1.Mechanism of the interaction between immunosuppressive therapy and intestinal microflora after liver transplantation
Yan WANG ; Yufeng LIU ; Haiyang ZHANG ; Zhiwei ZHANG ; Jun XU ; Zhiyong LAI
Journal of Clinical Hepatology 2026;42(4):980-986
The application of immunosuppressants has significantly reduced the incidence rate of rejection reaction after liver transplantation, but the clinical efficacy of immunosuppressants is greatly affected by individual differences between patients. This article systematically reviews the recent research advances in the interaction between immunosuppressants and gut microbiota, with a focus on the regulatory role and mechanism of intestinal microflora communities on the efficacy of immunosuppressants. Studies have shown that intestinal microbiome is one of the key factors influencing the efficacy of immunosuppressive therapy after liver transplantation. This review aims to provide a theoretical basis for in-depth research in this field and provide new insights for developing individualized immunosuppressive treatment regimens based on the regulation of intestinal microflora.
2.Characteristics of Traditional Chinese Medicine Syndromes and Their Correlation with Ocular Manifestations in Chronic Hepatitis B Complicated by Metabolic Dysfunction-associated Fatty Liver Disease
Jingdong CUI ; Dingqi LI ; Yichen PENG ; Xiaoxiao DENG ; Zhenglong ZHENG ; Zilin XIONG ; Haiyang HU ; Peijie WU ; Yuelian WANG ; Liang HUANG ; Quansheng FENG ; Baixue LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):144-154
ObjectiveThis paper aims to investigate the traditional Chinese medicine syndrome types in patients with chronic hepatitis B (CHB) complicated by metabolic dysfunction-associated fatty liver disease (MAFLD) and explore the correlations between these syndrome types and clinical indicators, as well as ocular manifestation characteristics, thereby providing a reference for syndrome differentiation and treatment strategies in traditional Chinese medicine. MethodsGeneral data, information from the four diagnostic methods of traditional Chinese medicine, clinical indicators, and ocular manifestation data were collected from 506 patients with CHB complicated by MAFLD enrolled at the Public Health Clinical Center of Chengdu between June 2024 and December 2024. Cluster analysis, principal component analysis, and complex network models were employed to identify the distribution patterns of traditional Chinese medicine syndromes. Correlations between different syndrome types and clinical indicators, as well as ocular manifestation characteristics, were further analyzed. ResultsThe predominant syndromes identified in patients with CHB complicated by MAFLD were dampness and heat accumulation (51.58%), liver depression with spleen deficiency (31.62%), blood stasis obstructing collaterals (8.89%), and Qi-Yin deficiency (7.91%). No statistically significant differences were found among the four syndrome types in routine blood tests and liver function indicators. However, patients with the dampness and heat accumulation type exhibited significantly higher levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), liver stiffness measurement (LSM), controlled attenuation parameter (CAP), and alpha-fetoprotein (AFP), along with lower levels of high-density lipoprotein cholesterol (HDL-C), compared with those with other syndrome types. Regarding ocular manifestations, the incidence of moon halo signs was significantly higher in patients with the blood stasis obstructing collaterals type than in those with other syndrome types. Additionally, the incidence in scleral zone 3 (corresponding to the large intestine) was higher in patients with the damp and heat accumulation type. ConclusionDampness and heat accumulation is the core syndrome type in patients with CHB complicated by MAFLD, commonly accompanied by spleen deficiency, liver depression, blood stasis, and Yin deficiency. A complex syndrome pattern characterized by a predominance of dampness and heat, along with a mixture of deficiency and excess, is formed. Different traditional Chinese medicine syndrome types are associated with distinct clinical indicators and ocular manifestation characteristics. Among them, patients with the dampness and heat accumulation type exhibit more pronounced metabolic disturbances and liver injury, whereas those with the blood stasis type show a higher incidence of moon halo signs. Abnormalities in scleral zone 3 are also more prevalent in patients with dampness and heat type.
3.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
4.Salviae Miltiorrhizae Radix et Rhizoma and Its Formulas in Treatment of Osteonecrosis of Femoral Head: A Review
Tao MA ; Yin LI ; Qingsheng XIE ; Haiyang YU ; Xuerui LIU ; Jinqiu WU ; Duoxian WANG ; Hairong HE ; Xiaogang ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(18):335-346
Osteonecrosis of femoral head (ONFH) is a disease that causes osteocyte death due to interruption of blood supply of the femoral head, which may cause symptoms such as joint movement disorders, pain, and even femoral head collapse. Currently, the commonly used methods for treating ONFH in clinical practice are accompanied by problems such as long-term side effects, inaccurate efficacy, technical limitations, and complication risks. Traditional Chinese medicine (TCM) has shown unique advantages of holistic regulation, mild side effects, and symptom alleviation. A review of the related literature shows that Salviae Miltiorrhizae Radix et Rhizoma, as a representative Chinese herbal medicine for activating blood and resolving stasis, has the effects of activating blood, resolving stasis, dredging meridians, and relieving pain. Its active ingredients (such as salvianolic acid B, tanshinone ⅡA, and tanshinone Ⅰ) interfere with bone metabolism balance, osteogenesis and differentiation, and improve bone microcirculation and bone microstructure. Salviae Miltiorrhizae Radix et Rhizoma is often combined with the herbal medicines with the effects of tonifying the liver and spleen or activing blood to form herb pairs (such as Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix, Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma, and Salviae Miltiorrhizae Radix et Rhizoma-Drynariae Rhizoma), which enhances the efficacy through synergistic effects. In the application of TCM compound formulas, Bushen Huoxue prescription, Bushen Huoxue capsules, Gubi Tongxiao granules, and Shenggu Zaizao pills can regulate signaling pathways such as Wnt/β-catenin, Hedgehog, Notch, transforming growth factor(TGF)-β1/Smads, and mitogen-activated protein kinase (MAPK) through multiple targets to significantly improve bone metabolism and hip joint function, playing an important role in preventing and treating ONFH. Through a review of available studies, this paper systematically explains the outstanding advantages of the active ingredients, herb pairs, and compound formulas of Salviae miltiorrhizae Radix et Rhizoma in the prevention and treatment of ONFH. The mechanisms may be related to factors such as promoting osteoblast generation and inhibiting osteoclast formation, increasing osteogenic differentiation, promoting angiogenesis, increasing bone density, inhibiting inflammatory response, and regulating signaling pathways. In the future, modern technology can be employed to optimize dosage forms, and high-quality clinical research should be conducted to further clarify its mechanism of action and promote the precise application of TCM. This review aims to provide more thinking directions for the application of Salviae miltiorrhizae Radix et Rhizoma in preventing and treating ONFH.
5.Clinical efficacy of intensive conservative treatment for acute aortic syndrome
Yinfan ZHU ; Lu DAI ; Haotian WU ; Yamin LI ; Dongjie LI ; Shipan WANG ; Jiajun LIANG ; Yan YAN ; Jianjun GAO ; Yeting LOU ; Zhenze TAO ; Yifan LU ; Zhiran YANG ; Jia LI ; Siji CHEN ; Chuang LIU ; Yazhe ZHANG ; Yuhong MI ; Haiyang LI ; Wenjian JIANG ; Hongjia ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(3):143-150
Objective:To evaluate the outcomes of intensive conservative treatment compared to conventional conservative treatment in patients with acute aortic syndrome(AAS).Methods:The study prospectively enrolled consecutive patients with AAS who were admitted to Beijing Anzhen Hospital, affiliated with Capital Medical University, and Beijing Dawanglu Emergency Rescue Hospital from January 2024 to December 2024. These patients with surgical contraindications or refused surgery for various reasons opted for conservative treatment. A total of 282 patients were included, and 15 patients with missing data or those who died without any treatment were excluded. Finally, 267 patients were enrolled, of whom 94 received intensive conservative treatment, and 173 received conventional conservative treatment, the inverse probability of treatment weighting (IPTW) was used to reduce the influence of confoundings. After adjusting of baseline datas via IPTW, the survival outcomes of the two groups were compared at 14 days, 30 days, and at the end of follow-up.Results:The results showed significant differences in acute phase survival rates between the enhanced conservative treatment group and the conventional conservative treatment group at 14 days(82.40%vs.53.20%, P<0.0001). Significant survival differences were also observed at 30 days and at 276-day mid-term follow-up (96.29% vs.51.60%, P<0.0001; 78.50% vs.48.50%, P<0.0001). In the subgroup analysis, for type A aortic dissection, the enhanced conservative treatment group had higher survival rates compared to the conventional conservative treatment group at 14, 30 and 276 days (63.46% vs.41.35%, P<0.05; 52.17% vs.37.90%, P<0.05; 50.00% vs. 31.97%, P<0.05). However, for type B aortic dissection, although the enhanced conservative treatment group had higher survival rates than the conventional conservative treatment group, no statistically significant differences were observed (96.29% vs. 80.00%, P=0.054; 95.65% vs.78.37%, P=0.067; 94.12% vs.74.20%, P=0.088). Conclusion:For patients diagnosed with AAS are forced to choose conservative treatment if emergency surgery is not possible in the first place, intensive conservative treatment strategies can significantly reduce the mortality in the acute phase compared with conventional conservative treatment. Mid-term follow-up, intensive conservative treatment still has a significant survival advantage.
6.Exploring the relationship between distal coronary fractional flow reserve derived from aortic CTA and intraoperative graft flow in off-pump coronary artery bypass graft
Yilin LI ; Yuan XUE ; Shipan WANG ; Zhiran YANG ; Haiyang LI
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(9):550-555
Objective:To investigate the relationship between the distal fractional flow reserve(FFR-CT) of the left anterior descending artery(LAD) measured by aortic CTA and the intraoperative left internal mammary artery(LIMA-LAD) graft flow during off-pump coronary artery bypass grafting(OPCABG). And to evaluate the role of FFR-CT in predicting intraoperative flow characteristics, competitive flow, and diffuse coronary lesions.Methods:Retrospectively included 162 OPCABG patients who underwent LIMA-LAD grafting. The primary outcome was the average flow value(Qm) of the LIMA-LAD graft measured intraoperatively. Smooth curve fitting and linear regression analysis were used to explore the relationship between preoperative LAD distal FFR-CT values and the intraoperative LIMA-LAD graft flow Qm.Results:Group analysis showed that Qm significantly decreased as the distal FFR-CT values increased. Smooth curve fitting revealed a " reverse U-shaped" relationship between LAD distal FFR-CT and Qm. When the FFR-CT value>0.64, Qm demonstrated a significant negative linear correlation with FFR-CT(regression coefficient β=-178.6432, P=0.004). Conclusion:A distal FFR-CT value of >0.64 in the LAD may increase the risk of competitive flow in the LIMA-LAD graft, while excessively low FFR-CT values likely reflect diffuse coronary lesions, leading to a reduction in graft flow.
7.Dynamic changes in genetic mutations in myelodysplastic neoplasms with progressive disease and leukemic transformation
Xin YAN ; Haiyang CHEN ; Lian WANG ; Yulu TIAN ; Yan GU ; Na LIU ; Zheng GE
Chinese Journal of Hematology 2025;46(3):252-260
Objective:To investigate the key genetic mutations during the progressive disease (PD) /leukemic transformation (LT) course in MDS by analyzing the dynamic changes of genetic mutations in patients with myelodysplastic neoplasms (MDS) with or without PD/LT.Methods:This study enrolled 84 patients with sequential MDS from May 2019 to August 2023 at ZhongDa Hospital Southeast University and used the next generation sequencing to detect gene mutations. The dynamic changes of genetic mutations in patients with MDS with or without PD/LT were retrospectively analyzed.Results:①This study analyzed data from 84 patients diagnosed with MDS with a median age of 63 (range: 31-95) years and consisting of 51 males and 33 females. Participants were distributed to the PD cohort ( n=20), LT cohort ( n=13), and non-PD/LT cohort ( n=51). Patients from the PD/LT cohorts demonstrated a higher proportion of bone marrow blasts than the non-PD/LT cohort at the first sequencing (1.6% vs. 0.4%, P=0.013). ②The most frequently mutated genes that were detected at first sequencing were ASXL1 ( n=21, 25.0%), TP53 ( n=17, 20.2%), TET2 ( n=12, 14.3%), DNMT3A ( n=11, 13.1%), and U2AF1 ( n=11, 13.1%). Further, patients from the PD/LT cohorts exhibited a higher median number of mutated genes than the non-PD/LT cohort (2 vs.1, P=0.014) at first sequencing. TET2 (27.3% vs. 5.9%, P=0.010), SETBP1 (15.2% vs.2.0%, P=0.033), and RUNX1 (18.2% vs. 2.0%, P=0.013) mutations were enriched in the PD/LT cohorts than in the non-PD/LT cohort. ③The most frequently detected acquired mutations (Ⅰ mutations) and clonally expanded mutations (Ⅱ mutations) were TP53 ( n=9, 10.7%), TET2 ( n=7, 8.3%), ASXL1 ( n=7, 8.3%), and RAS pathway ( n=7, 8.3%). Furthermore, patients from the PD/LT cohorts showed a higher median number of Ⅰ/Ⅱ genes than the non-PD/LT cohort (2 vs. 0, P<0.001), and Ⅰ/Ⅱ RAS pathway (21.2% vs. 0, P=0.001), TP53 (27.3% vs. 0, P<0.001), and TET2 (18.2% vs. 2.0%, P=0.013) mutations were enriched in PD/LT cohorts than in the non-PD/LT cohorts. ④Most of the TP53 mutations (9/12, 75.0%) in PD/LT cohorts were Ⅰ/Ⅱ mutations, whereas all of the TP53 mutations in non-PD/LT cohort were clone-decrease mutations (Ⅲ mutations) (5/8, 62.5%) or clone-stable mutations (Ⅳ mutations) (3/8, 37.5%). Most of the RAS pathway mutations (7/8,87.5%) in the PD/LT cohorts were Ⅰ/Ⅱ mutations, whereas only one patient in the non-PD/LT cohort demonstrated RAS pathway mutations, which belonged to Ⅳ mutations. Conclusion:Patients from the PD/LT cohorts demonstrated a higher proportion of bone marrow blasts and a higher median number of mutations than the non-PD/LT cohort at first sequencing; TET2, SETBP1, and RUNX1 mutations were enriched in the PD/LT cohorts than in the non-PD/LT cohort at first sequencing. Patients from the PD/LT cohorts exhibited a higher number of Ⅰ/Ⅱ mutations than the non-PD/LT cohort. Further, Ⅰ/Ⅱ TP53, RAS pathway, and TET2 mutations were enriched in the PD/LT cohorts, and Ⅰ/Ⅱ TP53 and RAS pathway mutations may contribute to the PD/LT.
8.The clinical value of NHR combined with MLR for predicting early rebleeding after endoscopic treatment in patients with cirrhosis complicated by acute esophageal-gastric variceal rupture and bleeding
Yan LI ; Haitao JIAO ; Haiyang HUA ; Wei LIU ; Shuling LIU ; Xinju CAO ; Xin HAO ; Aimin WANG
Tianjin Medical Journal 2025;53(11):1152-1157
Objective To evaluate the predictive value of neutrophil/high-density lipoprotein cholesterol ratio(NHR)combined with monocyte/lymphocyte ratio(MLR)for early rebleeding after endoscopic treatment in patients with cirrhosis complicated by acute esophagogastric variceal bleeding(AEVB).Methods A total of 228 patients with cirrhosis complicated by AEVB were included in this study.According to the occurrence of early rebleeding,patients were divided into the rebleeding group(96 cases)and the non-rebleeding group(132 cases).General information and laboratory indicators of both groups were collected,and the End-Stage Liver Disease(MELD)score,Child-Turcotte-Pugh(CTP)score,Fibrosis-4(FIB-4)index,NHR,and MLR were calculated.Logistic regression analysis was used to identify the risk factors for early rebleeding in patients with cirrhosis complicated by AEVB.A nomogram model based on NHR and MLR was constructed to predict the risk of early rebleeding.The predictive performance and goodness of fit of the model were evaluated using receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI).Results Compared with the non-rebleeding group,systolic blood pressure,platelet count(PLT),albumin/globulin ratio(A/G)and low-density lipoprotein cholesterol(LDL-C)were decreased in the rebleeding group,while total bile acids(TBA),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),activated partial thromboplastin time(APTT),thrombin time(TT),international normalized ratio(INR),Fibrosis-4(FIB-4),NHR,MLR,MELD score and CTP score were increased(P<0.05).NHR was positively correlated with AST,TBIL and INR(P<0.05).MLR was negatively correlated with PLT,and positively correlated with AST,TBIL and FIB-4(P<0.05).Logistic regression analysis results showed that prolonged TT,elevated NHR and MLR were independent risk factors for early rebleeding in patients with cirrhosis complicated by AEVB.The nomogram model based on NHR and MLR to predict early rebleeding had an area under the curve of 0.810(95%CI:0.754-0.866).The Hosmer-Lemeshow test suggested that the model fit well.IDI and NRI analyse showed that the combination of NHR and MLR had better predictive value for the early rebleeding than that of MELD score and CTP score.Conclusion NHR and MLR are effective indicators for predicting early rebleeding after endoscopic treatment in patients with cirrhosis complicated by AEVB.They are helpful in the early identification of high-risk patients and provide a reference for clinical intervention.
9.Feasibility and safety of open ventilation masks in vitrectomy for patients with PDR
Rui DAI ; Yuhao ZHU ; Suchang WANG ; Haiyang LIU ; Wei FAN ; Zhengpei ZHANG ; Sujuan JI ; Jie LI ; Aiqin SHENG ; Suyan LI
Chinese Journal of Experimental Ophthalmology 2025;43(11):1041-1045
Objective:To evaluate the feasibility and safety of open ventilation masks in patients with proliferative diabetic retinopathy (PDR) undergoing vitrectomy under local anesthesia.Methods:A randomized clinical trial was conducted.Eighty PDR patients (80 eyes) undergoing vitrectomy with local anesthesia were enrolled at Xuzhou Municipal Hospital from May to July 2024.Patients were randomly divided into an experimental group and a control group using a random number table method, with 40 cases (40 eyes) in each group.The experimental group received oxygen through an ophthalmic surgical open ventilation mask during the operation, while the control group used a traditional nasal cannula.The respiratory rate, heart rate, systolic blood pressure, diastolic blood pressure, and oxygen saturation before and after oxygen inhalation during the operation were compared between the two groups.Patient comfort level, airway patency, anxiety status, satisfaction level, operation time, surgical success rate, and incidence of intraoperative complications were also compared.This study adhered to the Declaration of Helsinki and the study protocol was appreed by the Ethics Committee of Xuzhou Municipal Hospital (No.2024-KY-065).Results:After oxygen inhalation during the operation, improvements in respiratory rate, heart rate, and oxygen saturation were greater in the experimental group than in the control group, with statistically significant differences ( t=4.671, 7.894, 1.588; all P<0.05).The Borg, and Hamilton Anxiety Scale scores were lower in the experimental group than in the control group, with statistically significant differences ( t=2.828, 4.880; both P<0.05), while the Bruggrmann Comfort Scale score was higher than that in the control group ( t=2.774, P<0.05).There were no statistically significant differences in operation time, surgical success rate or incidence of complications between the two groups ( t=0.595, P=0.554; χ2=0.346, 0.263; both P>0.05).Satisfaction rate of patients in the experimental group was 97.5%(39/40), which was higher than 85.0%(34/40) in the control group, with a statistically significant difference ( χ2=3.914, P=0.048). Conclusions:For PDR patients undergoing vitreous surgery under local anesthesia, using an ophthalmic surgical open ventilation mask for oxygen inhalation can effectively enhance respiratory comfort level, alleviate anxiety, maintain stable vital signs, improve overall comfort level, and ensure smooth surgery, without observed adverse reactions related to mask use, which makes it worthy of clinical promotion and application.
10.Correlation between auditory event-related potential and sedation depth during propofol sedation
Xinxin WANG ; Yi LIANG ; Yiwei CHEN ; Bo MA ; Haiyang LIU ; Ruquan HAN ; Minyu JIAN
Journal of Capital Medical University 2025;46(5):805-811
Objective To explore the neurophysiological signatures of auditory event-related potentials(AERP)during propofol-induced graded sedation depths,and their correlations with sedation levels and behavioral responsiveness,and further to evaluate the feasibility of AERP components as potential biomarkers for quantifying consciousness states.Methods An auditory Oddball paradigm was used to evoke AERP responses in healthy volunteers under propofol-induced graded sedation.Linear mixed model was applied to explore the relationships between the mean amplitudes of AERP components[mismatch negativity(MMN);P300]and both sedation-induced conscious states[Modified Observer's Assessment of Alertness/sedation Scale(MOAA/S)scores]and behavioral performance(response accuracy).Results Twenty-two healthy volunteers were included.Data analysis revealed significant negative correlations between the mean amplitudes of MMN components[MMN-Dev:β=-0.62(-2.70--0.07),P=0.04;MMN-Nov:β=-0.15(-0.27--0.03),P=0.02]and MOAA/S scores during propofol sedation.Novel stimulus-evoked MMN amplitudes also correlated with response accuracy[MMN-Nov:β=-5.08(-7.78--2.37),P<0.01].There was a weak positive correlation between novel stimulus-evoked P300 amplitudes and MOAA/S scores[β=0.16(0.04-0.39),P=0.04],however,the correlation was no significant difference after adjusting for confounding factors including age,education level,and cognitive level.Conclusion The mean amplitude of MMN component elicited during auditory tasks was correlated with conscious states and behavioral accuracy under propofol-induced graded sedation.MMN holds promise as a potential neurophysiological indicator for quantifying conscious states or behavioral responsiveness during sedation.

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