[The association of high-sensitivity C-reactive protein with new-onset hypertension in different age groups].

Objective: To investigate the association between high sensitivity C-reactive protein (hsCRP) level and new-onset hypertension in different age groups. Methods: This was a prospective cohort study involving non-hypertensive population in Kailuan Group community who participated in health examination between 2006 and 2007.Follow-up was conducted every 2 years, and the time of new onset of hypertension was used as the endpoint of follow-up. The endtime of follow-up for patients without hypertension was the time of death or the last follow-up (December 31, 2017).According to the baseline hsCRP level, the participants were divided into low-risk group (hsCRP<1.0 mg/L), medium-risk group (hsCRP ≥1.0 and ≤3.0 mg/L), and high-risk group (hsCRP>3.0 mg/L), and further stratified by age. Kaplan-Meier method was used to calculate the cumulative incidence of hypertension in each group. Multivariate Cox regression model was used to analyze the association between hsCRP level and new-onset hypertension. Results: A total of 51 179 participants were included in this study, including 38 606 males (75.43%) with an average age of (48.1±12.2) years. The baseline hsCRP was 0.64 (0.25, 1.60) mg/L. The baseline hsCRP was 0.30 (0.16, 0.59), 1.57 (1.20, 2.10), 5.17 (3.80, 7.10) mg/L respectively in low-, medium- and high-risk groups. During the follow-up of (8.1±2.2) years, a total of 9 523 (18.60%) patients developed hypertension, and the cumulative incidence rates of low-, medium- and high-risk groups were 17.41%, 20.48% and 20.73%, respectively. The cumulative incidence of hypertension in low-, medium- and high-risk groups of<45, 45-54, 55-64, ≥65 years old were 13.53%, 15.82%, 16.76%; 19.27%, 22.84%, 21.62%; 21.55%, 24.19%, 24.88%;20.20%, 22.35%, 19.11%, respectively. Except for people aged ≥65 years, there were significant differences in the cumulative incidence of hypertension in low-, medium- and high-risk groups (all P<0.05).Multivariate Cox regression analysis showed that the risk of new-onset hypertension in the high risk group was 1.11 times higher than that in the low risk group (HR=1.11, 95%CI 1.05-1.18). The risk of new-onset hypertension in the high-risk group was 1.22 times (HR=1.22, 95%CI 1.08-1.38), 1.14 times (HR=1.14, 95%CI 1.04-1.26), 1.16 times (HR=1.16, 95%CI 1.04-1.30), and 1.02 times (HR=1.02, 95%CI 0.86-1.20) of the low-risk group, in the<45, 45-54, 55-64, and ≥65 years old groups, respectively. Conclusion: Higher hsCRP level is a risk factor for new-onset hypertension, and the risk of developing hypertension caused by elevated hsCRP is age-dependent.

[Long-term follow-up of C(1)-C(2) pedicle screw fixation for pediatric atlantoaxial dislocation].

Objective: To investigate the clinical curative effect of C(1)-C(2) pedicle screw fixation for pediatric atlantoaxial dislocation after a long-term follow-up. Methods: From March 2005 to April 2011, a total of 12 male and 9 female patients were included, with age from 3 to 9 years old (mean, 6.1 years old). Among them, 14 cases (67%) had typeⅠinstability atlantoaxial dislocation, 7 cases (33%) had type Ⅱ reducible atlantoaxial dislocation. All 21 pediatric patients with atlantoaxial dislocation underwent posterior pedicle screw fixations. Frankel Grade was used to evaluate function before and after treatment. Furthermore, the information of C(1)-C(2) bony fusion, cervical spine alignment, angle of sagittal curvature, and instability of the subaxial spine were collected from all patients preoperatively, immediately postoperatively and during follow-up period. Results: All 21 patients had regular follow-up with an average duration of 96.4 months (range, 65 to 127 months). All children had good bony fusion within 6 months after treatment. There were 9 patients with lordotic alignment and 12 patients with straight alignment before surgery. After surgery, there were 12 patients with lordotic alignment and 9 patients with straight alignment. At the time of the last follow-up, 17 patients had lordotic alignment and 4 patients had straight alignment. No difference was found between pre- and post-operation (P=0.354). The same result was found between post-operation and last follow-up (P=0.095). Neither kyphotic nor swan-neck deformity was found in any of the 21 patients. The mean angle of sagittal curvature decreased from 31.7°±4.3°preoperatively to 15.5°±2.5°postoperatively (P<0.001). The mean angle of sagittal curvature increased from 15.5°±2.5°postoperatively to 19.1°±2.7°at the final follow-up (P=0.343). No spinal deformities or subaxial instabilities were found. Of the four patients with preoperative neurological defects, Frankel Grade was significantly improved at 3 months follow-up compared with pretreatment values. None of the patients experienced worsening neurological symptoms or injury to the vertebral artery. Conclusion: The results demonstrate that C(1)-C(2) pedicle screw fixation could achieve satisfactory clinical effects for the management of pediatric atlantoaxial dislocation with long-term follow-up.

Use a simple lower limb outrigger frame in intramedullary nailing fixation of a floating knee.

Closed intramedullary nailing is a classical therapeutic approach for floating knee injuries. An appropriate positioning is critical for a successful surgery. However, there is a lack of an ideal auxiliary device to facilitate the implantation of intramedullary nail. The authors developed a simple lower limb outrigger frame (SLLOF), which is made of nylon, to facilitate the nail implementation process. The SLLOF could be radiolucent and autoclavable. A total of 31 patients with floating knee injury underwent the closed intramedullary nailing assisted by SLLOF. The average operative duration was 91.0 min, and all tibial and femur fractures reached bony union. The SLLOF could assist well insertion of intramedullary nail for the treatment of floating knee injuries, with the advantages of simple operation, less manpower, easy imaging access but less radiation exposure, and more cost-effectiveness.

A retrospective cohort study of nasopharyngeal adenocarcinoma: a rare histological type of nasopharyngeal cancer.

OBJECTIVES: The purpose of this study was to investigate the clinical manifestations, Epstein-Barr virus (EBV) serology, and treatment outcome of patients with nasopharyngeal adenocarcinoma (NPAC). DESIGN: A retrospective study of clinical data from consecutive patients with NPAC identified between 1964 and 2000. SETTING: A tertiary cancer center in China. PARTICIPANTS: Forty-eight patients diagnosed with NPAC. MAIN OUTCOME MEASURES: Crosstabs and chi-square test were conducted to study the association of positive VCA-IgA levels among different pathological types of NPAC, and also to compare the proportions of local control rates in patients treated with different modalities. The survival rate was calculated using the Kaplan-Meier method, and the Log Rank test was used to compare the survival rates considering different factors. To balance the distribution bias, a multivariate COX model survival analysis was also performed. RESULTS: Of the 48 NPAC patients identified, 45% presented with cervical metastasis. Pathologically, 58% of NPAC cases were common type and 42% were salivary gland type. The positive rate for the EBV antibody VCA-IgA in all patients was 53% and only 24% in the salivary gland type of NPAC. The overall local control rate and the 5-year disease-free survival rates were 87% and 65% respectively. Patients treated with surgery plus radiotherapy (RT) had a significantly higher 5-year disease-free survival rate than patients receiving RT alone (89%versus 75% respectively) (P = 0.039). Multivariate analysis confirmed that treatment modality was the significant factor influencing patient survival (P = 0.027) and the pathological type was not a factor predicting survival. CONCLUSIONS: Nasopharyngeal adenocarcinoma is a distinct entity in all types of nasopharyngeal carcinoma and EBV serology has limited value in its diagnosis. The combination of surgery and RT should be considered for treatment of early lesions of NPAC.

Effects of age and food restriction on oxidative DNA damage and antioxidant enzyme activities in the mouse aorta.

In this study, DNA damage in mouse aortic cells was measured using the comet assay. The tail moment of the comet assay in aortic cells obtained from 26-month-old mice fed ad libitum (O-AL) was significantly increased as compared to 6-month-old mice fed ad libitum (Y-AL) after the cells were incubated with formamidopyrimidine-DNA glycosylase (Fpg), which specifically recognizes oxidized purines, endonuclease III (Endo III), which specifically recognizes oxidized pyrimidines, or the combination of Endo III and Fpg. The tail moment in aortic cells obtained from 26-month-old mice fed a food-restricted diet (O-FR) was significantly reduced as compared to O-AL mice after the cells were incubated with the combination of Endo III and Fpg. These results indicate that oxidative DNA lesions, i.e. the Endo III- and Fpg-sensitive sites, increase with age in mouse aortic cells and that FR attenuates the age-related increase in oxidative DNA damage. To determine if the changes in oxidative DNA damage in mouse aortic cells are related to the antioxidant status in these cells, we measured the activities of Cu/Zn-superoxide dismutase (SOD), Mn-SOD, extracellular-SOD, catalase and glutathione peroxidase-1 in the mouse aorta. We observed that the activities of all antioxidant enzymes studied were significantly increased with age and that FR attenuated the age-related increase. These data indicate that the age-related increase and FR-induced decrease in oxidative DNA damage, i.e. the Endo III- and Fpg-sensitive sites, in mouse aortic cells is not due to alteration of the antioxidant defense system.

Does oxidative damage to DNA increase with age?

The levels of 8-oxo-2-deoxyguanosine (oxo8dG) in DNA isolated from tissues of rodents (male F344 rats, male B6D2F1 mice, male C57BL/6 mice, and female C57BL/6 mice) of various ages were measured using sodium iodide to prevent oxidative damage to DNA during DNA isolation. Oxo8dG was measured in nuclear DNA (nDNA) isolated from liver, heart, brain, kidney, skeletal muscle, and spleen and in mitochondrial DNA (mtDNA) isolated from liver. We observed a significant increase in oxo8dG levels in nDNA with age in all tissues and strains of rodents studied. The age-related increase in oxo8dG in nDNA from old mice was shown not to the result of the tissue's reduced ability to remove the oxo8dG lesion. Rather, the increase in oxo8dG levels appears to arise from an age-related increase in the sensitivity of these tissues to oxidative stress. We also observed an age-related increase in oxo8dG in mtDNA isolated from the livers of the rats and mice. Dietary restriction, which is known to retard aging and increase the lifespan of rodents, was shown to significantly reduce the age-related accumulation of oxo8dG levels in nDNA in all tissues of male B6D23F1 mice and in most tissues of male F344 rats. Our study also showed that dietary restriction prevented the age-related increase in oxo8dG levels in mtDNA isolated from the livers of both rats and mice.

Low frequency of the ccr5delta32 HIV-resistance allele in mainland China: identification of the first case of ccr5delta32 mutation in the Chinese population.

A 32-bp deletion on the CCR5 gene (ccr5delta32) confers resistance to HIV-1 infection. This deletion is common in Caucasians, but rare in Asians. Since the frequency of the ccr5delta32 allele of Chinese in mainland China has been unknown we investigated the ccr5delta32 mutation in a cohort of 407 Chinese people in this area. A 225-bp fragment of CCR5 encompassing the 32-bp region was analysed by PCR, hybridization and sequencing. Only 1 out of 407 subjects was heterozygous for ccr5delta32 and no homozygotes were detected. The frequency of ccr5delta32 in this cohort is thus 0.00123, i.e. much lower than that of Caucasians. The ccr5delta32 heterozygote is a healthy young man. To our knowledge this is the first ccr5delta32 mutant found in Chinese people. The results indicate that ccr5delta32 does exist in Chinese people, but at very low frequency. This suggests that ccr5delta32 is not a significant factor for the genetic resistance to HIV-1 in Chinese people.

Effect of cAMP-induced transcription on the repair of the phosphoenolpyruvate carboxykinase gene by hepatocytes isolated from young and old rats.

The repair of UV-induced DNA damage in the phosphoenolpyruvate carboxykinase (PEPCK) gene was studied in primary cultures of hepatocytes isolated from young (6-month-old) and old (24-month-old) rats fed ad libitum and old rats fed a calorie-restricted diet. Incubation of the hepatocytes with cAMP rapidly induced PEPCK transcription and mRNA levels 4- to 5-fold. In absence of cAMP, the repair of the PEPCK fragment was similar in cultured hepatocytes isolated from young and old rats fed ad libitum. However, cAMP significantly increased the percentage of cyclobutane pyrimidine dimers (CPDs) removed from the PEPCK fragment 12 h after UV-irradiation in cultured hepatocytes isolated from young rats fed ad libitum. This increase was due to an increase in the repair of the transcribed strand of the PEPCK fragment. In contrast, cAMP did not increase the repair of the PEPCK fragment in cultured hepatocytes isolated from old rats fed ad libitum in spite of an increase in PEPCK transcription. Thus, it appears that the coupling of transcription and DNA repair is compromised in cultured hepatocytes isolated from old rats fed ad libitum. However, cultured hepatocytes isolated from old rats fed a calorie-restricted diet showed an induction in the rate of repair of the transcribed strand of the PEPCK fragment by cAMP that was similar to hepatocytes isolated from young rats fed ad libitum.

The efficacy of an albendazole-medicated block in controlling sheep nematodes in Xinjiang province, north-west China.

Medicated feed-blocks containing 2 mg/kg albendazole were fed for 12 days to ewe-lambs naturally infected with nematode worms in north-west China. The cumulative total average intake of albendazole was 15 mg/kg body weight. This treatment was compared with a single oral drench of 15 mg/kg albendazole and with no treatment. Both albendazole treatments were 99% effective in reducing the total strongyle egg counts. The medicated block was 100% effective in reducing the total trichostrongylid worm count, although only 86.4% of the sheep consumed an adequate amount. The single drench was 97% effective. Under the management conditions available to sheep herders in the northern provinces of China, albendazole-medicated feed blocks used at strategic times could effectively control trichostrongylid nematodes.

Role of atrial natriuretic peptide in disturbed water and electrolyte metabolism of guinea pigs infected with Pichinde virus.

Daily intake and output of water and electrolytes (Na+, K+, and Cl-) were determined for 14 days in control and Pichinde virus-infected strain-13 guinea pigs. Although water intake began to decrease 7 days after virus inoculation, total daily water output (insensible water loss, urine excretion, plus fecal water loss) had little change. However, insensible water loss alone increased markedly in the virus-infected animals. Both intake and excretions of urinary and fecal electrolytes decreased at the middle (days 7 to 10) and late (days 11 to 14) stages of viral infection. Differences between intake and output of water and electrolytes were reduced significantly during these periods. To determine a possible relationship between atrial natriuretic peptide (ANP) and urinary Na+ and water excretion over intake, we measured plasma ANP concentrations. The mean control value of plasma ANP was 24 +/- 1.0 pg/ml, and plasma ANP concentrations of infected animals increased significantly (P < 0.01) to 49.5 +/- 3.9 and 51.3 +/- 8.8 pg/ml on postinoculation days 7 and 12. Because the overall physiologic responses to Pichinde virus infection are complicated, it is difficult to postulate a single central theme concerning the pathogenesis. Nevertheless, we hypothesize that the virus-induced invisible tissue "biochemical lesions" and the consequential release of mediators and hormones were possible causes of death. Among other pathophysiologic mechanisms, the increased plasma ANP concentration may have played a role in the development of disturbed water and electrolytes metabolism during Pichinde virus infection.

Treatment and control of the intestinal fluke, Skrjabinotrema ovis.

The small intestinal fluke, Skrjabinotrema ovis, is common among sheep in the Xinjiang region of western China. Up to 65,000 flukes per sheep were found during September when sheep were grazing summer pastures at high altitudes. Efficacy studies of some common flukicides revealed that oxyclosanide and triclabendazole were not effective in reducing the egg output of S. ovis, whereas closantel and praziquantel reduced egg counts by up to 98%. Praziquantel at 25 and 50 mg kg-1 reduced worm counts by 99%. Albendazole at 15 mg kg-1 reduced egg counts by 83% and worm counts by 91% but at lower dose rates it was ineffective.

Changes in platelet-activating factor, catecholamine, and serotonin concentrations in brain, cerebrospinal fluid, and plasma of pichinde virus-infected guinea pigs.

Brain concentrations of platelet-activating factor (PAF), catecholamines, and serotonin were measured in control and Pichinde virus-infected strain 13 guinea pigs on postinoculation day (PID) 12. After virus inoculation, PAF concentrations increased 81% in cerebrum, 147% in diencephalon-brain stem, and 110% in cerebellum from baseline values of 2.6 +/- 0.3, 4.3 +/- 0.2, and 6.1 +/- 0.5 (ng/g wet tissue), respectively. Dopamine concentrations in the infected cerebrum and diencephalon-brain stem increased significantly, whereas norepinephrine concentration increased only in cerebrum. However, serotonin concentrations in all three regions of infected brain decreased significantly as compared with control values. There were no significant changes in epinephrine concentrations of infected brain. Norepinephrine and epinephrine concentrations in plasma and cerebrospinal fluid on PID 7 and 12 increased significantly as compared with control values, while plasma dopamine concentration increased significantly on PID 7. Increased brain PAF, dopamine, and and norepinephrine concentrations with decreased brain serotonin concentrations may mediate the hyperactivity of the hypothalamic-pituitary-adrenal axis and involve some unknown pathophysiologic processes of arenaviral infection. Furthermore, increased plasma catecholamine concentrations are associated with stress and may be partially responsible for the development of cardiovascular dysfunction and pulmonary edema during this viral disease.

Platelet-activating factor (PAF)-induced cardiopulmonary dysfunctions and their reversal with a PAF antagonist (BN 52021) in strain 13 guinea pigs.

Cardiovascular and respiratory responses to a 2 h intravenous constant infusion of PAF (5 and 10 ng/kg per min) were studied in strain 13 guinea pigs. PAF decreased arterial blood pressure, left systolic ventricular pressure, and cardiac output (CO). These cardiovascular changes were dose-dependent. The PAF-induced hypotension returned to a pre-infusion level spontaneously with increased total peripheral resistance despite continuous infusion of PAF. The decreased CO was most striking, and did not recover to pre-infusion levels due to depressed cardiac contractility and impaired ventricular relaxation. Respiratory responses to PAF infusion at these doses were mild and only occurred after serious cardiovascular dysfunctions developed. A higher dose of PAF (20 ng/kg per min) produced drastically decreased CO and dynamic lung compliance (Cdyn), increased pulmonary airway resistance, hypoventilation and apnea within 10-40 min. BN 52021, a PAF receptor antagonist, administered as a single i.v. dose (6 mg/kg) 15 min after PAF infusion, reversed most of cardiopulmonary dysfunctions and prevented death by increasing cardiac contractility, CO, and minute volume from extremely low values. The data suggest that marked cardiopulmonary disturbances induced by intravenous PAF infusion reflects certain pathophysiological mechanisms of diseases that may involve the cellular release of PAF. The administration of BN 52021 or other potent PAF antagonists may be beneficial under these circumstances.

Possible involvement of endogenous beta-endorphin in the pathophysiological mechanisms of Pichinde virus-infected guinea pigs.

Previously, we demonstrated that naloxone, an opiate antagonist, prolonged survival of strain 13 guinea pigs infected with Pichinde virus. Thus, endogenous opiates may be involved in the pathogenesis of this viral disease. To determine whether endogenous opiate levels were affected by Pichinde viral infection, beta-endorphin concentrations in plasma and cerebrospinal fluid (CSF) of normal and infected strain 13 guinea pigs were measured by radioimmunoassay. Cerebrospinal fluid beta-endorphin concentrations were 78.0 +/- 13.2 pg/ml on postinoculation day (PID) 7, 59.0 +/- 5.6 pg/ml on PID 12, and 58.8 +/- 5.4 pg/ml on PID 14. These values were significantly higher than baseline levels of CSF beta-endorphin: 30.8 +/- 1.9 pg/ml. Plasma beta-endorphin concentrations of infected animals increased significantly to 202.1 +/- 17.9 pg/ml on PID 7 and to 154.2 +/- 21.4 pg/ml on PID 12 from a mean baseline value of 84.2 +/- 13.1 pg/ml. After a primer intravenous injection of beta-endorphin (10, 15, or 30 micrograms/kg), followed by constant infusion of beta-endorphin (15, 45, or 90 micrograms/kg.hr) to control noninfected guinea pigs, heart rate (except with the lowest dose) and mean blood pressure decreased markedly. Under these experimental conditions, concentrations of plasma and CSF beta-endorphin increased simultaneously with different magnitude. Because both Pichinde viral infection and beta-endorphin administration produced a similar trend of cardiovascular disturbances, leading to hypotension and bradycardia, increased concentrations of plasma and CSF beta-endorphin may play a partial role in the pathophysiological mechanisms of Pichinde virus infection.

Cardiovascular responses to intracerebroventricular infusion of artificial cerebrospinal fluid in anesthetized strain 13 guinea pigs.

The cardiovascular effects of constant intracerebroventricular infusion in anesthetized strain 13 guinea pigs were studied. Bilateral cerebroventricles of the animals were catheterized stereotaxically with two 20-gauge blunt needles, penetrating 5 to 6 mm into the skull. Baseline cerebroventricular pressure values were 1.3 +/- 0.6 mmHg. After artificial cerebrospinal fluid was infused into the left ventricle at 0.5 ml/h, left cerebroventricular pressure increased to 8.1 +/- 1.6 mmHg (P less than 0.01), while right cerebroventricular pressure reached 5.6 +/- 2.2 mmHg within 20 minutes. No significant changes in mean blood pressure or heart rate were observed. When intracerebroventricular infusion rate increased to 5.0 ml/h, cerebrospinal fluid pressures of left and right cerebroventricles increased to 40.0 +/- 4.8 and 38.4 +/- 4.7 mmHg within 10 minutes from baseline values of 1.5 +/- 0.5 and 1.7 +/- 0.7 mmHg, respectively. Simultaneously, mean blood pressure and heart rate increased from 72 +/- 4 to 101 +/- 9 mmHg and from 195 +/- 11 to 218 +/- 17 beats/min, respectively. However, 30 to 50 minutes later, mean blood pressure, heart rate, and cerebrospinal fluid pressure decreased abruptly, and two of four animals died. We suggest that this technique with a low infusion rate (less than 0.5 ml/h) can be used to deliver certain drugs into the brain ventricles directly without producing undesirable effects on blood pressure or heart rate.

[Rejection of physico-chemical indices for pathological matrix in a quantitative drug design].

In a quantitative drug design, correlation of coefficient matrix of physico-chemical indices Xi is often pathological when these indices are highly correlated. The regression equation of biological activity Y about these indices Xi obtained in this case is not stable. In this paper, a method is given to obtain a stable regression equation: giving a critical valne alpha and finding out the indices among which correlation coefficient is not less than alpha. The following are the rules to reject some of them. If Xi and Xj is highly correlated (magnitude of rij greater than or equal to alpha, rij is the correlation coefficient of Xi and Xj), and magnitude of rin greater than magnitude of rjn (rin and rjn are correlation coefficients of Xi and Xj about Y, respectively), than the index Xj is rejected, otherwise, Xi is rejected. Stable equation can be obtained by stepwise regression with the remaining indices.

Pulmonary responses of conscious strain 13 guinea pigs to Pichinde viral infection.

A laboratory animal model for studying pulmonary responses to arenaviral infection was established with advanced technologies. Tidal volume (TV), respiratory rate (RR), minute volume (MV), expiratory time (TE), inspiratory time (TI), peak expiratory flow (PEF), and specific pulmonary airway resistance (RES) were measured with a double plethysmograph and a computer data-acquisition system in six conscious, strain 13 guinea pigs. Using the same animal, experiments were conducted before and after subcutaneous inoculation with 10(4) plaque-forming units of Pichinde virus. Pulmonary functions were determined for 1 minute every 10 minutes for 2 hours before and at postinoculation days (PID) 3, 6, 8, and daily thereafter until shortly before death. The mean time to death was 18 +/- 0.7 days. Tidal volume, RR, MV, PEF, RES, and rectal temperature increased slightly on PID 3 and reached peak values at the midpoint of disease. At 95% of the mean time to death (16.5 +/- 0.5 days), RR, MV, and rectal temperatures suddenly decreased to lower than baseline values; while TV, RES, and PEF values remained high. When TE decreased with the increase in RR, TI did not change. When RR decreased at the terminal stage, both TE and TI increased. Hyperventilation, increased specific pulmonary airway resistance, terminal hypoventilation, and respiratory arrest were noted in strain 13 guinea pigs infected with Pichinde virus.