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Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

Animal Models and Experimental Medicine 2024年第2期7卷 114-126页

作者： Xuyu Song Ying Liu Siyi Chen Lei Zhang Huijie Zhang Xianhui Shen Hang Du Rong Sun Orthopaedic trauma surgery The Second Hospital of Shandong UniversityJinanShandongChina Academy of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjinChina Department of Traditional Chinese Medicine The Second Hospital of Shandong UniversityJinanShandongChina College of pharmacy Shandong University of Traditional Chinese MedicineJinanShandongChina The second Clinical College of shandong university Shandong UniversityJinanShandongChina Advanced medical Research Institute Shandong UniversityJinanShandongChina The second hospital of shandong university JinanShandongChina

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging *** pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same ***,researchers are interested in studying KOA and require appropriate animal models for basic *** herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget *** potential benefits in the treatment of KOA continue to attract ***:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal *** will help researchers make informed decisions when choosing an animal ***:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to ***:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal ***:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

关键词： animal models knee osteoarthritis system review traditional Chinese medicine

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Chemotherapy induces breast cancer stem cell enrichment through repression of glutathione S-transferase Mu

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Genes & Diseases 2024年第2期11卷 528-531页

作者： Jing He Yiran Yu Yilin He Jie He Guangyu Ji Haiquan Lu The second hospital and Advanced medical Research Institute Cheeloo College of MedicineShandong UniversityJinanShandong 250012China Department of Nursing The First Affiliated Hospital of Shandong First Medical UniversityJinanShandong 250014China School of Medicine Xinjiang Medical UniversityUrumqiXinjiang 830054China School of Medicine Binzhou Medical UniversityYantaiShandong 264003China Oncology Department Jinan Zhangqiu District People's HospitalJinanShandong 250200China Key Laboratory for Experimental Teratology of the Ministry of Education Cheeloo College of MedicineShandong UniversityJinanShandong 250012China Center for Reproductive Medicine Shandong UniversityJinanShandong 250012China

Triple-negative breast cancer(TNBC)has aggressive characteristics as exemplified by the high risk of recurrence,metastasis,and patient mortality.1 Cytotoxic chemotherapy may reduce tumor burden initially,but leave behind chemo-resistant breast cancer stem cells(BCSCs)that lead to tumor recurrence and metastasis.2 Chemotherapy induces BCsC enrichment through the activation of glutathione biosynthesis pathways,which increases intracellular glutathione levels and specifies the BCSC phenotype through complicated downstream signaling pathways.3 Glutathione S-transferases(GSTs),a superfamily(which contains seven cytosolic classes:Alpha,Kappa,Mu,Omega,Pi,Theta,and Zeta,and one microsomal class MGSTs)of phase Il enzymes that catalyze the conjugation of glutathione with electrophilic compounds,play a critical role in detoxification and chemotherapy resistance of cancer ***,the role of GSTs in the regulation of BCSCs is largely elusive.

关键词： chemotherapy breast metastasis

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Clinically significant changes in anal sphincter hiatal area in patients with gestational diabetes mellitus and pelvic organ prolapse

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World Journal of Diabetes 2024年第8期15卷 1726-1733页

作者： Qing-Hong Wang Li-Hua Liu Hua Ying Ming-Xu Chen Chang-Jiang Zhou Hui Li Department of Sonography People's Hospital Affiliated to Shandong First Medical UniversityJinan 271100Shandong ProvinceChina Department of Obstetrics and Gynecology People's Hospital Affiliated to Shandong First Medical UniversityJinan 271100Shandong ProvinceChina

BACKGROUND The prevalence of pelvic organ prolapse(POP)increases with age and ***,the prevalence of POP among women aged 20 to 39 is 9.7%,while it rises to 49%among women over 80 years ***,as the number of deliveries increases,the prevalence of POP also rises accordingly,with a rate of 12.8%for women with one delivery history,18.7%for those with two deliveries,and 24.6%for women with three or more *** causes immense suffering for pregnant *** To evaluate the relationship between the levator ani muscle’s hiatus(LH)area and POP in patients with gestational diabetes mellitus(GDM)using perineal *** The study cohort comprised 104 patients aged 29.8±3.7 years who sought medical care at our institution between January 2021 and June *** were singleton pregnancies consisting of 75 primiparas and 29 multiparas,with an average parity of 1.7±*** to the POP diagnostic criteria,the 104 subjects were divided into two groups with 52 members each:POP group(patients with GDM combined with POP)and non-POP group(patients with GDM without POP).Perineal ultrasound was used to measure differences in the anteroposterior diameter,transverse diameter,and LH *** operating characteristic curves were drawn to determine the optimal cutoff values for the LH anteroposterior diameter,transverse diameter,and area for diagnosing *** Statistically significant increase in the LH area,anteroposterior diameter,and lateral diameter were observed in the POP group compared with the non-POP group(P<0.05).Both groups exhibited markedly elevated incidence rates of macrosomia and stress urinary *** the POP group,the area under the curve(AUC)for the LH area was 0.906 with a 95%confidence interval(CI):*** optimal cutoff was 13.54cm²,demonstrating a sensitivity of 83.2%and a specificity of 64.4%.The AUC for the anteroposterior diameter reached 0.836 with a 95%CI:*** optimal cutoff was 5

关键词： Ultrasound Levator ani muscle hiatus Gestational diabetes mellitus Pelvic organ prolapse

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Bile acids inhibit ferroptosis sensitivity through activating farnesoid X receptor in gastric cancer cells

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World Journal of Gastroenterology 2024年第5期30卷 485-498页

作者： Chu-Xuan Liu Ying Gao Xiu-Fang Xu Xin Jin Yun Zhang Qian Xu Huan-Xin Ding Bing-Jun Li Fang-Ke Du Lin-Chuan Li Ming-Wei Zhong Jian-Kang Zhu Guang-Yong Zhang Department of General Surgery Shandong Provincial Qianfoshan HospitalShandong UniversityJinan 250014Shandong ProvinceChina Department of General Surgery Linyi People's HospitalLinyi 276034Shandong ProvinceChina Department of Nursing Huantai TCM HospitalZibo 256400Shandong ProvinceChina Center for Translational medical Research The First Affiliated Hospital of Shandong First Medical UniversityJinan 250014Shandong ProvinceChina Department of General Surgery The First Affiliated Hospital of Shandong First Medical UniversityJinan 250014Shandong ProvinceChina

BACKGROUND Gastric cancer(GC)is associated with high mortality *** acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains *** GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic *** confers additional cancer phenotypes,including ferroptosis *** is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant ***,it is not fully defined if BAs can influence GC progression by modulating *** To reveal the mechanism of BAs regulation in ferroptosis of GC *** In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to *** used gain and loss of function assays to examine the impacts of farnesoid X receptor(FXR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism *** Our data suggested that BAs could reverse erastin-induced ferroptosis in GC *** effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPX4)expression ***,we confirmed that BAs exerted these effects by activating FXR,which markedly increased the expression of GSH synthetase and ***,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and ***,our results suggested that FXR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis *** This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSHGPX4 axis in GC *** work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

关键词： Gastric cancer Ferroptosis Bile acids Chenodeoxycholic acid Farnesoid X receptor Glutathione

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The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

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Neural Regeneration Research 2025年第7期20卷 1829-1848页

作者： Wenjing Ning Shi Lv Qian Wang Yuzhen Xu Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina Department of Central Laboratory The Affiliated Taian City Central Hospital of Qingdao UniversityTaianShandong ProvinceChina

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter ***,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective *** evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid ***,microglia play certain neuroprotective roles in the recovery phase of subarachnoid *** approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage *** provides new targets and ideas for the treatment of subarachnoid ***,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still *** review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter *** also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid ***,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese ***,most of these are still being evaluated at the laboratory *** clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemor

关键词： apoptosis blood–brain barrier brain edema microglia neuroinflammation neuron neuroprotection subarachnoid hemorrhage vasoconstriction white matter injury

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Engineered extracellular vesicles for targeted reprogramming of cancer-associated fibroblasts to potentiate therapy of pancreatic cancer

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3077-3096页

作者： Pengcheng Zhou Xuanlong Du Weilu Jia Kun Feng Yewei Zhang Department of General Surgery Affiliated Hospital of Nantong UniversityNantongChina School of Medicine Southeast UniversityNanjingChina Nanjing medical university NanjingChina Hepatobiliary and Pancreatic Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina

Pancreatic cancer is one of the deadly malignancies with a significant mortality rate and there are currently few therapeutic options for *** tumor microenvironment(TME)in pancreatic cancer,distinguished by fibrosis and the existence of cancer-associated fibroblasts(CAFs),exerts a pivotal influence on both tumor advancement and resistance to *** advancements in the field of engineered extracellular vesicles(EVs)offer novel avenues for targeted therapy in pancreatic *** study aimed to develop engineered EVs for the targeted reprogramming of CAFs and modulating the TME in pancreatic *** obtained from bone marrow mesenchymal stem cells(BMSCs)were loaded with miR-138-5p and the anti-fibrotic agent pirfenidone(PFD)and subjected to surface modification with integrinα5-targeting peptides(named IEVs-PFD/138)to reprogram CAFs and suppress their pro-tumorigenic ***α5-targeting peptide modification enhanced the CAF-targeting ability of ***-138-5p directly inhibited the formation of the FERMT2-TGFBR1 complex,inhibiting TGF-βsignaling pathway *** addition,miR-138-5p inhibited proline-mediated collagen synthesis by directly targeting the FERMT2-PYCR1 *** combination of miR-138-5p and PFD in EVs synergistically promoted CAF reprogramming and suppressed the pro-cancer effects of *** experiments using the orthotopic stroma-rich and patient-derived xenograft mouse models yielded promising *** particular,IEVs-PFD/138 effectively reprogrammed CAFs and remodeled TME,which resulted in decreased tumor pressure,enhanced gemcitabine perfusion,tumor hypoxia amelioration,and greater sensitivity of cancer cells to ***,the strategy developed in this study can improve chemotherapy *** IEVs-PFD/138 as a targeted therapeutic agent to modulate CAFs and the TME represents a promising therapeutic approach for pancreatic cancer.

关键词： inhibited targeted chemotherapy

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Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling

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World Journal of Diabetes 2024年第2期15卷 287-304页

作者： Huai-Jie Wang Li-Bin Zhang Si-Peng Sun Qing-Tao Yan Zhi-Qin Gao Fang-Ming Fu Mei-Hua Qu Translational medical Center Weifang Second People's HospitalWeifang 261041Shandong ProvinceChina Department of Endocrinology Weifang Second People's HospitalWeifang 261041Shandong ProvinceChina Department of Pediatric Surgery Weifang People’s HospitalWeifang 261041Shandong ProvinceChina School of Bioscience and Technology Weifang Medical UniversityWeifang 261053Shandong ProvinceChina Department of Endocrinology Jinan Central Hospital Affiliated to Shandong First Medical UniversityJinan 250013Shandong ProvinceChina

BACKGROUND Type 2 diabetes mellitus(T2DM)is often accompanied by impaired glucose utilization in the brain,leading to oxidative stress,neuronal cell injury and *** studies have shown that duodenal jejunal bypass(DJB)surgery significantly improves brain glucose metabolism in T2DM rats,the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain *** To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM *** A T2DM rat model was induced via a high-glucose and high-fat diet,combined with a low-dose streptozotocin injection.T2DM rats were divided into DJB operation and Sham operation *** surgical intervention was carried out on T2DM *** differential expression of hypothalamic proteins was analyzed using quantitative proteomics *** related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry,quantitative real-time PCR,Western blotting,and *** Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery,compared to the T2DM-Sham groups of *** stress-related proteins(glucagon-like peptide 1 receptor,Nrf2,and HO-1)were significantly increased(P<0.05)in the hypothalamus of rats with T2DM after DJB *** surgery significantly reduced(P<0.05)hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin(IL)-1βand *** surgery significantly reduced(P<0.05)the expression of factors related to neuronal injury(glial fibrillary acidic protein and Caspase-3)in the hypothalamus of T2DM rats and upregulated(P<0.05)the expression of neuroprotective factors(C-fos,Ki67,Bcl-2,and BDNF),thereby reducing hypot

关键词： Duodenal jejunal bypass surgery Type 2 diabetes mellitus Neuron apoptosis Inflammatory Oxidative stress Hypothalamic injury

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Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients

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World Journal of Diabetes 2024年第2期15卷 275-286页

作者： Ping Shi Yang Tian Feng Xu Lu-Na Liu Wan-Hong Wu Ying-Zhou Shi An-Qi Dai Hang-Yu Fang Kun-Xia Li Chao Xu Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina Department of Pediatric Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityYantai 264099Shandong ProvinceChina

BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose *** in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14(MODY14).Currently,only two mutations[c.1655T>A(***552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this *** the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 *** To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 *** Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the *** exome sequencing was performed on the patients as well as their family *** pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics *** addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional ***,the impact of these variants on APPL1 protein expression and the insulin pathway were assessed,and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further *** A total of five novel mutations were identified,including four missense mutations(Asp632Tyr,Arg633His,Arg532Gln,and Ile642Met)and one intronic mutation(1153-16A>T).Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all *** Asp632Tyr and Arg633His variants also had pathogenicity based on *** addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different ***,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations

关键词： Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1 Maturity-onset diabetes of the young Bioinformatics analysis Gene mutation Domain

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HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 344-352页

作者： Qing-Zhi Hu Zhen-Rui Cao Wei-Xiong Zheng Min-Jie Zhao Jun-Hua Gong Cong Chen Zhong-Jun Wu Rui Tao Department of Hepatobiliary Surgery Bishan Hospital of Chongqing Medical UniversityChongqing 402760China Department of Cardiothoracic Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China c Department of Hepatobiliary Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Hepatobiliary Surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune *** shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein ***:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using ***-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following *** blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular ***:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer *** HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

关键词： Ischemia-reperfusion injury Liver transplantation Inflammation HSP110 Heat shock proteins NF-κB

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Hemoglobin loss method calculates blood loss during pancreaticoduodenectomy and predicts bleeding-related risk factors

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 419-428页

作者： Chao Yu Yi-Min Lin Guo-Zhe Xian Department of Hepatobiliary Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina

BACKGROUND The common clinical method to evaluate blood loss during pancreaticoduoden-ectomy(PD)is visual inspection,but most scholars believe that this method is extremely subjective and ***,there is no accurate,objective me-thod to evaluate the amount of blood loss in PD *** retrospectively analyzed the clinical data of 341 patients who underwent PD in shandong Provincial hospital from March 2017 to February *** to different surgical methods,they were divided into an open PD(OPD)group and a laparoscopic PD(LPD)*** differences and correlations between the in-traoperative estimation of blood loss(IEBL)obtained by visual inspection and the intraoperative calculation of blood loss(ICBL)obtained using the Hb loss method were ***,IEBL and perioperative calculation of blood loss(PCBL)were compared between the two groups,and single-factor regression analysis was *** There was no statistically significant difference in the preoperative general patient information between the two groups(P>0.05).PD had an ICBL of 743.2(393.0,1173.1)mL and an IEBL of 100.0(50.0,300.0)mL(P200μmol/L(95%CI:7.09-644.26;P=0.045)were independent risk factors for *** ICBLs of the LPD group and OPD group were 767.7(435.4,1249.0)mL and 663.8(347.7,1138.2)mL,respectively(P>0.05).The IEBL of the LPD group 200.0(50.0,200.0)mL was slightly greater than that of the OPD group 100.0(50.0,300.0)mL(P>0.05).PCBL was greater in the LPD group than the OPD group[1061.6(612.3,1632.3)mL vs 806.1(375.9,1347.6)mL](P<0.05).CONCLUSION The ICBL in patients who underwent PD was greater than

关键词： Pancreaticoduodenectomy Hemoglobin loss Calculated blood loss Estimated blood loss

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