Hashimoto's encephalopathy presenting with isolated cerebellar ataxia in 13 children / 中华儿科杂志

Objective: To analyze the clinical characteristics, treatment and prognosis of Hashimoto's encephalopathy presenting with isolated cerebellar ataxia in children. Methods: A retrospective analysis was performed on the clinical features, laboratory tests, neuroelectrophysiological examination, imaging, treatment and outcomes of 13 patients with Hashimoto's encephalopathy presenting with isolated cerebellar ataxia, who were admitted to the Department of Pediatric Neurology of Guangzhou Women and Children's Medical Center from January 2016 to May 2021. Results: Among the 13 cases, 6 were males and 7 were females. The onset age was 2.6 (2.0,3.3) years, 9 children had precursor infection or vaccination before the first course of disease. All the 13 children had gait abnormalities or unsteady sitting, 10 had intentional tremor, 6 had dysarthria, 3 had body tremor, 2 had nystagmus, 3 had fatigue, 3 had hypotonia, 2 had vomiting and 1 had irritability. Thyroglobulin antibody (TgAb) was 500.0 (298.9,587.2) kU/L and thyroid peroxidase antibody (TPOAb) was 621.9 (449.6,869.4) kU/L in 13 cases. Autoantibodies were positive in 9 cases, and cerebrospinal fluid leukocytosis was seen in 4 cases. Regarding electroencephalography result, 4 cases had background slowing and 1 case had occasional sharp waves. Among the 3 patients who had relapses, 1 had cerebellar atrophy shown on cranial magnetic resonance imaging (MRI) during the recurrence. All the patients received intravenous immunoglobulin (IVIG) and intensive methylprednisolone therapy during the first onset, followed by the disappearance of the symptoms, 1 patient had repeated episodes which was decreased after immunosuppressive treatment with Rituximab.Followed up for 25.0 (22.5,33.3) months after the last episode, 12 achieved complete remission and 1 had a wide base gait. Conclusions: Trunk ataxia is the common symptom of Hashimoto's encephalopathy presenting with isolated cerebellar ataxia in children.Children with cerebellar ataxia should be tested for TgAb and TPOAb to detect Hashimoto's encephalopathy, avoiding missed diagnosis and treatment delays; IVIG and intensive steroid therapy is effective, and immunosuppressive therapy for patients with multiple relapses could reduce the recurrence.

Effect of Right Heart Systolic Function on Outcomes in Patients with Constrictive Pericarditis Undergoing Pericardiectomy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>To determine the influence of right ventricular function in patients with constrictive pericarditis (CP) undergoing surgery and to compare the outcomes of patients who received surgery with those managed medically.</p><p><b>METHODS</b>Patients with the diagnosis of CP and healthy volunteers were recruited from January 2006 to November 2011. Patients with CP chose to either receive pericardiectomy or medical management. Echocardiographic measurements were performed to evaluate heart function, and survival was recorded.</p><p><b>RESULTS</b>A total of 58 patients with CP (36 received pericardiectomy, 22 managed medically), and 43 healthy volunteers were included. CP patients who received surgery had a higher survival rate than those managed medically (P = 0.003), and higher survival was also seen in the subgroup of CP patients with severely impaired right systolic function. Albumin level, left ventricular end-diastolic dimension, and tricuspid regurgitation velocity were associated with survival in CP patients who received surgery.</p><p><b>CONCLUSIONS</b>Preoperative right heart function does not affect surgical outcomes. Patients with severely impaired preoperative right systolic function obtain a greater survival advantage with surgery than with medical treatment.</p>

Effects of Rapamycin and Rapamycin-loaded Poly(lactic-co-glycolic)Acid Nanoparticles on Apoptosis and Expression of bcl-2 and p27(kip1) Proteins of Human Umbilical Arterial Vascular Smooth Muscle Cell / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investgate the effects of rapamycin(RPM)and RPM-loaded poly(lactic-co-glycolic)acid(PLGA)nanoparticles(NPs)on the apoptosis of human umbilical arterial vascular smooth muscle cells(HUASMCs)in vitro and expression of bcl-2 and p27(kip1) protein.</p><p><b>METHODS</b>HUASMCs were cultured in vitro and divided to RPM and RPM-PLGA-NPs groups treated at 3 different concentration by 12 and 24 hours,with M231-smooth muscle growth supplements medium and null-PLGA-NPs treated groups as controlled. The apoptosis of HUASMCs was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and flow cytometry. The expressions of bcl-2 and p27(kip1) were detected by streptacidin/peroxidase immunohistochemical method. The effect on cellular proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidecolorimetry.</p><p><b>RESULTS</b>The proliferation of HUASMCs was inhibited by RPM and RPM-PLGA-NPs in a dose-dependent manner. DNA electrophoresis showed DNA ladder in RPM and RPM-PLGA-NPs groups and classical scalar strips in control groups. The apoptotic indexes of RPM 100 ng/ml group and RPM-PLGA-NPs 500 ng/ml group detected by flow cytometry were(45.45<2.36)% and(35.04<5.64)%,respectively,which were significantly higher than that of M231-smooth muscle growth supplements control group [(2.60<0.95)%,all P<0.01]. The apoptotic indexes of groups incubated with RPM and RPM-PLGA-NPs for 24 hours were significantly higher than those of groups which incubated for 12 hours(P<0.05,P<0.01). The positive expression indexes(PEI)of p27(kip1) and bcl-2 protein were higher in RPM and RPM-PLGA-NPs groups than that of control groups. The Spearman's rank correlation coefficient test showed that there was no significant correlation between the PEI of p27(kip1) and the apoptotic indexes in the RPM group and RPM-PLGA-NPs group(P>0.05).</p><p><b>CONCLUSIONS</b>Rapamycin-loaded PLGA nanoparticles and rapamycin have similar effects in inhibiting proliferation and inducing apoptosis;meanwhile,they upregulate the expression of p27(kip1) protein without downregulating the expression of bcl-2 protein in HUASMCs in vitro. RPM-PLGA-NPs has more potent pro-apoptotic effect than equivalent dose of RPM but is not linearly correlated with the p27(kip1) expression level.</p>

Growth Differentiation Factor 15 Inhibits Elevated Expression of Matrix Metalloproteinase 1 Induced by Pooled Serum in Patients with Coroanry Artery Ectasia / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the effects of coroanry artery ectasia (CAE) patients' pooled serum on the main proteinases and extracellular matrix (ECM) synthesis and explore whether the growth differentiation factor 15(GDF 15) can regulate the characteristic changes induced by CAE patients' pooled serum.</p><p><b>METHODS</b>Serum samples were collected from 32 CAE patients, 30 patients with coronary heart disease (CHD), and 31 subjects with normal coronary arteries (CON) and then mixed in the same volumes by groups. Then human umbilical vein smooth muscle cells were cultured with the media containing 25% pooled serum. After having been disposed, proteinase system and ECM synthesis system were detected in the cell and culture media samples. GDF15 or GDF15 antibodies was added into the 25% pooled serum in each group to observe if GDF 15 could impact the characteristic changes induced by CAE patients' pooled serum.</p><p><b>RESULTS</b>The expression of matrix metalloproteinases (MMP) 1 mRNA in CAE group was significantly higher than CON group (P=0.002) and CHD group (P=0.000), the secretory MMP1 protein and total MMPs activity in culture media were also upregulated in CAE group (both P<0.01). After adding GDF 15 into the culture media (GDF15+CAE group), the MMP1 mRNA ,secretory MMP1 protein, and total MMPs activity were significantly lower than CAE group (all P<0.01), while in the GDF15 antibody+CAE group, the MMP1 mRNA and total MMPs activities were significantly higher than in GDF15+CAE group (both P<0.01), but the secretory MMP1 protein was not different from GDF 15+CAE group (P>0.05).</p><p><b>CONCLUSION</b>The vascular smooth muscle cells may participate in the CAE process mainly by regulating MMPs system but not the elastase 2 or ECM synthesis system, and GDF15 may be an compensatory factor to prohibit the over-destruction of coronary ECM induced by MMPs.</p>

Importance of endomyocardial biopsy in unexplained cardiomyopathy in China: a report of 53 consecutive patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although endomyocardial biopsy (EMB) plays a crucial role in the final diagnosis in patients with heart failure of unknown etiology, the invasive nature of this technique limits its clinical application in China. The purpose of this study was to evaluate the clinical application of EMB in diagnosing cardiomyopathy with unexplained etiologies in China.</p><p><b>METHODS</b>Fifty-three consecutive patients (38 males, age 14 - 67 years, median 43 years) were included in the study who were initially diagnosed as unexplained cardiomyopathy and under EMB biopsy in Peking Union Medical College Hospital from 2006 to 2009. The patients were clinically divided into four groups: dilated, hypertrophic, restrictive and unclassified cardiomyopathy. Biopsies were performed via right internal jugular vein with the use of the bioptome under fluoroscopic guidance. Three to five endomyocardial samples were taken from each patient for light microscopy examination and one sample for electron microscopy was taken if necessary. For each patient, an initial clinical diagnosis, an EMB diagnosis and a final diagnosis prior to discharge were established. All the data were compared and analyzed for the evaluation of clinical utility of EMB in China.</p><p><b>RESULTS</b>In 26 patients initially diagnosed with restrictive cardiomyopathy (RCM), the etiology of the condition was finally diagnosed using EMB in 15; including 13 amyloidosis and two eosinophilic myocarditis. We employed EMB in 19 patients clinically diagnosed as dilated cardiomyopathy and detected viral myocarditis in one patient, cardiac involvement due to polymyositis in four and doxorubicin-induced cardiomyopathy in one. In five patients with severe left ventricle hypertrophy undergoing EMB, one patient was diagnosed as autophagic vacuolar cardiomyopathy and one as mitochondrial disease. In the remaining three patients with unclassified cardiomyopathy, EMB revealed infiltration of eosinophils as the cause of atrial ventricular block in one patient. Final diagnoses were made in 24 of the total 53 patients (45%) based on the combination of EMB and clinical data. Transient atrial ventricular block in a patient with prior complete left bundle branch block was the only complication occurred during the procedures.</p><p><b>CONCLUSION</b>The clinical application of EMB is safe. The combination of EMB and clinical data produced a better understanding of the mechanisms behind the clinically diagnosed cardiomyopathy in China.</p>

Effects of rapamycin-loaded poly(lactic-co-glycolic) acid nanoparticles on distribution of cell cycle, expression of p27 protein, and proliferation of human umbilical arterial vascular smooth muscle cell in vitro / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the effects of rapamycin (RPM)-loaded poly (lactic-co- glycolic) acid (PLGA) nanoparticles (NPs) on the proliferation, distribution of cell cycle, and expression of p27 protein in human umbilical arterial vascular smooth muscle cell (HUASMC) in vitro.</p><p><b>METHODS</b>The primarily culture model of HUASMC was successfully established by explant-attached method in vitro. The cells were administrated with different doses of RPM, and RPM-PLGA NPs were observed as treat groups compared with PLGA NPs and M231-SMGs medium cultured group. The effect of RPM-PLGA NPs on proliferation of HUASMC was assessed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetry method. The influences of RPM-PLGA NPs on the cell cycle and cellular growth kinetics of HUASMCs were tested by flow cytometry. The effect of RPM-PLGA NPs on the expression of p27 protein of HUASMCs was assessed through an immunohistochemical method.</p><p><b>RESULTS</b>Compared with the control group, the proliferation of HUASMCs was inhibited by 50 microg/L and higher concentration of RPM-PLGA NPs in a dose-dependent manner (P < 0.05). The numbers of cells entering cell cycle of S/G2/M phases were significantly lower in RPM-PLGA NPs and RPM treated groups. Histologically, the expression of p27 were up-regulated in 500 microg/L RPM-PLGA NPs and 100 microg/L RPM treated group (all P < 0.01 ) when compared with the control group.</p><p><b>CONCLUSIONS</b>RPM-PLGA NPs has a similar effects as RPM in inhibiting the growth of in vitro cultured HUASMC. It can remarkably suppress the expression of in vitro cultured HUASMC p27 protein, arrest its cell cycle at G1/S phase, and inhibit its proliferation.</p>

Clinical manifestations of young and aged patients with coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze clinical characteristics in young and aged patients with coronary artery disease (CAD).</p><p><b>METHODS</b>The clinical and coronary angiographic data were compared between young (PCAD, male < 55 years old, n = 74, female < 65 years old, n = 71) and aged (CAD, male > 55 years old, n = 106, female > 65 years old, n = 111) patients. Seventy-one patients excluded with CAD by angiography served as controls (non-CAD). The traditional risk factors (including age, smoking, blood pressure, lipid profile, blood glucose, BMI, family history), coronary angiographic changes were analyzed and compared among various groups.</p><p><b>RESULTS</b>(1) Compared with CAD group, PCAD patients had significantly higher rate of smoking (50.3% vs. 38.0%, P < 0.05), significantly higher positive CAD family history rate (29.7% vs. 19.9%, P < 0.05) and significantly higher TG level [(2.13 +/- 1.89) mmol/L vs. (1.78 +/- 1.14) mmol/L, P < 0.05], while had significantly fewer traditional risk factors (2.50 +/- 1.28 vs. 2.76 +/- 1.43, P < 0.05) and lower hypertension rate (59.3% vs. 73.3%, P < 0.05). There were significantly more PCAD patients with acute coronary syndrome (66.2% vs. 42.6%, P < 0.05), more PCAD patients had single vessel lesion (51.0% vs. 30.4%, P < 0.05), lower average lesion score (4.86 +/- 2.30 vs. 5.92 +/- 2.66, P < 0.05). (2) The logistic regression results showed that positive CAD family history (P = 0.029, OR = 1.766, 95% CI 1.060 - 2.940) and smoking (P = 0.066, OR = 1.561, 95% CI 0.971 - 2.510) are important independent risk factors for the development of PCAD.</p><p><b>CONCLUSIONS</b>Smoking, positive family history and the increased TG might contribute to the pathogenesis of PCAD.</p>

Rapamycin-loaded poly (lactic-co-glycolic) acid nanoparticles for intraarterial local drug delivery: preparation, characterization, and in vitro/in vivo release / 中国医学科学院学报

<p><b>OBJECTIVE</b>To sought to engineer and characterize a biodegradable nanoparticles (NPs) containing rapamycin which use poly (lactic-co-glycolic) acid (PLGA) as the carrier matrix and to assess its in vivo release characteristics by local drug delivery system intravascularly.</p><p><b>METHODS</b>Rapamycin-loaded PLGA NPs were prepared by an emulsification/solvent evaporation technique, and NPs size distribution was assessed by submicro laser defractometer. The particle morphology was observed by scanning electron microscopy. In vitro release from the NPs was performed in TE buffer at 37 degrees C under rotation utilizing double-chamber diffusion cells on a shake stander. In vivo NPs intravascular local delivery were performed by DISPATCH catheter in New Zealand rabbit abdominal aorta and Chinese experimental mini-pigs coronary artery models.</p><p><b>RESULTS</b>Biodegradable rapamycin loaded PLGA NPs were constructed successfully by emulsification solvent-evaporation technique. The diameter of rapamycin-PLGA NPs was around 246.8 nm with very narrow size distribution, and rapamycin-NPs showed good spherical shape with smooth uniform surface. Rapamycin loaded in NPs were around was 19.42%. Encapsulation efficiency of drug was over 77.53%. The in vitro release of rapamycin from NPs showed that 75% of the drug was sustained released over 2 weeks and controlled release in a linear pattern. After a single 10 minutes infusion of rapamycin-PLGA NPs suspension (5 mg/ml) under 20.27 kPa through DISPATCH catherter in vivo, the mean rapamycin levels at 7 day and 14 day were (2.438 +/- 0.439) and (0.529 +/- 0.144) microg/mg of the dry-weight of the artery segments (2 cm) which local delivery were administrated.</p><p><b>CONCLUSIONS</b>PLGA NPs controlled drug delivery system for intraarterial local anti-proliferative drug delivery can potentially improve local drug concentration and prolong drug residence time in animal model in vivo. It should be appropriate for further study of its therapy efficiency in human.</p>

Risk factors for coronary artery disease stimulate urokinase receptor expression on monocytes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effect of risk factors for coronary artery disease (CAD) on urokinase receptor (uPAR) expression on monocytes.</p><p><b>METHODS</b>A total of 106 patients were enrolled and divided into five risk-factor groups: sixteen with hypertension, twenty-four with dyslipidemia, eighteen with hypertension + obesity, eighteen with dyslipidemia + obesity and thirty with hypertension + dyslipidemia + obesity. Seventeen healthy volunteers were recruited as control group. Monocyte expression of uPAR and mean fluorescence intensity index (MFI Index) of uPAR were measured by flow cytometer (FACSCalibur).</p><p><b>RESULTS</b>No difference in monocyte uPAR expression was detected between hypertension and control group [(4.9 +/- 12.5)% vs. (7.7 +/- 10.3)%, P=0.74]. However, the uPAR expression was raised to (23.7 +/- 22.5)% in hyperlipidemia group, a 3.9- and a 2.1-fold increase compared with those in hypertension (P<0.01) and control group (P<0.05), respectively. When combined with obesity, uPAR expression was elevated further to (32.9 +/- 30.8)% in hypertension + obesity group, (37.4 +/- 31.4)% in dyslipidemia + obesity group and (23.8 +/- 20.5)% in hypertension + dyslipidemia + obesity group, all having statistical significance compared with control group or hypertension group (P<0.01). The results were the same when corrected by age, BMI and hs-CRP. uPAR MFI Index was increased from 0.78 +/- 0.86 in control group to 1.91 +/- 1.97 and 3.33 +/- 2.52 in dyslipidemia group and hypertension + obesity group, respectively, P<0.05. Linear regression analysis revealed a significant correlation between uPAR expression and FBG concentration in dyslipidemia group, r=0.72, P=0.04.</p><p><b>CONCLUSIONS</b>uPAR expression was elevated on monocytes in patients with risk factors for CAD. Dyslipidemia and obesity may contribute to the increase of uPAR expression.</p>

Urokinase receptor expression in atherosclerotic plaques of human femoral arteries / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the urokinase receptor (uPAR) expression in atherosclerotic plaques of human femoral arteries.</p><p><b>METHODS</b>Human femoral artery samples were collected from patients underwent femoral endarterectomy. Normal internal mammary artery samples were taken from bypass surgery served as control. uPAR protein distribution at shoulders, lipid pool and rupture sites of a plaque and the association with macrophages and smooth muscle cells (SMCs) were detected by immunohistochemistry methods.</p><p><b>RESULTS</b>There was no uPAR expression in intima or tunica media of normal internal mammary arteries. In atherosclerotic lesions of femoral artery, the mean optical density (A) of uPAR was 92 +/- 37 in intima and 46 +/- 28 in tunica media (P < 0.05). The intimal uPAR was coexisted with macrophages and SMCs. uPAR expression was observed at plaque shoulders and lipid pool, while the maximal expression was found at rupture sites.</p><p><b>CONCLUSION</b>The increased expression of uPAR in atherosclerotic lesion and uPAR distribution at shoulders, lipid pool, as well as rupture sites of plaques suggest a role of uPAR in plaque rupture process.</p>

Effects of valsartan and captopril on expressions and activities of tissue factor and tissue factor pathway inhibitor / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of ox-LDL, ACEI and ARB on expressions and activities of TF and TFPI in VSMC.</p><p><b>METHODS</b>(1) Rabbit VSMC was cultured by explant-attached method in vitro. (2) The effects of ox-LDL and valsartan on TF and TFPI expressions were analyzed by immunohistochemistry and immunofluorescence. Laser scanning confocal microscopy were applied to analyze the effects of ox-LDL and valsartan on TF expression. The effects of ox-LDL, valsartan and captopril on TF and TFPI antigen expressions were analyzed by ELISA. Chromogenic substrate method was used to determine the effects of ox-LDL, valsartan and captopril on TF activity. The effects of ox-LDL and valsartan on TF mRNA expression were analyzed by RT-PCR.</p><p><b>RESULTS</b>(1) ox-LDL could upregulate TF antigen, activity and TF expression at mRNA level and downregulate TFPI antigen. (2) Valsartan and captopril could reduce TF antigen and activity in VSMC treated by ox-LDL, and valsartan reduce it in a dose-dependent manner. Valsartan could also attenuate TF expression at mRNA level in VSMC treated by ox-LDL. (3) Using ELISA, valsartan and captopril could also enhance TFPI antigen in VSMC treated by ox-LDL.</p><p><b>CONCLUSION</b>Our study showed upregulated TF and downregulated TFPI expression and activity by ox-LDL and these effects could be reversed by ACEI and ARB indicating a new insight on the antiatherosclerotic effects of ACEI and ARB.</p>

Porcine MSC-derived CLC induced by rabbit's cardiomyocytes extract did not induce immune reaction in vivo / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the in vivo immune reaction of transplanting porcine MSC-derived CLC with rabbit cardiomyocytes extracts induced differentiation or in vitro cultured porcine MSC.</p><p><b>METHODS</b>After injecting the MSC-derived CLC or MSC to the original porcines, the number of CD4+, CD8+ T cells were determined by flow cytometry. The serum concentrations of IL-2, IL-4 were measured by ELISA, and the porcine spleen lymphocyte CTL cytotoxicity was determined by Cell Counting Kit-8 Assay.</p><p><b>RESULTS</b>The numbers of CD4+ and CD8+ T cells, the serum concentrations of IL-2, IL-4 and spleen lymphocyte CTL cytotoxicity were all similar in porcines received MSC-derived CLC induced by rabbit's CMs extract or MSC transplantation.</p><p><b>CONCLUSION</b>The porcine MSC-derived CLC induced by rabbit's CMs extract did not induce extra immune reaction when injected back to the original porcine.</p>

Differentiation of mesenchymal stem cells into cardio myogenic cells under the induction of myocardial cell lysate / 中华心血管病杂志

<p><b>OBJECTIVE</b>In order to understand the effects of cardiac microenvironment on the differentiation of bone marrow mesenchymal stem cells (MSCs) into myocardial-like cells, we simulated the cardiac microenvironment in vitro by adding myocardial cell lysate into the culture system of MSCs, and compared the differentiation promoting effect of myocardial cell lysate with that of well-established inducer 5-azacytidine (5-aza).</p><p><b>METHODS</b>Myocardial cells isolated from newly born rats were lysed by repeat freezing and defrosting. MSCs isolated from adult rat were cultured in four different systems. Medium A: medium with myocardial cell lysate; medium B: medium with 5-aza; medium C: medium with 5-aza and myocardial cell lysate; and control medium: ordinary medium without any addition reagent. The dynamic changes of MSCs morphology in different media were observed within 7 days after introduction of MSCs. Immunohistochemical staining against alpha-actin, cTnT, Connexin43 and CD31 were performed at the end of cultivation.</p><p><b>RESULTS</b>MSCs in both medium A and B were differentiated into myocardial-like cells expressing alpha-actin and cTnT after 7-day cultivation. Cells in medium A developed more myofilaments than those in medium B, and expressed CD31, whereas cells in medium B did not. MSCs in control medium only expressed alpha-actin.</p><p><b>CONCLUSIONS</b>Myocardial cell lysate is an ideal inducer to differentiate MSCs into myocardial-like cells in vitro. The differentiation promoting effect of myocardial cell lysate is more predominant than that of 5-aza.</p>