Objective To investigate the changes of membrane potential of mesenteric arteriolar smooth muscle cells (ASMCs) and large conductance calcium-activated potassium channel (BK Ca ) following hemorrhagic shock in rats. Methods (1) The Wistar rats were randomly divided into sham and shock groups. The hemorrhagic shock model was duplicated. The sham group was given operation rather than bloodletting. (2) ASMCs were isolated with pronase E and mesenteric arteries A2 and A3 from sham and shock rats also isolated. (3) The changes of membrane potential of ASMCs and potassium channel were recorded using cell-attach and inside-out patch lamps. Results (1) The membrane potential of ASMCs changed from -41 mV to -65 mV two hours after hemorrhagic shock. (2) After shock, the conductance of BK Ca did not change, while the open probability (NPo) of BK Ca was enhanced and the reversal potential of BK Ca changed significantly. Conclusions Membrane hyperpolarization of ASMCs occurs posterior to hemorrhagic shock, the cause for which may be the activation increase of BK Ca .

AIM: To detect the effect of intercellular adhesion molecule-1(ICAM-1) monoclonal antibody on microcirculation disorder in burn shock of Wistar rats. METHODS: The blood flow velocity and diameter of venule were measured with RBC tracking correlator and IV550 model video microscaler in burn shock models of rats. The number of leukocytes adhered on venule wall was calculated under microscope. The animal survival time was observed. RESULTS: ICAM-1monoclonal antibody could attenuate the falling of mean arterial pressure, significantly reduce the number of leukocytes adhered on venule wall, and obviously prolong the animal mean survival time, but less than 24h. CONCLUSION: ICAM-1 monoclonal antibody can decrease the number of adhered leukocytes to endothelial cells, attenuate the tether of leukocytes to venule and improve microcirculation and protect tissue cells in burn shock of rats. However, a comprehensive therapy should be taken in severe shock.

AIM: To elucidate the mechanism of polydatin(PD) in increasing the contractility of myocardial cells by observing the cytosolic free calcium concentration ([Ca 2+ ]i) of myocardial cells of rats. METHODS: The cells were labelled with fluo-3-AM, and [Ca 2+ ]i was determined by use of confocal microscopy (ACAS 570). RESULTS: In the study, we found that [Ca 2+ ]i of myocytes was elevated 10min after adding PD (0.6 mmol/L), but [Ca 2+ ]i of some cells increased to 111.80%?2.22% vs baseline, the others to 224.00%?24.33%. The effect of PD was inhibited remarkably by pretreated with EGTA(2mmol/L), verapamil (50 ?mol/L), a kind of L-calcium channel antagnist, and tetrodotoxin ( 1 ?mol/L), a kind of sodium channel blocker 10 min before PD, the fluorescence value were decreased to 53.00%?9.02% , 52.00%?7.07% and 72.67%?12.70% respectively vs baseline (P

AIM: To study the effect of microelement powder (MP) on membrane potential of vascular endothelial and smooth muscle cells of rats in order to elucidate the mechanism of microcirculation improvement by MP. METHODS: Cultured pulmonary vascular endothelial cells (EC) and aortic smooth muscle cells (SMC) of rats and detecting the changes of cellular membrane potentials by using potential-sensitive fluorescent probe and laser jet confocal microscope. RESULTS: MP hyperpolarized SMCs significantly. Glybenclamide (2 ?mol/L), a blocker of K ATP channel, which had no effect on membrane potential of SMCs, reversed the hyperpolarization of MP completely; MP hyperpolarized ECs slightly, but the effect was unaffected by glybenclamide. CONCLUSION: MP hyperpolarizes SMCs by activating K ATP channels and leads to dilation of microvessels and improvement of microcirculation.

AIM: To study I_ to channel function in severe burn and its contribution to cardiac dysfunction induced by severe burn. METHODS: CHO-K1 cells were transfected with human Kv4.3, the major subunit of human I_ to channel. The expressed Kv4.3 channels were recorded by whole-cell patch clamp and the effects of rat burn serum on Kv4.3 current densities and kinetics were observed. RESULTS: Kv4.3 channels expressed in CHO-K1 cells were endowed with the characterization of fast activation and inactivation, which was quite similar to that of native I_ to channels in cardiomyocytes. Rat's burn serum at the concentration of 2% decreased the current density significantly. At +40 mV, the current density in control group was (67.6?15.1) pA/pF, in contrast to (32.3?9.7)pA/pF in burn serum-treated group (P

AIM: To study the effect of microelement powder (MP) on membrane potential of vascular endothelial and smooth muscle cells of rats in order to elucidate the mechanism of microcirculation improvement by MP. METHODS: Cultured pulmonary vascular endothelial cells (EC) and aortic smooth muscle cells (SMC) of rats and detecting the changes of cellular membrane potentials by using potential-sensitive fluorescent probe and laser jet confocal microscope. RESULTS: MP hyperpolarized SMCs significantly. Glybenclamide (2 μmol/L), a blocker of KATP channel, which had no effect on membrane potential of SMCs, reversed the hyperpolarization of MP completely; MP hyperpolarized ECs slightly, but the effect was unaffected by glybenclamide. CONCLUSION: MP hyperpolarizes SMCs by activating KATP channels and leads to dilation of microvessels and improvement of microcirculation.

BACKGROUND:Recent studies have suggested that intranasal administration is one of the ways to target drugdelivery, and can effectively make the drug that cannot pass through the blood brain barrier by other pathways to bypass the blood brain barrier, resulting in targeted delivery to the brain. It provides a promising route for the treatment of central nervous system diseases. OBJECTIVE: To study the pharmacokinetic and brain-targeted channel-tropism tissue distribution character of cimicifugoside H-1 after nasal and intravenous administration in plasma and tissues in rats, in order to evaluate the feasibility of developing brain-targeted nasal delivery system of cimicifugoside H-1 by the passage between nose and brain in nasal olfactory area. METHODS: After intravenous injection and nasal administration of cimicifugoside H-1, the drug concentrations of plasma and channel-tropism organs (lung, spleen, stomach, large intestine, liver, kidney, brain, brain, cerebelum, cerebrospinal fluid, olfactory bulb and olfactory region) were detected. Drug-time curve was drawn. DAS program was used to select apartment model and pharmacokinetics parameters. RESULTS AND CONCLUSION:(1) The pharmacokinetics characters of cimicifugoside H-1 are rapidly absorbed and extensively distribution. Among major channel-tropism organs, drug concentrations were higher in the lung and brain than in the other organs. (2) Cimicifugoside H-1 could be straightly transported into brain by the intranasal administration. The molecule through olfactory mucosa in nasal cavity entered into olfactory bulb in arachno-hypostegal cavity, and then entered into olfactory region, cerebrospinal fluid, cerebrum and cerebelum gradualy. Olfactory bulb was the only way for drug molecule to go through nasal cavity into brain. (3) Compared with the intravenous injection, cimicifugoside H-1 through the intranasal administration has a significant

AIM: To study the effects of hypertonic NaCl-NaAc on microcirculation in hemorrhage-shocked rats.METHODS: SD rats were randomized into three groups of 7 5% NaCl(hypertonic saline, HS),5% NaCl-3 5% NaAc(hypertonic sodium acetate, HSA) and 0 9% NaCl(normal saline, NS) 4 mL/kg HS,HSA or NS was given intravenously following hemorrhagic shock The microcirculation of spinotrapezius muscle was observed RESULTS: HS increased mean aortic pressure more significant than HSA Variables including arteriolar and venular diameter,velocity and volumetric flow rate and open capillaries were increased and erythrocyte aggregation was decreased in 5 min after resuscitation with both HS and HSA solutions 5 min later,variables were deteriorated in HS group After local treatment, arteriolar and venular diameters were dilated significantly in HSA group CONCLUSION:HSA had superior effects to HS in improving microcirculation of hemorrhage-shocked rats

Objective:To analyze the clinical characteristics and risk stratification of 182 patients with acute pulmonary embolism (APE), and to investigate the correlation of neutrophil (N)/lymphocyte (L) ratio (NLR) and risk stratification/prognosis.Methods:The clinical data of 182 APE patients admitted to Peking University People’s Hospital from January 2015 to March 2021 were retrospectively collected, including age, sex, symptoms and signs, blood pressure, blood gas analysis, blood routine parameters, cardiac biomarkers, coagulation parameters, and right ventricular imaging parameters. The patients were divided into groups according to the risk stratification at admission and prognosis in hospital. χ2 test, t test or nonparametric test were used to analyze the differences in clinical characteristics, blood routine parameters, blood gas analysis, coagulation parameters and other parameters between the groups. Multivariate logistic regression analysis was used to study the independent risk factors for the prognosis of APE. Results:Among the 182 patients, 79 were male and 103 were female, 23 were in the high-risk group, 51 were in the intermediate-high-risk group, 46 were in the intermediate-low risk group, and 62 were in the low-risk group. There were 27 deaths and 155 survivors. The respiratory rate of the high/intermediate-high-risk group was significantly higher than that of the low/intermediate-low-risk group. Compared with the other three groups, pH, oxygen partial pressure (PO 2) and blood oxygen saturation (SO 2) in the high-risk group were significantly lower ( both P<0.05). There were statistically significant differences in WBC, N, and NLR levels between the high/intermediate-high-risk group and low/intermediate-low-risk group ( both P<0.05). However there were no significant differences in PLT, PLT/MPV, PLT/PDW, and coagulation related parameters PT, FIB, APTT and D-D between groups (all P > 0.05). MPV and PDW were only significantly different between the low-risk group, intermediate-low-risk group and high-risk group ( both P<0.05). Multivariate logistic regression analysis showed that NLR ( OR=1.179,95% CI:1.029-1.410, P=0.039) and PH ( OR=1.156,95% CI:1.031-1.522, P=0.041) were independent predictors of in-hospital mortality. The ROC curve was used to analyze the predictive value of NLR for in-hospital mortality. When the cutoff value of NLR was 8.38, the AUC of NLR was 0.824 (95% CI: 0.829-0.913), the corresponding sensitivity was 0.831, and the specificity was 0.887. Conclusions:NLR is correlated with risk stratification and prognosis of APE, and is an independent risk factor for poor prognosis.

Objective:To investigate the effects of treadmill training with different intensities on tendon-bone healing in rats after anterior cruciate ligament (ACL) reconstruction.Methods:Of the 99 adult male Sprague-Dawley (SD) rats used for this study, 90 were randomly selected to undergo ACL reconstruction with autologous caudal tendon. Two weeks after the surgical reconstruction, the 90 SD rats were randomized into a low-intensity group (group L, n=30) subjected to treadmill training at a speed of 12 m/min, a moderate-intensity group (group M, n=30) subjected to treadmill training at a speed of 18 m/min, and a free group (group C, n=30) subjected to free activities in the cage as a model control. The other 9 rats were set as a blank control (group N, n=9) subjected to no treatment at all. The treadmill training started at the end of 2 weeks after surgical reconstruction. Hematoxylin-eosin (HE), micro-CT analysis, mechanical testing, real-time quantitative polymerase chain reaction (qPCR) and western blot analysis were used to evaluate the quality of tendon-bone healing. Results:There were no significant differences in the areas of femoral and tibial lateral bone tunnels or the total bone volume ratio (BV/TV) between the 3 groups 2 weeks after surgery ( P > 0.05). At 4 weeks and 8 weeks after surgery, the areas of lateral tibial bone tunnel and lateral femoral tunnel in groups C, M and L showed a decreasing trend ( P < 0.05) while the BV/TV of lateral femoral tunnel and the BV/TV of lateral tibial tunnel in groups C, M and L showed an increasing trend ( P < 0.05). At 8 weeks after surgery, HE staining showed that the tendon-bone healing was the most mature in group L, followed by group M, and the least mature in group C, showing statistically significant differences ( P < 0.05). The stiffness and maximum failure load showed an increasing trend from group C to group M to group L to group N. The stiffness in group M and the stiffness and maximum failure load in groups N and L were significantly higher than those in group C ( P < 0.05). The relative mRNA expression levels of osteopontin (OPN) and collagen type Ⅱ alpha 1 chain gene (COL2 α 1), as well as the protein expression levels of osteocalcin, OPN, and COL2 α 1, showed an increasing trend from group C to group M to group L, showing significant differences between pairwise comparisons ( P < 0.05). Conclusions:Treadmill training starting at the end of 2 weeks after surgery is beneficial to tendon-bone healing and improves the biomechanical strength of the tendon-bone complex. Low-intensity mechanical stimulation is more conducive to new bone formation and collagen fiber remodeling in the tendon-bone complex.