Objective To observe the improved effect of propofol on vascular hyporeactivity in septic rats and its underlying mechanism. Methods A total of 96 SD rats (12 weeks old, both genders, weighing 200~220 g) were randomly divided into sham group (n=16), sepsis group (n=16, cecal ligation and puncture), propofol group (n=16), propofol+ROCK inhibitor Y-27632 group (n=16), propofol+PKCα inhibitor GO6976 group (n=16), propofol+IP3 inhibitor 2-APB group (n=8) and propofol+gap junction inhibitor metoclopramide sodium (Movens) group (n=8). In vitro vascular ring reactivity and vascular calcium sensitivity were measured to observe the improved effects of propofol on vascular hyporeactivity in septic rats and its relationships with RhoA/ROCK, PKCα, IP3 and cell gap junction. Results Determination of in vitro vascular ring and calcium sensitivity showed that the contractile reactivity to norepinephrine (NE) and to calcium sensitivity were significantly decreased in the arterial rings isolated from the septic rats compared with those from the sham group, with the dose-response curve shifting to the right, and most significant decrease by 51.42% in the superior mesenteric artery (SMA, P < 0.05). Propofol treatment significantly improved the hyporeactivity and calcium sensitivity of the vessels isolated from the septic rats, especially those of the femoral artery with a recovery rate of 89.57% (P < 0.05). In comparison with the propofol group, the dose-response curves of the propofol+Y-27632 group and the propofol+GO6976 group were shifting to right, indicating that Y-27632 and GO6976 could significantly inhibit the amelioration of propofol on calcium sensitivity of SMA in severely septic rats with an inhibitory rate of 146.95% and 88.63% (P < 0.05), respectively. Isolated vascular reactivity measurement demonstrated that Y-27632 and Movens treatment significantly antagonized the ameliorated role of propofol on hyporeactivity of blood vessels from the septic rats with an inhibitory rate of 40.79% and 169.90% (P < 0.05), separately, while no such effect was observed in the propofol+GO6976 and propofol+2-APB groups. Conclusion Propofol treatment can significantly improve vascular hyporeactivity of septic rats, which may attribute to the increase of vascular calcium sensitivity through RhoA/ROCK pathway.
Abstract Cognitive dysfunction is a common postoperative neurological complication in patients undergoing valve replacement surgery. This study aimed to compare the effects of sevoflurane versus propofol‐based total intravenous anesthesia on the incidence of cognitive dysfunction following valve replacement surgery. This multicenter, randomized, controlled double‐blinded study was conducted in three teaching hospitals in China. Patients receiving on‐pump valve replacement surgery were enrolled. Stratified block randomization was used to randomly assign patients 1:1 to receive sevoflurane (1.0–1.5 MAC) or propofol (2.0–3.0 mg/kg/h) for anesthesia maintenance. The primary outcome was the incidence of cognitive dysfunction assessed by four cognitive tests before, as well as 7–14 days after surgery. Patients were randomly assigned to receive sevoflurane anesthesia (n = 144) or propofol‐based total intravenous anesthesia (n = 145). The incidence of postoperative cognitive dysfunction in the sevoflurane anesthesia group (31.9%) was significantly lower than that in the total intravenous anesthesia group (43.4%; relative risk 0.61, 95% confidence interval [CI]: 0.38–0.97, p = 0.044). There was no difference in the incidence of delirium between patients receiving sevoflurane and total intravenous anesthesia (27.8% [35/144] vs. 25.9% [35/145], 1.10, 95% CI: 0.64 to 1.90, p = 0.736). There was a significant difference in the Katz Index on day 3 after surgery (3 [0.9) vs. 3 (1.0], 0.095, 95% CI: 0.05 to 0.43, p = 0.012). No difference was observed in other outcomes between the two groups. For patients undergoing on‐pump valve replacement surgery, sevoflurane anesthesia had a smaller effect on cognitive function and independence in daily life activities compared with propofol anesthesia.
BACKGROUND:The kidney-brain crosstalk has been involved in Alzheimer's disease (AD) with the mechanism remaining unclear. The anti-aging factor Klotho was reported to attenuate both kidney injury and AD pathologies.OBJECTIVE:To investigate whether plasma Klotho participated in kidney-brain crosstalk in AD.METHODS:We enrolled 33 PiB-PET-positive AD patients and 33 amyloid-β (Aβ)-negative age- and sex-matched cognitively normal (CN) controls from the Chongqing Ageing & Dementia Study (CADS). The levels of plasma Klotho, Aβ, and tau in the cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay.RESULTS:We found higher plasma Klotho and lower estimated glomerular filtration rate (eGFR) levels in AD patients compared with CN. The eGFR was positively associated with Aβ42, Aβ40 levels in CSF and negatively associated with CSF T-tau levels. Plasma Klotho levels were both negatively correlated with CSF Aβ42 and eGFR. Mediation analysis showed that plasma Klotho mediated 24.96% of the association between eGFR and CSF Aβ42.CONCLUSION:Renal function impacts brain Aβ metabolism via the kidney-brain crosstalk, in which the plasma Klotho may be involved as a mediator. Targeting Klotho to regulate the kidney-brain crosstalk provides potential therapeutic approaches for AD.
Background Cognitive impairment (CI) has become a worldwide health problem. The relationship between CI and uric acid (UA) is contradictory. Objective We included participants with a full spectrum of CI, from cognitively unimpaired (CU) to dementia, from the Chongqing Ageing & Dementia Study (CADS). Methods First, we identified the relationships between serum UA (sUA) and cognitive function in different stages of CI. Second, we analyzed these relationships among different stages and types of CI. Finally, we explored the association between sUA and amyloid/tangle/neurodegeneration (ATN) biomarkers. Results We recruited 427 participants from the CADS, including 382 participants with mini-mental state examination (MMSE) evaluation. The levels of sUA were positively correlated with MMSE scores ( p < 0.001), and the correlation was prominent in the course of dementia and in the type of Alzheimer’s disease (AD). The levels of UA had a positive correlation with plasma amyloid-β 42 (Aβ42) ( p = 0.004). Higher levels of sUA weakened the correlation of MMSE scores with CSF ATN biomarkers and the correlation of CSF Aβ42 with tau. Conclusion UA is positively correlated with cognitive function, especially in the advanced stage of AD. The probable neuroprotective effects of sUA mainly act on Aβ42 and the downstream pathological cascade.
Background The aim of this study is to evaluate cardiovascular and respiratory effects of intrathoracic pressure overshoot (higher than insufflation pressure) in patients who underwent thoracoscopic esophagectomy procedures with carbon dioxide (CO 2 ) pneumothorax. Methods This prospective research included 200 patients who were scheduled for esophagectomy from August 2016 to July 2020. The patients were randomly divided into the Stryker insufflator (STR) group and the Storz insufflator (STO) group. We recorded the changes of intrathoracic pressure, peak airway pressure, blood pressure, heart rate and central venous pressure (CVP) during artificial pneumothorax. The differences in blood gas analysis, the administration of vasopressors and the recovery time were compared between the two groups. Results We found that during the artificial pneumothorax, intrathoracic pressure overshoot occurred in both the STR group (8.9 mmHg, 38 times per hour) and the STO group (9.8 mmHg, 32 times per hour). The recorded maximum intrathoracic pressures were up to 58 mmHg in the STR group and 51 mmHg in the STO group. The average duration of intrathoracic pressure overshoot was significantly longer in the STR group (5.3 ± 0.86 s) vs. the STO group (1.2 ± 0.31 s, P < 0.01). During intrathoracic pressure overshoot, a greater reduction in systolic blood pressure (SBP) (5.6 mmHg vs. 1.1 mmHg, P < 0.01), a higher elevation in airway peak pressure (4.8 ± 1.17 cmH 2 O vs. 0.9 ± 0.41 cmH 2 O, P < 0.01), and a larger increase in CVP (8.2 ± 2.86 cmH 2 O vs. 4.9 ± 2.35 cmH 2 O, P < 0.01) were observed in the STR group than in the STO group. Vasopressors were also applied more frequently in the STR group than in the STO group (68% vs. 43%, P < 0.01). The reduction of SBP caused by thoracic pressure overshoot was significantly correlated with the duration of overshoot ( R = 0.76). No obvious correlation was found between the SBP reduction and the maximum pressure overshoot. Conclusions Intrathoracic pressure overshoot can occur during thoracoscopic surgery with artificial CO 2 pneumothorax and may lead to cardiovascular adverse effects which highly depends on the duration of the pressure overshoot. Trial registration Clinicaltrials.gov ( NCT02330536 ; December 24, 2014).
Cerebrospinal fluid (CSF) biomarkers are essential for the accurate diagnosis of Alzheimer’s disease (AD), yet their measurement levels vary widely across centers and regions, leaving no uniform cutoff values to date. Diagnostic cutoff values of CSF biomarkers for AD are lacking for the Chinese population. As a member of the Alzheimer’s Association Quality Control program for CSF biomarkers, we aimed to establish diagnostic models based on CSF biomarkers and risk factors for AD in a Chinese cohort. A total of 64 AD dementia patients and 105 age- and sex-matched cognitively normal (CN) controls from the Chongqing Ageing & Dementia Study cohort were included. CSF Aβ42, P-tau181, and T-tau levels were measured by ELISA. Combined biomarker models and integrative models with demographic characteristics were established by logistic regression. The cutoff values to distinguish AD from CN were 933 pg/mL for Aβ42, 48.7 pg/mL for P-tau181 and 313 pg/mL for T-tau. The AN model, including Aβ42 and T-tau, had a higher diagnostic accuracy of 89.9%. Integrating age and APOE ε4 status to AN model (the ANA’E model) increased the diagnostic accuracy to 90.5% and improved the model performance. This study established cutoff values of CSF biomarkers and optimal combined models for AD diagnosis in a Chinese cohort.
The objective of this study was to propose a new method for facilitating needle-beam alignment ultrasound-guided in-plane catheterization of the subclavian vein (SCV). Three hundred patients were recruited, and ultrasound examination of the SCV was performed. Then, the patients were divided into two groups and SCV catheterization was performed: ultrasound-guided catheterization with the aiming method (group A) and ultrasound-guided catheterization with needle guide (group NG). The success rate, insertion time, number of skin breaks, number of needle redirections, needle visibility and rate of mechanical complications were documented and compared for each procedure. To depict the optimum long-axis view of the SCV, there was a 30° ± 7.3° angle (rotation) between the long axis of the ultrasound probe and the clavicle, while there was a 39° ± 7.4° angle (tilt) between the ultrasound beam plane and the right chest wall. The aiming method was associated with fewer skin breaks [(mean (IQR): 1 (1–1) times vs 1 (1–2) times, P = 0.009], a shorter time to cannulation [(mean (IQR): 39 (32–48.5) s vs 48 (44–54.8) s, P = 0.000] and more needle redirections [(mean (IQR): 0 (0–1) vs 0 (0–0), P = 0.000]. There were no differences between group A and group NG in the overall success rate, first puncture success rate, needle visibility or mechanical complication rate. In conclusion, during ultrasound-guided in-plane catheterization of the SCV, the aiming method provides comparable needle-beam alignment with a lower cannulation time than the needle guide technique.
Abstract Background Laryngeal masks airway (LMA) has been increasingly used in surgical patients. However, the use of LMA in laparoscopic surgeries remains controversial. The major concerns include the potential risk of esophageal regurgitation, aspiration, and difficulties to achieve effective ventilation. The aim of this study was to evaluate the safety and effectiveness of the LMA® Protector™ in patients undergoing laparoscopic surgery. Methods Patients aged 18 to 70 years, scheduled for laparoscopic surgeries were included. The insertion time, successful insertion rate, and oropharyngeal leak pressure were measured. Airway complications and airway manipulations during the procedure were documented. Effective ventilation rate was calculated. Visible bloodstains and reflux content in the drainage channel were documented after the removal of LMA® Protector™. Results Three hundred patients were enrolled. The insertion of LMA® Protector™ failed in seven patients resulting with a successful insertion rate of 97.7%. During the maintenance of anesthesia, airway manipulation was required in 19 patients (19/293, 6.48%), in three of whom the LMA was replaced with endotracheal intubation resulting with an effective ventilation rate of 96.7% (290/300). The oropharyngeal leak pressure was 30.18 ± 5.88 cmH2O. Seventy-five patients (25.86%) reported mild sore throat on the first day after surgery. Bloodstains on study devices were noticed in 58 patients (20%). Seventy-five patients (25.86%) reported mild sore throat on the first day after surgery. Gastric reflux was noticed in the drainage tube in 5 patients (1.72%) with no signs of aspiration in any of those patients. Conclusions The LMA® Protector™ was shown to be safe and effective in patients undergoing laparoscopic surgeries. Although minor complications that require no further treatment, no clinically diagnosed aspiration was noticed in our study. Gastric reflux was noticed in the drainage tube in five patients undergoing laparoscopic gynecology surgery. Further research is needed to verify whether LMA® Protector™ is suitable for procedures in Trendelenburg position or other situations that a high risk of gastroesophageal reflux exists. Trial registration The trial was registered at the Chinese Clinical Trial Registry ( ChiCTR1800018300 , date of registration: September 2018).
The objective of this study was to identify the factors that complicate the needle visualization in ultrasound-guided in-plane needling procedures. Forty-nine residents were recruited and randomized to insert the simulated blood vessel with four different views including Neutral (the long axis of the probe along the visual axis and the ultrasonic beam vertical to the surface of gel phantom), 45°-rotation (45° angle between the long axis of probe and the operator’s visual axis), 45°-tilt (45° angle between the ultrasonic beam and the surface of gel phantom) and 45°-rotation plus 45°-tilt of probe. Number of needle redirections, insertion time, and needle visibility were documented and compared for each procedure. When the residents faced with 45°-tilt view, the needle redirections (2 vs 0) and insertion time increased significantly (39 vs 16) compared with that of the Neutral view. When faced with 45°-rotation plus 45°-tilt view, the residents’ performance decreased further as compared with that of the 45°-tilt view and the Neutral view. However, there was no performance difference between the Neutral view and 45°-rotation view. In conclusion, during ultrasound-guided in-plane procedures, tilting the ultrasound probe may increase the difficulty of needle-beam alignment.
Diluted epinephrine is often locally used to provide hemostasis and improve visualization. However, rapid absorption or inadvertent intravascular injection of epinephrine can cause unexpected cardiovascular effects. A 28-year-old man was scheduled to undergo a nasal septoplasty. After local application of 0.01% epinephrine-soaked nasal pledgets and infiltration of 3 mL 0.001% epinephrine, the patient developed a severe hypertension of 205/126 mmHg, followed by ventricular tachycardia. Cardiac arrest ensued after intravenous injection of lidocaine and esmolol in an attempt to control ventricular arrhythmia. After successful resuscitation, the patient was transferred to the intensive care unit (ICU) and fully recovered in 5 days. While another two epinephrine-induced hypertension cases were treated smoothly without β-blockers. Although the plausible explanation of this precipitating event is the usage of β-blocker, we reviewed the previous published similar clinical reports and proposed other possible explanations and differential diagnosis. It is important to recognize this potential cardiovascular side-effect in patients administrated with topical and/or submucosal epinephrine. Drugs used to treat hypertension and/or arrhythmia needed to be appreciated.
目的 观察地塞米松和右美托咪定作为罗哌卡因佐剂对超声引导下儿童前锯肌平面阻滞镇痛效果的影响.方法 选取90例择期行心脏直视手术的患儿,随机分为单纯罗哌卡因组(L组)、罗哌卡因+地塞米松组(LD组)和罗哌卡因+右美托咪定组(LY组),每组30例.L组在前锯肌浅面给予0.2%罗哌卡因3 mL/kg,LD组给予0.2%罗哌卡因3 mg/kg+地塞米松0.1 mg/kg,LY组给予0.2%罗哌卡因3 mg/kg+右美托咪定0.5μg/kg.在气管导管拔除后2 h、6 h、12 h、15 h、18 h、24 h进行FLACC镇痛评分,如果患儿镇痛评分>3分,则静脉给予舒芬太尼进行补救镇痛.记录患儿的舒芬太尼用量和镇痛相关并发症发生率.结果 LD组和LY组拔管后2 h、6 h、12 h、18 h、24 h的FLACC评分与L组比较,差异均无统计学意义(P>0.05);LD组和LY组拔管后15 h的FLACC评分均低于L组(P<0.05).LD组与LY组各时间点的FLACC评分比较,差异均无统计学意义(P>0.05).LD组和LY组拔管后24 h内的舒芬太尼用量小于L组(P<0.05),但LD组与LY组比较,差异无统计学意义(P>0.05).各组镇痛相关并发症发生率比较差异无统计学意义(P>0.05).结论 0.1 mg/kg地塞米松和0.5μg/kg右美托咪定可以有效延长罗哌卡因对儿童前锯肌平面阻滞的作用时间.
The article's abstract is no available.
Alzheimer's disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aβ) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aβ burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aβ generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.
Background A novel coronavirus pneumonia outbreak began in Wuhan, Hubei Province, in December 2019; the outbreak was caused by a novel coronavirus previously never observed in humans. China has imposed the strictest quarantine and closed management measures in history to control the spread of the disease. However, a high level of evidence to support the surgical management of potential trauma patients during the novel coronavirus outbreak is still lacking. To regulate the emergency treatment of trauma patients during the outbreak, we drafted this paper from a trauma surgeon perspective according to practical experience in Wuhan. Main body The article illustrates the general principles for the triage and evaluation of trauma patients during the outbreak of COVID-19, indications for emergency surgery, and infection prevention and control for medical personnel, providing a practical algorithm for trauma care providers during the outbreak period. Conclusions The measures of emergency trauma care that we have provided can protect the medical personnel involved in emergency care and ensure the timeliness of effective interventions during the outbreak of COVID-19.
目的 观察超声引导下前锯肌平面阻滞(SAPB)在儿童先天性心脏病腋下小切口手术后的镇痛效果.方法 选取150例择期先天性心脏病手术患儿,随机分为浅面SAPB组、深面SAPB组和对照组,每组50例.浅面SAPB组患儿前锯肌浅面给予0.2%罗哌卡因3 mL/kg,深面SAPB组患儿前锯肌深面给予0.2%罗哌卡因3 mL/kg,对照组患儿前锯肌浅面给予等量生理盐水.术后患儿气管拔管后0.5 h、2 h、6 h、12 h、24 h观察疼痛评分(FLACC法),若疼痛评分>3分,则给予舒芬太尼镇痛.记录患儿舒芬太尼用量和镇痛相关并发症.结果 浅面SAPB组FLACC疼痛评分在拔管后2 h、6 h、12 h显著低于对照组(P<0.05),并且在拔管后6 h、12 h显著低于深面SAPB组(P<0.05);深面SAPB组疼痛评分在拔管后2 h、6 h显著低于对照组(P<0.05).浅面SAPB组和深面SAPB组拔管后24 h的舒芬太尼用量均显著少于对照组(P<0.05),且浅面SAPB组显著少于深面SAPB组(P<0.05).各组镇痛相关并发症发生率比较差异无统计学意义(P=0.387).结论 SAPB是安全有效的术后镇痛手段,且浅面SAPB的阻滞效果优于深面SAPB.
Abstract. Background:. Recent studies suggest that a healthy diet helps to prevent the development of Alzheimer disease (AD). This study aimed to investigate whether spicy food consumption is associated with cognition and cerebrospinal fluid (CSF) biomarkers of AD in the Chinese population. Methods:. We enrolled 55 AD patients and 55 age- and gender-matched cognitively normal (CN) subjects in a case-control study, as well as a cohort of 131 participants without subjective cognitive decline (non-AD) in a cross-sectional study. Spicy food consumption was assessed using the Food Frequency Questionnaire (FFQ). Associations of FFQ scores with cognition and CSF biomarkers of AD were analyzed. Results:. In the case-control study, spicy food consumption was lower in AD patients than that in CNs (4.0 [4.0–8.0] vs. 8.0 [4.5–10.0], P < 0.001); FFQ scores were positively associated with Mini-Mental Status Examination scores in the total sample (r = 0.218, P = 0.014). In the cross-sectional study, the association between spicy food consumption and cognition levels was verified in non-AD subjects (r = 0.264, P = 0.0023). Moreover, higher FFQ scores were significantly associated with higher β-Amyloid (1–42) (Aβ42) levels and lower phospho-tau/Aβ42 and total tau/Aβ42 ratios in the CSF of non-AD subjects (P < 0.05). Conclusion:. Spicy food consumption is closely related to higher cognition levels and reversed AD biomarkers in the CSF, suggesting that a capsaicin-rich diet might have the potential to modify the cognitive status and cerebral pathologies associated with AD.
To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer’s disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.
Background: Whether time of day has impact on outcomes after out-of-hospital cardiac arrest (OHCA) remains controversial. However, there are no evidence syntheses describing the impact of time differences on outcomes from OHCA. Methods: A meta-analysis of cohort studies exploring the association between time of day and survival in patients with OHCA was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Results: Ten studies involving 252,848 patients and 24,646 survivals were included. Patients with night-time OHCA had significantly lower short-term survival compared to patients with daytime OHCA (OR, 1.20; 1.07-1.36;P < .001). The relationship between temporal differences and survival was consistent in most subgroups. For long-term survival, it remained unclear whether night-time was associated with reduced OHCA survival at 12 months (OR, 1.47; 0.71-3.06;P < .001). Three studies including 183,129 patients examined the association between weekend and survival in OHCA patients. Survival did not differ on weekends compared to weekdays (OR, 1.00; 0.9 7-1.04;P = .918). Conclusions: Night-time is associated with a lower survival in OHCA patients. However, similar findings are not observed in OHCA patients on weekends. Caution is required in interpretation of these results accounting for high level of heterogeneity and large, well designed, randomized trials are warranted.