1.Current Situation, Problems and Countermeasures of Experimental Research on Traditional Chinese Medicine Regulating PI3K/Akt Signaling Pathway in Rats with Polycystic Ovary Syndrome
Pengxuan YAN ; Yiqing LIU ; Nanxing XIAN ; Linjing PENG ; Kun LI ; Jingchun ZHANG ; Yukun ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):259-266
Polycystic ovary syndrome(PCOS) and its resulting infertility is one of the common diseases of gynecology and reproductive endocrinology. The phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway is relatively well-studied in the development of intervention in PCOS, and the experiments on PCOS in rats conducted by traditional Chinese medicine through this signaling pathway is also the main direction of mechanistic research. In this paper, 20 articles published in academic journals in the past 5 years were selected through the corresponding criteria, and the objective situation and existing problems of the selected research projects were analyzed from five aspects, namely, baseline data, modeling and treatment, grouping, evaluative indexes, and pharmacodynamic indexes. It is found that there were different degrees of problems in each research project, such as the observation indicators of modeling, criteria for judging the success of the model, the treatment period, the calculation of dosage of prescription/active ingredients and specific dosage were not clearly defined, which could easily lead the bias of the results or reduce the validity of experimental data. Based on this, the list of PCOS rat experimental research operations was formed, involving five categories of experimental rats, model construction, study implementation, outcome measures and analysis and report with a total of 21 operation lists, with a view to provide a reference for the subsequent PCOS experiments related to scientific research and helping to form high-quality results.
2.The Effects of Qufeng Tongqiao Cough-Relieving Decoction (祛风通窍止咳方) on Cough Sensitivity,TRPV4 in Lung and Nasal Mucosal Tissues,and Neurogenic Inflammation in a Guinea Pig Model of Upper Airway Cough Syndrome
Jingshu LUO ; Jianling MA ; Liqing SHI ; Kun JI ; Song LIU ; Yuhan FAN ; Xianli LI ; Zhaodi GUO
Journal of Traditional Chinese Medicine 2025;66(5):518-525
ObjectiveTo investigate the potential mechanism of action of the Qufeng Tongqiao Cough-relieving Decoction (祛风通窍止咳方, QTCD) in the treatment of upper airway cough syndrome (UACS). MethodsTwenty-four guinea pigs were randomly divided into blank group, model group, traditional Chinese medicine (TCM) group, and inhibitor group, with six guinea pigs in each group. Except for the blank group, guinea pigs were sensitized with ovalbumin and aluminum hydroxide via intraperitoneal injection, followed by ovalbumin nasal drops combined with smoke exposure to establish the UACS model. After modeling, the TCM group was administered QTCD 0.9 g/(100 g·d) by gavage, the inhibitor group received the transient receptor potential vanilloid receptor 4 (TRPV4) inhibitor GSK2193874 1 mmol/L, 5 min by nebulisation, and the blank group and model group were given 2 ml/(100 g·d) normal saline by gavage once daily. After 7 days of treatment, a cough provocation test was performed using 0.4 mol/L citric acid. The levels of IgE in serum and inflammatory cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8) in serum, bronchoalveolar lavage fluid (BALF), and nasal lavage fluid (NLF) were detected by enzyme-linked immunosorbent assay (ELISA). Histopathological changes in lung and nasal mucosal tissues were observed by hematoxylin-eosin (HE) staining. Immunohistochemistry was used to detect the protein levels of TRPV4, substance P (SP), and calcitonin gene-related peptide (CGRP) in lung and nasal mucosal tissues. Real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of TRPV4, SP, and CGRP in lung tissues. ResultsHE staining showed significant structural damage and infiltration of inflammatory cells in the lung and nasal mucosal tissues in the model group, while the TCM group and inhibitor group showed improved pathological changes. Compared with the blank group, the model group showed increased cough frequency, serum IgE level, and IL-6 and IL-8 levels in serum, BALF, and NLF. The protein levels of TRPV4, SP, and CGRP in lung and nasal mucosal tissues and their mRNA expression were elevated (P<0.05 or P<0.01). Compared with the model group, the TCM group and inhibitor group showed reduced cough frequency, serum IgE level, and TRPV4 and SP mRNA expression in lung tissues. The TCM group showed reduced IL-6 and IL-8 levels in serum, BALF, and NLF, and reduced TRPV4 and CGRP protein levels in lung and nasal mucosal tissues. The inhibitor group showed reduced IL-6 and IL-8 levels in serum, BALF, and NLF, reduced IL-6 in BALF, reduced IL-8 in NLF, and decreased TRPV4, SP, and CGRP protein levels in lung tissues and SP and CGRP protein levels in nasal mucosal tissues (P<0.05 or P<0.01). Compared with the TCM group, the inhibitor group had increased serum IgE, IL-6, and IL-8 levels, increased IL-6 level in BALF, and increased IL-8 levle in NLF, but decreased SP protein level in lung tissues and increased TRPV4 and SP mRNA expression in lung tissues (P<0.01). ConclusionQTCD effectively reduces cough frequency in the UACS guinea pig model. Its mechanism may involve inhibiting the activation of the TRPV4 pathway, improving airway neurogenic inflammation, alleviating inflammatory responses, and reducing cough hypersensitivity.
3.Efficacy of Fufang Lingjiao Jiangya Pills with Different Proportions of Goat Horn Replacing Antelope Horn on Spontaneous Hypertensive Rats
Tengjian WANG ; Wanlu ZHAO ; Yang YU ; Yan LIU ; Kun CAO ; Zheyuan LIN ; Yue WU ; Lilan LUO ; Weizhi LAI ; Zhaohuan LOU ; Qiaoyan ZHANG ; Quanlong ZHANG ; Luping QIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):68-78
ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats (SHR). In this experiment, 50 SHR rats were randomly grouped as follows: model (n=8), captopril (0.01 g·kg-1) (n=6), low-dose blank Fufang Lingjiao Jiangya pills (0.342 g·kg-1) (n=6), high-dose blank Fufang Lingjiao Jiangya pills (0.684 g·kg-1) (n=6), low-dose antelope horn-containing Fufang Lingjiao Jiangya pills (0.378 g·kg-1) (n=6), high-dose antelope horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1) (n=6), low-dose goat horn-containing Fufang Lingjiao Jiangya pills (0.378 g·kg-1) (n=6), and high-dose goat horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1) (n=6). Additionally, 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration, 3 h post administration, and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions, 48 SHR rats were randomly grouped as follows: model, blank Fufang Lingjiao Jiangya pills (0.684 g·kg-1), antelope horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1), 2× goat horn-containing Fufang Lingjiao Jiangya pills (0.824 g·kg-1), 4× goat horn Fufang Lingjiao Jiangya pills (0.969 g·kg-1), and 6× goat horn Fufang Lingjiao Jiangya pills (1.112 g·kg-1). The normal group included 8 WKY rats, and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks, and blood pressure was recorded at various time points (pre-administration, 3 h post administration, and on days 4, 7, 10, and 14 of administration). Serum levels of angiotensin-converting enzyme (ACE), angiotensin Ⅱ(Ang Ⅱ), renin, and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart, kidney, and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2, angiotensin Ⅱ type 1 receptor (AT1R), and angiotensinogen (AGT) in the kidney tissue were determined by Western blot, while the expression of nuclear factor (NF)-κB p65 and Toll-like receptor 4 (TLR4) in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group, all treatment groups showed lowered blood pressure (P<0.05, P<0.01), and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group, the model group showed elevated serum levels of ACE, Ang Ⅱ, renin, and IL-6, while the elevations were declined in the Fufang Lingjiao Jiangya pills groups (P<0.05, P<0.01). Pathological changes in the heart, kidney, and thoracic aorta were alleviated in all the treatment groups, with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R, AGT, NF-κB p65, and TLR4 and up-regulated protein levels of ACE2 (P<0.05, P<0.01) compared with model group, with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system (RAAS) and TLR4/NF-κB signaling pathways.
4.Influence evaluation of pharmaceutical quality control on medication therapy management services by the ECHO model
Kun LIU ; Huanhuan JIANG ; Yushuang LI ; Yan HUANG ; Qianying ZHANG ; Dong CHEN ; Xiulin GU ; Jinhui FENG ; Zijian WANG ; Yunfei CHEN ; Yajuan QI ; Yanlei GE ; Aishuang FU
China Pharmacy 2025;36(9):1123-1128
OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management (MTM) services for patients with coronary heart disease by using Economic, Clinical and Humanistic Outcomes (ECHO) model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 (pre-quality control implementation group, n=96) and June-August 2023 (post-quality control implementation group, n=164). Using propensity score matching analysis, 80 patients were selected from each group. The study subsequently compared the economic, clinical, and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching (P>0.05). Compared with pre-quality control implementation group, the daily treatment cost (16.26 yuan vs. 24.40 yuan, P<0.001), cost-effectiveness ratio [23.12 yuan/quality-adjusted life year (QALY) vs. 32.32 yuan/QALY, P<0.001], and the incidence of general adverse drug reactions (2.50% vs. 10.00%, P=0.049) of post-quality control implementation group were decreased significantly; the utility value of the EuroQol Five-Dimensional Questionnaire (0.74± 0.06 vs. 0.71±0.07, P=0.003), the reduction in the number of medication related problems (1.0 vs. 0.5, P<0.001), the medication adherence score ([ 6.32±0.48) points vs. (6.10±0.37) points, P=0.001], and the satisfaction score ([ 92.56±1.52) points vs. (91.95±1.56) points, P=0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups (1.25% vs. 3.75%, P=0.310). CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care, and the ECHO model can quantitatively evaluate the effect of MTM services, making pharmaceutical care better priced and more adaptable to social needs, thus being worthy of promotion.
5.Development and application of a three-dimensional digital visualization system for children's neck acupoints
Xiaojing AO ; Kun LI ; Yuhang LIU ; Xiaoxuan YANG ; Xing WANG ; Zhijun LI ; Xiaoyan REN ; Shaojie ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1834-1840
BACKGROUND:Currently,there have been studies on three-dimensional digitalization and visualization systems for adult acupoints,but there are not many reports on the visualization of pediatric acupoints based on real pediatric digital sectional anatomical datasets. OBJECTIVE:To design and develop a digital three-dimensional visualization system for children's neck acupoints,to provide a basis for acupuncture and moxibustion,meridian and acupoint science teaching,clinical practice,acupuncture manipulation practice,and acupuncture safety research,and to provide a basis for the development of children's acupoint simulation system. METHODS:Based on a real cross-sectional anatomical dataset of pre-school boys,a three-dimensional digital virtual anatomical model of the neck region of children and internal multi-organ three-dimensional reconstruction were completed using PhotoShop 2021 and Digihuman Reconstruction System software.A database of 11 acupoints was compiled,including Fengfu and Fengchi,using the Unity database language.A three-dimensional model of children's neck anatomy,acupoint database,and writing acupuncture operation codes were integrated in Unity3D software.A three-dimensional digital visualization system for children's neck acupoints was successfully created,which integrated simulation acupoint positioning,three-dimensional acupoint anatomy,acupuncture training,clinical teaching,and acupuncture safety research. RESULTS AND CONCLUSION:(1)This study was based on real child specimens.Manual layer by layer segmentation of cross-sectional images was used to ensure the accuracy of the three-dimensional model to the greatest extent possible.The 3D software Digihuman Reconstruction System was utilized to extract and save independent segmentation data.PhotoShop 2021 software was collaborated with to complete dozens of three-dimensional reconstruction anatomical models of the outer skin of the neck and its internal bone structure,cervical spinal cord,blood vessels and nerves,muscles,and ligaments in children.The basic morphology and overall contour integrity verification of each independent structure were completed in MeshLab software.The 3-material research 13.0 software was applied for final fine tuning and anatomical position confirmation,successfully simulating and restoring the true anatomical morphology of the neck of preschool children.(2)Based on and referring to the national standards of the People's Republic of China,a database of commonly used acupoints in children's neck region was collected and organized,including their names,meridians,positioning,local anatomy,needle insertion levels,acupuncture methods,acupuncture accidents and prevention,acupoint indications,and two-dimensional anatomical sectional images.(3)Unity3D software was employed to integrate the three-dimensional model of children's neck,acupuncture simulation operation,and acupoint database,and a three-dimensional digital children's neck acupoint acupuncture visualization system was successfully constructed.The system displayed information on children's neck acupoints,two-dimensional and three-dimensional anatomical structures,and achieved two-dimensional and three-dimensional acupuncture simulation functions and acupuncture safety research functions for children's neck acupoints.Based on the ultra-thin sectional anatomical dataset of real child specimens,the first three-dimensional digital and visualization system for acupoints in the neck region of children had been constructed.Compared with previous acupoint acupuncture systems,it is more in line with the anatomical and morphological development characteristics of Asian children and has high application value in the fields of acupuncture safety research,clinical teaching,and acupuncture simulation training.
6.Post-anesthesia care unit delirium in children with moyamoya disease undergoing indirect revascularization: incidence and risk factors
Korean Journal of Anesthesiology 2025;78(2):129-138
Background:
Delirium in the post-anesthesia care unit (PACU) may be associated with worse outcomes in children with moyamoya disease (MMD). This retrospective study aimed to describe the prevalence of PACU delirium in children with MMD and investigate its risk factors.
Methods:
Patients with MMD aged < 15 years who underwent indirect revascularization between January 2014 and October 2023 were included in this study. Delirium was assessed using the Pediatric Anesthesia Emergence Delirium Scale. Potential risk factors for PACU delirium were evaluated using multivariate logistic regression.
Results:
PACU delirium occurred in 245 (33%) of the 750 hemispheric procedures performed in 522 patients. Delirium was associated with a higher incidence in patients undergoing the first revascularization (37%) than in those undergoing the second (25%; P = 0.002). Cerebral infarction as the initial presentation (odds ratio [OR]: 4.64, first revascularization), high pediatric moyamoya magnetic resonance imaging (MRI) score (OR: 2.75, first revascularization; OR: 3.50, second revascularization), and high intraoperative mean arterial pressure variability (mmHg/min) (OR: 9.17, first revascularization; OR: 8.82, second revascularization) were associated with PACU delirium. Conversely, total intravenous anesthesia (TIVA) was associated with a lower incidence of PACU delirium (OR: 0.46, first revascularization; OR: 0.25, second revascularization).
Conclusions
A significant proportion of patients with MMD developed delirium in the PACU. High intraoperative blood pressure variability and preoperative MRI lesions are independent risk factors for PACU delirium in children with MMD. TIVA may exert a protective effect against PACU delirium. Further studies are required to clarify the causality of these associations.
7.Post-anesthesia care unit delirium in children with moyamoya disease undergoing indirect revascularization: incidence and risk factors
Korean Journal of Anesthesiology 2025;78(2):129-138
Background:
Delirium in the post-anesthesia care unit (PACU) may be associated with worse outcomes in children with moyamoya disease (MMD). This retrospective study aimed to describe the prevalence of PACU delirium in children with MMD and investigate its risk factors.
Methods:
Patients with MMD aged < 15 years who underwent indirect revascularization between January 2014 and October 2023 were included in this study. Delirium was assessed using the Pediatric Anesthesia Emergence Delirium Scale. Potential risk factors for PACU delirium were evaluated using multivariate logistic regression.
Results:
PACU delirium occurred in 245 (33%) of the 750 hemispheric procedures performed in 522 patients. Delirium was associated with a higher incidence in patients undergoing the first revascularization (37%) than in those undergoing the second (25%; P = 0.002). Cerebral infarction as the initial presentation (odds ratio [OR]: 4.64, first revascularization), high pediatric moyamoya magnetic resonance imaging (MRI) score (OR: 2.75, first revascularization; OR: 3.50, second revascularization), and high intraoperative mean arterial pressure variability (mmHg/min) (OR: 9.17, first revascularization; OR: 8.82, second revascularization) were associated with PACU delirium. Conversely, total intravenous anesthesia (TIVA) was associated with a lower incidence of PACU delirium (OR: 0.46, first revascularization; OR: 0.25, second revascularization).
Conclusions
A significant proportion of patients with MMD developed delirium in the PACU. High intraoperative blood pressure variability and preoperative MRI lesions are independent risk factors for PACU delirium in children with MMD. TIVA may exert a protective effect against PACU delirium. Further studies are required to clarify the causality of these associations.
8.Immunotherapy plus chemotherapy in patients with advanced endometrial cancer: a cost-effectiveness analysis
Youwen ZHU ; Kun LIU ; Hong ZHU
Journal of Gynecologic Oncology 2025;36(1):e6-
Objective:
Pembrolizumab and dostarlimab are immune checkpoint inhibitors that target programmed death receptor 1 (PD-1). Combination anti-PD-1 regimens have been shown to exhibit favorable survival benefits when treating advanced endometrial cancer (EC). Which treatment was preferable will need to be confirmed by a cost-effectiveness comparison between them.
Methods:
Based on patient and clinical parameters from RUBY and NRG-GY018 phase III randomized controlled trials, the Markov model with a 20-year time horizon was established to evaluate the cost-effectiveness of dostarlimab plus chemotherapy (DC), pembrolizumab plus chemotherapy (PC), and chemotherapy alone (C) treatment for patients with mismatch repair-proficient microsatellite-stable (pMMR-MSS) and mismatch repair-deficient microsatellite instability-high (dMMR-MSI-H) advanced EC from the American payers’ perspective. The main results include total cost, life-years (LYs), quality-adjusted lifeyears (QALYs), and the incremental cost-effectiveness ratio (ICER) at a $150,000/QALY of willingness-to-pay.
Results:
In the pMMR-MSS population, DC, PC, and C produced costs (QALYs) of $99,205 (3.02), $322,530 (3.25), and $421,923 (4.40), resulting in corresponding ICERs of $974,177/ QALY (PC vs. C), $234,527/QALY (DC vs. C), $86,671/QALY (DC vs. PC), respectively; In the dMMR-MSI-H population, DC, PC, and C obtained costs (QALYs) of $120,177 (5.73), $691,399 (8.43), and $708,787 (11.26), yielding ICERs of $266,423/QALY (PC vs. C), $135,165/QALY (DC vs. C), $7,866/QALY (DC vs. PC), respectively.
Conclusion
In the US, DC was a more cost-effective treatment than PC for patients with advanced EC irrespective of MMR status. However, compared to C, DC was associated with more cost-effectiveness in the dMMR-MSI-H population.
9.Immunotherapy plus chemotherapy in patients with advanced endometrial cancer: a cost-effectiveness analysis
Youwen ZHU ; Kun LIU ; Hong ZHU
Journal of Gynecologic Oncology 2025;36(1):e6-
Objective:
Pembrolizumab and dostarlimab are immune checkpoint inhibitors that target programmed death receptor 1 (PD-1). Combination anti-PD-1 regimens have been shown to exhibit favorable survival benefits when treating advanced endometrial cancer (EC). Which treatment was preferable will need to be confirmed by a cost-effectiveness comparison between them.
Methods:
Based on patient and clinical parameters from RUBY and NRG-GY018 phase III randomized controlled trials, the Markov model with a 20-year time horizon was established to evaluate the cost-effectiveness of dostarlimab plus chemotherapy (DC), pembrolizumab plus chemotherapy (PC), and chemotherapy alone (C) treatment for patients with mismatch repair-proficient microsatellite-stable (pMMR-MSS) and mismatch repair-deficient microsatellite instability-high (dMMR-MSI-H) advanced EC from the American payers’ perspective. The main results include total cost, life-years (LYs), quality-adjusted lifeyears (QALYs), and the incremental cost-effectiveness ratio (ICER) at a $150,000/QALY of willingness-to-pay.
Results:
In the pMMR-MSS population, DC, PC, and C produced costs (QALYs) of $99,205 (3.02), $322,530 (3.25), and $421,923 (4.40), resulting in corresponding ICERs of $974,177/ QALY (PC vs. C), $234,527/QALY (DC vs. C), $86,671/QALY (DC vs. PC), respectively; In the dMMR-MSI-H population, DC, PC, and C obtained costs (QALYs) of $120,177 (5.73), $691,399 (8.43), and $708,787 (11.26), yielding ICERs of $266,423/QALY (PC vs. C), $135,165/QALY (DC vs. C), $7,866/QALY (DC vs. PC), respectively.
Conclusion
In the US, DC was a more cost-effective treatment than PC for patients with advanced EC irrespective of MMR status. However, compared to C, DC was associated with more cost-effectiveness in the dMMR-MSI-H population.
10.Post-anesthesia care unit delirium in children with moyamoya disease undergoing indirect revascularization: incidence and risk factors
Korean Journal of Anesthesiology 2025;78(2):129-138
Background:
Delirium in the post-anesthesia care unit (PACU) may be associated with worse outcomes in children with moyamoya disease (MMD). This retrospective study aimed to describe the prevalence of PACU delirium in children with MMD and investigate its risk factors.
Methods:
Patients with MMD aged < 15 years who underwent indirect revascularization between January 2014 and October 2023 were included in this study. Delirium was assessed using the Pediatric Anesthesia Emergence Delirium Scale. Potential risk factors for PACU delirium were evaluated using multivariate logistic regression.
Results:
PACU delirium occurred in 245 (33%) of the 750 hemispheric procedures performed in 522 patients. Delirium was associated with a higher incidence in patients undergoing the first revascularization (37%) than in those undergoing the second (25%; P = 0.002). Cerebral infarction as the initial presentation (odds ratio [OR]: 4.64, first revascularization), high pediatric moyamoya magnetic resonance imaging (MRI) score (OR: 2.75, first revascularization; OR: 3.50, second revascularization), and high intraoperative mean arterial pressure variability (mmHg/min) (OR: 9.17, first revascularization; OR: 8.82, second revascularization) were associated with PACU delirium. Conversely, total intravenous anesthesia (TIVA) was associated with a lower incidence of PACU delirium (OR: 0.46, first revascularization; OR: 0.25, second revascularization).
Conclusions
A significant proportion of patients with MMD developed delirium in the PACU. High intraoperative blood pressure variability and preoperative MRI lesions are independent risk factors for PACU delirium in children with MMD. TIVA may exert a protective effect against PACU delirium. Further studies are required to clarify the causality of these associations.

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