Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.

Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.

BACKGROUND: The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication. METHODS: Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)-messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard. RESULTS: Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A . In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression ( P  <0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs. CONCLUSIONS This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.
Humans ; Female ; Genomics ; Carcinogenesis ; Carcinoma ; Breast Neoplasms ; Cell Transformation, Neoplastic ; Nucleotides ; Tumor Microenvironment

OBJECTIVE：To analyze th e general characteristics and application of the models used in the pharmacoeconomic evaluation of type 2 diabetes mellitus （T2DM）therapy during the past 5 years，and to provide reference for the selection and improvement of T 2DM pharmacoeconomic model. METHODS ：Retrieved from PubMed ，Embase，CNKI，Wanfang database and VIP during Jan. 1st，2015 to Dec. 31st，2019，pharmacoeconomic evaluation literatures about T 2DM therapy were collected ；the included model was analyzed in respects of general structure ，therapy plan establishment ， short-term therapeutic efficacy ， complication simulation ，model effectiveness validation ，application frequency. RESULTS ：A total of 81 literatures were included ， involving 14 models，such as CORE model ，Cardiff model ，ECHO model ，etc. Mostly ，Markov or micro Markov simulation method were adopted to measure the patient ’s lifetime health outcome and cost mostly from the point of view of third-party payer. Seven models could simulate 2-4 therapy plans ；short-term efficacy mainly included risk factors of diabetic complications （such as glycosylated hemoglobin level and body mass ）and adverse drug reactions. Most models used intermediate indexes to simulate the occurrence of complications ，and the number of complications ranged from 3 to 15；the validity of model effectiveness included surface validity ，internal validity and external validity ，etc. Among 14 models，the most frequently used models in the past 5 years were long-term models that had been validated ，among which CORE model had the most application times （38/81，46.91％）， followed by Cardiff model （12/81，14.81％）. CONCLUSIONS ：The 14 models have similar structure. The differences of the models are mainly reflected in 3 aspects as therapy plan setting， considered short-term efficacy ， the number of model are ideally choose based on available evidences.

OBJECTIVE：To comp are cytotoxicity and anti-inflammatory effects of raw Aconitium kusnezoffii and A. kusnezoffii processed with Terminalia chebula . METHODS ：Using H 9c2 cardiomyocytes isolated from rat as subjects ，CCK-8 assay was used to detect the effects of 0.5，1，2，4，6，8，10 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula on cell inhibition rate after cultured for 4，8，12，24 h. Hoechst 33258 staining was used to observe the effects on cell morphology characteristics after treated with 2，4，6 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula . Using macrophages RAW264.7 cells as subjects ，CCK-8 assay was used to detect the effects of 0.05，0.1，0.25，0.5，0.75，1，1.5，2 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula on cell survival rate after cultured for 24 h. ELISA assay was used to detect the effects of 0.05，0.1，0.25，0.5 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula on the release of NO ， TNF-α and IL-6 in RAW 264.7 inflammation cells induced by LPS. RESULTS ：When the mass concentration was 0.5，1 mg/mL， neither raw A. kusnezoffii and A. kusnezoffii processed with T. chebula had no inhibitory effect on H 9c2 cells. When the mass concentration was 2 mg/mL，the inhibitory effects of A. kusnezoffii processed with T. chebula on H 9c2 cells was higher than that of raw A. kusnezoffii （P＜0.05 or P＜0.01）；fluorescence intensity of cells treated for 24 h was stronger than that of raw A. kusnezoffii，but its nucleus was intact. When the mass concentration was 4-10 mg/mL，the inhibitory rate of A. kusnezoffii processed with T. chebula on H 9c2 cells at different time points （except for 24 h culture of 8，10 mg/mL）was significantly lower than raw A. kusnezoffii （P＜0.05 or P＜0.01）. The characteristics of cell morphology also showed that the fluorescence intensity of raw A. kusnezoffii group at 4，6 mg/mL was stronger than that of A. kusnezoffii processed with T. chebula group，and the cell nucleus fragmentation was more serious in the raw A. kusnezoffii group. 0.05-0.5 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula had no toxicity to RAW264.7 cells. 0.25，0.5 mg/mL raw A. kusnezoffii and 0.1，0.25，0.5 mg/mL A. kusnezoffii processed with T. chebula showed significant inhibitory effect on the release of NO ，0.05，0.1，0.25，0.5 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula showed significant inhibitory effect on the release of TNF-α and IL-6 in RAW 264.7 cell（P＜0.05 or P＜ 0.01）. The inhibitory effects of A. kusnezoffii processed with T. chebula at the same concentration on the release of NO was better than that of raw A. kusnezoffii ，but poorer than raw A. kusnezoffii in the inhibitory effects on the release of TNF-α and IL-6. CONCLUSIONS：The toxicity of A. kusnezoffii can be reduced after processed with T. chebula ，especially the toxicity of it in medium or high concentration and short-term use is lower than that of raw A. kusnezoffii . At the same time ，the anti-inflammatory effect of A. kusnezoffii processed with T. chebula is comparable to that of raw A. kusnezoffii at the same concentration.

Objective:To investigate the best neutralization ratio of protamine and heparin during off-pump coronary artery bypass grafting(OPCABG) by analyzing the advantages and disadvantages of heparin residue after OPCABG.Methods:From July 2018 to January 2019, 112 patients undergoing elective OPCABG were included in this study. The patients’ whole blood was drawn at 2 time points, including before entering operating room and entering intensive care unit, to receive thrombelastography(TEG) and heparinase-modified thromboelastography(hmTEG) . Conventional coagulation indexes such as activated coagulation time(ACT) were also detected. All the patients were divided into 3 groups, the non-heparin residue group(30 cases), heparin residue group 1(42 cases) and heparin residue group 2(40 cases) according to the laboratory results of TEG, hmTEG and ACT. We observed the dosage of each group of protamine and heparin, as well as the ratio of heparin and protamine. The changes of R time in TEG and ACT between 3 groups were analyzed and compared. Postoperative chest tube drainage at postoperative 12 h and 48 h, cTnI peak value, incidence of perioperative myocardial infarction(MI), incidence of reoperation and poor wound healing, amount of blood loss and transfusion, and acute renal injury were compared between the 3 groups.Results:No significant trio-group differences existed in basic clinical characteristics(all P>0.05). Postoperative R(CKH)time was similar in the 3 groups( P>0.05). Comparing with heparin residue group 1 and heparin residue group 2, the ACT after protamine neutralizing heparin and postoperative R time were decreased, the dosage of protamine, ratio of heparin and protamine, cTnI peak value were increased in the non-heparin residue group( P<0.05). Comparing with heparin residue group 2, the dosage of heparin, postoperative chest tube drainage at postoperative 12h and 48h, amount of blood transfusion and transfusion probability were significantly decreased in non-heparin residue group( P<0.05), but compared with group 1 of heparin residue, there was no significant difference in the above indexes( P>0.05). The perioperative myocardial infarction, incidence of reoperation and poor wound healing, postoperative acute renal injury and time of in ICU stay showed no significant differences between the 3 groups( P>0.05). Conclusion:Moderate heparin residue after OPCAB suggests that it has myocardial protective effect, and does not significantly increase the risk of bleeding. A large number of heparin residues can affect the coagulation function and lead to bleeding tendency, increase the amount of blood loss and transfusion. It is reasonable to make ACT after protamine neutralize heparin higher than the level of ACT before operation, and not higher than 20% of the level before operation.

Objective    To explore the relationship between glycated hemoglobin (HbA1c) level and blood glucose fluctuations after coronary artery bypass grafting (CABG) and adverse events in non-diabetic patients, thus providing theoretical support for intensive preoperative blood glucose management in patients undergoing CABG surgery. Methods    A total of 304 patients undergoing CABG with or without valvular surgery from October 2013 to December 2017 were enrolled in this prospective, single-center, observational cohort study. We classified them into two different groups which were a low-level group and a high-level group according to the HbA1c level. There were 102 males and 37 females, aged 36–85 (61.5±9.5) years in the low-level group, and 118 males and 47 females aged 34–85 (63.1±9.4) years in the high-level group. The main results were different in hospital mortality and perioperative complications including in-hospital death, myocardial infarction, sternal incision infection, new stroke, new-onset renal failure and multiple organ failure. To assess the effects of confounding factors, multivariate logistic regression analysis was used. Results     Postoperative blood glucose fluctuation was more pronounced in the high-level group than that in the low-level group before admission [0.8 (0.6, 1.2) mmol/L vs. 1.0 (0.8, 1.8) mmol/L, P<0.01]. This study also suggested that the  incidence of major adverse events was significantly lower in the low-level group compared with the high-level group (P=0.001). Multivariate logistic regression analyses to correct the influence of other confounding factors showed that HbA1c (OR=2.773, P=0.002) and postoperative blood glucose fluctuations (OR=3.091, P<0.001) could still predict the occurrence of postoperative adverse events. Conclusion    HbA1c on admission can effectively predict blood glucose fluctuations in 24 hours after surgery. Secondly, HbA1c on admission and postoperative blood glucose fluctuations can further predict postoperative adverse events. It is suggested that we control the patient's preoperative HbA1c at a low level, which is beneficial to control postoperative blood glucose fluctuation and postoperative adverse events.

Objective To construct a dual-luciferase reporter gene vector and validate the targeting relation ship between miR-299 and the COL4A3 gene,laying a foundation for the study on the effect of miR-299 in the chondrogenic differentiation of stem cells by regulating the COL4A3 gene.Methods This study was made from March,2018 to December,2018.Firstly,the potential binding sites between miR-299 and COL4A3-3'UTR were pre dicted using bioinformatics.Then,the wild and mutant COL4A3-3'UTR sequences were amplified by PCR and cloned into psiCHECK-2 plasmid to construct corresponding recombinant vectors.The vectors were validated by enzyme digestion and gene sequencing.Finally,the cells were resuscitated,amplified,transfected and divided into 4 groups:COL4A3-WT+miR-299/NC group,COL4A3-WT+miR-299-inhibitor/NC-inhibitor group,COL4A3-MUT+miR-299/NC group and COL4A3-MUT+miR-299-inhibitor/NC-inhibitor group.Each group contains 3 holes,respectively.Luciferase activity in each group was determined using a dual-luciferase assay kit.The statistical analysis was conducted and differences between groups were compared by t test.Probabilities lower than 5％(P＜0.05) were considered statistically significant.Results Enzyme digestion and DNA sequencing showed that the dual-luciferase reporter gene vector of psiCHECK-2-COL4A3 was constructed successfully.Luciferase assay demonstrated that in wild COL4A3 gene,luciferase activity reduced in the miR-299 transfection group (The average R/F value was 59.38％) compared with the NC group (The average R/F value was 100.00％),with a statistical significant difference (P＜0.05).In wild COL4A3 gene treated with inhibitor,luciferase activity increased in the miR-299-inhibitor group (The average R/F value was 153.98％) compared with the NC-inhibitor group (The average R/F value was 100.00％),with a statistical significant difference (P＜0.05).In mutant COL4A3 gene treated with inhibitor,no obvious statistical differences in luciferase activity were found between miR-299 transfection group (The average R/F value was 102.09％),miR-299-inhibitor group (The average R/F value was 108.51％) and NC group (The average R/F value was 104.70％),NC-inhibitor group (The average R/F value was 105.13％) and/9＞0.05.Conclusion The dual-luciferase reporter gene vector of the 3'UTR of the COL4A3 gene is constructed successfully.In addition,dual-luciferase assay further verifies the authenticity of miR-299 directly targeting the 3'UTR of the COL4A3 gene.

Objective To investigate the aberrant expression of long non-coding RNA(lncRNA) in chronic thromboembolic pulmonary hypertension,and explore the lncRNA role in pathogenesis of CTEPH.Methods A total of 5 pulmonary artery endarterium tissue of CTEPH patients and 5 pulmonary artery endarterium tissue of healthy controls were collected.Using high-throughput gene microarray technology to detect two groups of lncRNA and mRNA expression spectrum,build lncRNA-mRNA express network,Pathway and GO analysis to explore the gene function.Results Differential expression of 185 lncRNA was observed in the CTEPH tissues compared with healthy control tissues.Further analysis identified 464 regulated enhancerlike lncRNA and overlapping,antisense or nearby mRNA pairs.Coexpression networks were subsequently constructed and investigated.The expression levels of the lncRNA,NR_036693,NR_027783,NR_033766 and NR_001284,were significantly altered.Gene ontology and pathway analysis demonstrated the potential role of lncRNA in the regulation of central process,including inflammatory response,response to endogenous stimulus and antigen processing and presentation.Conclusion Differentially expressed lncRNA may exert a partial role in CTEPH,the results of this study will help in the future about diagnosis and treatment of CTEPH.

Objective To compare clinical effects and complications of patients with diabetes in off-pump coronary artery bypass grafting(OPCAB) between endoscopic saphenous vein harvesting(EVH) and conventional saphenous vein harvesting(CVH).Methods Sequence comparison analysis the clinical data of 339 patients with DM who underwent OPCAB in our department from Nov 2011 to Nov 2014.269 cases by EVH,70 cases by CVH.Observing two groups of patients with deprecated rate of SVG,intraoperative SVG blood flow and the value of PI,lower limb wound complications such as incision infection,poor healing,lower limb local hematoma and pain.SVG patency rate of part patients was follow-up by CT coronary angiography.Results To compare the two groups of patients by EVH and CVH,the perioperative death was 8 cases in EVH group (2.4％),2 cases in C VH group (2.9％).The deprecated SVG of patients was 3.9％ vs 2.9％.The blood flow was (17.36 ±11.24) ml/min vs(17.11 ± 8.37) ml/min,PI was 2.78 ± 2.37 vs 2.22 ± 2.17.The incision infection was 0 vs 4.4％,poor healing was 0.9％ vs 8.8％.The lower limb local hematoma was 5.7％ vs 1.5％.The visual pain analogue scale(VAS) was 0.53 ± 1.71 vs 1.26 ± 2.13 3 days after operation.The numbness of lower limb was 9.7％ vs 22.1％.The Edema of the legs was 8.5％ vs 19.1％ 7 days after operation.60 cases were follow-up by CT coronary angiography,the SVG patency rate was91.4％ vs 94.6％ 1 year after operation,83.3％ vs 86.1％ 2 years after operation,72.2％ vs 73.7％ 3 years after operation respectively.Conclusion EVH technology for SVG in the patients combined DM has good clinical result,the recent patency rate of SVG is perfect,postoperative limb complications is decreased by EVH.