Predictive Value of Exercise Blood Pressure Changes for Orthostatic Hypotension in Patients With Parkinson’s Disease

Background@#and Purpose Orthostatic hypotension (OH) is common in patients with Parkinson’s disease (PD). Early recognition OH is required with sensitive assessments. The purpose of this study was to determine whether blood pressure (BP) changes during exercise can predict the occurrence of OH in PD. @*Methods@#This prospective cohort study included 80 consecutive patients with PD. All patients agreed to participate in a baseline evaluation and cardiopulmonary exercise test (CPET).According to the initial active standing test (AST), those without OH (PD-nonOH) at baseline had their AST results followed up for 6 months. The main outcome was defined as whether patients without OH at baseline would develop OH after 6 months. Logistic regression analysis was applied to identify the relevant variables. A nomogram was constructed based on clinical features and identified variables. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were used to evaluate the accuracy and predictive ability of the nomogram, respectively. @*Results@#CPET results indicated that peak load, peak heart rate, heart rate recovery at 1 min, and systolic BP change (ΔSBP) were lower in those with OH than in the PD-nonOH group (p<0.05) at baseline. Logistic regression analysis indicated that peak load and ΔSBP during CPET had significant effects on OH (p<0.05). Age, sex, peak load, and ΔSBP were used to construct the nomogram model (C-index=0.761). The prediction model had an AUC of 0.782 (95% confidence interval=0.649–0.889) and a specificity and sensitivity of 70.0% and 81.8%, respectively. @*Conclusions@#This study has identified predictive factors for OH development in patients with PD. CPET could be used as a complementary examination to identify patients at a high risk of OH.

Preliminary report of using cardiopulmonary exercise testing guide exercise rehabilitation in patients with chronic heart failure / 中国应用生理学杂志

<p><b>OBJECTIVE</b>The exercise rehabilitation in patient with chronic heart failure (CHF) is standard clinical practice, but it is rare using CardioPulmonary Exercise Testing (CPET) guide to prescribe exercise rehabilitation in China.</p><p><b>METHODS</b>We performed symptom limited maximal CPET in 10 patients with CHF, randomly divided into two groups: 5 patients as control without exercise and 5 exercise patients used Δ50%W intensity to exercise 30 min/d, 5 d/w, x12 w. Before and after 12 w rehabilitation, we evaluated functions.</p><p><b>RESULTS</b>There were no significant difference between two groups patients (P > 0.05). The exercise duration was increased from 8 min to 23 min after rehabilitation (P < 0.001); distance 6 minutes walking was increased from 394 m to 470 m (P < 0.05); score of Minnesota quality of life was decreased from 25 to 3 in exercise group (P < 0.01). However, there were nosignificant changes in control group (P>0.05) and their changes were smaller than those in exercise group (P < 0.01).</p><p><b>CONCLUSION</b>The CPET guiding exercise rehabilitation is safe and effective for patients with CHF.</p>

Genetic characteristics of hemagglutinin in measles viruses isolated in Henan Province, China / 病毒学报

This study aims to investigate the genetic characteristics of hemagglutinin in wild-type measles viruses in Henan Province, China and to provide a basis for measles control and elimination. Specimens were collected from suspected measles cases in Henan during 2008-2012. Cell culture was performed for virus isolation, and RT-PCR was used to amplify hemagglutinin gene. The PCR products were sequenced and analyzed, including construction of phylogenetic tree and analysis of the distance between the isolated virus and the reference virus; then, the variations in predicted amino acids were analyzed. The results showed that 12 measles viruses were isolated in Henan Province and identified as H1a genotype; the nucleotide and amino acid homologies were 98.0%-100% and 97.2%-99.8%, respectively. One glycosylation site changed in all the 12 sequences because of the amino acid mutation from serine to asparagine at the 240th site, as compared with Edmonston-wt. USA/54/A. Overall, the wild-type measles virus genotype circulating in Henan Province from 2008 to 2012 was H1a, with high homology between strains; there were some variations in amino acid sequences, resulting in glycosylation site deletion.

Cardioprotective mechanism of calreticulin up-regulation induced by hypoxic postconditioning / 生理学报

Calreticulin (CRT) is an essential Ca(2+)-binding chaperone existing in endoplasmic reticulum (ER) or sarcoplasmic reticulum (SR), and is involved in intracellular Ca(2+) homeostasis and protein folding. Ischemic postconditioning (I-postC), a newly discovered endogenous protective phenomenon, induces CRT up-regulation. The present study aimed to investigate the cardioprotective mechanism of CRT up-regulation induced by hypoxic postconditioning (H-postC). Primary cultured neonatal rat cardiomyocytes were exposed to 2 h of hypoxia followed by 24 h of reoxygenation. Postconditioning was carried out by two cycles of 10 min of reoxygenation and 20 min of rehypoxia after 2 h of hypoxia. Antisense oligodeoxynucleotides (AS-ODNs) were used to inhibit CRT expression 36 h before hypoxia. Cardiomyocytes were randomly divided into 6 groups as follows (n=4): control, hypoxia/reoxygenation (H/R), H-postC, AS, AS + H/R, and AS + H-postC. Morphological studies, lactate dehydrogenase (LDH) activity assay in culture medium, and flow cytometry were used to detect cardiomyocyte necrosis and apoptosis. Intracellular Ca(2+) concentration was detected by fluorescent Fluo-3/AM staining through laser confocal microscope, and p-nitrophenyl phosphate (PNPP) was used as substrate to measure calcineurin (CaN) activity. The expression of CRT, CaN, nuclear factor kappa B (NFκB) and apoptosis-related proteins, such as Bcl-2, Bax and C/EBP homologous protein (CHOP) were detected by Western blot. The results were as follows. (1) H-postC protected neonatal cardiomyocytes from H/R injury. Compared with H/R group, cell survival rate increased by 17.1%, apoptotic rate and LDH leakage decreased by 6.67% and 27.9% in H-postC group, respectively (P<0.05). (2) H-postC induced mild up-regulation of CRT expression. Inhibition of CRT by AS-ODNs attenuated the cardioprotection of H-postC partly. Compared with H-postC group, cell survival rate decreased by 8.98%, and apoptotic rate and LDH leakage increased by 1.74% and 13.6% in AS + H-postC group, respectively (P<0.05), but intracellular Ca(2+) concentration, CaN activity, and expression of CaN and NFκB did not change significantly (P>0.05), suggesting that CRT participates in endogenous protection, not through Ca(2+)-CaN pathway. (3) H-postC inhibited the expression of pro-apoptosis proteins such as Bax and CHOP, but induced up-regulation of anti-apoptosis protein Bcl-2. Inhibition of CRT by AS-ODNs partly inhibited the changes in apoptosis-related proteins expression induced by H-postC, suggesting that CRT participates in the anti-apoptosis effect of H-postC through regulating expression of apoptosis-related proteins. These results indicate that CRT up-regulation induced by H-postC is involved in the cardioprotection through regulating expression of apoptosis-related proteins, not through Ca(2+)-CaN pathway in neonatal cardiomyocytes.

C/EBP homologous protein-mediated endoplasmic reticulum stress-related apoptosis pathway is involved in abdominal aortic constriction-induced myocardium hypertrophy in rats / 生理学报

Endoplasmic reticulum stress (ERS) is an adaptive process in response to circumstantial changes, but excessive and/or prolonged ERS can induce cell apoptosis. C/EBP homologous protein (CHOP) is a very important marker participating in ERS-associated cell apoptosis, while the role of the myocyte apoptosis induced by CHOP remains unclear in the development of hypertrophy. The present study aimed to investigate the effect of CHOP-mediated ERS-associated apoptosis on myocardial hypertrophy induced by abdominal aortic constriction in rats. Healthy male Wistar rats were randomly divided into model group (n=45) and control group (n=40). The rats in model group received abdominal aortic constriction. Hemodynamic changes, whole heart weight/body weight (HW/BW) and left ventricular weight/body weight (LVW/BW) were measured on 1 d, 3 d, 7 d, 14 d and 28 d after surgery, respectively. The mRNA expression of glucose-regulated protein 78 (GRP78), calreticulin (CRT) and CHOP, which are important markers of ERS, were detected by RT-PCR, and Western blot was used to assess the protein level of GRP78, CRT, CHOP, and apoptosis-associated proteins, Bax and Bcl-2. The results obtained were as follows. Compared with control group, the blood pressure, LVW/BW, and HW/BW of rats in model group increased significantly and cardiac function enhanced compensatively on 7 d after surgery, and increased progressively during the experiment. As early as 1 d after surgery, the mRNA level of CRT in model group increased by 136% (P< 0.01) compared with control, while the protein expression increased by 69.2% on 7 d after surgery (P<0.01). Both mRNA and protein expression of GRP78 increased by 20% and 186% (P<0.01) respectively on 7 d after surgery, and the expression sustained high level during the experiment afterwards. Correlation analysis indicated a positive correlation between +dp/dt(max) and CRT protein expression (r=0.780, P<0.01) as well as GRP78 protein expression (r=0.694, P<0.01). Prolonged ERS triggered myocyte apoptosis, as both the mRNA and protein level of CHOP in model group increased by 22.2% (P<0.01) and 76.0% (P<0.01) respectively compared with control on 7 d after hypertrophy (14 d after surgery), and meanwhile, the protein expression of pro-apoptotic Bax increased by 41.1% (P<0.01) and anti-apoptotic Bcl-2 protein expression decreased by 25.5% (P<0.01). Correlation analysis indicated a positive correlation between CHOP and Bax expression (r=0.654, P<0.01), and a negative correlation between CHOP and Bcl-2 expression (r=-0.671, P<0.01). These results suggest that abdominal aortic constriction induces a significant up-regulation in ER molecular chaperones at early stage of post-surgery, indicating that ERS response is activated in the rat heart; while prolonged ERS could lead to myocyte apoptosis, and CHOP-mediated ERS-associated apoptosis may contribute to myocardial hypertrophy. We speculate that cell apoptosis may take part in the regulation of myocardial hypertrophy and heart failure, and determine the progression of decompensated hypertrophy.

Genetic characterization of Chinese rubella virus isolates from 2003 to 2007 / 病毒学报

57 rubella virus strains were isolated using Vero cell line or Vero/SLAM cell line from patients' throat swabs during rubella outbreaks and sporadics in 10 provinces of China from 2003 to 2007. Fragments of 1107 nucleotides of E1 genes of the isolates were amplified by RT-PCR, the PCR products were directly sequenced and analyzed. The phylogenetic analysis based on 739 nucleotides showed that out of 57 Chinese rubella virus strains, 55 belong to a distinguish branch of 1E genotype when comparing with 1E genotype rubella strains from other countries, and the other 2 Chinese rubella virus strains belong to 2B genotype. Most of the nucleotide mutations of 57 rubella viruses were silent mutations, and the amino acid sequences were highly conserved. Except one amino acid change (Thr212 --> Ser212) in two rubella viruses at the hemagglutination inhibition and neutralization epitopes, there had no change found at the important antigenic epitope sites of the other rubella viruses. 1E genotype rubella viruses isolated from 10 provinces of China from 2003 to 2007, and two imported 2B genotype rubella viruses from Vietnam suggested that 1E genotype was the predominant genotype in this period of time. The rubella virus genotypes circulated during 2003 to 2007 were different from that circulating during 1979 to 1984 and 1999 to 2002, the rubella prevailed in recent years was mainly caused by 1E genotype rubella viruses with multi-transmission routes.

Calreticulin is involved in ischemic postconditioning-induced attenuation of ischemia/reperfusion injury in rat skeletal muscle / 生理学报

The present study was aimed to investigate the effect of ischemic postconditioning (I-postC) on ischemia/reperfusion (I/R) injury and whether calreticulin (CRT) is involved in its intracellular signal transduction both in vivo and in cultured skeletal muscle cells. I/R injury in the right hind limb of healthy male Wistar rats was induced by clamping the right femoral artery, and the rats were randomly divided into 3 groups (n=16): I/R group (4-hour ischemia/12- or 24-hour reperfusion), ischemic preconditioning (IPC) group (3 cycles of 1-minute ischemia/1-minute reperfusion) and I-postC group (3 cycles of 5-minute reperfusion/5-minute ischemia). The left hind limb was used as control. Lactate dehydrogenase (LDH) activity in blood plasma, wet/dry weight ratio (W/D) and ultramicrostructure of skeletal muscle were detected 12 h or 24 h after reperfusion. Cultured skeletal muscle cells from neonatal Sprague-Dawley (SD) rat were divided into 6 groups: hypoxia/reoxygenation (H/R) group, hypoxic postconditioning (H-postC) group, hypoxic preconditioning (HPC) group, cyclosporine A (CsA) + H-postC group, CsA + H/R group and control group. H/R was produced by 2-hour hypoxia/24-hour reoxygenation. The survival rate and apoptotic rate of skeletal muscle cells in each group were measured. Western blot was used to detect the expressions of CRT and calcineurin (CaN). The results were as follows: (1) During in vivo experiment, compared with I/R, I-postC significantly decreased LDH activity and W/D, attenuated the ultramicrostructure injury of skeletal muscle and the apoptosis of nucleolus. 12 h and 24 h after reperfusion, compared with that in I/R group, the expression of CRT in I-postC group increased by 439% and 102%, respectively (P<0.05), and the expression of CaN increased by 196% and 63%, respectively (P<0.05). Correlation analysis indicated a positive correlation between CRT and CaN expressions (r=0.865, P<0.01). (2) In cultured skeletal muscle cells, H-postC attenuated cell injury induced by H/R. Compared with those in H/R group, CRT and CaN expressions in H-postC increased by 31.8% (P<0.05) and 6.02%, respectively. The protection of H-postC and CaN up-regulation were eliminated when CsA, the inhibitor of CaN, was added before H-postC. Both in vivo and in vitro results indicate that I-postC, similar as IPC, can protect the skeletal muscle against I/R injury, and its effects may be mediated by CRT and CaN up-regulation. The inhibition of CaN expression may also attenuate the protective effects of I-postC.