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 investigate the differences in efficacy and long-term prognosis between locally progressive low and intermediate rectal cancer patients receiving fluorouracil-based neoadjuvant chemotherapy alone (mFOLFOX6/CapeOX) and neoadjuvant radiotherapy, and to compare the therapeutic efficacy in the two groups. 【Methods】 We retrospectively analyzed the clinicopathological data of 118 patients with locally progressive low and intermediate rectal cancer who received neoadjuvant therapy from January 2019 to December 2021 at The First Affiliated Hospital of Xi’an Jiaotong University, including gender, age, body mass index (BMI), and other clinicopathological parameters. The t-test, Mann Whitney test, chi-square test or Fisher’s exact test were used to compare the differences between the two groups of patients who received neoadjuvant chemotherapy alone or neoadjuvant radiochemotherapy in terms of short-term efficacy, lymph node manifestations and long-term prognosis, respectively. Survival rates were calculated and survival curves were plotted using the Kaplan-Meier method. 【Results】 In terms of efficacy, patients in the neoadjuvant radiotherapy group achieved better tumor regression (Z=-2.05, P=0.04) and solid tumor efficacy (Z=-2.42, P=0.015), but the difference between the two groups in terms of downstaging effect of clinical stage was not statistically significant. The number of lymph nodes detected was significantly lower in the neoadjuvant radiotherapy group (neoadjuvant chemotherapy vs. neoadjuvant radiochemotherapy, 13.19±3.83 vs. 9.55±4.00, t=5.02, P<0.001), but the two groups did not differ significantly in the number of lymph node positives and lymph node positive ratio. In terms of long-term prognosis, there was no statistically significant difference in the overall survival rate or disease-free survival rate of the two groups. 【Conclusion】 Compared with neoadjuvant chemotherapy alone, neoadjuvant radiotherapy showed better short-term efficacy in patients with locally progressive low and intermediate rectal cancer, but there was no statistically significant difference between the two treatment regimens in terms of long-term prognosis.

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.

Osteoarthritis (OA) is a chronic degenerative joint disease whose main characteristic is the destruction of articular cartilage, causing pain and disability in patients and seriously affecting their quality of life. OA can be induced by a variety of causes, and pathological changes in articular cartilage are considered to be one of the key driving factors for the occurrence of OA. High mobility group box-1 protein (HMGB1), as a non-histone protein in eukaryotic cells, can participate in regulating the inflammation and apoptosis process of OA chondrocytes, thus leading to the occurrence of OA. This article reviews the research on the mechanism of HMGB1 in OA chondrocytes, with a view to providing new ideas for the clinical prevention and treatment of OA.

Objective To construct a pelvic floor muscle training program for patients undergoing radical prostatectomy,and to provide a reference for clinical practice.Methods The evidence related to pelvic floor muscle training in patients undergoing radical prostatectomy was systematically searched and the quality was evaluated.The draft of pelvic floor muscle training program for patients undergoing radical prostatectomy was constructed based on the KAP theory and it was demonstrated and revised by expert meetings.From February to March 2023,Delphi method was used to determine the final scheme.37 patients were selected as the control group and 38 patients as the experimental group to implement the scheme and evaluate the application effect.Results 2 rounds of Delphi consultations were conducted among 17 experts,and the recovery rate of the questionnaire was 100％.The expert authority coefficient was 0.89.The Kendall harmony coefficients of the importance and feasibility of the second round of consultation were 0.270 and 0.209(P＜0.001).The coefficient of variation of importance and feasibility of items were 0～0.18 and 0～0.20.The final program included 3 first-level items,8 second-level items and 29 third-level items.1 month after surgery,there was no significant difference in urinary incontinence score(P=0.242)and there was significant difference in pelvic floor muscle training compliance(P=0.011)between 2 groups.Conclusion The program was applied preliminary in clinical practice and it was confirmed with scientific and practical meaning,so it can provide a reference for clinical nursing.

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 esketamine combined with fascia iliaca compartment-subarachnoid block in optimizing anesthesia in elderly patients undergoing hip fracture surgery.Methods:Sixty-two American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ elderly patients of either sex, aged 60-85 yr, with body mass index of 18.5-30.0 kg/m 2, were divided into 2 groups ( n=31 each) using a random number table method: fascia iliaca compartment-subarachnoid block group (FS group) and esketamine combined with fascia iliaca compartment-subarachnoid block group (ES group). In FS group, patients underwent ultrasound-guided fascia iliaca compartment block at 30 min before the operation of subarachnoid anesthesia on the surgical side. In ES group, esketamine 0.25 mg/kg was intravenously administered at 5 min before skin incision based on the fascia iliaca compartment-subarachnoid block. Patient-controlled intravenous analgesia was used for postoperative analgesia, and tramadol 1 mg/kg was intravenously given for rescue analgesia when numerical rating scale score > 4. The pressing times of patient-controlled analgesic pump, the number of rescue analgesia and consumption of tramadol were recorded within 48 h after operation. The occurrence of postoperative adverse reactions (respiratory depression, nausea and vomiting, dizziness, drowsiness, pruritus, illusion, nightmares) was recorded. Results:Compared with FS group, the consumption of postoperative tramadol was significantly decreased, and the pressing times of patient-controlled analgesic pump and the number of rescue analgesia were reduced in ES group ( P<0.05). There were no significant differences in the incidence of postoperative adverse reactions between the two groups ( P>0.05). Conclusions:Combination of esketamine with fascia iliaca compartment-subarachnoid block for hip fracture surgery can raise postoperative analgesia and optimize clinical management strategies in elderly patients.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

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 learn about the genotyping of human Brucella isolated from Sichuan Province. Methods:BCSP31-PCR and AMOS-PCR were used to identify the genus and biotype of the 66 strains isolated from confirmed human brucellosis cases in Sichuan Province from 2014 to 2020, respectively. The isolated strains were genotyped by multi-locus sequence typing (MLST)-9. The sequence type (ST) was compared trough the online MLST database. A minimum spanning tree (MST) was constructed to cluster the newly discovered and known ST using the BioNumerics software version 7.6.Results:The 66 strains isolated from human cases of brucellosis in Sichuan Province from 2014 to 2020 were Brucella, and 65 of them were Brucella melitensis while one strain was Brucella abortus. The MLST method identified three known STs (ST-8, ST-39 and ST-2) and one newly type (ST-101). Among them, ST-8 was the main ST in Sichuan Province (90.91%, 60/66), another 4 strains of Brucella melitensis were ST-39, and 1 strain of Brucella abortus was ST-2. The newly type ST-101 was isolated from Leshan City in 2019, belonging to the Brucella melitensis and closely related to the evolution of ST-8. Conclusion:Brucella melitensis is the main epidemic Brucella strain in Sichuan Province, ST-8 is predominant genotype, with a small amount of ST-39, ST-101 and ST-2.