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BACKGROUND:Kidney deficiency and blood stasis syndrome are common traditional Chinese medicine syndromes observed in knee osteoarthritis,which serve as fundamental pathogenesis factors.There exists a significant connection between the two.Previous studies have demonstrated that kidney deficiency and blood stasis syndrome effectively contribute to knee joint cartilage degeneration and the progression of knee osteoarthritis.However,the mechanisms underlying the promotion of knee joint cartilage damage remain unclear and require further investigation. OBJECTIVE:To investigate the influence of kidney deficiency and blood stasis syndrome on the progression of knee osteoarthritis in Sprague-Dawley rats. METHODS:Sixteen Sprague-Dawley rats were randomly divided into two groups:a model observation group and a control group,with eight rats in each group.Animal models of kidney deficiency were induced by ovary removal in the model observation group,while the control group was given a sham procedure for ovarian removal.Two months after modeling,both groups underwent modified HULTH surgery to induce knee osteoarthritis.One week after modified HULTH surgery,the model observation group was subcutaneously given adrenaline hydrochloride to make blood stasis models,while the control group was subcutaneously given normal saline.At the 5th week after modified HULTH surgery,blood rheology,coagulation parameters,triiodothyronine,tetraiodothyronine,and estradiol levels were measured.Knee joint X-ray images were taken,and knee joint sections were stained with safranin O-fast green,hematoxylin-eosin,and immunohistochemistry. RESULTS AND CONCLUSION:Compared with the control group,the model observation group exhibited significant increases in whole blood viscosity at low,medium,and high shear rates,as well as increased plasma viscosity.Fibronectin levels in the coagulation parameters were significantly increased,while prothrombin time and activated partial thromboplastin time were significantly decreased.Triiodothyronine,tetraiodothyronine,and estradiol levels were all significantly decreased.Radiographic results showed that the model observation group exhibited more severe degree of knee joint space narrowing and surface roughness,with the appearance of high-density shadows.Hematoxylin-eosin and safranin O-fast green staining demonstrated more severe cartilage damage in the model observation group,with significantly higher OARSI and Mankin scores compared with the control group.Compared with the control group,immunohistochemistry results showed a significant reduction in the expression of extracellular matrix type II collagen and aggrecan protein in the cartilage of the model observation group rats.Moreover,there was a significant increase in the expression of matrix metalloproteinase 13 and aggrecanase 5,which are inflammatory factors.These results indicate that the Sprague-Dawley rat model of knee osteoarthritis with kidney deficiency and blood stasis was successfully established.Kidney deficiency and blood stasis syndrome further aggravate cartilage extracellular matrix degradation and cartilage degeneration by promoting the expression of inflammatory factors,thereby promoting the progression of knee osteoarthritis in rats.
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Objective:To investigate the etiological mechanism in single small subcortical infarction (SSSI) with different imaging features.Methods:The patients registered in a database of ischemic stroke in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were analyzed. According to the lowest slice (LS) and the total number of involved slices (TNS) on diffusion-weighted imaging, the SSSI was divided into 3 types: proximal SSSI (pSSSI; LS≤2), distal and large SSSI (dl-SSSI; LS>2, TNS>2) and distal and small SSSI (ds-SSSI; LS>2, TNS≤2). The clinical and imaging features among 3 different lesion patterns were compared by using χ 2 test, Kruskal-Wallis H test and multiple Logistic regression analysis, etc. Results:In the 3 groups of ds-SSSI ( n=205), dl-SSSI ( n=157) and pSSSI ( n=166), the prevalences of parent artery disease (PAD)[10.7% (22/205) , 19.1% (30/157) , 42.8% (71/166), respectively, χ 2=54.89, P<0.001], coronary artery disease [8.3% (17/205), 14.0% (22/157), 16.9%(28/166), respectively, χ 2=6.44, P=0.040] and severe white matter hyperintensities (sWMHs)[58.0% (119/205), 43.3% (68/157), 41.0% (68/166), respectively, χ 2=12.94, P<0.001], the level of serum homocysteine (Hcy)[18.01 (13.54, 25.56), 16.03 (12.50, 21.09), 14.72 (11.12, 19.14) μmol/L, respectively, H=19.36, P<0.001], and the National Institutes of Health Stroke Scale (NIHSS) score[2(1, 3), 3(1, 4), 3(2, 6), respectively, H=39.53, P<0.001] showed statistically significant differences. Multiple Logistic regression analysis showed that compared with dl-SSSI patients, the lesion pattern of patients with higher proportion of PAD ( OR=3.12, 95% CI 1.86-5.24, P<0.001) was closer to pSSSI; the lesion pattern of patients with higher serum Hcy level ( OR=1.02, 95% CI 1.00-1.04, P=0.046) or higher proportion of sWMHs ( OR=1.79, 95% CI 1.12-2.86, P=0.015) was closer to ds-SSSI, and the lesion pattern of patients with higher proportion of PAD ( OR=0.50, 95% CI 0.27-0.93, P=0.029) or higher NIHSS score ( OR=0.84, 95% CI 0.77-0.92, P<0.001) was closer to dl-SSSI. Conclusions:The pathogenesis of ds-SSSI tends to be cerebral small vessel disease. The pathogenesis of pSSSI is related to atherosclerosis. The patients with dl-SSSI have the intermediate characteristics of pSSSI and ds-SSSI and may be unstable.
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Sarcopenia is an age-related disease that mainly involves decreases in muscle mass, muscle strength and muscle function. At the same time, the body fat content increases with aging, especially the visceral fat content. Adipose tissue is an endocrine organ that secretes biologically active factors called adipokines, which act on local and distant tissues. Studies have revealed that some adipokines exert regulatory effects on muscle, such as higher serum leptin levels causing a decrease in muscle function and adiponectin inhibits the transcriptional activity of Forkhead box O3 (FoxO3) by activating peroxisome proliferators-activated receptor-γ coactivator -1α (PGC-1α) and sensitizing cells to insulin, thereby repressing atrophy-related genes (atrogin-1 and muscle RING finger 1 [MuRF1]) to prevent the loss of muscle mass. Here, we describe the effects on muscle of adipokines produced by adipose tissue, such as leptin, adiponectin, resistin, mucin and lipocalin-2, and discuss the importance of these adipokines for understanding the development of sarcopenia.
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Humans , Adipokines , Leptin , Adiponectin , Sarcopenia , MusclesABSTRACT
Objective To examine the expression profile of programmed death-ligand 1 (PD-L1) on lung endothelial or epithelial cells,and to determine the specific role of PD-L1 in mouse model of indirect acute lung injury (i-ALI).Methods Eighty male C57BL/6 mice were randomly divided into two parts (both n =40).The effects of different administration routes on the expression of PD-L1 were observed.The mice in each part were randomly divided into sham,i-ALI,i-ALI+small interfering RNA (siRNA) random sequence control,and i-ALI+PD-L1 siRNA which could specifically inhibit PD-L1 expression groups,with l0 mice in each group.i-ALI was reproduced in a mouse model of hemorrhagic shock in combination with a subsequent cecal ligation and puncture (CLP).In sham group,only bilateral femoral arteries were ligated without catheterization or bleeding,and only cecum was separated but perforation was not ligated.Intravenous or intratracheal delivery of PD-L1 siRNA was performed 2 hours following the resuscitation to suppress the expression of PD-L1 on lung endothelial or epithelial cells.The mice in i-ALI+siRNA random sequence control group were given siRNA random sequence without inhibition effect on PD-L1 expression,and those in sham group and i-ALI group were given 100 μL phosphate buffered saline (PBS).The mice were sacrificed at 24 hours after CLP,and samples of blood,lung tissue and bronchoalveolar lavage fluid (BALF) were harvested.Expressions of PD-L1 were determined with flow cytometry.Cytokines and chemokines in plasma,lung tissue and BALF were determined by enzyme linked immunosorbent assay (ELISA).The protein concentration in plasma and BALF and the activity of myeloperoxidase (MPO) in lung tissue were quantitatively measured.The pathological changes in lung tissue were observed under light microscope.Results ① Compared with sham group,PD-L1 expression on lung endothelial or epithelial cells were significantly elevated in i-ALI group [endothelial cells:(27.88 ± 1.53)% vs.(19.64 ± 1.03)%,epithelial cells:(58.70 ± 8.21)% vs.(29.23 ± 3.94)%,both P < 0.05].② Mice received intravenous delivery of liposomal-encapsulated siRNA had significantly lower expression of PD-L1 on lung endothelial cells as compared with that of i-ALI group [(21.37 ± 0.76)% vs.(27.88 ± 1.53)%,P < 0.05].Intratracheal delivery of naked PD-L1 siRNA mainly inhibited the PD-L1 expression on epithelial cell as compared with that of i-ALI group [(31.23±4.71) % vs.(58.70±8.21) %,P < 0.05].The expression of PD-L1 in pulmonary microvascular endothelial cells or pulmonary epithelial cells of i-ALI mice was not affected by siRNA random sequence.③ PD-L1 silencing on pulmonary endothelial cells induced by intravenous delivery of PD-L1 siRNA led to a lower protein ratio of BALF/plasma [(4.48 ± 0.35) × 10-3 vs.(6.11 ± 0.56) × 10-3,P < 0.05] and a decreased MPO activity in lung tissue (U · μg-1 · min-1:2.48 ± 0.47 vs.4.56 ± 0.52,P < 0.05) as compared with that of i-ALI group.Moreover,inflammatory mediator levels such as interleukin-6 (IL-6),monocyte chemoattractant protein-1 (MCP-1),macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) in lung tissue or plasma were significantly reduced following PD-L1 suppression on endothelial cells as compared with those of i-ALI group [IL-6 (ng/g):177.4±23.2 vs.287.9±57.3,MCP-1 (ng/g):839.6±91.7 vs.1 395.7±211.9,MIP-2 (ng/g):923.7± 107.3 vs.1 700.9±240.2 in lung tissue;IL-6 (ng/L):950.2±192.7 vs.1 828.2±243.6,TNF-α (ng/L):258.7±29.1 vs.443.0 ± 58.1,MCP-1 (ng/L):2 583.8±302.3 vs.4 328.1 ±416.4,MIP-2 (ng/L):1 512.9± 165.6 vs.2 005.9 ± 85.7 in plasma,all P < 0.05],however,there was no significant change in the levels of inflammatory factors in BALF.It was shown in lung tissue histology that PD-L1 silencing on pulmonary endothelial cells induced by intravenous delivery of PD-L1 siRNA led to lessened pulmonary edema and reduced immune cells emigration.Intratracheal delivery of PD-L1 siRNA for PD-L1 suppression on epithelial cells had minimal effects on protein ratio of BALF/plasma,MPO activity,inflammatory mediator expressions in lung tissue,plasma,and BALF as well as lung tissue histology.Conclusion PD-L1 silencing on endothelial cells but not epithelial cells protected mice against hemorrhagic shock-sepsis induced i-ALI.
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Objective This study was to evaluate the relative applicability of serum cystatin C(Cys C)-based formulas and serum creatinine-based formulas for renal glomerular filtration rate(GFR) of Chinese children with chronic kidney disease(CKD).Methods Six hundred and nine Chinese CKD patients of less than 18 years old were enrolled from January 2011 to October 2016 in Shengjing Hospital of China Medical University.The value for estimated GFR (eGFR) was derived from using the 11 formulas,and 99mTc-DTPA renal dynamic imaging was the golden standard of standard GFR(sGFR).SPSS 22.0 statistical software was used to compare the accuracy of each assessment formula and the correlation between GFR markers(Cys C, β2-MG) and sGFR.Results A total of 609 children were enrolled,including 332 patients in CKD stage 1 (211 males and 121 females),165 patients in CKD stage 2(99 males and 66 females),70 patients in CKD stage 3(43 males and 27 females),22 patients in CKD stage 4(13 males and 9 females),and 20 patients in CKD stage 5(16 males and 4 females).All of the formulas either overestimate or underestimate GFR in chil-dren with CKD. In contrast with other formulas,CKD-EPI formula and Filler formula performed better regardless of gender and age difference.Serum β2-MG and serum Cys C all showed a negative relationship with sGFR(respectively r= -0.478 and r= -0.585,P<0.01).Conclusion CKD-EPI formula and Filler formula provide the better approximation to sGFR than other formulas in Chinese children with CKD.Howev-er,we need to try our best to enroll more patients to develop a more accurate GFR estimation formula in Chinese children.
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Objective To estimate the absorbed dose and effective dose to the examined adult patients during digital tomosynthesis and to provide reference data for radiation dosimetry.Methods The phantom experiments were grouped according to the examined site(main beam scanned site),and the data displayed in real time during digital tomosynthesis are used as conditions for the phantom experiments.The effective doses to the examined patients were estimated on the basis of phantom scanning and tissue-absorbed dose calculation.Results During digital tomosynthesis,the effective doses to the examined patients of various groups were 0.524 mSv for head,0.736 mSv for cervical spine,2.719 mSv for thoracic vertebra,1.810 mSv for chest,1.240 mSv for lumbar spine,2.317 mSv for abdomen and 2.316 mSv for pelvis,respectively.Conclusions During digital tomography,the highest value of effective doses was estimated to be 2.719 mSv in thoracic vertebra group,followed by abdominal group 2.317 mSv and pelvic group 2.316 mS,with the lowest 0.524 mSv in head group.The main factors influencing the effective dose include tube voltage,total mAs,irradiation field size,main beam irradiation range,and the number of tissues or organs in scanned range.
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Objective To evaluate the prognostic value of human antibacterial peptide LL-37 in elderly patients with sepsis. Methods Elderly sepsis patients over 65-year-old satisfied the diagnostic criteria for sepsis and septic shock admitted to intensive care unit of East Hospital of Tongji University from January 2016 to December 2017 were enrolled (elderly sepsis group). Aged community-acquired pneumonia (CAP) patients hospitalized during the same period were enrolled as a control group for pneumonia, and the aged health check-ups served as a healthy control group during the same period. The peripheral blood LL-37 levels of all patients on the 1st, 3rd, 7th day of admission and the results on the day of physical examination in the healthy control group and on the day of admission in aged CAP group were recorded. C-reactive protein (CRP), arterial blood lactate (Lac), procalcitonin (PCT) were monitored, and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) scores were calculated based on the worst values within 24 hours. The correlation between LL-37 and various indicators was analyzed by Spearman method. According to the 28-day clinical outcome, the elderly patients with sepsis were divided into survival group and non-survival group. The differences in all parameters between the two groups were compared. The statistically significant indicators were analyzed by receiver operating characteristic (ROC) curve, and the predictive value of each indicator for prognosis was evaluated. Results ① A total of 113 elderly patients with sepsis were enrolled in the final analysis, including 67 patients in sepsis group and 46 patients in septic shock group. Thirty-two patients were enrolled as healthy controls and 31 elderly patients with CAP as elderly pneumonia group. The PCT, CRP, Lac, APACHEⅡ and SOFA scores of the patients in the three groups were higher than those of the healthy control group, and they were gradually increased with the severity of infection. There was no significant difference in gender or age among the groups. Compared with the healthy control group, the other three groups had higher LL-37 level after admission, the LL-37 levels in the sepsis group and the septic shock group were decreased with the prolongation of the hospitalization time, and they were lower than the pneumonia group at 7 days after admission [LL-37 (μg/L): 1 403.9±501.9, 1 517.1±676.4 vs. 1 608.4±816.2, both P > 0.05]. It was shown by correlation analysis that the LL-37 level in peripheral blood of elderly patients with sepsis was significantly negatively correlated with APACHEⅡ score (r = -0.329, P = 0.007) and SOFA score (r = -0.344, P = 0.005), but no significant correlation with Lac was found (r = -0.128, P = 0.311). ② The 28-day survival analysis revealed that of the 113 elderly patients with sepsis, 54 (47.8%) survived at 28 days and 59 (52.2%) died. There was no significant difference in gender, age, PCT or CRP levels at 1 day after admission between the two groups. The 1-day Lac, APACHEⅡ and SOFA scores of the patients in the non-survival group were significantly higher than those in the survival group, they were gradually increased with the prolongation of the hospitalization time, and they were significantly higher than those in the survival group at 7 days after admission [Lac (mmol/L): 2.4 (1.4, 4.4) vs. 1.0 (0.8, 1.7), APACHEⅡ score: 21.77±5.85 vs. 13.74±4.99, SOFA score: 9.62±4.78 vs. 3.18±2.71, all P < 0.01]. With the prolongation of admission, there was no significant change in LL-37 level of peripheral blood in the survival group. The LL-37 level in the non-survival group showed a downward tendency, and it was significantly lower than that in the survival group at 7 days after admission (μg/L: 1 277.8±642.6 vs. 1 620.6±461.6, P < 0.05). It was shown by ROC curve analysis that the LL-37 in peripheral blood, Lac, APACHEⅡ score and SOFA score at 7-day of admission of elderly patients with sepsis had predictive value for prognosis, and LL-37 had the best predicted effect for 28-day death, the area under the ROC curve (AUC) of LL-37 was 0.670, 95% confidence interval (95%CI) = 0.513-0.757, when the optimal cut-off value was 1 283.0 μg/L, the sensitivity was 75.7%, and the specificity was 61.5%. Conclusions The expression of LL-37 increased in the early course of the disease in elderly patients with sepsis. However, as the disease progressed and worsened, the level of LL-37 had a decline tendency and was associated with death. The dynamic monitoring of LL-37 combined with APACHEⅡ and SOFA scores had clinical guidance value in predicting the prognosis of sepsis in the elderly.
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Objective To analyze the clinical manifestations and genetic mutations in 3 pedigrees with hereditary spastic paraplegia (HSP).Methods Three pedigrees diagnosed as having HSP in our hospital from January 2014 to November 2015,were chosen;the clinical manifestations,electrophysiology and imaging features of the patients in these three families were analyzed.Genomic DNA was extracted from peripheral venous blood,and the targeted gene capturing was employed to identify the disease-causing genes of these patients.Results The patients from the first family was familiar HSP,and the main clinical features were progressive lower limbs weakness and abnormal gait without cognitive impairment;the patients from the second family were familiar HSP and those from the third family were HSP without family history,and the main clinical features of the two pedigrees were slowly progressive spastic paraplegia and cognitive impairment.In addition,thin corpus callosum was visible in MR imaging of family three.Genetic testing showed the first family presented with a known mutation c.715C>T ofA TL1 exon 7 and the loci co-segregated in the family.The second family presented with novel compound heterozygous mutations in the SPG11 gene:c.3099_3103delGTTTG mutation of exon 17and c3817 3818insTGA mutation of exon 22;novel compound heterozygous mutations in the SPG11 gene in the third family were detected as follows:c.6194C >G mutation of exon 32 and c.5121+1C>T splicing mutation ofintro 29.Conclusions Four novel mutations in SPG11 gene and one known mutation in A TL1 gene are found,which enriches the known HSP mutation types.Targeted gene capture is an efficient and rapid tool for identifying the causation of some complex and genetically heterogeneous neurodegenerative diseases.
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Objective To evaluate the effect of retention time of urokinase on hematoma dissipation in the treatment of severe ventricular hemorrhage by lateral ventricle drainage. Methods The clinical data of 62 patients with severe ventricular hemorrhage and having received bilateral ventriculostomy were retrospectively analyzed. These patients was divided into 3 groups according to the retention time of urokinase: A group (20 patients, retention time 1 h), B group (22 patients, retention time 2 h) , and C group (20 patients , retention time 3 h).The number of patients with complete hematoma dissipation at different time in each group were compared. Results At 5-6 d, 7-9 d and 10-12 d after operation, the number of hematoma dissipation in A group was 2, 5, 13 cases, in B group was 5, 13, 4 cases, and in C g group was 3, 13, 4 cases. The number of hematoma dissipation patients in three groups had significant difference (P=0.008), the number of hematoma dissipation patients between A group and B group, and between A group and C group had significant differences (P=0.005, 0.012), but there was no significant difference between B group and C group (P=0.621). The complication rate in three groups had no significant difference (χ2=2.540, P=0.281). Conclusions The 2 h retention time of urokinase is more suitable for the patients with severe ventricular hemorrhage who underwent external drainage.
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Objective Cerebral venous sinus thrombosis (CVST) is easily misdiagnosed for lack of specificity in its pathogenesis and clinical symptoms and characteristics.This study was to investigate the association of the clinical features of CVST with the time of diagnosis and the impact of diagnostic delay on the prognosis of the disease.Methods We retrospectively studied the clinical data about 94 cases of CVST treated in our hospital from March 2004 to August 2016.According to the interquartile-range time of diagnosis, we divided the patients into four groups, 16 d, and analyzed the correlation between the time of diagnostic delay with the clinical characteristics of the patients.The primary and secondary endpoints were the modified Rankin Scale score (mRS) ≤1 and ≤2 respectively at 3 months after discharge.Results Papilledema, isolated intracranial hypertension syndrome, and Glasgow Coma Score of 14-15 were associated with a longer diagnostic delay than seizure and hemorrhagic or infarction lesions (P<0.05).A significantly higher rate of earlier diagnosis was found in patients with lower levels of albumin and total protein, longer thrombin time, and a higher level of C-reaction protein (P<0.05).However, no significant correlation was observed between the time of diagnostic delay and the prognosis CVST.Conclusion The symptoms and laboratory indexes of the CVST patients at admission can be used as markers for the diagnosis of CVST, which may provide some new idea for its early diagnosis.
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Objective To compare the diagnostic efficacy of digital mammography,ultrasonography and MRI for breast non-mass enhancement (NME).Methods The digital mammography,ultrasonography and MRI data of 1 1 6 patients with 123 NME lesions on MRI were analyzed retrospectively.Results 99 lesions were malignant and 24 lesions were benign according to the pathologiacl result.The sensitivity of digital mammography,ultrasonography and MRI was 72.73%,65.66%,and 84.85%,respectively;The specificity was 66.67%,79.1 7%,and 79.1 7%,respectively;The accuracy was 71.54%,68.29%,and 83.74%,respectively;The positive pretictive value was 90.00%,92.86%,and 94.88%,respectively;The negative pretictive value was 37.21%,35.85%,and 55.88%,respectively.The sensitivity,specificity,accuracy,positive pretictive value and negative pretictive value of MRI were obviously higher than those of digital mammography and ultrasonography (P <0.05).The difference between the combinations and MRI alone were no statistically significant.Conclusion MRI have better diagnostic value,and could be used as the first choice examination for breast NME lesions.
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Objective To study the safety and availability of extended resection,gland reconstruction and mammary gland lavage in treatment of mammary duct expansion.Methods 41 patients with duct expansion admitted from Mar.2012 to Jan.2015 were studied and they were randomly divided into two groups.15 patients in the control group received normal surgical treatment,and 26 patients in the observation group received extended resection,gland reconstruction and mammary gland lavage treatment.Results The operation time,intraoperatve blood loss,length of hospital stay and degree of satisfaction of the observation group were superior to those of the control group while the recurrence rate was lower than that of control group.The gland expanded resection reduced the recurrence rate,the shape of the breast was improved,and the continuous irrigation was the guarantee for the immediate formation of the gland.The three kinds of surgical procedures were organically combined and complement each other.Conclusion The surgical methord of extended resection,gland reconstruction and mammary gland lavage is worth of further exploring due to its advantages of easy to operate,good cosmetic effect and low recurrence rate.
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BACKGROUND:Both osteopontin and hyaluronic acid involve in the pathological process of osteoarthritis, resulting in the abnormal expression levels of various cytokines and enzymes. However, the relationship between the high expression of osteopontin and hyaluronic acid in chondrocytes remains unclear. OBJECTIVE:To investigate the effect of osteopontin on the expression of hyaluronic acid in human knee osteoarthritic chondrocytes in vitro by modulating the level of osteopontin. METHODS:Chondrocytes from human knee osteoarthritic cartilage were cultured in vitro, and were then divided into three groups:blank control group without any treatment;osteopontin group and and pontin siRNA group were treated with 1 mg/L recombinant human osteopontin and osteopontin siRNA, respectively. Expression levels of osteopontin, hyaluronic acid synthase 1, 2 and 3 mRNA were detected by real-time PCR, and the levels of hyaluronic acid were measured using ELISA. RESULTS AND CONCLUSION:Compared with the blank control group, the mRNA expressions of hyaluronic acid synthase 1, 2 and 3 were remarkably increased in the osteopontin group, while siRNA made the significantly inhibitory effects on the hyaluronic acid synthase 1, 2 and 3 mRNA expressions (P<0.05). The level of hyaluronic acid in chondrocytes in the osteopontin group was significantly higher than that in the other two groups (P<0.05). Our results suggest that osteopontin induces the synthesis of hyaluronic acid in osteoarthritic chondrocytes through upregulating the hyaluronic acid synthases expression levels.
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Objective To investigate the influence of one kind of defective gene NOTCH3 (R90C) of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in proliferation of oligodendrocyte lineage cells HS683 and their related molecular mechanism.Methods (1) A pCMV-Sport6.0 was chosen as the expression vector and site-directed mutation was used to construct the mutant NOTCH3 (p.R90C) expression vector;eukaryotic cell transfection technique was used to respectively transfect the pCMV-Sport6.0 empty vector,wild NOTCH3 vector (p.NOTCH3) and mutant NOTCH3 (p.R90C) expression vector to HS683 cells (blank control vector group,wild NOTCH3 vector group,and mutant NOTCH3 vector group);the protein expressions of NOTCH3,p53,phosphorylated p53 and p21 were detected by Westem blotting.(2) Wild NOTCH3 vector group,mutant NOTCH3 vector group and mutant NOTCH3 vector+pifithrin-α group were divided,and after wild NOTCH3 vector (p.NOTCH3) and mutant NOTCH3 (p.R90C) vector transfection,the latter two groups were added 0 or 1 μmol/L pifithrin-α,respectively;CCK-8 assay was employed to test the proliferation oftransfected HS683 cells 24,48 and 72,and 96 h after transfection.Results (1) As compared with wild NOTCH3 vector group,mutant NOTCH3 vector group had significantly lower absorbance value 24,48 and 72 h after transfection (P<0.05);72 h after transfection,wild NOTCH3 vector group and mutant NOTCH3 vector group had significantly higher NOTCH3 protein expression as compared with blank control vector group (P<0.05),and mutant NOTCH3 vector group had significantly higher p53,phosphorylated-p53 and p21 protein expressions as compared with wild NOTCH3 vector group and blank control vector group (P<0.05).(2) The absorbance value in the mutant NOTCH3 vector+pifithrin-α group was significantly increased as compared with that in the mutant NOTCH3 vector group 48,72 and 96 h after transfection (P<0.05).Conclusion Mutation of NOTCH3 (R90C) may inhibit the proliferation of oligodendrocyte cell lineage via p53 dependent way,which might play a direct role in demyelination pathology of CADASIL caused by NOTCH3(R90C).
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Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a newly defined inflammatory central nervous system disorder.Ataxia,dysphasia,and diplopia are the most common clinical symptoms.The radiological distribution is focused on the brain stem and cerebellum;the perivascular and T cell predominant inflammatory cell infiltrates in the affected lesions.Rapid clinical and radiological improvements of symptoms were observed with the use of glucocorticosteroid based immunosuppression,while any attempts to withdrawal or taper GCS below a particular lower dose limit may provoke the recurrence of clinical or radiological symptoms.
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AIM:Toinvestigatetheeffectofrhynchophylline(Rhy)onbloodpressure,cardiachypertrophy and myocardial fibrosis in spontaneously hypertensive rats ( SHR) .METHODS:Spontaneously hypertensive rats were ran-domly divided into model group , high dose (10 mg? kg-1? d-1 ) and low dose (2.5 mg? kg-1? d-1 ) group of rhyncho-phylline, captopril group (17.5 mg? kg -1? d-1).Wistar-Kyoto rats were used as normal control.Respectively, systolic blood pressure was measured by tail cuff every 2 weeks.After 10 weeks, heart weight index and left ventricular weight in-dex were calculated .The myocardial hydroxyproline and plasma angiotensin Ⅱwere detected .Moreover , basic myocardial histopathological changes and myocardial collagen fibres were observed by HE staining and Masson staining , respectively . The protein expression of TGF-β1 and Smad3 in the myocardium was measured by the methods of immunohistochemistry and Western blot .RESULTS:Compared with SHR model group , Rhy significantly reduced blood pressure ( P<0.05 ) , the levels of HYP in the myocardium (P<0.05) and the levels of AngⅡin the plasma (P<0.01).The pathological dama-ges of the myocardial tissues and collagen deposition were attenuated .The protein expression of TGF-β1 and Smad3 was sig-nificantly reduced by the treatment with Rhy (P<0.01).CONCLUSION:Rhynchophylline reduces blood pressure and adjusts to improve ventricular remodeling of SHR .The mechanism may be involved in the TGF-β1/Smad pathway and re-ducing AngⅡcontent.
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Objective To explore the way of contrast-enhanced ultrasound(CEUS)and quantitative analysis technology to assess testicular microvascular ischemia-reperfusion inj ury.Methods Twenty-four healthy adult rabbits were randomly divided into the control group and the microvascular mild,moderate, serve ischemic inj ury group (group Ⅰ,including group Ⅰ1 ,Ⅰ2 ,Ⅰ3 ).The spermatic cord of the control group were threaded but not ligated.The group Ⅰ1 ,Ⅰ2 ,Ⅰ3 were reperfused 2 h after 2 h,4 h,6 h complete testicular ischemia respectively.The ultrasound contrast angiographic parameters of each group were analyzed by the quantitative analysis techniques,including peak intensity(PI),time to peak(TP),slope,mean transmit time(MTT),DT/2 and area.The levels of plasma vWF,NO and ET-1 were tested after the CEUS. The pathological changes of the ipsilateral testicular were observed by the HE and immunohistochemical staining.Statistical analysis was performed by SPSS 13.0 software.Results Preoperativeiy,each parameter of the experimental group and the control group showed no statistical significance (P > 0.05 ). Postoperatively,the PI,slope,area of the group Ⅰ1 increased significantly,while the TP,MTT were prolonged(P <0.05).Contrast time-intensity curve was significantly higher peak and retrusion.The groupⅠ2's PI,slope,area increased further,DT/2 was significantly prolonged,but TP significantly reduced (P <0.05).The contrast curve significantly increased,forward and decreased slowly.The contrast curves of the group Ⅰ3 was approximate a straight line.The vWF,NO,ET-1 levels of each experimental group were significantly higher than those in control group (P <0.05),among them,the levels of group Ⅰ2 were the highest (P <0.05 ).With the aggravation of ischemia,the testicular capillaries expansion,erythrocyte sedimentation,leakage,infiltration of inflammatory cells,MMP-9 expression in vascular basement membrane gradually increased.Conclusions The CEUS and quantitative analysis techniques can effectively evaluate testicular microvascular inj ury.
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BACKGROUND:Osteoarthritis and osteoporosis are two aging-related degenerative diseases. There are a lot of studies on their correlation, but no consensus has been reached yet. OBJECTIVE: To examine the cross-sectional association between phalangeal bone mineral density and radiographic knee osteoarthritis. METHODS:A total of 2 855 participants were included in this study. Phalangeal bone mineral density and anteroposterior films of the bilateral knees were detected. A multivariable logistic analysis model was applied to test the relationship between phalangeal bone mineral density and radiographic knee osteoarthritis after adjusting a number of potential confounding factors. RESULTS AND CONCLUSION:A positive association was observed between phalangeal bone mineral density and radiographic knee osteoarthritis in the model that was adjusted for sex, age, bone mass index, smoking status, alcohol drinking status, total energy intake, mean calcium intake, as wel as vitamin and Ca supplementation. This association existed in the total sample and the female subgroup, but not in the male. These findings suggest a positive relationship between phalangeal bone mineral density and radiographic knee osteoarthritis in the female subgroup, which means that bone mineral density is a protective factor to knee osteoarthritis.
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Hemodynamic situation is an important factor of recurrence of postoperative carotid artery aneurysm. In order to investigate the hemodynamic factors of postoperative carotid artery aneurysm affect carotid artery aneurysm recurrence, we established a 3D finite element carotid artery aneurysm for the preoperative and postoperative periods using the three-dimensional reconstruction techniques. And then we measured the hemodynamic factors of carotid artery aneurysm of preoperative and postoperative by the finite element method. The carotid artery aneurysm model has an accurate and realistic shape; the pressure of the recurrence of aneurysm was reduced significantly after surgery,wall shear stress increased significantly at residual neck, and blood flow velocity increased significantly, which will increase the risk of recurrence. The hemodynamic analysis provides a reference for development of aneurysm clinical treatment programs and prevention of recurrence.
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Humans , Aneurysm , Pathology , General Surgery , Blood Flow Velocity , Carotid Arteries , Pathology , General Surgery , Computer Simulation , Hemodynamics , Stress, MechanicalABSTRACT
The study of mechanical properties on heart valves can provide an important theoretical basis for doctors to repair heart valves and prosthetic valve materials research. In this paper, we present the current status of the mechanical property study methods of heart valve, expound the methods and special requirements about uniaxial tensile test and biaxial tensile test of the heart valve, and further discuss several establishment methods of heart valve constitutive models. We also discuss the development trend of heart valve mechanics.