PD-1/CD80+ small extracellular vesicles from immunocytes induce cold tumours featured with enhanced adaptive immunosuppression.

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.

Cost-Effective Engineered Cementitious Composites with Hybrid PVA and Basalt/PP Fiber: A Study on Compressive, Tensile and Impact Performance.

Currently, oil-coated PVA fibers are the most commonly used material in ECC research. However, the high price limits the application of PVA-ECC in practical engineering. In order to reduce the cost, one of the methods is to partially replace the PVA fibers in ECC. In order to demonstrate the feasibility of PVA/BF-ECC and PVA/PP-ECC, polyvinyl alcohol fibers (PVA), basalt fibers (BFs) and polypropylene fibers (PP) were added at 0.5%, 1.0% and 1.5% by volume of PVA in addition to 1% by volume of PVA. Subsequently, tensile, compression and drop-weight impact tests were conducted on single or hybrid fiber concrete. The results showed that the post-peak compression toughness, tensile strength, and initial cracking impact strength of PVA/BF-ECC and PVA/PP-ECC increased significantly with the increase in the volume ratio of BF and PP fibers, while the performance of PVA-ECC materials with the same fiber volume ratio decreased slightly. Therefore, the cost can be reduced by designing hybrid PVA/BF-ECC materials that meet the performance requirements. The experimental evidence presented in this study demonstrates the feasibility and reasonable prospect of the new hybrid PVA/BF-ECC.

HRS Regulates Small Extracellular Vesicle PD-L1 Secretion and Is Associated with Anti-PD-1 Treatment Efficacy.

PD-L1 localized to immunosuppressive small extracellular vesicles (sEV PD-L1) contributes to tumor progression and is associated with resistance to immune-checkpoint blockade (ICB) therapy. Here, by establishing a screening strategy with a combination of tissue microarray (TMA), IHC staining, and measurement of circulating sEV PD-L1, we found that the endosomal sorting complex required for transport (ESCRT) member protein hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) was the key regulator of circulating sEV PD-L1 in head and neck squamous cell carcinoma (HNSCC) patients. Increased HRS expression was found in tumor tissues and positively correlated with elevated circulating sEV PD-L1 in patients with HNSCC. The expression of HRS was also negatively correlated to the infiltration of CD8+ T cells. Knockdown of HRS markedly reduced PD-L1 expression in HNSCC cell-derived sEVs, and these sEVs from HRS knockdown cells showed decreased immunosuppressive effects on CD8+ T cells. Knockout of HRS inhibited tumor growth in immunocompetent mice together with PD-1 blockade. Moreover, a higher HRS expression was associated with a lower response rate to anti-PD-1 therapy in patients with HNSCC. In summary, our study reveals HRS, the core component of ESCRT-0, regulates sEV PD-L1 secretion, and is associated with the response to ICB therapy in patients with HNSCC, suggesting HRS is a promising target to improve cancer immunotherapy.

Brief analysis of the relationship between " of foot- stomach-meridian syndrome and stomach / 中国针灸

"" is a word describing the syndrome of cold sensation, which is one of the foot- stomach-meridian syndromes. The lesions of stomach and meridian could cause changes of and superficial symptoms of the interior syndrome, leading to "". In this study, the specific manifestation of the "" is analyzed from the aspect of word meaning, and the relationship between the "" and stomach is further discussed through the perspectives of and the exterior-interior relationship. In addition, combined with typical clinical case, it is suggested that attention should be paid on the relationship between exterior and interior syndromes, and the clinical application of and method (activating and promoting circulation of organs) should be strengthened, which could expand the new thinking of clinical treatments for viscera diseases through acupuncture and moxibustion.

Extracorporeal Cardiopulmonary Resuscitation in Children of Asia Pacific: A Retrospective Analysis of Extracorporeal Life Support Organization Registry.

BACKGROUND: Recent advances in extracorporeal membrane oxygenation (ECMO) have led to increasing interest in its use during cardiopulmonary resuscitation (CPR). However, decisions regarding extracorporeal CPR (ECPR) in children are difficult as a result of limited studies, especially in Asia Pacific. The objective of this study was to investigate trends in survival and demographic details for children with ECPR in Asia Pacific recorded in the Extracorporeal Life Support Organization (ELSO) registry from 1999 to 2016 and identify the risk factors associated with in-hospital mortality. METHODS: The data of children younger than 18 years of age who received ECPR over the past 18 years in Asia Pacific were retrospectively analyzed. The data were extracted from the ELSO registry and divided into two 9-year groups (Group 1: 1999-2007 and Group 2: 2008-2016) to assess temporal changes using univariate analysis. Then, univariate and multiple logistic regression analyses were performed between survivors and nonsurvivors to identify factors independently associated with in-hospital mortality. RESULTS: A total of 321 children were included in final analysis, with an overall survival rate of 50.8%. Although survival rates were similar between Group 1 and Group 2 (43.1% vs. 52.5%, χ2 = 1.67, P = 0.196), the median age (1.7 [0.3, 19.2] months for Group 1 vs. 5.6 [0.8, 64.9] months for Group 2, t = -2.93, P = 0.003) and weight (3.7 [3.0, 11.5] kg for Group 1 vs. 6.0 [3.4, 20.3] kg for Group 2, t = -3.14, P = 0.002) of children increased over time, while the proportion of congenital heart disease (75.9% for Group 1 vs. 57.8% for Group 2, χ2 = 6.52, P = 0.011) and cardiogenic shock (36.2% for Group 1 vs. 7.2% for Group 2, χ2 = 36.59, P < 0.001) decreased. Patient conditions before ECMO were worse, while ECMO complications decreased across time periods, especially renal complications. Multiple logistic regression analysis of ECMO complications showed that disseminated intravascular coagulation (DIC), myocardial stunning, and neurological complications were independently associated with increased odds of hospital mortality. CONCLUSIONS: The broader indications and decreased complication rates make EPCR to be applicated more and more extensive in children in Asia Pacific region. ECMO complications such as myocardial stunning are independently associated with decreased survival.

TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury.

Dynamin-related peptide 1 (Drpl)-mediated mitochondrial fission is an important process associated with cardiac dysfunction under different pathological conditions. The aim of the present study was to investigate the expression of Drpl during inflammatory myocardial injury. Sprague­Dawley rats were treated intraperitoneally with lipopolysaccharides (LPS). Furthermore, cultured H9C2 cardiomyocytes were treated with LPS, interleukin­6 (IL­6) and tumor necrosis factor­α (TNF­α). Total and mitochondrial proteins were isolated from the heart tissue of rats and from the H9C2 cardiomyocytes. Expression levels of Drp1 and RhoA were analyzed by western blotting. Mitochondrial morphology was determined using confocal laser microscopy. The levels of mitochondrial Drp1 and phosphorylated­Drp1 (p­Drp1) Ser616 were revealed to be increased in rats 6 h after injection with LPS (5, 10 or 20 mg/kg). Furthermore, treatment with LPS and IL­6 did not demonstrate a significant effect on the expression of total and mitochondrial Drp1 in H9C2 cardiomyocytes in vitro; however, treatment with TNF­α (20 ng/ml) significantly enhanced the levels of mitochondrial Drp1 and p­Drp1 Ser616. Following TNF­α treatment, the expression of Ras homolog gene family member A (RhoA) was also revealed to increase. Treatment with both Y­27632 and fasudil, [Rho kinase (ROCK) inhibitors], was demonstrated to attenuate the otherwise TNF­α­induced increase in p­Drp1 Ser616 and mitochondrial Drp1. In addition, it was revealed that Y­27632 and fasudil may also attenuate the TNF­α­induced increase in mitochondrial fragmentation and cell viability. Therefore, the findings of the present study suggest that TNF­α is the predominant inducer of Drp1 S616 phosphorylation during sepsis. The results of the present study also suggest that the RhoA/ROCK pathway may be involved in the phosphorylation and mitochondrial translocation of Drp1, which leads to mitochondrial fragmentation.

Systemic inflammation mediates the detrimental effects of obesity on asthma control.

BACKGROUND: Obesity negatively impacts asthma control, but the inflammatory mechanisms are poorly understood. OBJECTIVE: To explore which systemic inflammatory mediators mediate the effects of obesity on asthma control. METHODS: The subjects with stable asthma (n = 108) underwent assessment of clinical characteristics, which included using The Asthma Control Questionnaire (ACQ)-6. Obesity was defined as a body mass index (BMI) of ≥30 kg/m2, overweight was defined as BMI between 25 to 29.9 kg/m2, and lean weight was defined as BMI < 25 kg/m2. Body composition, including fat mass (FM), visceral fat area (VFA), and percentage body fat (PBF) was analyzed by bioimpedance. Serum interleukin (IL) 4, IL-5, IL-8, IL-13, IL-17, chemokine (C-C motif) ligand (CCL) 17, CCL22, leptin, adiponectin, C-reactive protein (CRP), and interferon (IFN) gamma were measured by using ELISA. Linear regression models were fitted according to the Baron and Kenny procedures for mediation analysis. RESULTS: FM (12.73 ± 3.95 versus 18.59 ± 2.95 versus 27.82 ± 5.17 kg; p < 0.0001), VFA (65.99 ± 23.17 versus 93.96 ± 10.28 versus 123.10 ± 18.34 cm2; p < 0.0001), PBF (23.86 ± 7.46 versus 30.74 ± 5.08 versus 36.21 ± 6.28 %; p = 0.0003) and ACQ-6 values (0.83 [0, 1.17]) versus 1.15 [0.50, 1.75] versus 1.33 [0.83, 1.83] score; p = 0.002) were different among lean (n = 52), overweight (n = 37), and obese (n = 19) subjects. Serum levels of leptin, IL-5, IL-13, IL-17, CCL17, CRP, and IFN-gamma in the obese group were significantly elevated compared with the subjects who were lean or overweight (all p < 0.05). The mediation analyses found that the effect of obesity, assessed by BMI, on ACQ-6 was significantly mediated through IL-13 and CCL17. Furthermore, IL-13 and CCL17 mediated the effects of body composition (FM, VFA and PBF) on ACQ-6. The effects of obesity assessed by body composition, but not by using BMI, on ACQ-6 were mediated by leptin. CONCLUSION: Our mediation analysis confirmed that systemic inflammation biomarkers, such as leptin, CCL17, IL-4, and IL-13, mediated the effects of obesity on asthma control. This warrants prospective exploration in this distinct asthma phenotype in the future.

Benefit of oral nutritional supplements for children with acute lymphoblastic leukaemia during remission-induction chemotherapy: a quasi-experimental study.

BACKGROUND AND OBJECTIVES: To determine the effect of oral nutritional supplements (ONS) on children with acute lymphoblastic leukaemia undergoing remission-induction chemotherapy. METHODS AND STUDY DESIGN: We included 127 paediatric patients who were diagnosed with acute lymphoblastic leukaemia and undergoing remission- induction chemotherapy in the First Affiliated Hospital of Zhengzhou University. Children from two paediatric wards who met the inclusion criteria were enrolled. One ward was randomly chosen as the intervention group and the other ward as the control group. Children in the two groups were matched for age and sex. The ONS group was administered Peptamen® (n=60) and the control group was administered a low-fat diet (n=67). RESULTS: The baseline information before treatment was not significantly different between groups (p>0.05). In the control group, weight loss at the end of chemotherapy was significantly higher than that of ONS group (p<0.05). The hemoglobin level and the concentrations of total protein, albumin, and pre-albumin were significantly higher in the ONS group than in the control group (p<0.05 and p<0.01, respectively). The incidences of hypoalbuminaemia, gastrointestinal complications, and infection were lower in the ONS group than in the control group (p<0.05). The ONS group also used lower amount of albumin infusion, fewer blood-product infusion, and had lower hospital costs than the control group. CONCLUSIONS: During remission-induction chemotherapy, oral nutritional supplements can improve the nutritional status of children, reduce the incidence of complications, and decrease the costs of hospitalization.

Quantitative Assessment of Airway Pathology in Subjects With COPD Using Low-Dose High-Resolution Computed Tomography.

BACKGROUND: The purpose of this study was to correlate airway parameters of COPD determined by low-dose high-resolution computed tomography (HRCT) with pulmonary function testing (PFT) results. METHODS: PFT data were collected for subjects with COPD and healthy controls. All subjects received inspiratory and expiratory phase low-dose HRCT. Bronchi in the apical segment of the right upper lobe (RB1), posterior segment of the right lower lobe (RB6), and lower lingual segment of the left upper lobe (LB5) were the target bronchi. Software automatically calculated airway wall area, inner area, and airway wall area percentage (percentage wall area for bronchial external area). RESULTS: A total of 75 COPD and 20 control subjects were included. The subjects with COPD were classified according to COPD stage, with 20 grade I, II, and III subjects, respectively, and 15 grade IV subjects. In COPD grade II, residual volume/total lung capacity was negatively correlated with airway wall area in LB5 (r = -0.51). In COPD grade III, FVC was negatively correlated with airway wall area percentage in LB5 (r = -0.49) but positively correlated with airway wall area in RB6 (r = 0.52); percent-of-predicted FEV1 was negatively correlated with airway wall area percentage in RB1 (r = -0.49); residual volume was negatively correlated with airway wall area (r = -0.47), and total lung capacity was negatively correlated with airway wall area in RB1 (r = -0.52) (all, P < .001). CONCLUSIONS: The results of this study suggest that airway parameters in different COPD grades have no uniform tendency of correlation with PFT, but some HRCT parameters are correlated to some PFT parameters.

Mechanism of uncoupling protein 2­mediated myocardial injury in hypothermic preserved rat hearts.

In the present study, the alterations in uncoupling protein 2 (UCP2) expression following hypothermic preservation in rat hearts were investigated. Isolated rat hearts were preserved in Celsior solution for 3­12 h followed by 60 min of reperfusion. The cardiac function was evaluated using the Langendorff perfusion system. UCP2 and silent mating type information regulation 2 homolog 1 (SIRT1) proteins were detected by western blot analysis. The ATP production and mitochondrial reactive oxygen species (ROS) levels were assessed. Subsequent to preservation in ice­cold Celsior solution for 3­12 h, the UCP2 protein expression in rat hearts was observed to increase in a time­dependent manner. The UCP2 inhibitor genipin inhibited the hypothermic preservation­induced cardiac dysfunction, prevented a decline in ATP production induced by 9 h of preservation, however had no effect on the hypothermic preservation­induced increase in mitochondrial ROS levels. Compared with the control group, the SIRT1 protein expression in rat hearts reduced following hypothermic preservation. Compared with the 9­h preservation group, Celsior solution supplemented with the SIRT1 activator resveratrol (20 or 40 µmol/l) inhibited UCP2 protein overexpression, prevented the decline in ATP production and resulted in an improvement cardiac function. The SIRT1 inhibitor EX­527 abolished the resveratrol­induced inhibition of UCP2 overexpression and cardiac protection in the hypothermic preserved rat heart. These observations suggest that downregulation of UCP2 expression in the hypothermic preserved rat heart in part initiated the protective mechanism via the SIRT1 pathway.

[Effects of land use change on soil active organic carbon in deep soils in Hilly Loess Plateau region of Northwest China].

Response of soil active organic carbon to land-use change has become a hot topic in current soil carbon and nutrient cycling study. Soil active organic carbon distribution characteristics in soil profile under four land-use types were investigated in Ziwuling forest zone of the Hilly Loess Plateau region. The four types of land-use changes included natural woodland converted into artificial woodland, natural woodland converted into cropland, natural shrubland converted into cropland and natural shrubland converted into revegetated grassland. Effects of land-use changes on soil active organic carbon in deep soil layers (60-200 cm) were explored by comparison with the shallow soil layers (0-60 cm). The results showed that: (1) The labile organic carbon ( LOC) and microbial carbon (MBC) content were mainly concentrated in the shallow 0-60 cm soil, which accounted for 49%-66% and 71%-84% of soil active organic carbon in the profile (0-200 cm) under different land-use types. Soil active organic carbon content in shallow soil was significantly varied for the land-use changes types, while no obvious difference was observed in soil active organic carbon in deep soil layer. (2) Land-use changes exerted significant influence on soil active organic carbon, the active organic carbon in shallow soil was more sensitive than that in deep soil. The four types of land-use changes, including natural woodland to planted woodland, natural woodland to cropland, natural shrubland to revegetated grassland and natural shrubland to cropland, LOC in shallow soil was reduced by 10%, 60%, 29%, 40% and LOC in the deep layer was decreased by 9%, 21%, 12%, 1%, respectively. MBC in the shallow soil was reduced by 24% 73%, 23%, 56%, and that in the deep layer was decreased by 25%, 18%, 8% and 11%, respectively. (Land-use changes altered the distribution ratio of active organic carbon in soil profile. The ratio between LOC and SOC in shallow soil increased when natural woodland and shrubland were converted into farmland, but no obvious difference was observed in deep soil. The ratio of MBC/SOC in shallow soil decreased when natural shrubland was converted into farmland, also, no significant difference was detected in the ratio of MBC/SOC for other land-use change types. The results suggested that land-use change exerted significant influence on soil active organic carbon content and distribution proportion in soil profile. Soil organic carbon in deep soil was more stable than that in shallow soil.

[Characteristics of Soil Respiration along Eroded Sloping Land with Different SOC Background on the Hilly Loess Plateau].

This study aimed to characterize soil respiration along eroded sloping land at erosion and deposition area under different soil organic carbon(SOC) levels, and linked the relationship between soil respiration and soil temperature, soil moisture, SOC and slope position. Experiments were carried out in the plots of S type slopes include five different soil organic carbon levels in the Loess Hilly Region. The S type slopes were divided into control area at the top of the slope, erosion area at the middle of the slope and deposition area at the toe of the slope. We found that soil temperature had a greater impact on soil respiration in the deposition area, whereas soil moisture had a greater impact on soil respiration in the erosion area compared among control area, erosion area and deposition area. In addition, SOC was the most important factor affecting soil respiration, which can explain soil respiration variation 54. 72%, followed by soil moisture, slope position and soil temperature, which explain soil respiration variation 18. 86% , 16. 13% and 10. 29%, respectively. Soil respiration response to erosion showed obvious on-site and off-site effects along the eroded sloping land. Soil respiration in the erosion area was reduced by 21. 14% compared with control area, and soil respiration in the deposition area was increased by 21. 93% compared with control area. Erosion effect on source and sink of carbon emission was correlated with SOC content of the eroded sloping land. When SOC content was higher than 6. 82 g.kg-1, the slope. erosion tended to be a carbon sequestration process, and when SOC content was lower than 3.03 g.kg-1, the slope erosion tended to be a process of the carbon emission source. The model could reflect the relationship between soil respiration and independent variables of soil organic carbon content, soil temperature and moisture.

[Decreased amplitude of [Ca²âº]i elevation induced by menthol in pulmonary arterial smooth muscle cells of pulmonary hypertensive rats].

The study was designed to explore the alteration of intracellular calcium concentration ([Ca²âº]i), induced by transient receptor potential melastatin 8 (TRPM8) channel-specific agonist menthol, in pulmonary arterial smooth muscle cells (PASMCs) between control and pulmonary hypertensive (PH) rats. PH rat models were established by means of chronic hypoxia (CH) and monocrotaline (MCT) injection, respectively. PASMCs from control and PH rats were cultured. The change of [Ca²âº]i in PASMCs induced by menthol, and the effect of TRPM8 channel-specific antagonist BCTC on the change of [Ca²âº]i, were observed. Cellular localization of TRPM8 was examined by using immunohistochemistry. Results showed that menthol increased [Ca²âº]i in the control PASMCs both in Ca²âº -normal and Ca²âº - free Tyrode's solutions, and at the same time BCTC could inhibit these two kinds of elevations. Compared with the control group, elevations of [Ca²âº]i were decreased notably in CH- and MCT-pretreated PASMCs superfused with 2 mmol/L Ca²âº - or 0 Ca²âº -Tyrode's solutions. Immunohistochemical localization experiments showed that the whole PASMCs were dyed brown except for the nucleus. This study verified that TRPM8 exists both in membrane and sarcoplasmic reticulum of PASMCs. In addition, CH- and MCT-pretreatment could independently down-regulate the Ca²âº influx and Ca²âº release mediated by TRPM8 channel.

[Distribution laws of Chinese medical syndrome types and analyses of risk factors in senile hypertension patients: a clinical study].

OBJECTIVE: To explore the distribution laws of TCM syndrome types and to analyze the distribution of dynamic blood pressure curve, atherosclerosis, and age in senile hypertension patients. METHODS: Totally 1 131 senile hypertension patients were recruited from 7 provinces and municipal cities. Features of TCM syndromes, classification and distribution curves, and syndrome distribution laws were observed. The distribution curves of dynamic blood pressure, carotid atherosclerosis, and age were compared in each TCM syndrome types. RESULTS: There were four main syndrome types in 736 cases (56.15%), i.e., excessive accumulation of phlegm-dampness syndrome (210 cases, 16.02%), yin deficiency and hyperactivity of yang syndrome (177 cases, 13.50%), Gan-Shen yin deficiency syndrome (79 cases, 6.03%), and deficiency of qi and yin syndrome (252 cases, 19.22%). Besides, there were two more sub-types, i.e., collateral obstruction by blood stasis syndrome and collateral obstruction by phlegm and stasis. Circadian blood pressure monitor was completed in 211 cases. Of them, abnormal circadian blood pressure occurred in 152 cases (accounting for 72. 38%); yin deficiency and hyperactivity of yang syndrome, excessive accumulation of phlegm-dampness syndrome, deficiency of qi and yin syndrome plus collateral obstruction by blood stasis syndrome were most often seen. Color ultrasound of carotid artery was performed in 660 patients of main syndromes. The incidence was quite higher in those of excessive accumulation of phlegm-dampness syndrome (182 cases, 27. 58%), deficiency of qi and yin syndrome plus collateral obstruction by blood stasis syndrome or collateral obstruction by phlegm and stasis (322 cases, 48.79%). Yin deficiency and hyperactivity of yang syndrome was dominant in patients 60 -79 years old, while deficiency of qi and yin syndrome and Gan-Shen yin deficiency syndrome were dominant in patients older than 80 years. CONCLUSIONS: Excessive accumulation of phlegm-dampness syndrome, yin deficiency and hyperactivity of yang syndrome, Gan-Shen yin deficiency syndrome, and deficiency of qi and yin syndrome were main syndrome types in senile hypertension patients. There was statistical difference in the distribution curves of blood pressure, atherosclerosis, and age of various TCM syndrome types.

[Association between left ventricular diastolic function and blood pressure variability in essential hypertensive patients].

OBJECTIVE: To investigate the relationship between blood pressure variability (BPV) and left ventricular diastolic function in patients with essential hypertension. METHODS: Left ventricular diastolic function of 252 hypertensive patients were assessed by early (E) diastolic transmitral flows to early diastolic mitral annular velocity (Ea) (E/Ea) ratio derived from Doppler echocardiography. Patients were divided into two groups according to normal left ventricular diastolic function group (E/Ea<15, n = 168) and left ventricular diastolic dysfunction group (E/Ea ≥ 15, n = 84). All patients were monitored by ambulatory blood pressure. Standard deviation (SD) and coefficient of variation (CV) of blood pressure were calculated as the BPV. Relationship between BPV and left ventricular diastolic function were analyzed by multivariate logistic regression analysis. RESULTS: All-day average diastolic blood pressure(DBP), the day systolic blood pressure (SBP), night SBP, night DBP, SBPSD, DBPSD and DBPCV in the left ventricular diastolic dysfunction group were significantly higher than in the normal diastolic function group (all P < 0.05). Multivariate logistic regression analysis showed that left ventricular diastolic dysfunction was associated with SBPSD (OR:1.126, 95%CI:1.054-1.203, P < 0.01), SBPCV (OR:1.127, 95%CI:1.036-1.225, P < 0.01) in this patient cohort. CONCLUSION: High variability of SBP is correlated with left ventricular diastolic dysfunction in hypertensive patients.

Down-regulation of TRPM8 in pulmonary arteries of pulmonary hypertensive rats.

BACKGROUND: Pulmonary hypertension (PH) is characterized by profound vascular remodeling and alterations in Ca(2+) homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Multiple transient receptor potential melastatin-related (TRPM) subtypes have been identified in vascular tissue. However, the changes in the expression and function of TRPM channels in pulmonary hypertension have not been characterized in detail. METHODS: We examined the expression of TRPM channels and characterized the functions of the altered TRPM channels in two widely used rat models of chronic hypoxia (CH)- and monocrotaline (MCT)-induced PH. RESULTS: CH-exposed and MCT-treated rats developed severe PH and right ventricular hypertrophy, with a significant decrease in TRPM8 mRNA and protein expression in pulmonary arteries (PAs). The downregulation of TRPM8 was associated with significant reduction in menthol-induced cation-influx. Time-profiles showed that TRPM8 down-regulation occurred prior to the increase of right ventricular systolic pressure (RVSP) and right ventricular mass index (RVMI) in CH-exposed rats, but these changes were delayed in MCT-treated rats. The TRPM8 agonist menthol induced vasorelaxation in phenylephrine-precontracted PAs, and the vasorelaxing effects were significantly attenuated in PAs of both PH rat models, consistent with decreased TRPM8 expression. CONCLUSION: Downregulation of TRPM8 may contribute to the enhanced vasoreactivity in PH.

[Clinical observation of the role of Chenxia Sijunzi decoction in promoting the recovery of gastrointestinal function in critically ill patients].

OBJECTIVE: To observe the clinical effects of Chenxia Sijunzi decoction on promoting gastrointestinal function recovery in severe patients. METHODS: A prospective randomized controlled study was conducted. Eighty severe patients feeding with enteral nutrition from September 2011 to March 2012 were divided into three groups according to the method of random number table. The traditional Chinese medicine group and western medicine group were consisted of 35 cases respectively, and 10 cases were control group. Control group was routine symptomatically treated without any medicines for promoting gastrointestinal power function, helping the lower extremities to move and enhancing the turn over, letting the gastrointestinal function recover by its self. Chinese medicine group was tube fed with Chenxia Sijunzi decoction on the basis of control group, western medicine group was tube fed with the multienzyme tablets and mosapride dispersible tablets on the basis of control group. Then the differences in bowel sound recovery time and the time for passage of gas by anus and the bowel movement time and length of stay in hospitals within three groups were observed. RESULTS: The time of bowel sound recovery (41.02±7.52 hours, 44.02±6.23 hours), gas passage time by anus (49.90±6.95 hours, 51.32±5.12 hours) and the bowel movement time (58.22±6.71 hours, 60.91±3.72 hours) in both traditional Chinese medicine and the western medicine group were significantly reduced compared with the control group (54.62±5.51 hours, 64.68±9.47 hours, 78.20±7.11 hours, all P<0.01), and the days in hospital (5.1±1.7 days, 5.0±1.5 days) were shortened significantly compared with the control group (8.9±1.4 days, both P<0.01). However, results did not demonstrate any significant differences in each testing index between traditional Chinese medicine and western medicine group (all P>0.05). CONCLUSION: Chenxia Sijunzi decoction can promote severe patient's gastrointestinal function recovery and reduce hospitalization days.

[Studies on chemical constituents of flavonoid from Verbena officinals].

Five compounds have been isolated from Verbena offcinals L. On the basis of spectral analysis and physicochemical properties, the compounds were identified as luteolin (1), kaempferol (2), quercetin (3), apigenin (4) and 4'-hydroxywogonin (5). 1, 2 and 3 were obtained from the genus for the first time.