Objective:To evaluate the role of transient receptor potential vanillic acid 4 (TRPV4) in dexmedetomidine-induced improvement in cognitive function in mice with mechanical ventilator-caused brain injury.Methods:Ninety clean-grade healthy male C57BL6 mice, weighing 20-25 g, aged 8-12 weeks, were divided into 5 groups ( n=18 each) using a random number table method: control group (group C), mechanical ventilation group (group V), HC-067047 group (group H), dexmedetomidine group (group D), and dexmedetomidine+ GSK1016790A group (group DG). In group C, the animals breathed air spontaneously for 6 h without mechanical ventilation. In group V, the animals were mechanically ventilated for 6 h. In group H, TRPV4 blocker HC-067047 10 mmol was injected into the cerebral ventricle at 3 and 6 h of mechanical ventilation. In D and DG groups, dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation. In group DG, TRPV4 agonist GSK1016790A 5 μmol was injected into the cerebral ventricle at 60 min before mechanical ventilation. Morris water maze test was performed on 6 mice in each group at 1 day before mechanical ventilation and 3 and 7 days after mechanical ventilation. Six mice in each group were randomly selected and sacrificed at 1 day after mechanical ventilation, and the brain tissue was taken for determination of the neuronal apoptosis in hippocampal CA1 area by TUNEL method, and the apoptosis index was calculated. Six mice in each group were randomly selected and sacrificed at 1 day after mechanical ventilation, and the hippocampal tissues were taken for determination of the expression of TRPV4, serine-threonine protein kinase (Akt), phosphorylated Akt (p-Akt), Bcl-2, Bax and caspase-3 by Western blot. Results:Compared with group C, the escape latency was significantly prolonged and the number of crossing the original platform was reduced at 3 and 7 days after mechanical ventilation, the expression of TRPV4 and caspase-3 was up-regulated, the ratio of Bcl-2/Bax was decreased, and the apoptosis index of neurons was increased in group V and group DG ( P<0.05). Compared with group V, the escape latency was significantly shortened and the number of crossing the original platform was increased at 3 and 7 days after mechanical ventilation, the expression of TRPV4 and caspase-3 was down-regulated, the expression of p-Akt was up-regulated, the ratio of Bcl-2/Bax was increased, and the apoptosis index of neurons was decreased in group D and group H ( P<0.05). Compared with group D, the escape latency was significantly prolonged at 3 and 7 days after mechanical ventilation, the number of crossing the original platform was reduced, the expression of TRPV4 and caspase-3 was up-regulated, the expression of p-Akt was down-regulated, the ratio of Bcl-2/Bax was decreased, and the apoptosis index of neurons was increased in group DG ( P<0.05). Conclusions:TRPV 4 is involved in dexmedetomidine-induced improvement in cognitive function, which is related to up-regulation of p-Akt expression and inhibition of apoptosis in hippocampal neurons in mice with mechanical ventilation-caused brain injury.

Objective:To evaluate the efficacy of ultrasound-guided superior laryngeal nerve block(SLNB) combined with intravenous anesthesia for improving pediatric fiberoptic bronchoscopy.Methods:Forty pediatric patients of either sex, aged 3-6 yr, of American Society of Anesthesiologists Physical Status classificationⅠor Ⅱ, with body mass index of 18-24 kg/m 2, undergoing fiberoptic bronchoscopy in Cangzhou Central Hospital in 2022, were divided into 2 groups ( n=20 each) by a random number table method: ultrasound-guided SLNB plus intravenous anesthesia group (group A) and topical anesthesia plus intravenous anesthesia group (group B). After sedation with dexmedetomidine and esketamine, ultrasound-guided bilateral SLNB was performed with 1% lidocaine 0.5 ml (for each side)in group A, and topical anesthesia was performed with 1% lidocaine in nasal and pharyngeal cavities in group B. After completion of the surgery procedure, propofol was continuously infused at 5 mg·kg -1·h -1 until completion of diagnosis and treatment. An increment of propofol 1 mg/kg was intravenously given if severe bucking or body movement occurred during operation. Mean arterial pressure (MAP), heart rate (HR) and SpO 2 were recorded on admission to the operating room (T 0), immediately after sedation (T 1), immediately after bronchoscopy entering the glottis (T 2), 5 min after start of treatment (T 3) and at the end of examination (T 4). The occurrence of intraoperative hypoxemia, HR <60 bpm, and MAP <50 mmHg were recorded, and the additional dose of propofol was recorded. The venous blood samples were collected at T 0 and T 4 to determine plasma cortisol concentrations by chemiluminescence.The surgeon′s satisfaction score was recorded. The complications of SLNB were also recorded within 2 h after operation in group A. Results:Compared with group B, HR was significantly decreased at T 2 and T 3, SpO 2 was increased, the intraoperative additional dosage of propofol and incidence of hypoxemia were decreased, and the surgeon′s satisfaction score was increased, and the concentrations of cortisol were decreased at T 4 in group A ( P<0.05). No HR<60 bpm and MAP<50 mmHg were found in two groups. No SLNB-related complications were observed after operation in group A. Conclusions:Ultrasound-guided SLNB combined with intravenous anesthesia is safer for pediatric fiberoptic bronchoscopy and can improve the analgesic effect and is more helpful in inhibiting intraoperative stress responses when compared with conventional anesthesia.

Objective:To investigate the effect of baicalin on cognitive function of mice with brain injury induced by mechanical ventilation and its mechanism.Methods:Seventy two C57BL6 mice, weighing 20-25 g, aged 8-12 weeks, were randomly divided into control group (group C), mechanical ventilation group (group V), baicalin group (group B), baicalin+ Akt inhibitor MK-2206 group (group BM) according to random number table method, with 18 in each group.Mice in group C did not have mechanical ventilation and breathed air independently for 6 hours.Mice in group V received mechanical ventilation for 6 hours.Mice in group B and group BM were intraperitoneally injected with baicalin 100 mg/kg 30 minutes before mechanical ventilation, and mice in group BM were injected intraventricular with Akt inhibitor MK-2206 300 μg/kg 60 minutes before mechanical ventilation.Six mice in each group were randomly selected to test their learning and memory abilities by Morris water maze test 1st day before mechanical ventilation and 3rd day and 7th day after mechanical ventilation.One day after mechanical ventilation, six mice in each group were killed, and the brain tissue was taken.TUNEL method was used to detect the neuronal apoptosis in hippocampal CA1 area, and the apoptosis index was calculated.One day after mechanical ventilation, six mice in each group were killed, and the hippocampus was taken, Western blot was used to detect the protein expressions of caspase-3, caspase-9, Akt, p-Akt, GSK-3β and p-GSK-3β.SPSS 22.0 software was used for statistical analysis of data, repeated measure ANOVA and one-way ANOVA were used for comparison between multiple groups.LSD- t test was used for further pairwise comparison. Results:The results of water maze test showed that the time and group interaction of the four groups were not significant ( F=1.14, P>0.05), the main effect of time and group were both significant ( F=47.36, 59.65, both P<0.05). At 3rd day and 7th day after mechanical ventilation, the escape latencies of mice in group V were higher than those in group C (both P<0.05), and the numbers of platform crossing were lower than those in group C (both P<0.05). And 3 days and 7 days after mechanical ventilation, the escape latencies of mice in group B were lower than those in group V (both P<0.05) and the numbers of platform crossing were higher than those in group V (both P<0.05). The escape latenies of mice in BM group on the 3rd and 7th day were higher than those in group B (both P<0.05), and the numbers of platform crossing were lower than those in group B on the 3rd day and 7th day after mechanical ventilation(both P<0.05). TUNEL and Western blot results showed that apoptosis index of hippocampal neurons and expression levels of apoptosis-related proteins caspase-3 and caspase-9 were significant different in the four groups ( F=51.42, 41.21, 40.19, all P<0.05). The apoptosis index of hippocampal neurons ((40.6±3.9)%), the expression levels of caspase-3 (4.93±0.92) and caspase-9 (4.81±0.88) in the hippocampus of mice in group V were higher than those in group C ((13.7±1.4)%, (1.87±0.27), (1.71±0.25), all P<0.05), the apoptosis index of hippocampal neurons ((15.6±1.6)%), the expression levels of caspase-3 (1.95±0.30) and caspase-9 (1.76±0.28) in group B were lower than those in group V ((40.6±3.9)%, (4.93±0.92), (4.81±0.88), all P<0.05), the apoptosis index of hippocampal neurons ((27.8±2.7)%), the expression levels of caspase-3 (3.58±0.61) and caspase-9 (3.49±0.57) in BM group were higher than those in group B ((15.6±1.6)%, (1.95±0.30), (1.76±0.28), all P<0.05). Expression level of p-Akt, p-GSK-3β in hippocampal tissues of the four group of mice were significantly different ( F=37.54, 43.23, both P<0.05). The expression level of p-Akt (0.51±0.06) and p-GSK-3β (0.47±0.05) of hippocampal tissues of mice in group V were lower than those of group C ((1.07±0.10), (1.11±0.12), both P<0.05), the expression level of p-Akt (0.99±0.10) and p-GSK-3β (1.08±0.09) of hippocampal tissues of mice in group B were higher than those of group V (both P<0.05), the expression level of p-Akt (0.83±0.08) and p-GSK-3β (0.81±0.07) of hippocampal tissues of mice in group BM were lower than those in group B (both P<0.05). Conclusion:Baicalin can improve the cognitive function of mice with brain injury induced by mechanical ventilation, which is related with activation of Akt/GSK-3β signaling pathway and inhibition of hippocampal neuron apoptosis.

Objective:To evaluate the effects of dexmedetomidine on alveolar epithelial barrier function in rats with ventilator-induced lung injury (VILI), and the role of protein kinase C (PKC).Methods:One hundred clean-grade male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 5 groups ( n=20 each) using a random number table method: control group (group C), VILI group (group V), PKC inhibitor group (group B), dexmedetomidine group (group D), and dexmedetomidine plus PKC agonist group (DP group). The VILI model was developed by mechanical ventilation with a tidal volume of 40 ml/kg for 4 h in anesthetized animals.Group C breathed air autonomously for 4 h without mechanical ventilation.Group V was mechanically ventilated for 4 h. In group B, bisindolvlmaleimide I 0.12 mg/kg was injected intramuscularly 1 h before mechanical ventilation.In D and DP groups, dxmedetomidine 5.0 μg/kg was injected intravenously at 20 min before mechanical ventilation, and dexmedetomidine was intravenously infused at the rate of 5.0 μg·kg -1·h -1 during mechanical ventilation.In group DP, PKC agonist phorbol-12-myristic acid-13-acetate 15 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation.At 4 h of mechanical ventilation, oxygenation index (OI), lung permeability index (LPI) and wet/dry lung weight (W/D) ratio were measured, the pathological changes of lung tissues were observed, and lung injury was assessed and scored.The expression of PKC, occludin and ZO-1 protein was detected by Western blot, and the expression of PKC mRNA, occludin mRNA and ZO-1 mRNA was determined by real-time polymerase chain reaction. Results:Compared with group C, OI was significantly decreased, LPI, W/D ratio and lung injury score were increased, the expression of PKC protein and mRNA was up-regulated, and the expression of occludin and ZO-1 protein and mRNA was down-regulated in V and DP groups ( P<0.05), and no significant change was found in the parameters mentioned above in B and D groups ( P>0.05). Compared with group V, OI was significantly increased, LPI, W/D ratio and lung injury score were decreased, the expression of PKC protein and mRNA was down-regulated, and the expression of occludin and ZO-1 protein and mRNA was up-regulated in B, D and DP groups ( P<0.05). Compared with group D, OI was significantly decreased, LPI, W/D ratio and lung injury score were increased, the expression of PKC protein and mRNA was up-regulated, and the expression of occludin and ZO-1 protein and mRNA was down-regulated in group DP ( P<0.05). Conclusions:Dexmedetomidine can reduce the damage to alveolar epithelial barrier function in rats with VILI, and the mechanism is related to inhibition of PKC activation and up-regulation of the expression of occludin and ZO-1.

Objective:To evaluate the role of transient receptor potential vanilloid receptor 1 (TRPV1)/nuclear factor-κB (NF-κB) signaling pathway in dexmedetomidine-induced alleviation of ventilator-induced lung injury (VILI) in rats.Methods:One hundred clean-grade healthy male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 5 groups ( n=20 each) using a random number table method: control group (group C), VILI group (group V), AMG9810 group (group A), dexmedetomidine group (group D), and dexmedetomidine + RTX group (group DR). VILI model was prepared by mechanical ventilation with a tidal volume of 40 ml/kg for 4 h. In group A, TRPV1 inhibitor AMG9810 30 mg/kg was intraperitoneally injected at 1 h before mechanical ventilation.Dexmedetomidine 5.0 μg/kg was intravenously infused at 20 min before mechanical ventilation, and dexmedetomidine was intravenously infused at the rate of 5.0 μ g·kg -1·h -1 during ventilation in group D and group DR.In group DR, RTX 70 μ g/kg was intraperitoneally injected for 3 consecutive days before mechanical ventilation.At 4 h of mechanical ventilation, the concentrations of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 in bronchoalveolar lavage fluid (BALF) were detected, oxygenation index (OI) and wet/dry lung weight (W/D) ratio were measured, the histopathological changes of lung tissues were observed, and lung injury was assessed and scored.The expression of TRPV1 and NF-κB in lung tissues was detected by Western blot, and real-time polymerase chain reaction was used to detect the expression of TRPV1 and NF-κB mRNA. Results:Compared with group C, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly increased, OI was decreased, the W/D ratio and lung injury scores were increased, and the expression of TRPV1 and NF-κB protein and mRNA was up-regulated in group V ( P<0.05). Compared with group V, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly decreased, OI was increased, the W/D ratio and lung injury scores were decreased, and the expression of TRPV1 and NF-κB protein and mRNA was down-regulated in A, D and DR groups ( P<0.05). Compared with group D, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly increased, OI was decreased, the W/D ratio and lung injury scores were increased, and the expression of TRPV1 and NF-κB protein and mRNA was up-regulated in group DR ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates VILI is partially related to inhibition of the activation of TRPV1/NF-κB signaling pathway and inhibition of the inflammatory responses in lung tissues of rats.

Objective:To evaluate the relationship between the mechanism underlying methylprednisolone-induced alleviation of ventilator-induced lung injury (VILI) and p38 mitogen-activated protein kinase (p38 MAPK)/nucleotide binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway in lung tissues of rats.Methods:Sixty clean-grade male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), mechanical ventilation group (group V), and methylprednisolone group (group M). Group C breathed air spontaneously for 4 h without mechanical ventilation.Group V was mechanically ventilated (RR 40 times/min, V T 40 ml/kg, I∶E 1∶1, PEEP 0, FiO 2 21%) for 4 h. Group M received intravenous methylprednisolone 10 mg/kg at 20 min before mechanical ventilation.At 4 h of mechanical ventilation, broncho-alveolar lavage fluid (BALF) was collected to measure the concentrations of interleukin-1beta (IL-1β), IL-18, and tumor necrosis factor-alpha (TNF-α) and wet/dry lung weight ratio (W/D ratio), and lung tissues were obtained for microscopic examination of the histopathological changes and for detection of the expression of p38MAPK, phosphorylated p38MAPK (p-p38MAPK), NLRP3, apoptosis-related speck-like protein containing a CARD (ASC), and cysteinyl aspartate-specific protease-1 (caspase-1) (using Western blot). Results:Compared with group C, the W/D ratio of lung tissues and concentrations IL-1β, IL-18 and TNF-α in BALF were significantly increased, and the expression of p-p38MAPK, NLRP3, ASC and caspase-1 was up-regulated in group V ( P<0.05), and no significant change was found in group M ( P>0.05). Compared with group V, the W/D ratio of lung tissues and concentrations of IL-1β, IL-18 and TNF-α in BALF were significantly decreased, and the expression of p-p38MAPK, NLRP3, ASC and caspase-1 was down-regulated in group M ( P<0.05). Conclusion:The mechanism by which methylprednisolone alleviates VILI may be related to inhibition of p38MAPK/NLRP3 pathway activity and reduction of inflammatory responses in lung tissues of rats.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Objective:To evaluate the accuracy of lung recruitment maneuver (LRM) combined with brachial artery peak velocity variation (ΔVp) in predicting fluid responsiveness.Methods:Sixty-four patients of both sexes, aged 18-64 yr, with body mass index 19-26 kg/m 2, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with New York Heart Association class Ⅰor Ⅱ, scheduled for elective open gastrointestinal surgery under general anesthesia, were enrolled in this study.LRM (positive airway pressure was maintained at 30 cmH 2O for 10 s) and volume loading test were performed in sequence after anesthesia induction.ΔVp was measured by ultrasonography at the beginning of LRM.Mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP) and stroke volume (SV) were recorded before LRM (T 1), during LRM (T 2), before volume expansion (T 3) and after volume expansion (T 4). The changing rate of each index before and after LRM (ΔMAP LRM, ΔHR LRM, ΔCVP LRM, ΔSV LRM) and before and after volume expansion (ΔMAP VE, ΔHR VE, ΔCVP VE, ΔSV VE) were calculated.ΔSV VE≥15% was considered to be a positive response after volume expansion, and patients were divided into response group (≥ 15%, R group) and non-response group (< 15%, NR group). Results:There were 34 cases in R group and 30 cases in NR group.Compared with NR group, MAP at T 2 and SV at T 1, 2 were significantly decreased, ΔMAP LRM, ΔMAP VE, ΔSV LRM and ΔSV VE were increased, and ΔVp was increased in group R ( P<0.05). There was a positive correlation between ΔVp and ΔSV VE ( r=0.829, P<0.05), a negative correlation between ΔSV LRM and ΔSV VE ( r=-0.876, P<0.05), and a negative correlation between ΔVp and ΔSV LRM ( r=-0.819, P<0.05). The area under the receiver operating characteristic curve of LRM combined with ΔVp was 0.808, and the cut-off value was 32.3%, the sensitivity 75.3%, and the specificity 88.2%. Conclusion:LRM combined with ΔVp (≥32.3%) can accurately predict the intraoperative fluid responsiveness in patients.

Objective:To evaluate the effect of dexmedetomidine on the extracellular signal-regulated kinase(ERK)/sodium-potassium ATPase(Na + -K + -ATPase)signaing pathway in lung tissues of rats with mechanical ventilation-induced lung injury (VILI). Methods:Forty-eighty clean-grade male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 4 groups ( n=12 each) using a random number table method: control group (group C), VILI (alpha2-adrenergic receptor antagonist) group (group V), dexmedetomidine group (group D), and dexmedetomidine plus yohimbine group (group DY). Group C underwent no mechanical ventilation and breathed air spontaneously for 4 h. Mechanical ventilation (respiratory rate 40 breaths/min, tidal volume 40 ml/kg, inspiratory/expiratory ratio 1∶1, PEEP 0, fraction of inspired oxygen 21%) lasted 4 h in group V. Dexmedetomidine was infused intravenously in a dose of 5.0 μg/kg at 20 min before ventilation followed by an infusion of 5.0 μg·kg -1· h -1 throughout ventilation in group D. In group DY, yohimbine 0.1 mg/kg was injected intravenously at 10 min before dexmedetomidine, and the other treatments were similar to these previously described in group D. Blood samples and lung tissues were taken at 4 h of mechanical ventilation to determine the wet/dry weight ratio (W/D ratio), lung permeability index (LPI), alveolar fluid clearance rate (AFC), and expression of extracellular signal-regulated kinase (ERK), phosphorylated extracellular signal-regulated kinase (p-ERK), and Na + -K + -ATPase in lung tissues (by Western blot) and to observe pathological changes of lung tissues. Results:Compared with group C, LPI and W/D ratio were significantly increased, AFC was decreased, p-ERK expression was up-regulated, and Na + -K + -ATPase expression was down-regulated in group V and group DY ( P<0.05), and no significant change was found in the incidence of the parameters mentioned above in group D ( P>0.05). Compared with group V, LPI and W/D ratio were significantly decreased, AFC was increased, p-ERK expression was down-regulated, Na + -K + -ATPase expression was up-regulated ( P<0.05), and the pathological changes of lung tissues were significantly attenuated in group D, and no significant change was found in the incidence of the parameters mentioned above in group DY ( P>0.05). Compared with group D, LPI and W/D ratio were significantly increased, AFC was decreased, p-ERK expression was up-regulated, Na + -K + -ATPase expression was down-regulated ( P<0.05), and the pathological changes of lung tissues were accentuated in group DY. Conclusion:The mechanism by which dexmedetomidine alleviates VILI may be related to activating alpha2-adrenergic receptors and inhibiting ERK/Na + -K + -ATPase signaling pathway in rats.