural area .After population standardization , it's 23. 21%(18.66% in men and 16. 13% in women) , there was no significant difference in prevalence rate of hypertension be‐tween men and women in any age layer , P>0. 05 all.Multivariate Logistic regression analysis indicated that age , overweight (BMI≥24 kg/m2 ) , high triglyceride and fasting blood glucose were independent risk factors for hyper‐tension in north Fujian rural area (OR=1.107-2.096 , P<0. 05 or <0. 01).Conclusion : Prevalence rate of hyper‐tension is high in north Fujian rural area , age , overweight , smoking , high triglyceride and fasting blood glucose are the main risk factors .
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OBJECTIVE:To provide reference for the study of optimal sampling points in clinical pharmacokinetics.METHODS:The literatures about optimal sampling points in clinical pharmacokinetics were searched from CNKI,Wanfang database,VIP,PubMed,Medline,ScienceDirect and other databases during Jan.2011-Jun.2016 using "Bayesian estimate(s)""Bayesian estimator(s) Bayesian analysis" "Limited" "Optimal" "Sparse" "Minimal sampling" as retrieval words.The systematic analysis and evaluation were conducted.RESULTS:A total of 1 Chinese literature and 13 English literatures were involved respectively.The drugs they focused on were mainly immunosuppressive agents,antiviral drugs,antibiotics,pediatric individualized medication,etc.Multiple linear regression (MLR) was still the most widely used method in China,while maximum a posteriori Bayesian (MAPB) method was more popular in foreign studies.MLR equation was simple and easy to use,but the sampling was very strict.MAPB method could be completed with less sampling points and sampling time;it was more suitable for clinical practice,but needed professional software.The precision and accuracy of the two methods were similar.The research methods of optimal sampling strategy were quite different but all included 4 steps as prior information ganining,reference value determination,sampling point optimization,prediction capability verification.CONCLUSIONS:MAPB method requires less sampling points and it results are relatively accurate and reliable.It is more suitable for clinical practice and optimal sampling study of clinical pharmacokinetics.
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Spinal tuberculosis (ST) is the tuberculosis caused by Mycobacterium tuberculosis (Mtb) infections in spinal curds. Isoliquiritigenin 4,2′,4′-trihydroxychalcone, ISL) is an anti-inflammatory flavonoid derived from licorice (Glycyrrhiza uralensis), a Chinese traditional medicine. In this study, we evaluated the potential of ISL in treating ST in New Zealand white rabbit models. In the model, rabbits (n=40) were infected with Mtb strain H37Rv or not in their 6th lumbar vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg and 100 mg/kg of ISL respectively. After 10 weeks of treatments, the adjacent vertebral bone tissues of rabbits were analyzed through Hematoxylin-Eosin staining. The relative expression of Monocyte chemoattractant protein-1 (MCP-1/CCL2), transcription factor κB (NF-κB) p65 in lymphocytes were verified through reverse transcription quantitative real-time PCR (RT-qPCR), western blotting and enzyme-linked immunosorbent assays (ELISA). The serum level of interleukin (IL)-2, IL-4, IL-10 and interferon γ (IFN-γ) were evaluated through ELISA. The effects of ISL on the phosphorylation of IκBα, IKKα/β and p65 in NF-κB signaling pathways were assessed through western blotting. In the results, ISL has been shown to effectively attenuate the granulation inside adjacent vertebral tissues. The relative level of MCP-1, p65 and IL-4 and IL-10 were retrieved. NF-κB signaling was inhibited, in which the phosphorylation of p65, IκBα and IKKα/β were suppressed whereas the level of IκBα were elevated. In conclusion, ISL might be an effective drug that inhibited the formation of granulomas through downregulating MCP-1, NF-κB, IL-4 and IL-10 in treating ST.
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Rabbits , Blotting, Western , Bone and Bones , Chemokine CCL2 , Enzyme-Linked Immunosorbent Assay , Glycyrrhiza , Granuloma , Interferons , Interleukin-10 , Interleukin-4 , Interleukins , Lymphocytes , Medicine, Chinese Traditional , Mycobacterium tuberculosis , New Zealand , Phosphorylation , Real-Time Polymerase Chain Reaction , Reverse Transcription , Transcription Factors , Tuberculosis , Tuberculosis, SpinalABSTRACT
Objective To evaluate the accuracy of changing rate of the left ventricular outflow tract velocity time integral (△VTI) in predicting fluid responsiveness in septic patients.Methods Twenty patients diagnosed with sepsis or septic shock and received mechanical ventilation,aged more than or equal to 18 yr,in whom the ventilation mode was SIMV plus VC,were enrolled in this study.The left ventricular outflow tract VTI,stroke volume (SV) and cardiac output (CO) were measured using ultrasound.Sodium potassium magnesium calcium and glucose injection 100 ml was intravenously infused over 1 min,ultrasound measurement was completed within 1 min,and then Sodium potassium magnesium calcium and glucose injection 400 ml was intravenously infused over 14 min.Fluid responsiveness was defined as increase in SV or CO more than 15% after infusion of 500 ml colloid solution,and then the patients were divided into responsiveness group and non-responsiveness group.△VTI,△SV and △CO were calculated after fluid replacement with 100 ml solution.The receiver operating characteristic curve was used to assess the accuracy of △VTI,△SV and △CO in predicting fluid responsiveness.Results The areas under the receiver operating characteristic curve of △VTI,△SV and △CO were 0.95,0.91 and 0.88,respectively.When △ VTI ≥ 10% was used as the cut-off point,the sensitivity and specificity of △VTI in predicting fluid responsiveness was 90% and 80%,respectively.Conclusion △VTI can accurately predict the fluid responsiveness in septic patients.
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We hereby reported the clinical manifestations and genetic diagnosis of a rare case of congenital adrenal hyperplasia (CAH) caused by cytochrome P450 oxidoreductase ( POR ) gene mutation. The case was an 11-year-old girl presented with craniofacial and skeletal malformation such as a depressed nasal bridge, radiohumeral synostosis and camptodactyly in feet. Moreover, she was diagnosed with ambiguous genitalia, and her mother had obvious masculine features during pregnancy. Laboratory tests showed that the levels of peripheral blood progesterone, 17-hydroxyprogesterone and adrenocorticotrophic hormone (ACTH) had increased significantly, which were consistent with the symptom of CAH. Genetic testing revealed a complex heterozygous mutation in POR gene of maternally inherited c.744C>G (p.Tyr248Ter) and paternal inherited c.1370G>A (p.Arg457His). Therefore, she was diagnosed with cytochrome P450 oxidoreductase deficiency (PORD), which is a rare type of CAH. The patient received oral glucocorticoid therapy and underwent knee arthroplasty.
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Objective:To study the safety and efficacy of doxofylline for treating the patients with ticagrelor caused dyspnea.Methods:A total 172 coronary artery disease (CAD) patients with ticagrelor caused dyspnea in our hospital from 2015-02 to 2016-07 were studied.The patients were divided into 2 groups:Intervention group,patients received doxofylline at 200 mg twice per day for 5 days and Control group,patients received placebo.n=86 in each group.Dyspnea remission rate of was recorded at 1 day after treatment;platelet aggregation rate before and after treatment,cardiac death,myocardial infarction (MI),stroke,bleeding and other adverse cardiovascular and cerebral events were compared at 6 month after treatment.Results:Compared with Control group,Intervention group had improved dyspnea remission rate at 1 day after treatment (93% vs 63%),P<0.05;platelet aggregation rate [before doxofylline application:(35.53±5.1)% vs (35.16±4.6)%,after doxofylline application:(26.48±4.3)% vs(25.98±4.7)%]adverse cardiovascular and cerebral events were similar between 2 groups before and after doxofylline application,P>0.05.Conclusion:Doxofylline was effective for treating the patients with ticagrelor caused dyspnea,it does not affect platelet aggregation effect of ticagrelor.
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Objective:To study the safety and efficacy of doxofylline for treating the patients with ticagrelor caused dyspnea.Methods:A total 172 coronary artery disease (CAD) patients with ticagrelor caused dyspnea in our hospital from 2015-02 to 2016-07 were studied.The patients were divided into 2 groups:Intervention group,patients received doxofylline at 200 mg twice per day for 5 days and Control group,patients received placebo.n=86 in each group.Dyspnea remission rate of was recorded at 1 day after treatment;platelet aggregation rate before and after treatment,cardiac death,myocardial infarction (MI),stroke,bleeding and other adverse cardiovascular and cerebral events were compared at 6 month after treatment.Results:Compared with Control group,Intervention group had improved dyspnea remission rate at 1 day after treatment (93% vs 63%),P<0.05;platelet aggregation rate [before doxofylline application:(35.53±5.1)% vs (35.16±4.6)%,after doxofylline application:(26.48±4.3)% vs(25.98±4.7)%]adverse cardiovascular and cerebral events were similar between 2 groups before and after doxofylline application,P>0.05.Conclusion:Doxofylline was effective for treating the patients with ticagrelor caused dyspnea,it does not affect platelet aggregation effect of ticagrelor.
ABSTRACT
Objective The objective of this study was to evaluate the correlation between maximum standard uptake values( SUVmax ) of 18 F-FDG PET/CT and BRAF mutation in patients with papillary thyroid car-cinoma(PTC).Methods Atotalof51patients(meanageof49.3±12.9years)whounderwent18F-FDGPET/CT imaging and biopsy before thyroidectomy were retrospectively analyzed. Based on the pathological results, there were 48 patients with PTC and 3 patients with follicular thyroid carcinoma(FTC). The SUVmax of thyroid nodule was measured by semi-quantitative analysis. The correlation between clinical data( gender,age,tumor size and thyroglobulin concentration) and SUVmax was also analyzed. The difference of SUVmax between the two groups was analyzed by comparing the BRAF V600E mutation group and the non-mutation group. Results In patients with PTC,27 patients had BRAF V600E mutations and 11 patients had no tumor mutation. The SUVmax of BRAF V600E mutation group was significantly higher than that in the non-mutated group(5. 5 ± 3. 9 vs. 2. 2 ± 1. 2,P=0. 002). The SUVmax of patients with tumor diameter≥1 cm was significantly higher than that in patients with tumor <1 cm(P<0. 05). The SUVmax of patients with elevated thyroglobulin concentration was higher than that in normal patients(P<0. 05). No BRAF V600E mutation was observed in the FTC group. Conclusion The BRAF V600E mutant gene has a high SUVmax value in patients with PTC. There were significant difference in SUVmax among different tumor size and serum thyroglobulin concentration.
ABSTRACT
Objective To evaluate the value of ultrasound-measured changes in diaphragmatic excursion (DE) in predicting successful weaning from mechanical ventilation during the spontaneous breathing trial (SBT).Methods Sixty-three patients of both sexes,who were mechanically ventilated for more than 24 h and screened for ascertained readiness to wean,aged 45-64 yr,were enrolled in the study.Bilateral DE was measured using ultrasound at 0,10 and 30 min of SBT.The patients who successfully completed 30 min of SBT were extubated.The patients were divided into either success group or failure group according to whether or not weaning was successful.Receiver operating characteristic (ROC) curves were used to evaluate the value of bilateral △DE30-10 in predicting successful weaning.Results There were 48 cases in success group and 15 cases in failure group.Bilateral △DE30-10 was significantly higher in failure group than in success group (P<0.05).The area under the ROC curves of the right △DE30-10 in predicting successful weaning was 0.958,<0.175 cm was used to predict successful weaning,and the sensitivity and specificity were 93.3% and 87.5%,respectively.The area under the ROC curves of the left △DE30-10 in predicting successful weaning was 0.903,<0.275 cm was used to predict successful weaning,and the sensitivity and specificity were 80.0% and 89.6%,respectively.Conclusion The fight △DE30-10 measured using ultrasound can serve as an assistant index in predicting successful weaning from mechanical ventilation during SBT.