ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:To evaluate the role of aquaporin 4 (AQP4) in dexmedetomidine-induced reduction of blood-brain barrier permeability in mechanically ventilated mice and the relationship with protein kinase C (PKC).Methods:One hundred and fifty clean-grade healthy male C57BL6 mice, weighing 20-25 g, aged 8-12 weeks, were divided into 5 groups ( n=30 each) using a random number table method: control group (group C), mechanical ventilation group (group V), LY317615 group (group L), dexmedetomidine group (group D), and dexmedetomidine+ PMA group (group DP). Group C spontaneously breathed air for 6 h. The animals were mechanically ventilated for 6 h in group V. PKC inhibitor LY3176 15 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation in group L. Dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation in D and DP groups. PKC activator PMA 15 μg/kg was intraperitoneally injected at 60 min before mechanical ventilation in group DP. Mice were anesthetized at 1 day after mechanical ventilation, then sacrificed and hippocampal tissues were taken for microscopic examination of pathological changes in the hippocampal CA1 and CA3 areas (with a light microscope). Brain tissues were also taken to measure the water content and content of Evans blue (EB) and to detect the expression of PKC and AQP4 (by Western blot). The cognitive function was evaluated using a novel object recognition task at 3 days after mechanical ventilation. Results:Compared with group C, the water content and EB content of brain tissues were significantly increased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was up-regulated, the percentage of novel object exploration and discrimination index were decreased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was aggravated in group V and group DP. Compared with group V, the water content and EB content of brain tissues were significantly decreased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was down-regulated, the percentage of novel object exploration and discrimination index were increased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was significantly attenuated in group D and group L. Compared with group D, the water content and EB content of brain tissues were significantly increased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was up-regulated, the percentage of novel object exploration and discrimination index were decreased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was aggravated in group DP. Conclusions:AQP4 is involved in dexmedetomidine-induced reduction of blood-brain barrier permeability in mechanically ventilated mice, and the mechanism is related to inhibiting activation of PKC.

Objective:To explore the clinical safety and effectiveness of self-draining ureteral stent with thread in kidney transplant recipients in renal transplantation.Methods:This study is a prospective cohort clinical study in the Department of Urology of Peking University People's Hospital from November 2022 to January 2024.The ureteral stent with thread group,in which a 2-0 Mersilene suture of 20-30 cm was used at the bladder end of the ureteral stent during the operation.On the 9th day after the opera-tion,the suture attached to the end of the ureteral stent was expelled out of the urethral orifice with the urine when the catheter was removed.The ureteral stent could be removed along with the suture.As to the cystoscope group,a ureteral stent was routinely placed during kidney transplantation,and the ureteral stent was removed under local infiltration anesthesia through cystoscopy after the operation.The pain scores[numerical rating scale(NRS)-11]during catheter removal and the incidence of urinary tract in-fections were observed and compared between the two groups.t test was used to compare the pain scores of indwelling ureteral stents and ureteral stents removal between the two groups,and Chi-square test was used to compare the occurrence of urinary system complications within 3 months after operation between the two groups.P＜0.05 was considered statistically significant.Results:As of March 2024,all the re-cipients were followed up for an average of 6 months(3 to 12 months)postoperatively.A total of 46 kid-ney transplantation patients were included,with 21 in the ureteral stent with thread group and 25 in the cystoscope group.There were no statistically significant differences between the two groups in age distri-bution,male-to-female ratio,and deceased versus live donor grafts.Three months after renal transplanta-tion,there were 15 cases of urinary tract infection in the cystoscope group and 4 cases in the ureteral stent with thread group(P=0.007).No significant urinary fistula,wound infection,or ureteral stenosis occurred in either group.No stent-related complications,stent migration,or stone formation were ob-served.The postoperative bladder spasm symptom scores for indwelling ureteral stents in the cystoscope group and the ureteral stent with thread group were 4.4±2.5 and 4.6±2.4,respectively,with no sta-tistically significant difference(t=0.29,P=0.773).However,the pain scores during ureteral stent re-moval were 4.9±1.6 and 3.0±1.0 in the two groups,respectively,with a statistically significant diffe-rence(t=5.017,P＜0.001).The total costs of indwelling and removing ureteral stents in the cystosco-py group and the ureteral stent with thread group were 6 452.0(5 539.5,6 452.0)yuan and 3 225.0(3 225.0,3 225.0)yuan,respectively,and the difference was statistically significant(P＜0.001).Conclusion:Compared with the conventional transplanted kidney ureteral stent,the self-discharge ure-teral stent technique with sutures is simpler,has a shorter ureteral stent inlay time,reduces the symptoms of bladder spasms,significantly reduces the cost of catheterization,and has fewer postoperative urinary system complications.It is a worthy improved surgical method to be promoted.

Objective To observe the application effect of different doses of dexmedetomidine in thyroid surgery under recurrent laryngeal nerve monitoring.Methods A total of 60 patients with thyroid surgery un-der general anesthesia,moreover adopting recurrent laryngeal nerve monitoring during the operation,in this hospital from October 2021 to June 2023 were selected as the study subjects and divided into the control group(group A),low dose group(group B)and high dose group(group C)by the random number table method.The group B and group C respectively used dexmedetomidine 0.3 μg/kg and 0.6 μg/kg as a loading dose be-fore anesthesia induction,0.3 μg·kg-1·h-1 and 0.6 μg·kg-1·h-1 were respectively injected by mi-cropump for anesthesia maintenance,while the group A adopted the same amount of normal saline.The other anesthesia management methods were the same in the three groups.The mean arterial pressure(MAP)and heart rate after entering the room(T0),before anesthesia induction(T1),after anesthesia intubation(T2),at 1 min after anesthesia intubation(T3),immediately after surgical incision(T4),isolation of the thyroid gland(T5)and at 1 min after extubation(T6),incidence rate of adverse reactions,choking reaction score,extubation time after stopping medication and dosage of propofol and remifentanil were recorded.Results The choking reaction score,extubation time after stopping medication and propofol dosage were manifested as the group C＜group B＜group A(P＜0.05).The remifentanil dosage in group C and group B was less than that in group A(P＜0.05).MAP at T1 in the group C was lower than that in the group A and group B(P＜0.05),but there was no statistical difference between the group A and group B(P＞0.05).MAP at T2-T6 in the group B and group C was lower than that in the group A(P＜0.05),but the difference between the group B and group C had no statistical significance(P＞0.05).The heart rate at T1-T6 in the group B and group C was lower than that in the group A(P＜0.05).The heart rate at T1,T2,T4,T5 and T6 in the group C was lower than that in the group B(P＜0.05).Bradycardia during operation did not occur in various groups.The intraoperative recurrent laryngeal nerve monitoring process was smooth without appearing interference.The incidence rate of adverse reactions had no statistical difference in various groups(P＞0.05).Conclusion He-modynamics by using 0.6 μg/kg dexmedetomidine in the patients with thyroid operation under recurrent la-ryngeal nerve monitoring is more smooth and steady,which could reduce the use amounts of anesthetic drugs,decrease the occurrence of choking reaction,shorten the operation extubation time after operation,moreover does not increase the incidence rate of postoperative adverse reactions.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Objective:To compare the efficacy of modified single-incision and traditional double-incision for flexor hallucis longus tendon transfer in the treatment of Myerson type III chronic Achilles tendon ruptures in the middle-aged and elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 106 patients with Myerson type III chronic Achilles tendon ruptures admitted to Ningbo No.6 Hospital from January 2015 to May 2021, including 54 males and 52 females; aged 48-82 years [(67.2±8.4)years]. Flexor hallucis longus tendon transfer was assigned to 60 patients using modified single-incision (modified single-incision group) and to 46 patients using traditional double-incision (traditional double-incision group). The operation time, intraoperative blood loss as well as American foot and ankle society (AOFAS) ankle-hindfoot score, foot and ankle outcome score (FAOS), visual analogue score (VAS) before operation, at postoperative 12 months and at the last follow-up were compared between the two groups. Time to recover walking and self-care ability, and incidence of complications were compared as well.Results:All patients were followed up for 16-52 months [(37.4±9.5)months]. The operation time and intraoperative blood loss were (51.6±7.4)minutes and (16.6±3.9)ml in modified single-incision group compared to (72.8±7.5)minutes and (32.9±5.2)ml in traditional double-incision group (all P<0.01). There was no significant difference in the AOFAS ankle-hindfoot score, FAOS and VAS between the two groups before operation (all P>0.05). At postoperative 12 months and at the last follow-up, AOFAS ankle-hindfoot score and VAS were not significantly different between the two groups (all P>0.05), but FAOS in modified single-incision group [(112.6±3.0)points, (114.4±3.1)points] was improved significantly compared with traditional double-incision group [(110.8±4.1)points, (112.7±4.3)points] ( P<0.05 or 0.01). At postoperative 12 months and at the last follow-up, the AOFAS ankle-hindfoot score, FAOS and VAS in both groups were improved or decreased significantly compared with those before operation (all P<0.05). All patients recovered their pre-injury daily activities. The time to recover walking and self-care ability were (9.6±2.0)weeks and (12.7±1.7)weeks in modified single-incision group compared to (10.8±1.8)weeks and (13.7±1.9)weeks in traditional double-incision group (all P<0.01). In modified single-incision group, superficial incision infection ( n=1) was found and cured after oral antibiotics. In traditional double-incision group, superficial incision infection ( n=2), deep incision infection ( n=1), deep venous thrombosis ( n=1) and medial plantar nerve injury ( n=1) were found and cured after symptomatic internal medical therapy; claw toe deformity ( n=2) was found and relieved after wearing customized insoles and functional exercise. The incidence of complications was 1.7% (1/60) in modified single-incision group compared to 15.2% (7/46) in traditional double-incision group ( P<0.01). Conclusion:In contrast with traditional double-incision surgery, modified single-incision for flexor longus tendon transfer in the treatment of Myerson type III chronic Achilles tendon ruptures in the middle-aged and elderly patients has advantages such as shorter operation time, less intraoperative blood loss, better functional recovery, faster postoperative recovery and less complications.

Objective To conduct a scoping review on studies of tele-health management for stroke patients at home.Methods According to the reporting framework of scoping review,a system-atic literature search was performed in 9 databases or websites from January 1,2013 to May 1,2023.Results A total of 52 literatures from 12 countries were included,most of which were interventional studies.Tele-health management was gradually becoming a trend in the application of stroke patients at home,relying on rehabilitation robots,virtual reality rehabilitation games,social platforms,home health network platforms and other carriers for rehabilitation training,disease monitoring,health edu-cation and guidance,follow-up and reminder.Conclusion The contents of tele-health management for stroke patients at home are abundant,with many evaluation indexes.In the future,rehabilitation training should enhance the gameplay of rehabilitation video games,improve patient's experience,and use artificial intelligence based on medical big data to provide auxiliary support for patients;at the same time,the content of each module of the tele-health management program should be standardized,and caregivers are encouraged to participate in the tele-health management of stroke patients at home,so as to better play the role of tele-health management in the field of post-stroke health management at home.

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.