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Homozygous familial hypercholesterolemia (HoFH) is a rare and serious autosomal genetic metabolic disease. Patients without intervention often die younger than 30 years old from early atherosclerotic cardiovascular disease (ASCVD)incurred by extremely high levels of low-density lipoprotein cholesterol (LDL-C). We present a case of HoFH, a child with compound heterozygous mutation in this study. The effect of conventional lipid-lowering therapy through diet control and lipid-lowering drugs was unsatisfactory. The blood-lipid purification proves effective but has poor compliance and difficult to maintain for a longer time. The patient received orthotopic liver transplantation and had been followed for 2 years, with the patient shows normal LDL-C, well growth and development. We hope the case will provide the clinician with better understanding of the diagnosis and treatment of the rare disease of HoFH.
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ObjectiveTo evaluate the effect of standardized blood pressure measurement in consulting room （SBPM） model on blood pressure screening of non-hypertensive patients in community. MethodsFour communities were randomly selected from Fengxian District of Shanghai， and non-hypertensive patients in the communities were included for screening. Based on the communities， participants were further classified into the intervention group and control group. A one-year intervention study was conducted from January 1， 2021 to December 31， 2021. The intervention group received the intervention measures of standardized measurement， and the control group remained the routine measurement. The distribution of blood pressure values and last digit of the values between the intervention group and control group were tested using Chi-square test and normality test. Then changes in abnormal blood pressure rate before and after the intervention were determined by double difference method. Statistical analysis was performed using SPSS 20.0. ResultsA total of 15 368 participants were included in the intervention group， and 19 811 participants in the control group. After the intervention， range of the last digit of blood pressure values in the intervention group was 9.55%‒10.41%， of which that of systolic and diastolic blood pressure were equally distributed （P=0.932 and 0.871， respectively）. The range of the last digit in the control group was 1.31%‒42.58%， of which that of systolic and diastolic blood pressure showed unequal distribution （P<0.001）. Through one-year standardized measurement intervention， the abnormal rate of blood pressure in the intervention group was 26.29%， which was 7.61 times as high as that in the control group （OR=7.55， 95%CI： 6.75‒8.57， P<0.001）. ConclusionStandardized blood pressure measurement in consulting room is suitable for the screening of blood pressure measurement in community， which has higher data quality than that of routine measurement.
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In China, patients with hepatocellular carcinoma (HCC) are usually with late stage and long medical history when diagnosed, resulting in a lower 5-year survival rate. For advanced HCC, guidelines from different countries have different indications for local treatment. The applica-tion of hepatic artery chemoembolization has brought new treatment opportunities to patients with advanced HCC. Due to tumor heterogeneity, the response to immunotherapy is different in patients with intrahepatic recurrent lesions and extrahepatic metastatic lesions of primary hepatic carcinoma. Therefore, hepatic artery chemoembolization combined with systemic treatment is beneficial to prolong the survival of patients. The authors introduce the clinical experience of a patient with recurrent advanced HCC combined with abdominal lymph node metastasis who was treated with hepatic artery chemoembolization combined with atezolizumab plus bevacizumab. The results show that tumor is controlled in a short period with a good clinical effect.
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Objective:To investigate the efficacy and safety of comprehensive therapy in the treatment of advanced unresectable hepatocellular carcinoma.Methods:Clinical data of 34 patients with primary liver cancer admitted to Peking Union Medical College Hospital from Nov 2018 to Dec 2020 initially evaluated as unresectable were treated firstly by combined therapy and then underwent reevaluation for further management.Results:A total of 34 patients completed the integrative treatment, and no serious adverse events occurred. Among them, 6 patients were evaluated as partial remission, and underwent successful tumor resection, tumors in 7 patients were stable, and 21 patients suffered from disease progression.Conclusion:After comprehensive therapy, unresectable tumors in some patients could reduce and be rendered resection.
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Objective:To observe the influence of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) 4 inhibitors on epithelial-mesenchymal transition (EMT) of human retinal pigment epithelial (RPE) cells induced by bevacizumab.Methods:The cultured ARPE-19 cells were divided into blank control group, bevacizumab group, bevacizumab+ VAS2870 group and bevacizumab+ GKT137831 group.Cells were cultured with 0.25 g/L bevacizumab, 0.25 g/L bevacizumab plus 3 μmol/L VAS2870 (a NOX4 inhibitor), 0.25 g/L bevaczumab plus 20 μmol/L GKT137831 (a NOX4 inhibitor) for 72 hours according to grouping.No intervention was administered to the blank control group.The mRNA and protein expression levels of NOX4 and EMT markers including fibronectin (FN), vimentin, α-smooth muscle actin (α-SMA) and tight junction related protein zonula occludens-1 (ZO-1) were measured by real-time PCR and Western blot assay, and the expression levels in different intervention groups were compared.The expressions of NOX4 and EMT markers were verified by immunofluorescence staining.Results:There were statistically significant differences in the relative mRNA and protein expression levels of FN, vimentin, α-SMA, ZO-1 and NOX4 among blank control group, bevacizumab group, bevacizumab+ VAS2870 group and bevacizumab+ GKT137831 group (mRNA: F=97.07, 195.40, 722.40, 38.56, 70.81; all at P<0.001.Protein: F=23.09, 64.58, 58.19, 26.97, 63.19; all at P<0.001). The relative mRNA and protein expression levels of FN, vimentin, α-SMA and NOX4 were significantly higher and the relative mRNA and protein expression level of ZO-1 was significantly lower in bevacizumab group than those in blank control group (all at P<0.05). The relative mRNA and protein expression levels of FN, vimentin, α-SMA and NOX4 were significantly lower and the relative mRNA and protein expression levels of ZO-1 were significantly higher in bevacizumab+ VAS2870 and bevacizumab+ GKT137831 groups than those in bevacizumab group (all at P<0.05). The immunofluorescence intensity of FN, vimentin and α-SMA was stronger and the immunofluorescence intensity of ZO-1 was weaker in bevacizumab group than blank control group.The immunofluorescence intensity of FN, vimentin and α-SMA were weaker and the immunofluorescence intensity of ZO-1 was stronger in bevacizumab+ VAS2870 group and bevacizumab+ GKT137831 group than those in bevacizumab group. Conclusions:NOX4 is involved in the bevacizumab-induced EMT of human RPE cells, the degree of which can be reduced by NOX4 inhibitors.
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Objective To investigate the value of optical trocar insertion technique in establishing pneumoperitoneum in patients undergoing laparoscopic surgery after previous abdominal surgery. Methods A total of 29 patients, with a history of abdominal surgery, who planned to undergo laparoscopic liver surgery were enrolled and randomly divided into optical trocar insertion group and open approach group. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the Fisher's exact test was used for comparison of categorical data between groups; the Mann-Whitney U test was used for comparison of ranked data between groups. Results There were no procedure-related complications in either group. Compared with the open approach group, the optical trocar insertion group had a significantly shorter time required to establish pneumoperitoneum [35.00 (21.00-46.00) seconds vs 180.00 (152.50-252.50) seconds, U =0, P < 0.001] and a significantly smaller incision length [1.10(1.00-1.20) cm vs 2.80(2.45-3.00) cm, U =0, P < 0.001]. Conclusion Both optical trocar insertion and open approach for establishing pneumoperitoneum is relatively safe in patients undergoing laparoscopic liver surgery after previous abdominal surgery, while optical trocar insertion has the advantages of high efficiency and minimal invasiveness in establishing pneumoperitoneum.
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Objective To investigate the value of optical trocar insertion technique in establishing pneumoperitoneum in patients undergoing laparoscopic surgery after previous abdominal surgery. Methods A total of 29 patients, with a history of abdominal surgery, who planned to undergo laparoscopic liver surgery were enrolled and randomly divided into optical trocar insertion group and open approach group. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the Fisher's exact test was used for comparison of categorical data between groups; the Mann-Whitney U test was used for comparison of ranked data between groups. Results There were no procedure-related complications in either group. Compared with the open approach group, the optical trocar insertion group had a significantly shorter time required to establish pneumoperitoneum [35.00 (21.00-46.00) seconds vs 180.00 (152.50-252.50) seconds, U =0, P < 0.001] and a significantly smaller incision length [1.10(1.00-1.20) cm vs 2.80(2.45-3.00) cm, U =0, P < 0.001]. Conclusion Both optical trocar insertion and open approach for establishing pneumoperitoneum is relatively safe in patients undergoing laparoscopic liver surgery after previous abdominal surgery, while optical trocar insertion has the advantages of high efficiency and minimal invasiveness in establishing pneumoperitoneum.
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Purpose@#Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. @*Materials and Methods@#Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. @*Results@#MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. @*Conclusion@#MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.
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Purpose@#Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. @*Materials and Methods@#Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. @*Results@#MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. @*Conclusion@#MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.
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Purpose@#The systemic inflammation response index (SIRI) has been reported to have prognostic ability in various solid tumors but has not been studied in gallbladder cancer (GBC). We aimed to determine its prognostic value in GBC. @*Materials and Methods@#From 2003 to 2017, patients with confirmed GBC were recruited. To determine the SIRI’s optimal cutoff value, a time-dependent receiver operating characteristic curve was applied. Univariate and multivariate Cox analyses were performed for the recognition of significant factors. Then the cohort was randomly divided into the training and the validation set. A nomogram was constructed using the SIRI and other selected indicators in the training set, and compared with the TNM staging system. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram’s clinical utility. @*Results@#One hundred twenty-four patients were included. The SIRI’s optimal cutoff value divided patients into high (≥ 0.89) and low SIRI (< 0.89) groups. Kaplan-Meier curves according to SIRI levels were significantly different (p < 0.001). The high SIRI group tended to stay longer in hospital and lost more blood during surgery. SIRI, body mass index, weight loss, carbohydrate antigen 19-9, radical surgery, and TNM stage were combined to generate a nomogram (C-index, 0.821 in the training cohort, 0.828 in the validation cohort) that was significantly superior to the TNM staging system both in the training (C-index, 0.655) and validation cohort (C-index, 0.649). @*Conclusion@#The SIRI is an independent predictor of prognosis in GBC. A nomogram based on the SIRI may help physicians to precisely stratify patients and implement individualized treatment.
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Objective To observe the effects of repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs on vitreous macular interface (VMI) in patients with exudative age-related macular degeneration (AMD).Methods Retrospective study.Thirty-four exudative AMD patients who treated with intravitreal anti-VEGF drugs were included in this study.There were 26 males and 8 females.The age ranged from 50 to 80 years,with the average of (62.8± 8.35) years.The eyes with at least 6 treatments during the 1-year follow-up were taken as the study eyes,and the eyes with no anti-VEGF drug treatment were the control eyes.Optical coherence tomography (OCT) examination was used to observe the VMI status of both eyes before treatment.Vitreous macular adhesion (VMA),macular epiretinal membrane (MEM),and complete vitreous detachment (C-PVD) were defined as abnormalities in VMI.The VMA was classified as focal (≤ 1500 μrn) and broad (＞ 1500 μtm) depending on the diameter of the vitreous and macular adhesions on the OCT images.Before treatment,there were 12 eyes with abnormal VMI in study eyes,including 8 eyes with broad VMA,3 eyes with focal VMA,and 1 eye with MEM;12 eyes with abnormal VMI in control eyes:broad VMA in 7 eyes,focal VMA in 2 eyes,C-PVD in 2 eyes,and MEM in 1 eye.The average follow-up time after treatment was 16.4 months.During the follow-up period,OCT was performed monthly in a follow-up mode.Comparing the changes on VMI between before and after treatment in both eyes of patients,respectively.The chi-square test was used to compare the difference on VMI.Because the number of samples was ＜40,Fisher's exact test was used for the analysis.Results At the final follow-up,12 eyes with abnormal VMI in the study eyes,including 5 eyes with broad VMA,2 eyes with focal VMA,3 eyes with C-PVD,and 2 eyes with MEM.There were 6 eyes altered comparing with baseline.In the control eyes,there were 13 eyes with abnormal VMI,including 5 eyes with broad VMA,7 eyes with C-PVD,and 1 eye with MEM.A total of 6 eyes changed on VMI comparing with baseline.At the final follow-up,there was no significant difference on VMI changes between the study eyes and its corresponding control eyes (P=0.053).In all eyes,a total of 4 eyes changed from focal VMA to C-PVD at the final follow-up,accounting for 80.0％ of the total focal VMA;3 eyes changed from broad VMA to C-PVD,accounting for 21.4％ of the total broad VMA.Conclusions Repeated anti-VEGF treatment has little effect on VMI.Regardless of anti-VEGF therapy,eyes with focal VMA appears to be more prone to C-PVD than the broad one.
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Objective To analyze histomorphometrical characteristics of the bone and bone marrow tissues of the lumbar vertebrae in rabbits with fluoride treatment,and its correlation with signal intensity of MRI.Methods Forty New Zealand albino rabbits aged three months old were randomly divided into fluoride exposure of 30 cases and control of 10 cases,male and female,half each.One hundred milligrams of sodium fluoride were added to the municipal water each liter (fluoride content 100 mg/L) as drinking waterto fluorine for 180 days.Twenty-four of 30 cases with fluoride exposure had complete data (male10 casesand female14 cases).The same municipal water was used as control drinking water (fluoride content ＜ 0.9 mg/L).Eight of 10 cases with control had complete data (male andfemale in half).Twenty-four cases with fluoride treatment and complete data were classified into sensitive and resistant type according to the MRI signal intensity of the lumbar vertebra.Histomorphometrics of the vertebra and its correlation with the MRI signal intensity,and sensitivity in early diagnosis of osteofluorosis and feasibility of susceptibility to osteofluorosis detected with MRI were analyzed.Results Theratios of trabecular bone volume (BV),hematopoietic cell volume (HV) and fluid volume (FV) in bone marrow tissue to total cavernous tissue volume (TT) in group with fluoride treatment were 18.3％±2.6％,45.2％±6.0％ and 10.4％±5.7％ respectively.These were 14.5％±2.8％,36.3％±7.3％ and 6.2％±2.1％ in control group respectively.These parameters in fluoride group were significantly increased compared to control group.The ratio 26.0％± 8.0％ of adipocyte volume (AV) to TV in fluoride group was significantly lower than that 43.3％±5.6％ in control group.Two of 24 cases with fluoride exposure (8.3％,2/24) were sensitive and the remaining 22 (91.7％,22/24) were in resistance.The valuesof BV/TT,HV/TV and FV/TV were considered to be sensitive,resistant and control from large to small,while AV/TV value were opposite.A comparison resuhs of signal intensity in MRI showed that vertebra T1WI contrast to noise ratio (CNR) in the sensitive was the minimum (3.0±0.8),followed by resistance (21.3±3.8) andmaximum in the control (28.3±3.1),but CNR of FsT2WIwas opposite.There were positive associations between T1WI and AV/TV,FV/TV and BV/TV,and between FsT2WI and FV/TV and BV/ TV.There were inverse associationsbetween FsT2WI and AV/TV.Theoptimal threshold value of the vertebra T1WI CNR was 23.2 or lessin early diagnosis of skeletal fluorosis,with sensitivity of 83.3％ and specificity of 100％.FsT2WI was 5.7 or more,with sensitivity of 45.8％ and specificity of 100％.Conclusion The pathogenesis of osteofluorosis is relative to changes in bone marrow microenvironment and cells number in bone marrow tissue,and is correlated to MRI signal intensity.
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Objective To investigate the effects of bevacizunab on the antioxidative function of human retinal pigment epithelium (RPE),in order to explore the possible mechanism of macular atrophy induced by the application of anti-vascular epithelial growth factor (VEGF) agents in age-related macular degeneration.Methods Human RPE cells were incubated in DMEM/F12 medium containing 0.25 g · L-1 bevacizumab and divided into 5 groups according to incubation period:0 hour(control),12 hours,24 hours,48 hours and 72 hours,and then the oxidative stress was induced by adding H2O2.Cell viability was measured by the CCK8 assay.MitoSox Red was used to determine mitochondrial reactive oxygen species (mtROS) production.Mitochondrial membrane potential was measured using the JC-1 assay.The expression levels of NOX4 and HO-1 were detected by RT-PCR and Western blot,respectively.Results CCK8 assay determination showed that the above treatment had no significant effect on cell viability,the cell viability of 0 hours,12 hours,24 hours,48 hours and 72 hours were (100.2 ±3.3)％,(99.2 ±2.7)％,(102.5 ±6.4)％,(103.9 ±3.7)％,(103.6 ±3.3)％,the difference was not statistically significant (P ＞ 0.05).Compared with the control group,the levels of mtROS increased at 12 hours,24 hours,48 hours and 72 hours,the difference was statistically significant (P ＜ 0.05).Mitochondrial membrane potential at 12 hours,24 hours,48 hours,72 hours were lower than the control group,the difference was significant,48 hours reached the lowest,72 hours significantly increased,but still lower than the control group.RT-PCR and western blot results demonstrated that the expression of NOX4 mRNA and protein increased at 12 hours,24 hours,48 hours and 72 hours,and reached the highest at 24 hours,then decreased significantly,but still higher than the control group,the difference was statistically significant (P ＜0.01).Compared with the control group,the expression of HO-1 mRNA decreased at 24 hours,48 hours and 72 hours,while the expression of HO-1 protein decreased at 48 hours and 72 hours,the difference was statistically significant (P ＜ 0.05).Conclusion The clinical concentration of bevacizumab can reduce the anti-oxidative function of RPE cells,which may be one of the causes of progressive macular atrophy after long-term anti-VEGF therapy.
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Objective@#To explore the safety and feasibility of associating diaphragm resection and liver-diaphragmatic metastasis lesions resection for patients with advanced ovarian cancer.@*Methods@#Retrospectively analysis 83 cases(98 times) of advanced ovarian cancer with liver-diaphragmatic metastasis between January 2012 and December 2016 at Department of Liver Surgery, Peking Union Medical College Hospital.The patients were aged from 19 to 75 years.Surgical procedure included metastatic lesions resection(43 times) and stripping(55 times). Operation status, post-operative complications, pathology results and follow-up of the patients were analyzed.@*Results@#Fifteen patients received twice surgical treatment and 68 patients received one time surgical treatment. Postoperative hemorrhage in chest and between liver and diaphragm was not occurred in all cases.Dyspnea and low oxygen saturation were occurred in two cases of stripping patients and 1 case of metastatic lesions resection patients.Results of CT examination indicated that there was medium to large amount of ascites in right chests.The symptoms were relieved after placing thoracic closed drainage.Other patients were recovered smoothly.All patients were diagnosed as ovarian cancer by pathological examination.@*Conclusion@#Associating diaphragm resection is safe and feasible for liver-diaphragmatic metastasis lesions from ovarian cancer.
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Objective To analyze histomorphometrical characteristics of bone and bone marrow tissue in the vertebral lamina of patients with osteofluorosis, and to explore the influencing factors on signal intensity in MRI. Methods Spinal MRI of 109 patients (57 men, 52 women;age range 32-80 years;mean age 52 years) with osteofluorosis from December 2001 to May 2012 was analyzed retrospectively, including 48 patients in cervical segment, 31 in thoracic segment and 30 in lumbar segment. 36 pa?tients (16 men, 20 women;mean age 51 years;age range 34-68 years) had undergone laminectomy and the vertebral lamina speci?mens were collected. The cervical MRI of 48 patients with matching gender and age (26 men, 22 women;mean age 51 years, age range 34-71 years) was selected as control group, who were from areas where fluorosis is not endemic. All patients were divided in?to vertebra low, medium and high signal groups according to T1WI of MRI. The vertebra signal to noise ratio measure and stan?dardization of signal intensity were performed. Osteosclerosis, osteoporosis and normal bone were differentiated under spinal X?ray plain film. Combined with histomorphometric analysis of vertebra lamina in 36 patients, correlation between MRI signal intensity, histomorphometric parameters of the vertebra lamina and influencing factors on signal intensity were studied. Results 77 pa?tients (70.6%, 77/109) had osteosclerosis indicated by appearance of spine under X?ray, 29 (26.6%, 29/109) osteoporosis and 3 (2.8%, 3/109) normal bone. T1WI of MRI showed 25 cases had low signal vertebra, 52 medium signal and 32 high signal. The ver? tebra SNR in patients with osteofluorosis was lower on T1WI, T2WI and short time inversion recovery (STIR) sequences, compared with control group. Those with a low versus high signal on T1WI had 6.04 times the odds of osteosclerosis (OR=6.04, 95%CI 2.44-14.91, P<0.001). Histomorphometry of vertebral lamina in 36 patients with osteofluorosis was performed, revealing that not only the trabecular bone volume had changed, but also did the adipocyte volume and hemopoietic cell volume in the bone marrow tis?sues. Compared with normal reference values, trabecular bone volume was significantly increased (47.7%± 13.3% vs. 14.7%± 4.3%) (P<0.001);adipocyte volume was significantly decreased (12.3%±9.1%vs. 50.5%±8.7%);hematopoietic cell volume was decreased (40.0%±7.0%vs. 42.5%±8.5%) (P=0.038). There were inverse associations between trabecular bone volume and adipo?cyte volume (r=-0.869, P<0.001), and between trabecular bone volume and T1WI (r=-0.851, P<0.001) found by Pearson correla?tion test. In contrast, there were positive associations between T1WI and adipocyte volume (r=0.927, P<0.001). Conclusion The vertebra T1WI signal intensity is decreased in patients with osteofluorosis, resulting from increase of trabecular bone volume and re?duction of adipocyte volume. The vertebra STIR signal intensity is decreased, mainly caused by increase of trabecular bone volume.
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Background Retinal neovascularization is pathological basis of a variety of fundus diseases,but its pathogenesis is unclear.Studies showed that the expression level of radixin in retina is remarkably increased in retinal neovascularization-related diseases.It is presumed that silencing or down-regulating the abnormal expression of radixin is helpful for curing retinal neovascularization-related diseases.Objective This study was to investigate the inhibitory effect of radixin short hairpin RNA (shRNA) plasmid on expression of radixin gene in retina of oxygen-induced retinopathy (OIR) mice.Methods Sixty-four 7-day-old C57BL/6J mice were randomly divided into normal control group, model control group, radixin shRNA plasmid group and shRNA plasmid group by random number table.There were 16 mice in every group.OIR models were established by exposing the mice in an environment of (75±2) ％ oxygen for 5 days and then returned to the normal air in the model control group,radixin shRNA plasmid group and shRNA plasmid group,while the mice of the normal control group were fed in the normal air environment.Radixin shRNA plasmid or control shRNA plasmid at the dose of 1 μg was intravitreally injected in 12-day-old mice of the radixin shRNA plasmid group or shRNA plasmid group, respectively.Five days later, FD-2000S angiography was performed on the mice of each group and then retinal flatmounts were prepared for the observation of retinal vessels.The mice from various groups were sacrificed and retinal sections were prepared.The vascular endothelial nucleus and new blood vessels extending inner limiting membrane (ILM) were examined by hematoxylin and eosin staining;the expression of radixin in the retinas was detected using immunochemistry;the relative expression levels of radixin mRNA and protein were quantitative assayed by real-time quantitative RCR and Western blot, respectively.The use and care of the animals adhered to the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research.Results The distribution of retinal vessels was normal in the normal control group.Non-perfusion zone at the posterior pole of retina, circuity of blood vessels,leakage of vessel wall and new blood vessels were found in the mice of the model control group.Non-perfusion zone and microaneurysms were also exhibited in the shRNA plasmid group.However,these findings were slight in the radixin shRNA plasmid group.The surface of ILM was in discontinuity in the model mice and shRNA-injected mice with more vascular endothelial cell nucleus and more tubes extending ILM than that in the radixin shRNA plasmid group.The immunochemistry results showed that the expressions of radixin in the normal control group and radixin shRNA plasmid group were weaker than those in the model control group and control shRNA plasmid group.The relative expression levels of radixin mRNA were 1.002±0.043,2.236-±0.093,0.556±0.015 and 2.272±0.096 in the normal control group, model control group,radixin shRNA plasmid group and control shRNA plasmid group,and those in the radixin shRNA plasmid group were significantly reduced in comparison with the normal control group, model control group and the shRNA plasmid group (all at P＜0.01).The relative expression levels were 1.000±0.082,1.193±0.021,0.263± 0.016 and 1.235±0.005 in the normal control group,model control group,radixin shRNA plasmid group and shRNA plasmid,with the lowest expression level in the radixin shRNA plasmid group (all at P＜0.01).Conclusions Radixin shRNA can downregulate the expression of radixin gene in the retinas of OIR mice and further inhibit pathological retinal neovascularization.
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Background Hypoxia is the main factor of retinal neovascularization and is closely associated with retinal ganglial cells (RGCs) degeneration.However, the study of retinal neural tissue lesions is rare.Objective This study was to investigate the influence of hypoxia environment on the expression of annexin A2 (ANXA2) in mouse RGC-5 cells and explore the mechanism of RGCs damage induced by hypoxia.Methods Immortalized mouse RGC-5 cells were cultured in high glucose DMEM with 10％ fetal bovine serum.The cells were identified by detecting the expression of Thy-1 ,a specific biomarker of RGCs.CoCl2 was added into the medium at the final concentrations of 50,100,200 and 300 μmol/L, and the cells without CoCl2 served as the control group.Cell viability (absorbance) was assayed by cell counting kit-8 (CCK-8) method in 12,24 and 48 hours after addition of CoCl2.The hypoxic cell models were established in DMEM with 100 μmol/L CoCl2 and divided into the hypoxic 3-hour group, hypoxic 6-hour group, hypoxic 12-hour group and hypoxic 24-hour group,with the normal cultured cells as the normal control group.Apoptotic cells were determined by using hoechst 33342 stain.The expression levels of ANXA2 mRNA and protein in the cells were detected by real-time quantification PCR and Western blot,respectively.The expression and location of ANXA2 in the cells were examined by using immunofluorescence technique.Results The cultured cells grew well and showed the fusiform and polygonal shape,with positive expression of Thy-1 protein.Compared with the normal control group, the viabilities of the cells were insignificantly changed in the 50 μ mol/L CoCl2 group and 100 μmol/L CoCl2 group (all at P＞0.05) ,but the cell viabilities were significantly reduced in the 200 μμmol/L CoCl2 group and 300 μmol/L CoCl2 group in various time points (all at P＜0.05).Hoechst 33342 staining showed that the apoptotic cells with nuclear condensation and high green fluorescence intensity were obtained in the hypoxia groups.The relative expression levels of ANXA2 mRNA were significantly lower in the hypoxic groups than those in the normal control group (all at P ＜ 0.05).The relative expression levels of ANXA2 protein were significantly lower in the hypoxia 3-,6-, 12-and 24-hour group than those in the normal control group (all at P＜ 0.05).Apoptotic cells were seen in the hypoxic 3-hour group, hypoxic 6-hour group, hypoxic 12-hour group and hypoxic 24-hour group compared with the normal control group, showing the bright blue fluorescence in cellular nucleus for hoechst 33342.The relative expressing levels of ANXA2 mRNA in the cells were 0.80±0.14,0.67±0.33, 0.49±0.17 and 0.39±0.02 in the hypoxic 3-hour group,hypoxic 6-hour group, hypoxic 12-hour group and hypoxic 24-hour group, which were significantly declined in comparison with the normal control group, with a statistically difference among the groups (F=434.354, P =0.000).The relative expression values of ANXA2 protein were 0.552 6±0.012 3,0.425 9± 0.033 4,0.344 9 ± 0.017 8 and 0.382 7 ± 0.022 1 in the hypoxic 3-hour group, hypoxic 6-hour group, hypoxic 12-hour group and hypoxic 24-hour group,which were remarkably lower than 0.602 1 ±0.001 4 in the normal control group, showing considerably difference among the groups (F =3.057, P =0.000).ANXA2 proteins were highly expressed in the cellular nucleus and less expressed in the cell membrane and cytoplasm in the normal cells.Compared with the normal control group, the ANXA2 protein showed weak expression in the hypoxia group and primarily in the cytoplasm.Conclusions The expression of ANXA2 down-regulates in hypoxic mouse RGC-5 cells,which may participate in the apoptosis process of RGCs in high glucose environment.
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Objective To explore the effect of flexible ureteroscope in treatment of retained kidney calculi after percutaneous nephrolithotomy.Methods Thirty-six patients with retained kidney calculi after percutaneous nephrolithotomy who were treated with flexible ureteroscope were selected,and clinical data of the patients were retrospectively analyzed.Results In the 36 patients,26 patients were through the percutaneous nephroscope channel,and 10 patients were through the ureter channel.Except for 1 patient who stopped the operation because of poor visibility caused by active bleeding in percutaneous nephroscope channel lithotripsy 7 d after percutaneous nephrolithotomy,other patients did not appear severe complication.All the patients were rechecked plain abdominal radiograph the second,seventh and fourteenth day after this operation,and the eradication rates of calculi were 13.9％ (5/36),69.4％ (25/36) and 94.4％ (34/36).Two patients still had less than 0.4 cm retained calculi in lower renal calices and were followed up.Conclusions The retained kidney calculi after percutaneous nephrolithotomy can be effectually treated by flexible ureteroscope,and it can avoid secondary percutaneous nephrolithotomy or multichannel percutaneous nephrolithotomy,and inprove the eradication rate of complex kidney calculi by percutaneous nephrolithotomy.The method is economical,safe,simple and with little injury,and it is the effective supplement protocol of percutaneous nephrolithotomy.
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Objective To investigate the clinical application of a new thermosensitive embolic agent in interventional arterial embolization treatment, and to evaluate its effectiveness and safety in treating inoperable advanced hepatocellular carcinoma (HCC). Methods Prospective, open and single center clinical study of a new thermosensitive embolic agent was conducted. A total of 10 patients with clinically confirmed inoperable advanced HCC were treated with percutaneous arterial embolization using thermosensitive embolic agent; a maximum of 4 therapeutic cycles were performed until the disease progressed. Objective effect was evaluated at (30 ±7) days after the treatment according to mRECIST standard; the progression free survival (PFS) time and the survival period (OS) were recorded. The adverse reactions and adverse events were determined by NCI-CTC 3.0 version standard. Results Ten patients (23 target lesions in total) were enrolled in this study. After the treatment, complete remission (CR) was obtained in one patient, partial remission (PR) in 3 patients, stable disease (SD) in 5 patients, and progress disease (PD) in one patient. The objective response rate (CR+PR) was 40%, and the disease control rate (CR+PR+SD) was 90%. The PFS of hepatic lesions was 18.4 weeks (95%CI:14.15-22.65), the cumulated median survival period was 46.2 weeks (95%CI:38.18-54.22). The most common adverse reactions included pain, fever, hepatic function damage, small amount of ascites, diarrhea, etc. Conclusion The new thermosensitive embolic agent is not sticky to vessel and is visible under X-ray; it has reliable embolization effect, and the therapeutic results can be easily evaluated. This embolic agent is not perfect, and it has some limitations in clinical use. The adverse reactions are mild, which can be easily tolerated by the patients. It is worth trying to carry out large sample and randomized controlled studies in order to open up more areas for arterial chemoembolization therapy of tumors.
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Objective To investigate the effect of immunotherapy of recombinant chimeric epitopes of major allergen group 1 from Dermatophagoides farina on asthma of mice. Methods Forty mice were randomly divided into 4 groups:a negative con?trol group,an asthma group,an immunotherapy group of Der f 1,and an immunotherapy group of Der f 1A. On the 1st,7th and 14th day,the mice in the asthma group,immunotherapy group of Der f 1,and immunotherapy group of Der f 1A were injected intraperitoneally with the extract of D. farina 3 times to sensitize;and on the 21st day,the atomized inhalation was carried out for 7 days. In the control group,phosphate buffer solution(PBS)was applied for sensitization and inhalation. In the immunother?apy groups,Der f 1 and Der f 1A were applied to carry out the specific immunotherapy respectively for 30 min before the inhala?tion. Then,the leukocytes in the bronchoalveolar lavage fluid(BALF)were numbered and the pathological sections of lung tis?sues were observed;IL?5 and IFN?γin BALF and spleen cell culture supernatants(SCCS)as well as the specific IgE,IgG2a in the sera were detected. Results Compared with the asthma group,the lung inflammation of mice in the immunotherapy groups was lightened,and the total numbers of leukocytes in BALF were significantly reduced;IL?5 was significantly reduced and IFN?γwas significantly increased in BALF and SCCS of mice in the immunotherapy groups;and the specific IgE was significantly re?duced and IgG2a was significantly increased in the sera of mice in the immunotherapy groups(all P<0.01). Conclusion The recombinant chimeric epitopes of major allergen group 1 from D. farina could effectively relieve the symptom of asthma in mice, so as to provide the evidence for specific immunotherapy.