Sex difference in nocturnal blood pressure dipping in adolescents with varying degrees of adiposity.

BACKGROUND: For adolescents, abnormal dipping patterns in blood pressure (BP) are associated with early-onset organ damage and a higher risk of cardiovascular disorders in adulthood. Obesity is one of the most common reasons for abnormal BP dipping in young people. However, it is unknown whether the severity of obesity is associated with BP dipping status and whether this association is sex-dependent. METHODS: 499 participants between 12 and 17 years old with overweight or obesity underwent ambulatory blood pressure monitoring (ABPM) between April 2018 and January 2019 in Beijing and Baoding. Participants were grouped by body mass index (BMI) into overweight (BMI 85th-95th percentile), obese (BMI ≥ 95th percentile) and severely obese (BMI ≥ 120% of 95th percentile or ≥ 35 kg/m2) groups. Non-dipping was defined as a < 10% reduction in BP from day to night. The interaction effect between sex and obesity degree was also analyzed. RESULTS: 326 boys and 173 girls were included, of whom 130 were overweight, 189 were obese, and 180 were severely obese. Girls with severe obesity had a higher prevalence of non-dipping, but boys showed no significant differences in BP dipping status between obesity categories. In addition, as obesity severity went up, a more evident increase in night-time SBP was observed in girls than in boys. CONCLUSIONS: Severely obese is associated with a higher prevalence of non-BP dipping patterns in girls than in boys, which suggests that the relationship between the severity of obesity and BP dipping status might be sex-specific.

Association between length of daily siesta and brachial-ankle pulse wave velocity (baPWV): a community-based cross sectional study in North China.

INTRODUCTION: To date, many studies have shown a link between siesta and cardiovascular events. Little is known regarding the connection between siesta and brachial-ankle pulse wave velocity (baPWV) levels, even though baPWV can determine the degree of atherosclerosis and vascular stiffness. Thus, we examined the relationship between siesta time and baPWV in a cross-sectional study. METHODS: Interviews, physical examinations, lab testing, and electron beam computed tomography were all part of the baseline evaluation for participants aged older than 35. Baseline data were compared for 3 different siesta habits: irregular or no siestas, daily short siestas (1 h or less), and daily long siestas (> 1 h). Utilizing logistic regression models and multivariate linear regression, the link between siesta time and baPWV was determined. RESULTS: Among all 6566 participants, the different siesta groups had a significant difference of the degrees of AS (P < 0.001). The same outcome was true for both males (P < 0.001) and females (P < 0.001). Numerous cardiovascular risk variables and markers of subclinical atherosclerosis were positively correlated with daily extended siestas. Results from the fully adjusted model showed that long siestas (> 60 min, OR = 1.18, 95%CI: 1.06-1.31, P = 0.002) were linked to a more severe level of the baPWV. For age or gender stratification, we found significant differences between non-siesta and > 60 min siesta groups. Multiple linear regression analysis revealed a positive connection between siesta duration and baPWV (ß = 0.197, P = 0.038). CONCLUSIONS: An elevated risk of atherosclerosis was shown to accompany prolonged siestas. These results need to be followed up on with prospective studies and additional lab work.

Flocking Behaviors under Hierarchical Leadership of Thermodynamic Cucker-Smale Particles with Multiplicative White Noise and Perturbation.

The thermodynamic Cucker-Smale model (TCS model) describes dynamic consistency caused by different temperatures between multi-agent particles. This paper studies the flocking behaviors of the TCS model with multiplicative white noise under hierarchical leadership. First, we introduce the corresponding model of two particles. Then, by using mathematical induction and considering the properties of differential functions, it is proved that, under certain conditions, the group can achieve flocking. Finally, we verify the conclusion through numerical simulation results. Similarly, this paper studies the above model with perturbation functions.

An Optimal Geometry Configuration Algorithm of Hybrid Semi-Passive Location System Based on Mayfly Optimization Algorithm.

In view of the demand of location awareness in a special complex environment, for an unmanned aerial vehicle (UAV) airborne multi base-station semi-passive positioning system, the hybrid positioning solutions and optimized site layout in the positioning system can effectively improve the positioning accuracy for a specific region. In this paper, the geometric dilution of precision (GDOP) formula of a time difference of arrival (TDOA) and angles of arrival (AOA) hybrid location algorithm is deduced. Mayfly optimization algorithm (MOA) which is a new swarm intelligence optimization algorithm is introduced, and a method to find the optimal station of the UAV airborne multiple base station's semi-passive positioning system using MOA is proposed. The simulation and analysis of the optimization of the different number of base stations, compared with other station layout methods, such as particle swarm optimization (PSO), genetic algorithm (GA), and artificial bee colony (ABC) algorithm. MOA is less likely to fall into local optimum, and the error of regional target positioning is reduced. By simulating the deployment of four base stations and five base stations in various situations, MOA can achieve a better deployment effect. The dynamic station configuration capability of the multi-station semi-passive positioning system has been improved with the UAV.

Dynamic Event-Triggered Predictive Control for Interval Type-2 Fuzzy Systems with Imperfect Premise Matching.

This paper investigates the dynamic event-triggered predictive control problem of interval type-2 (IT2) fuzzy systems with imperfect premise matching. First, an IT2 fuzzy systems model is proposed, including a dynamic event-triggered mechanism, which can save limited network resources by reducing the number of data packets transmitted, and a predictive controller, which can predict the state of the system between the two successful transmitted instants to deal with unreliable communication networks. Then, according to the Lyapunov stability theory and imperfect premise matching method, sufficient conditions for system stabilization and the controller gain are obtained. Finally, the validity of the proposed method is demonstrated by the numerical examples.

Adaptive Event-Triggered Synchronization of Uncertain Fractional Order Neural Networks with Double Deception Attacks and Time-Varying Delay.

This paper investigates the problem of adaptive event-triggered synchronization for uncertain FNNs subject to double deception attacks and time-varying delay. During network transmission, a practical deception attack phenomenon in FNNs should be considered; that is, we investigated the situation in which the attack occurs via both communication channels, from S-C and from C-A simultaneously, rather than considering only one, as in many papers; and the double attacks are described by high-level Markov processes rather than simple random variables. To further reduce network load, an advanced AETS with an adaptive threshold coefficient was first used in FNNs to deal with deception attacks. Moreover, given the engineering background, uncertain parameters and time-varying delay were also considered, and a feedback control scheme was adopted. Based on the above, a unique closed-loop synchronization error system was constructed. Sufficient conditions that guarantee the stability of the closed-loop system are ensured by the Lyapunov-Krasovskii functional method. Finally, a numerical example is presented to verify the effectiveness of the proposed method.

Chinese siblings with hereditary medullary thyroid carcinoma caused by RET mutation: implications for RET oncogene detection.

BACKGROUND: Hereditary medullary thyroid carcinoma (MTC) is mainly caused by germline mutations in the RET proto-oncogene, which accounts for 20-30% of all MTC according to foreign studies. However, no English literatures have reported Chinese hereditary MTC. Here, we reported two Chinese brothers with MTC that caused by germline RET mutation. CASE PRESENTATION: The younger brother was diagnosed with MTC at 29 years ago and suffered recurrence more than 10 years. For elder brother, the diagnosis of MTC was made by postoperative pathological examination at age 61. Both patients received total thyroidectomy and lymph node dissection. Since they had a significant family history for MTC, genetic detection was performed and identified a germline mutation in RET exon 10 (p.C620Y). This mutation was also detected in their offspring, indicating a moderate risk of MTC. CONCLUSIONS: This is the first report presenting a Chinese family with hereditary MTC caused by the RET p.C620Y variant. This case series emphasize the importance of genetic detection of RET proto-oncogene for MTC patients, and bring out managements for individuals after detection of RET mutations.

CAT-1 as a novel CAM stabilizes endothelial integrity and mediates the protective actions of L-Arg via a NO-independent mechanism.

Interendothelial junctions play an important role in the maintenance of endothelial integrity and the regulation of vascular functions. We report here that cationic amino acid transporter-1 (CAT-1) is a novel interendothelial cell adhesion molecule (CAM). We identified that CAT-1 protein localized at cell-cell adhesive junctions, similar to the classic CAM of VE-cadherin, and knockdown of CAT-1 with siRNA led to an increase in endothelial permeability. In addition, CAT-1 formed a cis-homo-dimer and showed Ca(2+)-dependent trans-homo-interaction to cause homophilic cell-cell adhesion. Co-immunoprecipitation assays showed that CAT-1 can associate with ß-catenin. Furthermore, we found that the sub-cellular localization and function of CAT-1 are associated with cell confluency, in sub-confluent ECs CAT-1 proteins distribute on the entire surface and function as L-Arg transporters, but most of the CAT-1 in the confluent ECs are localized at interendothelial junctions and serve as CAMs. Further functional characterization has disclosed that extracellular L-Arg exposure stabilizes endothelial integrity via abating the cell junction disassembly of CAT-1 and blocking the cellular membrane CAT-1 internalization, which provides the new mechanisms for L-Arg paradox and trans-stimulation of cationic amino acid transport system (CAAT). These results suggest that CAT-1 is a novel CAM that directly regulates endothelial integrity and mediates the protective actions of L-Arg to endothelium via a NO-independent mechanism.

[Change of peripheral blood appetite regulation factor of anorexia children and infect of child anorexia granule].

Study the infect of child anorexia granule on serum ghrelin and leptin of anorexia children and its clinical efficacy. Selected 81 cases of anorexia children aged 1-6 years old into treatment group (42 cases) and control group (39 cases), in addition, 30 case healthy children as healthy control group. The control group children were treated with domperidone suspension 0.3 mg x kg(-1) x d(-1), tid, orally 30 minutes before meals. Treatment group were treated with child anorexia granule, 1-3 years 1 package, bid; 4-6 years 1 package, tid; po, 4 weeks as a course of treatment. Study the change of serum ghrelin and leptin before and after therapy. The study demonstrates that before treatment, the serum ghrelin level of disease group was lower than healthy group (P < 0.01), and the serum leptin level was higher than healthy group (P < 0.01). After treatment, the serum ghrelin level both increase, and the serum leptin decline. And the change of treatment group was significantly different with control group (P < 0.01). And the clinical effective rate are 95.23% and 74.35% (P < 0.01). After 6 months of follow-up visit, the children weight significantly increase in treatment group (P < 0.01). Results indicate that child anorexia granule can facilitate secretion of ghrelin, and inhibit secretion of leptin, so as to work up an appetite. And the molecular mechanism is its infect on serum ghrelin, leptin.

A family with Liddle syndrome caused by a novel missense mutation in the PY motif of the beta-subunit of the epithelial sodium channel.

OBJECTIVE: To identify the gene mutation in ß and γ subunits of the epithelial sodium channel (ENaC) in an adolescent and family members with Liddle syndrome, an autosomal dominant form of secondary hypertension. STUDY DESIGN: We screened an adolescent with severe hypertension who was clinically diagnosed with Liddle syndrome for mutations in the C-terminus of the SCNN1B and SCNN1G genes. We also screened for these mutations in his family members, in 100 hypertensive patients, and in 100 controls. RESULTS: The index case, a 14-year-old boy, was diagnosed with Liddle syndrome by the identification of a novel missense mutation, P614L, in the PY motif of the ß subunit of the ENaC. Testing of relatives considered at risk revealed 6 subjects heterozygous for the mutation. All genetically affected subjects had a history of severe hypertension as well as hypokalemia. No other variants in the ß or γ subunits of the ENaC were detected. CONCLUSION: Based on direct DNA sequencing, we have detected a novel mutation that causes Liddle syndrome. This confirms the diagnosis and helps guide effective therapy for this adolescent and his affected relatives. These findings provide further evidence that the conserved PY motif is critical to regulation of ENaC activity.

Perindopril treatment promote left ventricle remodeling in patients with heart failure screened positive for autoantibodies against angiotensin II type 1 receptor.

BACKGROUND: Autoantibodies specific to the angiotensin II type I receptor (anti-AT1-AR) have been implicated in the pathology of congestive heart failure (CHF). Anti-AT1-AR may be associated with left ventricular function in CHF patients treated with perindopril. METHODS: Synthetic angiotensin II type 1 receptor (AT1-R) peptides served as the target antigen. ELISA was used to screen the sera of 156 CHF patients, which were divided into positive and negative groups based on their anti-AT1-AR reactivity. Echocardiography and a 6-minute walk test were performed at baseline and after one year of perindopril therapy. The end-point events were compared over a 5-year follow-up. RESULTS: Final analysis covered 138 patients, including 82 positive and 56 negative. The frequency and geometric mean titre of anti-AT1-AR were significantly lower in the positive group after one year of treatment (all P < 0.01, from 100% to 73.2% and from 1:125.3 ± 1.0 to 1:69.2 ± 1.1). Of these, 22 patients showed no antibodies. Both groups showed improvement in left ventricular end-diastole, end-systolic dimensions, ejection fraction, and a 6-minute walk test by perindopril in combination with standard treatment regime for one year (all P < 0.01). However, the 82 patients positive for anti-AT1-AR showed more pronounced improvement than the 56 negative patients (all P < 0.05). However, after 5 years of follow-up, the rate of all causes and cardiovascular mortality attributable to any cause and the re-hospitalisation rate showed no significant differences between the two groups (all P > 0.05). CONCLUSIONS: Perindopril treatment significantly decreased the frequency and geometric mean titre in patients positive for anti-AT1-AR, even to complete ablation. These patients showed greater improvement in left ventricular remodeling and heart function than negative that in patients after one year of perindopril treatment in combination with standard treatment, but no significant differences in endpoint events were observed in the following 5 years. Anti-AT1-AR might be a useful biomarker of over-activation of the renin-angiotensin-aldosterone system for clinical medication.

Nanoparticles Targeting Delivery Antagomir-483-5p to Bone Marrow Mesenchymal Stem Cells Treat Osteoporosis by Increasing Bone Formation.

BACKGROUND: Promoting bone marrow mesenchymal stem cell (BMSC) osteoblastic differentiation is a promising therapeutic strategy for osteoporosis (OP). The present study demonstrates that miR- 483-5p inhibits the osteogenic differentiation of BMSCs. Therefore, selectively delivering the nanoparticles carrying antagomir-483-5p (miR-483-5p inhibitor) to BMSCs is expected to become an effective treatment drug for OP. METHODS: Real-time PCR assays were used to analyze miR-483-5p, ALP and Bglap levels in BMSCs of ovariectomized and aged osteoporotic mice. Immunoglobulin G and poloxamer-188 encapsulated the functional small molecules, and a BMSC-targeting aptamer was employed to confirm the direction of the nanoparticles to selectively and efficiently deliver antagomir-483-5p to BMSCs in vivo. Luciferase assays were used to determine the target genes of miR-483-5p. Western blot assays and immunohistochemistry staining were used to detect the targets in vitro and in vivo. RESULTS: miR-483-5p levels were increased in BMSCs of ovariectomized and aged osteoporotic mice. Inhibiting miR-483-5p levels in BMSCs by antagomir-483-5p in vitro promoted the expression of bone formation markers, such as ALP and Bglap. The FAM-BMSC-aptamer-nanoparticles carrying antagomir- 483-5p were taken up by BMSCs, resulting in stimulation of BMSC osteoblastic differentiation in vitro and osteoporosis prevention in vivo. Furthermore, our research demonstrated that mitogen-activated protein kinase 1 (MAPK1) and SMAD family member 5 (Smad5) were direct targets of miR-483-5p in regulating BMSC osteoblastic differentiation and osteoporosis pathological processes. CONCLUSIONS: The important therapeutic role of FAM-BMSC-aptamer-nanoparticles carrying antagomir- 483-5p in osteoporosis was established in our study. These nanoparticles are a novel candidate for the clinical prevention and treatment of osteoporosis. The optimized, targeted drug delivery platform for small molecules will provide new ideas for treating clinical diseases.

Keeping obesity status is a risk factor of hypertension onset: evidence from a community-based longitudinal cohort study in North China.

Objective: The purpose of our study was to investigate the association of obesity status change with hypertension onset based on a community-based longitudinal cohort study in North China. Methods: This longitudinal study included 3,581 individuals free of hypertension at baseline in the first survey (2011-2012). All participants were followed up (2018-2019). According to the criteria, a total of 2,618 individuals were collected for analysis. We used adjusted Cox regression models and Kaplan-Meier survival analysis to estimate the association between obesity status change and hypertension onset. Additionally, we applied the forest plot to visualize the subgroup analysis including age, gender, and the differences in some variables between baseline and follow-up. Finally, we conducted a sensitivity analysis to examine the stability of our results. Results: Over nearly 7 years of follow-up, a total of 811 (31%) developed hypertension. The new hypertension incidence was mostly observed in those who were obese all the time (P for trend < 0.01). In the fully adjusted Cox regression model, being obese all the time increased the risk of hypertension by 30.10% [HR 4.01 (95% CI 2.20-7.32)]. The Kaplan-Meier survival analysis revealed the change in obesity status as an important feature to predict the occurrence of hypertension. Sensitivity analysis shows a consistent trend between the change in obesity status and hypertension onset in all populations. Subgroup analysis showed that age above 60 years was an important risk factor for hypertension onset, that men were more likely than women to develop hypertension, and that weight control was beneficial in avoiding future hypertension in women. There were statistically significant differences in ΔBMI, ΔSBP, ΔDBP, and ΔbaPWV between the four groups, and all variables, except baPWV changes, increased the risk of future hypertension. Conclusion: Our study shows that obese status was notably associated with a significant risk of hypertension onset among the Chinese community-based cohort.

IL-13-induced changes in endogenous glucocorticoid metabolism in the lung regulate the proasthmatic response.

Endogenous glucocorticoid (GC) activation is regulated by the intracellular GC-activating and -inactivating enzymes 11ß-hydroxysteroid dehydrogenase (11ß-HSD)1 and 11ß-HSD2, respectively, that catalyze interconversion of inert cortisone and its bioactive metabolite cortisol. Because endogenous GCs are critically implicated in suppressing the asthmatic state, this study examined the roles of the 11ß-HSD enzymes in regulating GC activation and bronchoprotection during proasthmatic stimulation. Airway hyperresponsiveness to methacholine and inflammation were assessed in rabbits following inhalation of the proasthmatic/proinflammatory cytokine IL-13 with and without pretreatment with the 11ß-HSD inhibitor carbenoxolone (CBX). Additionally, IL-13-induced changes in 11ß-HSD isozyme expression and GC metabolism were examined in epithelium-intact and -denuded tracheal segments and peripheral lung tissues. Finally, the effects of pretreatment with CBX or 11ß-HSD2-targeted siRNAs were investigated with respect to cortisol prevention of IL-13-induced airway constrictor hyperresponsiveness and eotaxin-3 production by airway epithelial cells. IL-13-exposed rabbits exhibited airway hyperresponsiveness, inflammation, and elevated bronchoalveolar lung fluid levels of eotaxin-3. These responses were inhibited by pretreatment with CBX, suggesting a permissive proasthmatic role for 11ß-HSD2. Supporting this concept, extended studies demonstrated that 1) IL-13-treated tracheal epithelium and peripheral lung tissues exhibit upregulated 11ß-HSD2 activity, 2) the latter impairs cortisone-induced cortisol accumulation and the ability of administered cortisol to prevent both IL-13-induced heightened airway contractility and eotaxin-3 release from epithelial cells, and 3) these proasthmatic responses are prevented by cortisol administration in the presence of 11ß-HSD2 inhibition. Collectively, these data demonstrate that the proasthmatic effects of IL-13 are enabled by impaired endogenous GC activation in the lung that is attributed to upregulation of 11ß-HSD2 in the pulmonary epithelium.

Nitric oxide preserves XIAP and reduces hypoxia/reoxygenation-induced cardiomyocytes apoptosis via ERK1/2 activation.

The signaling pathways that control the hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis have not been fully defined. In this study, we investigated whether extracellular signal-regulated kinase1/2 (ERK1/2) plays a role in NO's anti-apoptotic effect against H/R injury. Primary cultures of adult rat ventricular myocytes (ARVMs) were exposed to 3 h of hypoxia followed by 30, 60, 90 and 120 min of reoxygenation in presence of a vehicle, NO donor (GSNO, 50 µmol/L) and inhibitors of ERK1/2 (PD98059, 10 µmol/L). GSNO protected the cardiomyocyte from reoxygenation injury, as evidenced by decreased apoptosis, and this protective effect was inhibited by co-treatment with PD98059 during reoxygenation. Consistent with this, when administered with adenoviral vector encoding dominant negative ERK (Ad-dnERK), GSNO's effect was also blocked. Western blotting revealed that GSNO increased the ERK phosphorylation during reoxygenation. Furthermore, H/R-induced activation of caspase-3 and -9 were attenuated by GSNO. Interestingly, X-linked inhibitor of apoptosis protein (XIAP) protein levels decreased in myocytes subjected to reoxygenation, and ERK phosphorylation can improve XIAP expression, which involved inhibiting caspase-3, -7 and -9 activities. Overexpression experiment with adenoviral vector containing constitutively active ERK (Ad-caERK) alone acquired protection against apoptosis triggered by H/R injury and positively regulated XIAP expression compared with control adenovirus (Ad-LacZ). Our data demonstrated that, GSNO's antiapoptotic effect against reoxygenation injury involves ERK signaling pathway. The activation of ERK increased XIAP expression and led to decreased caspase activation.

[Quantitative evaluation of the degrees of traditional Chinese medicine qualitative syndromes of osteoporosis].

OBJECTIVE: To establish a quantitative estimate model for diagnosing traditional Chinese medicine (TCM) syndromes of patients with osteoporosis. METHODS: Symptoms and signs of osteoporosis and methodology related to syndrome research were collected by reviewing medical literature. The symptoms and sighs were quantitatively classified into three, two or one category according to a 100-mm visual analog scale. Fuzzy comprehensive evaluation model of TCM qualitative syndromes was performed based on analytic hierarchy process. Then "Hall for Workshop of Metasynthetic Engineering" expert symposium was held on subjects of syndrome quantification method and weight of evaluation indices in different levels for developing the analysis model of common syndromes. For clinical verification, the created models were applied to patients with osteoporosis for discriminating syndromes. Syndrome of each patient was also identified by 8 experts major in integrative medicine treating osteoporosis for comparing the coincidence rate using a self-made clinical questionnaire. RESULTS: Through literature reviewing, symptoms and signs quantification and expert discussing, the authors formed estimate models of essence deficit, qi deficiency, yin deficiency, yang deficiency, and blood stasis. A total of 220 patients with osteoporosis were enrolled and filled the clinical questionnaire. All 8 experts completed and returned the questionnaire (1 760 cases), and 1 545 of them were filled in completely. Experts' opinion on syndrome differentiation was exactly coincidence to estimate model in 611 cases and almost coincidence in 639 cases. The total coincidence rate reached to 94.05%. CONCLUSION: The estimate model for syndrome differentiation of osteoporosis has a high-coincidence rate with the fuzzy evaluation from experts, with good rationality and feasibility, and is worthy of promotion in the clinical study.

Construction and In Vitro Evaluation of a Tumor Acidic pH-Targeting Drug Delivery System Based on Escherichia coli Nissle 1917 Bacterial Ghosts.

Synthetic nanocarriers are a promising therapeutic delivery strategy. However, these systems are often hampered by inherent disadvantages such as strong biotoxicity and poor biocompatibility. To overcome these issues, biological carriers with commonly used chemotherapy drugs have been developed. In this work, engineered bacterial ghosts (BGs) originated from probiotic Escherichia coli Nissle 1917 (EcN) were devised to specifically target acidic extracellular environments of tumor tissue. To improve the production efficiency and safety, a novel lysis protein E from phage α3 was applied to produce EcN BGs under high growth densities in high quality. In addition, the acidity-triggered rational membrane (ATRAM) peptides were displayed in EcN BGs to facilitate specific cancer cell internalization within the acidic tumor microenvironment before drug release. In conclusion, the engineered EcN BGs offer a promising means for bionic bacteria construction for hepatocellular carcinoma therapy.

Seasonal variation of ambulatory blood pressure in Chinese hypertensive adolescents.

Background: Blood pressure (BP) exhibits seasonal variation with lower levels at higher temperatures and vice versa. This phenomenon affects both sexes and all age groups. So far, only a few research studies have investigated this condition in adolescents and none of them were based on hypertensive population or ever applied ambulatory blood pressure monitor (ABPM). Therefore, we carried out the first study that used ABPM to record seasonal variation of blood pressure in hypertensive adolescents. Methods: From March 2018 to February 2019, 649 ABPMs from hypertensive adolescents between 13 and 17 years who were referred to wear an ABPM device in Beijing and Baoding were extracted. Seasonal change in ambulatory BP value, dipping status, and prevalence of different BP phenotypes were analyzed and compared. Results: Mean age of participants was 14.9 ± 1.5 years and 65.8% of them were boys. Of the participants, 75.3% met the criteria of overweight or obesity. From summer to winter, average 24-hour, day-time, and night-time BP showed significant rise, which was 9.8/2.8, 9.8/3.0, and 10.9/3.4 mmHg, respectively. This seasonal effect on BP was not dependent on the obesity degree. In addition, higher prevalence of nondippers and risers existed in winter while white coat hypertension was more frequent in warmer seasons. Conclusion: Hypertensive adolescents showed evident seasonal change in their ABPM results, which was featured by elevated BP level and more frequent abnormal dipping patterns in winter. On the contrary, higher prevalence of white coat hypertension was found in warmer seasons. Physicians should take seasonal variation into consideration when managing adolescent hypertension.

Mechanism of glucocorticoid protection of airway smooth muscle from proasthmatic effects of long-acting beta2-adrenoceptor agonist exposure.

BACKGROUND: Chronic use of long-acting beta2-adrenergic receptor agonists (LABAs), resulting in beta2-adrenergic receptor desensitization, has been associated with increased asthma morbidity. When LABAs are used in combination with inhaled glucocorticoids, however, asthma control is improved, raising the following question: Do glucocorticoids inhibit the proasthmatic mechanism that mediates altered contractility in LABA-exposed airway smooth muscle (ASM)? OBJECTIVE: This study aimed to identify the potential protective role and mechanism of action of glucocorticoids in mitigating the effects of prolonged LABA exposure on ASM constrictor and relaxation responsiveness. METHODS: Cultured human ASM cells and isolated rabbit ASM tissues were examined for induced changes in agonist-mediated cyclic adenosine monophosphate accumulation, constrictor and relaxation responsiveness, and expression of specific glucocorticoid-regulated molecules after 24-hour exposure to the LABA salmeterol in the absence and presence of dexamethasone. RESULTS: Salmeterol-exposed ASM exhibited impaired cyclic adenosine monophosphate and relaxation responses to isoproterenol and increased acetylcholine-induced contractility. These proasthmatic effects of prolonged LABA exposure were attributed to upregulated phosphodiesterase 4 (PDE4) activity and were ablated by pretreatment with dexamethasone. Further studies demonstrated that (1) dexamethasone suppressed activation of the mitogen-activated protein kinases extracellular signal-regulated kinases 1 and 2 (ERK1/2), which upregulate PDE4 expression in salmeterol-exposed ASM; and (2) the inhibitory actions of dexamethasone on salmeterol-induced ERK1/2 activation and resultant PDE4-mediated changes in ASM responsiveness were prevented by gene silencing or pharmacologic inhibition of dexamethasone-induced expression of mitogen-activated protein kinase phosphatase 1, an endogenous deactivator of ERK1/2 signaling. CONCLUSION: Glucocorticoids prevent the adverse proasthmatic effects of prolonged LABA exposure on airway responsiveness as a result of glucocorticoid-induced upregulation of mitogen-activated protein kinase phosphatase 1, which inhibits proasthmatic ERK1/2 signaling in the LABA-exposed ASM.

[A study of diagnostic criteria for traditional Chinese medicine syndromes in osteoporosis].

OBJECTIVE: To establish diagnostic criteria for common traditional Chinese medicine (TCM) syndromes in osteoporosis. METHODS: Based on the collection and analysis of related medical literature, clinical investigation, and expert discussion, a draft of preliminary diagnostic criteria for the basic syndromes of TCM in patients with osteoporosis was formulated. Then it was used in clinic for verification and revised repeatedly until a formal version of diagnostic criteria was satisfactorily achieved. RESULTS: The basic syndromes listed in the diagnostic criteria for patients with osteoporosis consisted of two parts: qualitative diagnosis and localization diagnosis. Results of qualitative diagnosis showed that the qualitative syndromes included damage of essence, deficiency of vital energy, deficiency of yin, deficiency of yang and blood stasis. The localization diagnosis showed that location of osteoporosis is bone and corresponds to the kidney, and also involves liver, lung, spleen (stomach) and heart. The diagnostic content has established the specific symptoms and the non-specific symptoms during various stages. Each of the above syndromes could be diagnosed according to a specific combination of its corresponding symptoms or signs. The clinical verification results showed that the total matching ratio of qualitative diagnosis was 80.56% between the diagnoses made according to the criteria and the diagnoses acquired from the experts' experience, and the total matching ratio of localization diagnosis was 85.56%. CONCLUSION: The TCM syndrome diagnostic criteria for osteoporosis is generally consistent with TCM clinical practice, worthy of further popularization and application in clinical practice.