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UFMylation is a ubiquitination-like modification that is related to endoplasmic reticulum stress and unfolded protein response. A recent study reported that Ufl1, a key enzyme of UFMylation, protects against heart failure, indicating that UFMylation may be associated with heart function regulation. In the present study, we initially constructed a Flag-6×His-tagged Ufm1ΔSC transgenic (Tg-Ufm1) mouse model that enables UFMylation studies in vivo. Tg-Ufm1 mice showed significant activation of UFMylation in hearts. By using this model, we identified 38 potential Ufm1-binding proteins in heart tissues through LCâMS/MS methods. We found that these proteins were associated with mitochondria, metabolism and chaperone binding. By using transcriptomic screening, we identified Tnfaip2 as a novel UFMylation-associated gene. Overexpression of Ufm1 significantly upregulated the protein expression of Tnfaip2, whereas isoproterenol treatment decreased Tnfaip2 expression in Tg-Ufm1 mice. These data may provide novel clues for UFMylation in cardiac hypertrophy.
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Proteins , Tandem Mass Spectrometry , Animals , Mice , Carrier Proteins/genetics , Chromatography, Liquid , Mice, Transgenic , Proteins/geneticsABSTRACT
Objective: The association between serum uric acid (UA) and spontaneous hemorrhagic transformation (HT) has been seldom studied, and the role of UA in spontaneous HT remains unclear. This study aims to investigate the sex-dependent association between UA and spontaneous HT in patients with ischemic stroke. Method: We retrospectively included patients with ischemic stroke in a tertiary academic hospital between December 2016 and May 2020. Patients were included if they presented within 24 h after the onset of symptoms and did not receive reperfusion therapy. Spontaneous HT was determined by an independent evaluation of neuroimaging by three trained neurologists who were blinded to clinical data. A univariate analysis was performed to identify factors related to spontaneous HT. Four logistic regression models were established to adjust each factor and assess the association between UA and spontaneous HT. Results: A total of 769 patients were enrolled (64.6% were male patients and 3.9% had HT). After adjusting the confounders with a P < 0.05 (model A) in the univariate analysis, the ratio of UA and its interquartile range (RUI) was independently associated with spontaneous HT in male patients (OR: 1.85; 95% CI: 1.07-3.19; P = 0.028), but not in female patients (OR: 1.39; 95% CI: 0.28-6.82; P = 0.685). In models B-D, the results remain consistent with model A after the adjustment for other potential confounders. Conclusions: Higher serum UA was independently associated with a higher occurrence of spontaneous HT in male patients who were admitted within 24 h after the stroke onset without receiving reperfusion therapy.
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ObjectiveTo characterize the chemical constituents of Dayuanyin based on ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS). MethodThe detection was performed on a Thermo Acclaim™ RSLC 120 C18 column(2.1 mm×100 mm, 2.2 μm), the mobile phase was acetonitrile(A)-0.1% formic acid aqueous solution(B) for gradient elution (0-7.5 min, 10%-19%A; 7.5-12 min, 19%-22.5%A; 12-23 min, 22.5%-27%A; 23-27 min, 27%-56%A; 27-35 min, 56%-84%A; 35-36 min, 84%-90%A), the flow rate was 0.3 mL·min-1, and the column temperature was 30 ℃. The data were collected in the positive and negative ion modes by heated electrospray ionization(HESI), and the detection range was m/z 80-1 200. Combining the retention time of the reference substance, fragment ions, databases such as PubChem and related literature, Xcalibur 3.0 was used to identify the chemical constituents of Dayuanyin. ResultA total of 161 compounds were identified, including 14 alkaloids, 60 flavonoids, 16 terpenoids, 26 saponins, 18 phenylpropanoids, 16 organic acids and 11 others. ConclusionThe established method can effectively and quickly identify the chemical components in Dayuanyin, and clarify its chemical composition, which can provide a basis for the development of compound preparations of this famous classical formula.
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Objective@#To verify effects of rs1061622 at tumor necrosis factor-α receptor II (TNF-RII) gene (TNF-RII) on post-traumatic stress disorder (PTSD) and its interactive effects with PTSD on serum lipids levels in adolescents. @*Methods@#PTSD was measured by PTSD Checklist-Civilian Version (PCL-C) in 699 adolescent survivors at 6 months after Wenchuan earthquake in China. A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for TNF-RII rs1061622 genotyping followed by verification using DNA sequencing. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were tested using routine methods. @*Results@#G (deoxyguanine) allele carriers had higher PCL-C scores than TT (deoxythymidine) homozygotes in female subjects. Female adolescents had higher PCL-C scores than male subjects in TT homozygotes. Predictors of PTSD prevalence and severity were different between G allele carriers and TT homozygotes. Subjects with PTSD had lower TG, TG/HDL-C, TC/HDL-C, and higher HDL-C than adolescents without PTSD in male G allele carriers. G allele carriers had higher TG/HDL-C and TC/HDL-C than TT homozygotes in male adolescents without PTSD, and lower TG and TG/HDL-C in male PTSD patients. G allele carriers had higher TG than TT homozygotes only in female adolescents without PTSD. @*Conclusion@#These results suggest reciprocal actions of TNF-RII rs1061622 with other factors on PTSD severity, interplays of TNF-RII rs1061622 with PTSD on serum lipid levels, and novel treatment strategies for PTSD and comorbidities of PTSD with hyperlipidemia among adolescents with different genetic backgrounds of TNF-RII rs1061622 after experiencing traumatic events.
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Objective:To assess the safety and feasibility of hepatic pedicle-first approach laparoscopic anatomical hepatectomy for central segments.Methods:The clinical data of 19 patients with hepatocellular carcinoma who underwent hepatic pedicle-first approach laparoscopic anatomical hepatectomy for the central segments in the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from September 2020 to January 2023 were retrospectively analyzed. In this procedure, hepatic pedicles of the central segments were divided first to delineate the ischemic demarcation and guide the liver parenchymal transection. The methods of operation, operation time, intraoperative blood loss, postoperative complications and hospital-stay were analyzed.Results:Hepatic pedicle-first approach laparoscopic anatomical hepatectomy for the central segments was successfully performed in all patients, including 5 cases of segment Ⅳ, 2 cases of segment Ⅳ+ Ⅷ, 3 cases of segment Ⅳ+ ventral segment Ⅷ, 3 cases of segment Ⅳa+ Ⅴ+ Ⅷ and 6 cases of segment Ⅴ+ Ⅷ. The mean operation time, intraoperative blood loss and postoperative hospital stay was (253.1±86.1) min, [ M( Q1, Q3)] 100.0(100.0, 250.0) ml, and (5.1±1.2) d respectively. There was no intraoperative blood transfusion and postoperative complications. Conclusion:Hepatic pedicle-first approach can help delineate the segemental demarcation in laparoscopic anatomical hepatectomy for the central segments, which is technically feasible and worth more practice.
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AIM: To investigate the effect of peripheral defocus spectacles and orthokeratology lenses on the control of axial length in children and adolescents with myopia.METHODS: Prospective study. A total of 71 cases(134 eyes)of children and adolescents with myopia who visited the Second Hospital of Longyan from June 2019 to June 2021 were selected. They were fitted with peripheral defocus spectacles for 12mo and then switched to orthokeratology lenses. The growth of axial length was observed at 3, 6, and 12mo after wearing peripheral defocus spectacles and orthokeratology lenses.RESULTS: The median axial length growth after wearing peripheral defocus spectacles and orthokeratology lenses for 12mo was 0.35 and 0.14mm, respectively. The axial growth at 3, 6, and 12mo after wearing orthokeratology lenses was lower than those after wearing peripheral defocus spectacles(P&#x003C;0.001), and the growth rate of axial length was significantly reduced. The patients were divided into a rapid progression group(axial growth ≥0.4 mm, 29 cases, 54 eyes)and a non-rapid progression group(axial growth &#x003C;0.4mm, 42 cases, 80 eyes)according to the axial growth of peripheral defocus spectacles for 12mo. The median axial growth after wearing peripheral defocus spectacles for 12mo in the two groups was 0.70 and 0.24mm, respectively, while the median axial growth after wearing orthokeratology lenses was 0.31 and 0.09mm, respectively. The growth rate was reduced by 56% and 63% respectively in the two groups after wearing orthokeratology lens. The axial growth of cases wearing orthokeratology lenses for 12mo in the non-rapid progression group was lower than that in the rapid progression group, and it did not change with age or diopter. There was no significant difference among different ages and different diopters in the rapid progression group(P&#x003E;0.05). In the non-rapid progression group, axial growth of cases aged 7-12 years was higher than those aged 13-16 years(P&#x003C;0.05), but there was no significant difference among different diopters(P&#x003E;0.05).CONCLUSION: Orthokeratology lens is more effective than peripheral defocus spectacles in controlling axial growth in children and adolescents with myopia, and the control effect of orthokeratology lens on rapid-progressing myopia is remarkable.
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Immune checkpoint inhibitors (ICIs) change the prognosis of many cancer patients. With the increasing use of ICIs, immune-related adverse events are occurring, including acute kidney injury (AKI). This study aimed to assess the incidence of AKI during ICI treatment and its risk factors and impact on mortality. Patients treated with ICIs at the First Medical Center of the Chinese PLA General Hospital from January 1, 2014, to December 30, 2019, were consecutively enrolled, and risk factors affecting AKI development in patients treated with ICIs were analyzed using univariate and multivariate logistic regression. Medical record surveys and telephone inquiry were used for follow-up, and Kaplan-Meier survival analysis and Cox regression were used to analyze independent risk factors for death. Among 1615 patients, 114 (7.1%) had AKI. Multivariate logistic regression analysis showed that anemia, Alb < 30 g/L, antibiotic use, diuretic use, NSAID use and proton pump inhibitor use were independent risk factors for AKI development in patients treated with ICIs. Stage 2 or 3 AKI was an independent risk factor for nonrecovery of renal function after AKI onset. Multivariate Cox regression analysis showed that anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs, while high baseline BMI, other tumor types, ACEI/ARB use, and chemotherapy use were protective factors for patient death. AKI occurs in 7.1% of patients treated with ICIs. Anemia, Alb < 30 g/L, and combined medication use are independent risk factors for AKI in patients treated with ICIs. Anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs.
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Acute Kidney Injury , Immune Checkpoint Inhibitors , Humans , Retrospective Studies , Immune Checkpoint Inhibitors/adverse effects , Incidence , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Risk Factors , Prognosis , Diuretics/adverse effectsABSTRACT
Objective:To evaluate the effect of different reconstruction images on cardiac dose evaluation by comparing the differences between 4D-CT series and special reconstruction images in evaluating the dose-volume index of cardiac structures.Methods:ECG 4D-CT series were scanned in 15 female patients with left breast cancer. The images of 0-95% 20 phases were reconstructed at an interval of 5% cardiac cycle. The maximum intensity projection (MIP), minimum intensity projection (MinIP), average intensity projection (AIP) and sum intensity projection (SIP) images were obtained by special reconstruction of 4D-CT series. Left ventricle (LV) and left anterior descending coronary artery (LADCA) were delineated on 4D-CT and special reconstruction series, respectively. The intensity-modulated radiation therapy plan of the left breast cancer was designed on the basis of 0% phase, and the cumulative dose (Dose-cumulate) of 20 phases was obtained by deformation registration. The doses of 0% phase were deformed and registered to MIP, MinIP, AIP and SIP images to obtain the corresponding dose distribution. The dose-volume indexes of LV and LADCA based on different CT images were compared.Results:In the evaluation of dose-volume index of LV, compared with 4D-CT series, the change rates of V 5Gy, V 30Gy, V 40Gy, D max and D mean on MIP images were 3.8%, 2.0%, 0.9%, 3.8% and 1.7%, respectively. There was significant difference in V 5 and D max between MIP and 4D-CT (both P<0.05). Compared with 4D-CT, the change rates of D max on MinIP, SIP and AIP images were 2.5%, 3.1% and 1.5%, respectively (all P<0.05). In the evaluation of dose-volume index of LADCA, only the change rate of D max on four special reconstructed images was<5%( P<0.05). Conclusions:In the dose-volume evaluation of LV, the V 30Gy, V 40Gy and D mean obtained by MIP are basically equivalent to those obtained by 4D-CT series, which can be used to substitute 4D-CT series to evaluate the dose-volume. The special reconstruction image of LADCA can not replace 4D-CT series.
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OBJECTIVE@#To investigate the efficacy and safety of ultrasound-guided selective nerve branch blockage in the treatment of lumbar spinal nerve posterior branch syndrome.@*METHODS@#A total of 40 patients with lumbar spinal nerve posterior branch syndrome treated by Pain Clinic from May 2017 to December 2018 were selected. According to the method used in locating site for nerve blockage, the patients were divided into ultrasound-guided group and anatomical positioning group, with 20 cases in each group. In anatomical positioning group, there were 7 males and 13 females, aged (63.42±7.71) years old, weighted (63.65±10.72) kg, numerical rating scale (NRS) was (6.61±1.52) scores, course of disease was (16.55±4.68) months. Pain sites:4 cases at L@*RESULTS@#There were no statistically significant differences in gender, age, weight, NRS, course of disease and pain segment distribution between two groups (@*CONCLUSION@#Comparedwith anatomicalpositioning, ultrasound-guided selective nerve branch block for the treatment of posterior branch of the lumbar spinal cord syndrome can reduce the number of treatments and maintain a longer therapeutic effect, but it is also necessary to pay attention to the time of each treatment to avoid dizziness and other adverse reactions.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Lumbosacral Region , Nerve Block , Spinal Nerves/diagnostic imaging , Ultrasonography , Ultrasonography, InterventionalABSTRACT
Objective:To study the use of perfluorobutane contrast-enhanced ultrasound (CEUS) in preoperative detection of microvascular invasion (MVI), and postoperative short-term recurrence of hepatocellular carcinoma (HCC).Methods:Patients who underwent hepatectomy with curative intent at the Chinese PLA General Hospital from January 2021 to April 2021 were prospectively enrolled into this study. Of 42 patients in this study, there were 36 males and 6 females, with age of (56.51±11.95) years old. All patients underwent preoperative perfluorobutane CEUS, and the characteristics of ultrasound, the vascular phase and Kupffer phase of perfluorobutane CEUS were recorded. Based on the pathological results, these patients were divided into the MVI and non-MVI groups. These patients underwent liver MRI once every 3 months postoperatively to diagnose tumor recurrence. According to the recurrence of HCC 6 months after operation, these patients were divided into the non-recurrence and the recurrence groups. Independent risk factors for MVI and short-term recurrence were analyzed by univariate and multivariate analyses.Results:Two patients had two lesions, and the remaining 40 patients had a single lesion. The pathological diagnosis of all the lesions were HCC (14 patients in the MVI group and 28 patients in the non-MVI group). The median follow-up was 6 (3, 6) months, and there were 8 patients in the recurrence group and 34 patients in the non-recurrence group. On logistic analysis, independent risk factors for MVI included the number of vessels detected on color Doppler flow imaging (CDFI) ( OR=5.762, 95% CI: 1.597-20.785, P=0.007), increased tumor size by more than 10% after CEUS arterial enhancement ( OR=10.186, 95% CI: 3.647-28.447, P=0.037), and thickness of corona enhancement at Kupffer phase of greater than 5 mm ( OR=17.340, 95% CI: 6.124-49.095, P=0.040). Cox regression showed the independent risk factors for short-term recurrence to include the number of vessels in CDFI ( RR=7.519, 95% CI: 1.086-52.051, P=0.041) and thickness of corona enhancement at Kupffer phase of greater than 5 mm ( RR=10.623, 95% CI: 1.265-89.218, P=0.030). Conclusion:Preoperative perfluorobutane CEUS had potential values in detecting MVI and in predicting postoperative short-term recurrence of HCC.
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Objective:To provide a feasible method for the evaluation of cardiac function based on cardiac gated 4DCT, the radiomics technology combined with enhanced ECG gated 4DCT images were used to quantitatively analyze the changes of left ventricular CT radiomics characteristics in cardiac cycle.Methods:The enhanced ECG 4DCT images of 14 patients were reconstructed at intervals of 5% of cardiac cycle. The left ventricular muscle (LVM) and the contrast agent well filled area of left ventricular were delineated with a 13 mm diameter sphere (Cardiac Region of Interest, cardiac ROI) in a single phase. 3Dslicer software was used to extract 92 features of all the sketches, analyze the distribution of CT values on the cardiac ROI and LVM, and preliminarily screen the stable features based on the cardiac ROI (one-way ANOVA). The stable features were used to further screen LVM (one-way ANOVA) to get the difference features. Wilcoxon rank sum test was used to analyze the change of characteristics with heartbeat in the heartbeat cycle.Results:In the heartbeat cycle the mean CT values of cardiac cavity ROI in cardiac cavity changed less than that in LVM, with the change rates of 9.23% and 17.88%, respectively. There were 36 stable features with no significant difference in cardiac cavity ROI ( P>0.05). 20 of them were statistically significant ( F=1.641-6.206, P<0.05), and the average change rate was 98.63%, such as median (-103.96%) and mean (123.67%) of the first order matrix, gray level non uniformity (99.81%) of GLDM matrix and other changes reached more than 99%. The differences between the maximum and minimum values in different cardiac cycles were statistically significant ( Z=-3.921--3.173, P<0.05). Conclusions:With the combination of radiomics and enhanced ECG 4DCT image, the microscopic changes of CT image features in the cardiac cycle can be amplifed. A new method for the assessment of left ventricular function changes was provided. The features such as median, mean may have more application potential.
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Objective:To evaluate the cumulative dose of the target volume and organs at risk (OARs) in intensity-modulated radiation therapy (IMRT) for large volume non-small cell lung cancer (NSCLC) based on rigid and deformation registration methods. The dosimetric changes between the initial and second treatment plans were compared.Methods:Thirty patients treated with IMRT for large volume NSCLC with twice 4DCT scans acquired before radiotherapy and after 20 fractions of radiotherapy were recruited. The initial treatment plan (Plan 1) based on the average density projection CT (CT 1-avg) of the first 4DCT images and the second treatment plan (Plan 2) based on the average density projection CT (CT 2-avg) of the second 4DCT images were calculated. Then, the dose distributions of Plan 1 and Plan 2 were accumulated based on rigid and deformation registration methods to obtain Planrig and Plandef, respectively. Finally, the volume changes of gross tumor volume (GTV) and OARs between two CT scans were compared. The dose-volume parameters between Plan 1 and other plans (including Plan 2, Planrig and Plandef) were also statistically compared. Results:Compared with the initial CT scan, the mean volume of GTV and heart on the second CT was decreased by 44.2% and 5.5%, respectively, while the mean volume of ipsilateral lung, contralateral lung and total lung was increased by 5.2%, 6.2% and 5.8%, respectively (all P<0.05). Compared with Plan 1, the D 95%, D 98% and V 100% of target volume IGTV (GTV fusion of 10 4DCT phases) and PTV in Plan 2 did not significantly change (all P>0.05), and those in Planrig and Plandef were decreased (all P<0.05). The dose-volume parameters of spinal-cord, heart, ipsilateral lung and total lung in Plan 2, Planrig and Plandef were significantly lower than those in Plan 1(all P<0.05). Among them, the V 30Gy and D mean of heart were decreased by 27.3%, 16.5%, 15.3% and 15.2%, 6.6%, 5.6%, respectively. The V 20Gy and D mean of total lung were decreased by 15.6%, 4.5%, 3.7% and 15.7%, 6.2%, 5.1%, respectively. Some dose-volume parameters (including D 95% and D 98% of target volume, V 40Gy of heart, V 20Gy and D mean of the ipsilateral lung and the total lung) of Plandef were higher than those in Planrig (all P<0.05). The Dice similarity coefficients (DSCs) of OARs after deformation registration were significantly higher than those after rigid registration ( P<0.05). Conclusions:The dose-volume parameters of OARs significantly differ between Plan 1 and Plan 2. Hence, all these parameters have a large degree of deviation in predicting radiation-induced injury of OARs. Nevertheless, the dose-volume parameters obtained by deformation registration can enhance the prediction accuracy.
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Objective:To analyze CYP2C9 and VKORC1 gene polymorphisms in Chinese Han population and their correlation with the maintenance dosage of warfarin.Methods:From October 2017 to April 2018, 458 Chinese Han patients (213 males and 245 females, aged from 26 to 94 years old) who underwent coagulation analysis in Peking University People′s Hospital were included in this retrospective study. PCR-Fluorescent probe method was applied to detect CYP2C9*3 and VKORC1-1639A>G gene polymorphisms in 458 patients, and among them, 130 patients who took warfarin for anticoagulant therapy and reached the international standard ratio of prothrombin time (INR) within the range of 2.0-3.0 were recorded. The basic information, dosage of warfarin and INR were also recorded. The statistical analysis data were compared with the reference table of recommended dosage of warfarin for different genotypes of patients recommended by FDA and the formula of predicted dosage of warfarin was simply verified by SPSS.Results:Among the 458 patients who took anticoagulant therapy, the genotype frequencies of CYP2C9*1/*1(AA), CYP2C9*1/*3(AC) and CYP2C9*3/*3(CC) were 90.8%, 8.5%, and 0.7%; the genotype frequencies of VKORC1-1639GG and VKORC1-1639AG were 0.9% and 14.2%; the genotype frequencies of VKORC1-1639AA was 84.9%. After INR was reached, the results showed that the variant CYP2C9*1/*3 and CYP2C9*3/*3 required lower daily maintain dosage [(2.92±1.29) mg] than wild-type CYP2C9*1/*1 patients did [(3.91±1.63) mg], with statistically significant difference ( P=0.018). And variant VKORC1-AA required lower daily maintain dosage [(3.68±1.64) mg] than variant VKORC1-AG patients did [(4.54±1.29) mg], with statistically significant difference ( P=0.001). The application dosage of warfarin in patients with different VKORC1+CYP2C9 genotypes was consistent with the recommended dosage of the FDA reference table. The prediction accuracy of miao 2007 formula was lower than that of IWPC formula, and 94.1% of patients′ dosages of warfarin were underestimated. Conclusion:Patients with CYP2C9*3 or VKORC1-AA genotype required lower warfarin dosage. The CYP2C9 and VKORC1 gene polymorphisms had a certain correlation with maintenance dosage of warfarin.
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Objective@#To analyze CYP2C9 and VKORC1 gene polymorphisms in Chinese Han population and their correlation with the maintenance dosage of warfarin.@*Methods@#From October 2017 to April 2018, 458 Chinese Han patients (213 males and 245 females, aged from 26 to 94 years old) who underwent coagulation analysis in Peking University People′s Hospital were included in this retrospective study. PCR-Fluorescent probe method was applied to detect CYP2C9*3 and VKORC1-1639A>G gene polymorphisms in 458 patients, and among them, 130 patients who took warfarin for anticoagulant therapy and reached the international standard ratio of prothrombin time (INR) within the range of 2.0-3.0 were recorded. The basic information, dosage of warfarin and INR were also recorded. The statistical analysis data were compared with the reference table of recommended dosage of warfarin for different genotypes of patients recommended by FDA and the formula of predicted dosage of warfarin was simply verified by SPSS.@*Results@#Among the 458 patients who took anticoagulant therapy, the genotype frequencies of CYP2C9*1/*1(AA), CYP2C9*1/*3(AC) and CYP2C9*3/*3(CC) were 90.8%, 8.5%, and 0.7%; the genotype frequencies of VKORC1-1639GG and VKORC1-1639AG were 0.9% and 14.2%; the genotype frequencies of VKORC1-1639AA was 84.9%. After INR was reached, the results showed that the variant CYP2C9*1/*3 and CYP2C9*3/*3 required lower daily maintain dosage [(2.92±1.29) mg] than wild-type CYP2C9*1/*1 patients did [(3.91±1.63) mg], with statistically significant difference (P=0.018). And variant VKORC1-AA required lower daily maintain dosage [(3.68±1.64) mg] than variant VKORC1-AG patients did [(4.54±1.29) mg], with statistically significant difference (P=0.001). The application dosage of warfarin in patients with different VKORC1+CYP2C9 genotypes was consistent with the recommended dosage of the FDA reference table. The prediction accuracy of miao 2007 formula was lower than that of IWPC formula, and 94.1% of patients′ dosages of warfarin were underestimated.@*Conclusion@#Patients with CYP2C9*3 or VKORC1-AA genotype required lower warfarin dosage. The CYP2C9 and VKORC1 gene polymorphisms had a certain correlation with maintenance dosage of warfarin.
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The aim of this study was to investigate the role of S100 calcium binding protein A16 (S100A16) in lipid metabolism in hepatocytes and its possible biological mechanism. HepG2 cells (human hepatoma cell line) were cultured with fatty acid to establish fatty acid culture model. The control model was cultured without fatty acid. Each model was divided into three groups and transfected with S100a16 over-expression, shRNA and vector plasmids, respectively. The concentration of triglyceride (TG) in the cells was measured by kit, and the lipid droplets was observed by oil red O staining. Immunoprecipitation and mass spectrometry were used to find the interesting proteins interacting with S100A16, and the interaction was verified by immunoprecipitation. The further mechanism was studied by Western blot and qRT-PCR. The results showed that the intracellular lipid droplet and TG concentrations in the fatty acid culture model were significantly higher than those in the control model. The accumulation of intracellular fat in the S100a16 over-expression group was significantly higher than that in the vector plasmid transfection group. There was an interaction between heat shock protein A5 (HSPA5) and S100A16. Over-expression of S100A16 up-regulated protein expression levels of HSPA5, inositol-requiring enzyme 1α (IRE1α) and pIREα1, which belong to endoplasmic reticulum stress HSPA5/IRE1α-XBP1 pathway. Meanwhile, over-expression of S100A16 up-regulated the mRNA expression levels of adipose synthesis-related gene Srebp1c, Acc and Fas. In the S100a16 shRNA plasmid transfection group, the above-mentioned protein and mRNA levels were lower than those of vector plasmid transfection group. These results suggest that S100A16 may promote lipid synthesis in HepG2 cells through endoplasmic reticulum stress HSPA5/IRE1α-XBP1 pathway.
Subject(s)
Humans , Endoplasmic Reticulum Stress , Endoribonucleases , Physiology , Heat-Shock Proteins , Physiology , Hep G2 Cells , Lipid Metabolism , Protein Serine-Threonine Kinases , Physiology , S100 Proteins , Physiology , Triglycerides , X-Box Binding Protein 1 , PhysiologyABSTRACT
Objective To investigate the changes of accumulated dose in target area and organs at risk (OARs) for radiotherapy of left breast cancer by deformable and rigid image registration.Methods A total of 16 left breast cancer patients treated with 6 MV X-ray IMRT were analyzed retrospectively.All targets included the lymph node drainage area and the chest wall.All patients underwent simulation of the primary positioning and repositioning to obtain CT images.Primary and secondary treatment plans were developed using primary positioning CT (CT1) and repositioning CT (CT2),denoted as Plan1 and Plan2 respectively.The dose distribution of Plan2 was mapped to CT1 with rigid and deformable registration from CT2 to CT1 and then added to the dose distribution of Planl to obtain Plan-rigid and Plan-deform,respectively.The dosimetric differences between targets and the OARs of the four plans were compared.Results The CTV volume on CT2 was reduced by 6.64% from that on CT1.The homogeneity index (HI)increased by 23.05% after deformation-based accumulation.The Dice similarity coefficients (DSCs) of the heart,left lung and right lung were lower than those before deformable registration (0.94±0.01 vs.0.89± 0.05,0.96±0.01 vs.0.91±0.03,and 0.96±0.01 vs.0.92±0.03,respectively),and the differences were statistically significant (Z =-3.208,-3.533,-3.535,P < 0.05).There were no significant differences in dose-volume indices of heart and left lung between Plan1 with other plans (P>0.05),while the dose-volume indices in Plan-rigid were higher than that in Plan-deform.Conclusions Rigid registration is recommended in patients undergoing radical resection of left breast cancer with little change in the volume and dose-volume index of the target area and organs at risk.The dose-volume index of the initial intensity modulation plan can basically reflect the dose-volume statistics of both lungs and heart.
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Objective@#To investigate the changes of accumulated dose in target area and organs at risk (OARs) for radiotherapy of left breast cancer by deformable and rigid image registration.@*Methods@#A total of 16 left breast cancer patients treated with 6 MV X-ray IMRT were analyzed retrospectively. All targets included the lymph node drainage area and the chest wall. All patients underwent simulation of the primary positioning and repositioning to obtain CT images. Primary and secondary treatment plans were developed using primary positioning CT (CT1) and repositioning CT (CT2), denoted as Plan1 and Plan2 respectively. The dose distribution of Plan2 was mapped to CT1 with rigid and deformable registration from CT2 to CT1 and then added to the dose distribution of Plan1 to obtain Plan-rigid and Plan-deform, respectively. The dosimetric differences between targets and the OARs of the four plans were compared.@*Results@#The CTV volume on CT2 was reduced by 6.64% from that on CT1. The homogeneity index (HI) increased by 23.05% after deformation-based accumulation. The Dice similarity coefficients (DSCs) of the heart, left lung and right lung were lower than those before deformable registration (0.94±0.01 vs. 0.89±0.05, 0.96±0.01 vs. 0.91±0.03, and 0.96±0.01 vs. 0.92±0.03, respectively), and the differences were statistically significant (Z=-3.208, -3.533, -3.535, P<0.05). There were no significant differences in dose-volume indices of heart and left lung between Plan1 with other plans(P>0.05), while the dose-volume indices in Plan-rigid were higher than that in Plan-deform.@*Conclusions@#Rigid registration is recommended in patients undergoing radical resection of left breast cancer with little change in the volume and dose-volume index of the target area and organs at risk. The dose-volume index of the initial intensity modulation plan can basically reflect the dose-volume statistics of both lungs and heart.
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Objective To investigate the difference of hepatic microvessel density, neovasculariza-tion of regenerating liver tissue after ablation of two ways of irreversible electroporation and radiofrequency ablation in rats. Methods 90 male Sprague-Dawley rats were randomly divided into 3 groups, including the control group ( n =30), the irreversible electroporation group ( n =30 ) and the radiofrequency ablation group (n=30). 3,7 and 10 days were executed after the operation and draw material, expression of vascu-lar endothelial growth factor(VEGF) and CD34 in tissue was studied by immunohistochemistry, and the mi-crovascular density of tissue and VEGF positive cells were measured. Results The microvascular density of 3, 7 and 10 days in the control group was 50. 3 ± 12. 5, 54. 6 ± 11. 9 and 58. 2 ± 14. 7, the microvascular density of the radiofrequency ablation group was 18. 4 ± 4. 7, 17. 3 ± 5. 1 and 18. 1 ± 5. 9, respectively. The microvascular density of the irreversible electroporation group was 42. 8 ± 10. 4, 45. 6 ± 10. 2 and 49. 2 ± 13. 8, respectively. The positive cells of VEGF in control group was 50, 56 and 57 at 3, 7 and 10 days, and 32, 30 and 33 at 3, 7 and 10 days in radiofrequency ablation group, 44, 43 and 45 at 3, 7 and 10 days in irreversible electroporation group; expression of VEGF and CD34 in 3, 7, 10 d and the microvascular density of ablation area in radiofrequency ablation group was significantly lower than those in control group after irreversible electroporation and radiofrequency ablation. No significant differences were found between irreversible electroporation group and control group. Conclusion The irreversible electroporation can effectively protect the microvessels in the ablation area, ensure the tissue’s blood supply after the ablation, and provide a guarantee for the repair and regeneration of the tissue.
ABSTRACT
Disseminated intravascular coagulation(DIC)is one of the major etiologies behind the pathological change of amniotic fluid embolism(AFE).The depletion of coagulation factor and the damage of red blood cell were common manifestations of DIC,which can also promote the formation of pulmonary hypertension.Meanwhile,DIC is also the main reason of hemorrhage of AFE.The detection of DIC at an early stage facilitates the clinical diagnosis of AFE.Preventing procoagulants from getting into the maternal circulation and anticoagulant therapy may be profitable to prevent the deterioration of DIC.Heparin should be both employed at the stage of hypercoagulation and the early stage hypocoagulation.Simultaneously,the supplement of coagulation factor is also crucial.The change of coagulation function must be closely monitored.
ABSTRACT
BACKGROUND: Whether there is a relationship between glomerular filtration rate (GFR) and hemorrhagic transformation (HT) after acute ischemic stroke (AIS) is still under debate. The aim of our study was to determine whether the GFR level is a predictor of HT in AIS patients without thrombolytic therapy (TT). METHODS: Consecutive AIS patients without TT were included in this prospective study from January 2014 to December 2016 in the First Affiliated Hospital of Chongqing Medical University. We divided them into two groups (HT and non-HT group) and meticulously collected baseline characteristics and laboratory and imaging data of interested individuals. Multivariate regression analysis was performed to assess the correlation between GFR and HT in stroke patients without TT. RESULTS: Among 426 consecutive patients, 74 (17.3%) presented HT (mean age: 65 ± 12 years, number of male patients: 47) on the follow-up scans. In multivariate regression analysis, HT was significantly associated with low GFR (odds ratio [OR] = 3.708, confidence interval [CI] = 1.326-10.693, P = 0.013), atrial fibrillation (AF; OR = 2.444, CI = 1.087-5.356, P = 0.027), large cerebral infarction (OR = 2.583, CI = 1.236-5.262, P = 0.010), and hypoalbuminemia (HA; OR = 4.814, CI = 1.054-22.153, P = 0.037) for AIS patients without TT. CONCLUSIONS: The present study strongly showed that lower GFR is an independently predictor of HT; in addition, large infarct volume, AF, and HA are also important risks of HT for AIS patients without TT, which offered a practical information that risk factors should be paid attention or eliminated to prevent HT for stroke patients though the level of evidence seems to be unstable.