1.An RNA-cleaving DNAzyme and G-Quadruplex DNAzyme-Cascade System for Sensing of Small Molecules in Organic Cosolvent
Su-Hui LI ; Shuai-Qi ZHANG ; Yi-Bo ZHANG ; Quan ZHENG ; Tian-Jun CHANG
Chinese Journal of Analytical Chemistry 2025;53(6):914-923
Detection of poor-water-soluble substances typically requires an organic solvent containing solution,and therefore,the biosensors that can operate in such conditions are highly promising for practical applications.However,most existing biosensors have been developed in aqueous solution and it is hard to work effectively in organic solvent systems.In this work,we uncovered that the G-quadruplex(G4)/hemin DNAzyme(G4HD)could be strongly reactivated by NH4 in organic solvents at concentration up to 30%,and the activity was significantly higher than that in aqueous solutions containing K+.Based on this discovery,a biosensing system was developed for small molecule in 40%methanol by coupling G4HD with our previously identified RNA-cleaving DNAzyme(E3).This system comprised an ATP-activated aptazyme that was made of E3 and a G4HD that was activated by the cleavage product of the aptazyme.By using a manmade pipette tip filter to separate the reaction products,the subsequent colorimetric reaction of the G4HD could be triggered.This biosensing system enabled the visualization of target molecules in organic cosolvents without any other instruments.The activable DNAzyme-cascade sensing system had potential in point-of-care detection of poor-water-soluble pollutants,thereby enhancing the practical values of functional nucleic acid-based biosensors in real-world detection conditions.
2.Simultaneous Determination of 21 Kinds of Aconitum Alkaloids in Biological Specimens and Herbal Wines Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry
Ju YANG ; Guo-Jun LI ; Xian-Mou FAN ; Rui-Bin ZHAO ; Shao-Ming SU ; Xu-Xian FU ; En-Jin ZHU ; Qi-Lin HUANG ; Yao QIN ; Li-Na LI
Chinese Journal of Analytical Chemistry 2025;53(8):1391-1401,后插1-后插6,封3
A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.
3.Primary intraosseous synovial sarcoma:a case report and literature review
Wen ZHAO ; Wei-Jun QIAN ; Li LI ; Yan-Min WANG ; Peng-Hui SU ; Chao-Xin ZHANG ; Liang XU ; Tie-Cheng WU ; Jun-Qi LIU ; Ya-Jun WANG
Medical Journal of Chinese People's Liberation Army 2025;50(11):1419-1425
Objective To report a case of tibial synovial sarcoma and review relevant literature to enhance understanding of this disease.Methods The clinical data of a patient with tibial synovial sarcoma treated at Kaifeng Central Hospital were retrospectively analyzed.A literature search was conducted in domestic and international databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,PubMed,Web of Science,and Embase,up to July 2024.Relevant literature was comprehensively reviewed to summarize the imaging and pathological characteristics,treatment,and prognosis of synovial sarcoma.Results A 29-year-old female patient was admitted with left lower extremity pain.X-ray examination revealed a proximal tibia space-occupying lesion suggestive of malignancy,and a mid-tibial space-occupying lesion considered benign.Contrast-enhanced computed tomography(CT)and plain magnetic resonance imaging(MRI)of the proximal tibial lesion also suggested malignancy.Ultrasound-guided biopsy of the proximal tibial tumor revealed a poorly differentiated malignant tumor.Immunohistochemistry results indicated monophasic synovial sarcoma,requiring genetic testing for definitive diagnosis.The patient underwent wide resection of the proximal left tibial malignancy with tumor-type artificial joint replacement,combined with curettage and bone cement filling for the left mid-tibial lesion under anesthesia.Postoperative pathology of space-occupying lesions in the proximal tibia confirmed monophasic synovial sarcoma,and fluorescence in situ hybridization(FISH)demonstrated a rupture of the synovial sarcoma translocation gene(SYT)(i.e.,SS18 positive).There was no recurrence or metastasis found in the patient during the reexamination 6 months after postoperative chemotherapy.As of July 2024,15 cases of genetically confirmed primary intraosseous synovial sarcoma have been reported internationally.Symptoms included pain and swelling,with a medical history of 1-2 years.The X-ray and CT findings showed osteolytic destruction with bone cortical discontinuity.In 13 cases,the intraosseous masses extended to the extraosseous area;in 2 cases,punctate calcifications were detected within the masses.Plain MRI scan showed iso-signal or hypo-signal on T1WI and hyper-signal,iso-signal,and hypo-signal on fat-suppressed T2WI,and enhanced MRI scan demonstrated heterogeneous enhancement.Pathological examination showed spindle-shaped cells under microscopy.Immunohistochemistry results showed positive epithelial membrane antigen(EMA),broad-spectrum cytokeratin(AE1/AE3),Ewing's sarcoma marker(CD99),and transducin-like enhancer of Split 1(TLE1).Twelve patients underwent surgical treatment;6 patients received adjuvant chemotherapy after surgery,of whom 4 developed local recurrence or distant metastasis at initial diagnosis,and 3 died during follow-up.Among the 6 patients who did not receive adjuvant chemotherapy,3 suffered from recurrence or distant metastasis.Conclusions Primary intraosseous synovial sarcoma is a rare malignant tumor with non-specific clinical manifestations.Imaging features typically include osteolytic destruction and intraosseous masses extending extraosseously,suggesting an intraosseous origin.Pathology and immunohistochemistry aid diagnosis,but definitive confirmation relies on further genetic testing.At present,the main treatment regimens for synovial sarcoma involve comprehensive therapies such as surgery and adjuvant chemotherapy,and the prognosis of patients is poor.
4.Clinical characteristics of Behçet syndrome in 45 children.
Chen-Xi WEI ; Shu-Feng ZHI ; Li-Jun JIANG ; Xue ZHAO ; Qing-Xiao SU ; Xing-Jie QI ; Zan-Hua RONG
Chinese Journal of Contemporary Pediatrics 2025;27(10):1253-1258
OBJECTIVES:
To study the clinical characteristics of pediatric Behçet syndrome (BS).
METHODS:
A retrospective review was conducted on the medical records of children hospitalized in the Department of Pediatrics at the Second Hospital of Hebei Medical University between December 2014 and December 2024 who met diagnostic criteria for BS.
RESULTS:
Among 45 children with BS, 26 (58%) were male. Oral aphthous ulcers were the most common manifestation (43/45, 96%), followed by genital ulcers (23/45, 51%) and gastrointestinal involvement (18/45, 40%). Genital ulcers were more frequent in girls, whereas ocular involvement was more common in boys (P<0.05). The pathergy test was positive in 10 (22%), and HLA-B51 was positive in 13 (29%). Fecal calprotectin (FC) was elevated in 16 (36%); gastrointestinal involvement was more frequent in children with elevated FC than in those with normal FC (P<0.05). According to the respective criteria, 17 (38%) patients met the International Study Group criteria (1990), 33 (73%) met the International Criteria for Behçet Disease (2014), and 13 (29%) met the Pediatric Behçet Disease criteria (2015).
CONCLUSIONS
Pediatric BS shows marked clinical heterogeneity. HLA-B51 is associated with disease susceptibility.
Humans
;
Behcet Syndrome/genetics*
;
Male
;
Female
;
Child
;
Retrospective Studies
;
Adolescent
;
Child, Preschool
;
Leukocyte L1 Antigen Complex/analysis*
;
HLA-B51 Antigen
5.Associations of reproductive health indicators with lung function and COPD among female community residents aged 40 years and above in Songjiang District,Shanghai
Xin YIN ; Yi-Ling WU ; Shan-Shan HOU ; Jing LI ; Wei LUO ; Min-Jun YU ; Jin-Xin ZANG ; Wei WANG ; Xu-Yan SU ; Qi ZHAO ; Yin-Feng ZHU ; Gen-Ming ZHAO ; Yong-Gen JIANG ; Qing-Wu JIANG ; Na WANG
Fudan University Journal of Medical Sciences 2024;51(6):882-889
Objective To investigate the associations of reproductive health indicators with lung function and chronic obstructive pulmonary disease(COPD)among women aged 40 years and above.Methods From Jul to Sep,2021,female subjects aged 40 years and above were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for COPD screening.A questionnaire was used to obtain information on demographic characteristics and reproductive health indicators.Linear regression was used to analyze the effects of reproductive health indicators on forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1).Logistic regression was also used to analyze the effects of reproductive health factors on FVC as a percentage of the predicted value(FVC%Pred)and FEV1%Pred as well as on COPD.Results A total of 1876 women aged 40 years and above were enrolled with mean age of(62.1±8.2)years old,among them,78.1%were menopausal,and 40.9%had been pregnant≥3 times.Multivariate analysis showed that FVC and FEV1 decreased in postmenopausal women,but menopause was not associated with a decrease in their percentage of predicted values.Pregnancies≥3 times was a risk factor for COPD(for 3 times,OR=4.92,95%CI:1.48-19.95,P<0.05;for≥4 times,OR=9.06,95%CI:2.32-41.57,P<0.01),while pregnancies of 2 times did not increase the risk of COPD.Conclusion In women aged 40 years and above,menopause is associated with poorer FVC and FEV1,and excessive pregnancy(≥3 times)is a risk factor for COPD.
6.Effects of dapagliflozin on inflammatory cytokines and cardiac function in elderly patients with preserved ejection fraction heart failure complicated with type 2 diabetes mellitus
Jianpei SU ; Yongli WANG ; Zhimin WANG ; Qi WU ; Jun GU ; Jin LI ; Bijuan LIANG
Journal of Clinical Medicine in Practice 2024;28(7):85-89
Objective To investigate the effects of dapagliflozin on inflammatory cytokines, blood glucose control and cardiac function in elderly with preserved ejection fraction heart failure (HFpEF) combined with type 2 diabetes. Methods A total of 80 elderly HFpEF patients with type 2 diabetes mellitus were randomly divided into control group (40 cases) and study group (40 cases). The control group received hypoglycemic and anti-heart failure standard therapy, and the study group received hypoglycemic and anti-heart failure standard therapy and dapagliflozin therapy. Both groups were treated for 6 months. The levels of inflammatory factors, blood glucose control, myocardial markers, exercise endurance [6 min walking distance (6MWD)], cardiac ultrasound related indexes and adverse drug reactions were compared between the two groups. Results After 6 months of treatment, serum interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP) and tumor necrosis factor (TNF)-α in the study group were significantly lower than those in the control group (
7.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
8.Causal association between depression and stress urinary incontinence:A two-sample bidirectional Mendelian randomization study
Cheng-Xiao JIANG ; Wei-Qi YIN ; Jing-Jing XU ; Ying-Jiao SHI ; Li WANG ; Zhi-Bo ZHENG ; Rui SU ; Qin-Bo HU ; Jun-Hai QIAN ; Shu-Ben SUN
National Journal of Andrology 2024;30(3):217-223
Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.
9.Retrospective study on authorized aeromedical identification of overage military flying personnel
Nan SU ; Di ZHU ; Linsong QI ; Jiakang ZHANG ; Dongrui YU ; Jun WANG ; Junhua XING ; Hongyang JI ; Xianrong XU
Space Medicine & Medical Engineering 2024;35(2):112-115
Objective To retrospectively investigate and analyze the specially permitted aeromedical evaluation results of overage military flying personnel,in order to provide references for health management and related evaluation methods improvement.Methods The clinical data and evaluation results of overage flying personnel were collected from 2012 to 2023.Disease spectrum was analyzed,and qualified rates among different airplane types and aviation duties were compared.Results 79.57%of the 509 flying personnel were detected with diseases,and the top ten were hyperlipidemia,fatty liver,thyroid nodule,renal cyst,hepatic cyst,gallbladder polyps,hyperuricemia,carotid artery arteriosclerosis,hypertension and hepatic hemangioma.96.08%of the personnel were qualified to continue flying,1.96%were disqualified and 1.96%were temporarily disqualified.The qualified rates among different airplane types and aviation duties were not significantly different(P?>?0.05).Conclusion Overage military flying personnel could apply for specially permitted aeromedical evaluation to extend their flying lifespan.Attention should be paid to metabolic and cardiovascular diseases in aeromedical support and evaluation for these experienced flying personnel.
10.Effect of preoperative oral ibuprofen on postoperative pain after dental implantation: a randomized controlled trial
Kang GAO ; Xuezhu WEI ; Bin ZHAO ; Zhiguang LIU ; Conglin DU ; Xin WANG ; Yao WANG ; Changying LIU ; Dezheng TANG ; Qi ZHANG ; Ruiqing WU ; Mingming OU ; Wei LI ; Qian CHENG ; Yilin XIE ; Pan MA ; Jun LI ; Hao WANG ; Zuomin WANG ; Su CHEN ; Wei ZHANG ; Jian ZHOU
Chinese Journal of Stomatology 2024;59(8):777-783
Objective:To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application.Methods:A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively.Results:A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] ( Z=-1.99, P=0.047; Z=-3.01, P=0.003; Z=-2.10, P=0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ 2=0.79, P=0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference ( Z=-0.78, P=0.439). Conclusions:Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.


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