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Recently, due to the growth in machine learning and data mining, for scheduling applications in China's industrial intelligence, we are quite fortunate to witness a paradigm of evolutionary scheduling via learning, which includes a new tool of evolutionary transfer optimization (ETO). As a new subset in ETO, single-objective to multi-objective/many-objective optimization (SMO) acts as a powerful, abstract and general framework with wide industrial applications like shop scheduling and vehicle routing. In this paper, we focus on the general mechanism of selection that selects or gathers elite and high potential solutions towards gathering/transferring strength from single-objective problems, or gathering/transferring storms of knowledge from solved tasks. Extensive studies in vehicle routing problems with time windows (VRPTW) on well-studied benchmarks validate the great universality of the SMO framework. Our investigations (1) contribute to a deep understanding of SMO, (2) enrich the classical and fundamental theory of building blocks for genetic algorithms and memetic algorithms, and (3) provide a completive and potential solution for VRPTW. [ABSTRACT FROM AUTHOR]

Background: Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series. Method: A total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed. Results: A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien–Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384, P < 0.001), traditional low anterior resection (tumor at low rectum) (OR 1.968, P = 0.017) and intersphincteric resection (OR 5.468, P = 0.006) were significant independent risk factors for anastomotic leakage. Female gender (OR 0.557, P = 0.005), age ≥ 60 years (OR 0.684, P = 0.040), and preventive stoma (OR 0.496, P = 0.043) were significant independent protective factors. Body mass index, preoperative chemotherapy/radiotherapy, tumor size, and TNM stage did not independently affect the occurrence of anastomotic leakage. Conclusion: Robotic colorectal cancer surgery was safe and reliable and might have advantages in patients at high risk of anastomotic leakage. [ABSTRACT FROM AUTHOR]

In recent years, diverse energy has been integrated into the power system, which constitutes a regional integrated energy system (IES). However, the coupling and complementation of multiple energy sources make load forecasting more difficult. For the time‐sequence and non‐linear characteristics of electric load and the complementarity of different energy in IES, this paper proposed an attention‐based convolutional neural network (CNN) combined with long short‐term memory (LSTM) and bidirectional long short‐term memory (BiLSTM) model for short‐term load forecasting in IES. The historical load, temperature, cooling load, and gas consumption of the past 5 days are used as the input features. CNN integrated with attention block is utilized to extract effective features of the load impact factors. Then the load of the next hour is forecasted by the LSTM combined with BiLSTM layers. Finally, the model is verified by the data from an integrated energy park in North China. The results show that the proposed method has better forecasting performance than CNN‐BiLSTM, CNN‐LSTM, BiLSTM, LSTM, backpropagation neural network (BPNN), random forest regression (RFR), and support vector machine regression (SVR). [ABSTRACT FROM AUTHOR]

Background: Threatened premature labor (TPL) is a severe obstetric complication which affects the mental and physical health of both the mother and fetus. Family resilience may have protective role against psychological distress in women experiencing these pregnancy complications. There may be resilience related risk factors in TPL women, and interplays may exist among psychological variables and within couples. This study aims to examine psychological outcomes influenced by different levels of resilience, and explore psychological interactions in TPL women, spouses, and between women and spouses.Methods: Six validated questionnaires were used to measure the psychological outcomes (Connor-Davidson resilience scale CD-RISC, Edinburgh postnatal depression scale EPDS, positive and negative affect scale PANAS, pregnancy pressure scale PPS, simplified coping style questionnaire SCSQ, social support rating scale SSRS) in 126 TPL women hospitalized in three tertiary hospitals and 104 spouses in Southwest China.Results: Low resilient women had significantly more complicated placenta praevia, longer pediatric observation, more pressure than high resilient women. They also had significantly less active coping and positive affect, more negative affect and depression compared to high resilient women and their spouses. Although the socio-demographic characteristics of both TPL women and spouses and psychometric parameters of spouses had no significant differences, the prevalence rates of depression in spouses were notable. Compared with spouses, TPL women had a more complex interaction among these psychometric factors, with women's resilience negatively associated with their partners' negative affect, and their pressure positively correlated with pressure and negative affect of spouses.Conclusions: Pregnancy complicated with placenta praevia and pediatric observation may be risk factors for resilience of women with TPL. Maternal resilience has an important impact on the psychological outcomes in TPL women. A screening for resilience, depression and other psychological outcomes in couples with TPL and early psychological intervention of low resilient couples may be appropriate to promote resilience and well-being of these families. [ABSTRACT FROM AUTHOR]

Importance: With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment., Objective: To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir., Design, Setting, and Participants: This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir., Interventions: Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60., Main Outcomes and Measures: The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set., Results: The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P = .70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P = .82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case., Conclusions and Relevance: In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound., Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200066811.

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs., (© 2023. Higher Education Press.)

Background: Robotic surgery for rectal cancer is gaining popularity, but evidence on long-term oncological outcomes is scarce. We aimed to compare surgical quality and long-term oncological outcomes of robotic and conventional laparoscopic surgery in patients with middle and low rectal cancer. Here we report the short-term outcomes of this trial., Methods: This multicentre, randomised, controlled, superiority trial was done at 11 hospitals in eight provinces of China. Eligible patients were aged 18-80 years with middle (>5 to 10 cm from the anal verge) or low (≤5 cm from the anal verge) rectal adenocarcinoma, cT1-T3 N0-N1 or ycT1-T3 Nx, and no evidence of distant metastasis. Central randomisation was done by use of an online system and was stratified according to participating centre, sex, BMI, tumour location, and preoperative chemoradiotherapy. Patients were randomly assigned at a 1:1 ratio to receive robotic or conventional laparoscopic surgery. All surgical procedures complied with the principles of total mesorectal excision or partial mesorectal excision (for tumours located higher in the rectum). Lymph nodes at the origin of the inferior mesenteric artery were dissected. In the robotic group, the excision procedures and dissection of lymph nodes were done by use of robotic techniques. Neither investigators nor patients were masked to the treatment allocation but the assessment of pathological outcomes was masked to the treatment allocation. The primary endpoint was 3-year locoregional recurrence rate, but the data for this endpoint are not yet mature. Secondary short-term endpoints are reported in this article, including two key secondary endpoints: circumferential resection margin positivity and 30-day postoperative complications (Clavien-Dindo classification grade II or higher). The outcomes were analysed according in a modified intention-to-treat population (according to the original assigned groups and excluding patients who did not undergo surgery or no longer met inclusion criteria after randomisation). This trial was registered with ClinicalTrials.gov, number NCT02817126. Study recruitment has completed, and the follow-up is ongoing., Findings: Between July 17, 2016, and Dec 21, 2020, 1742 patients were assessed for eligibility. 502 patients were excluded, and 1240 patients were enrolled and randomly assigned to receive either robotic surgery (620 patients) or laparoscopic surgery (620 patients). 69 patients were excluded (34 in the robotic surgery group and 35 in the laparoscopic surgery group). 1171 patients were included in the modified intention-to-treat analysis (586 in the robotic group and 585 in the laparoscopic group). Six patients in the robotic surgery group received laparoscopic surgery and seven patients in the laparoscopic surgery group received robotic surgery. 22 (4·0%) of 547 patients in the robotic group had a positive circumferential resection margin as did 39 (7·2%) of 543 patients in the laparoscopic group (difference -3·2 percentage points [95% CI -6·0 to -0·4]; p=0·023). 95 (16·2%) of patients in the robotic group had at least one postoperative complication (Clavien-Dindo grade II or higher) within 30 days after surgery, as did 135 (23·1%) of 585 patients in the laparoscopic group (difference -6·9 percentage points [-11·4 to -2·3]; p=0·003). More patients in the robotic group had a macroscopic complete resection than in the laparoscopic group (559 [95·4%] of 586 patients vs 537 [91·8%] of 585 patients, difference 3·6 percentage points [0·8 to 6·5]). Patients in the robotic group had better postoperative gastrointestinal recovery, shorter postoperative hospital stay (median 7·0 days [IQR 7·0 to 11·0] vs 8·0 days [7·0 to 12·0], difference -1·0 [95% CI -1·0 to 0·0]; p=0·0001), fewer abdominoperineal resections (99 [16·9%] of 586 patients vs 133 [22·7%] of 585 patients, difference -5·8 percentage points [-10·4 to -1·3]), fewer conversions to open surgery (10 [1·7%] of 586 patients vs 23 [3·9%] of 585 patients, difference -2·2 percentage points [-4·3 to -0·4]; p=0·021), less estimated blood loss (median 40·0 mL [IQR 30·0 to 100·0] vs 50·0 mL [40·0 to 100·0], difference -10·0 [-20·0 to -10·0]; p<0·0001), and fewer intraoperative complications (32 [5·5%] of 586 patients vs 51 [8·7%] of 585 patients; difference -3·3 percentage points [-6·3 to -0·3]; p=0·030) than patients in the laparoscopic group., Interpretation: Secondary short-term outcomes suggest that for middle and low rectal cancer, robotic surgery resulted in better oncological quality of resection than conventional laparoscopic surgery, with less surgical trauma, and better postoperative recovery., Funding: Shenkang Hospital Development Center, Shanghai Municipal Health Commission (Shanghai, China), and Zhongshan Hospital Fudan University (Shanghai, China)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Erlotinib combined with whole-brain radiotherapy (WBRT) demonstrated a favorable objective response rate in a phase II single-arm trial of non-small cell lung cancer (NSCLC) patients with brain metastases. We assessed whether concurrent erlotinib with WBRT is safe and benefits patients in a phase III, randomized trial., Methods: NSCLC patients with two or more brain metastases were enrolled and randomly assigned (1:1) to WBRT (n = 115) or WBRT combined with erlotinib arms (n = 109). The primary endpoint was intracranial progression-free survival (iPFS) and cognitive function (CF) was assessed by the Mini-Mental State Examination (MMSE)., Results: A total of 224 patients from 10 centers across China were randomized to treatments. Median follow-up was 11.2 months. Median iPFS for WBRT concurrent erlotinib was 11.2 months vs 9.2 months for WBRT-alone (P = .601). Median PFS and overall survival (OS) of combination group were 5.3 vs 4.0 months (P = .825) and 12.9 vs 10.0 months (P = .545), respectively, compared with WBRT-alone. In EGFR-mutant patients, iPFS (14.6 vs 12.8 months; P = .164), PFS (8.8 vs 6.4 months; P = .702), and OS (17.5 vs 16.9 months; P = .221) were not significantly improved in combination group over WBRT-alone. Moreover, there were no significant differences in patients experiencing MMSE score change between the treatments., Conclusion: Concurrent erlotinib with WBRT didn't improve iPFS and excessive CF detriment either in the intent-to-treat (ITT) population or in EGFR-mutant patients compared with WBRT-alone, suggesting that while safe for patients already taking the drug, there is no justification for adding concurrent EGFR-TKI with WBRT for the treatment of brain metastases. Trial registration: Clinical trials.gov identifier: NCT01887795., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background It is unknown if there are cardiac abnormalities in persons who have recovered from coronavirus disease 2019 (COVID-19) without cardiac symptoms or in those who have normal biomarkers and normal electrocardiograms. Purpose To evaluate cardiac involvement in participants who had recovered from COVID-19 without clinical evidence of cardiac involvement by using cardiac MRI. Materials and Methods This prospective observational cohort study included 40 participants who had recovered from COVID-19 with moderate ( n = 24) or severe ( n = 16) pneumonia and who had no cardiovascular medical history, were without cardiac symptoms, had normal electrocardiograms, had normal serologic cardiac enzyme levels, and had been discharged for more than 90 days between May and September 2020. Demographic characteristics were recorded, serum cardiac enzyme levels were measured, and cardiac MRI was performed. Cardiac function, native T1, extracellular volume fraction (ECV), and two-dimensional (2D) strain were quantitatively evaluated and compared with values in control subjects ( n = 25). Comparisons among the three groups were performed by using one-way analysis of variance with Bonferroni-corrected post hoc comparisons (for normal distribution) or Kruskal-Wallis tests with post hoc pairwise comparisons (for nonnormal distribution). Results Forty participants (mean age, 54 years ± 12 [standard deviation]; 24 men) were enrolled; participants had a mean time between admission and cardiac MRI of 158 days ± 18 and between discharge and cardiac MRI examination of 124 days ± 17. There were no left or right ventricular size or functional differences between participants who had recovered from COVID-19 and healthy control subjects. Only one (3%) participant had positive late gadolinium enhancement located at the mid inferior wall. Global ECV values were elevated in participants who had recovered from COVID-19 with moderate or severe pneumonia compared with those in healthy control subjects (median ECV, 29.7% vs 31.4% vs 25.0%, respectively; interquartile range, 28.0%-32.9% vs 29.3%-34.0% vs 23.7%-26.0%, respectively; P < .001 for both). The 2D global left ventricular longitudinal strain was reduced in both groups of participants (moderate COVID-19 group, -12.5% [interquartile range, -15.5% to -10.7%]; severe COVID-19 group, -12.5% [interquartile range, -15.4% to -8.7%]) compared with the healthy control group (-15.4% [interquartile range, -17.6% to -14.6%]) ( P = .002 and P = .001, respectively). Conclusion Cardiac MRI myocardial tissue and strain imaging parameters suggest that a proportion of participants who had recovered from COVID-19 had subclinical myocardial abnormalities detectable months after recovery. © RSNA, 2021 Online supplemental material is available for this article.

Objective: To explore the clinical significance of thymidine synthase (TYMS) expression in circulating tumor cells (CTC)., Methods: Patients (n=43) were recruited upon reference to the Department of Surgery at a local hospital. Arterial-portal blood samples were harvested from all patients. Patient baseline information was collected when individuals were recruited into the study and include age, sex, and tumor stage. Complete response (CR) events and progressive disease (PD) events were recorded after follow-up. The CTC positive rate and the CTC number were assessed in blood samples. Epithelial-mesenchymal transition (EMT) subgroups and related TYMS expressions were examined for their correlation with colon cancer prognosis. The TYMS expression differed among various EMT subgroups., Results: In our study, the CTC number was not associated with the prognosis index of colon cancer patients. These non-associated indices also include TNM tumor stage, CEA factor, primary tumor position, pathological pattern, age, and sex. However, the total CTC positive rate was correlated with tumor stage. For patients with right colon cancer (10/35), mixed type EMT was in the majority, while epithelial type EMT was the main subgroup in patients with left colon cancer (25/35). The TYMS expression differed among various subgroups of EMT. Left colon cancer (25/35) had the negative expression level of TYMS (75%)., Conclusions: CTC positive rate is a promising index for the diagnosis of colon cancer. The lack of TYMS in CTC makes EMT cells prone to becoming epithelial-like cells, and TYMS silence in CTC indicates that the tumor is in the left colon., (© 2020 by the Association of Clinical Scientists, Inc.)

Human stress recovery response to landscapes is under discussion in Chinese settings. The present study aimed to clarify the stress recovery effects of campus street trees on graduate students in autumn. A total of 150 participants (23.75 ± 1.01 years old) completed the Trier Social Stress Test (TSST) and were then randomly assigned to view one of five virtual environments, including the street trees Sophora japonica , Ginkgo biloba , Platanus acerifolia , Koelreuteria paniculata , and the indoor environment (control). Physiological responses were measured by R-R interval and electroencephalography (EEG). Psychological responses were examined through the state version of the State-Trait Anxiety Inventory (STAI-S) and the Perceived Restorativeness Scale (PRS). Results showed that R-R intervals significantly increased while viewing all street trees. Both alpha and beta brainwave activities while viewing S. japonica and G. biloba were remarkably higher than those while viewing P. acerifolia and K. paniculata . The STAI-S scores significantly decreased, and the positive PRS scores were registered after viewing street trees. We concluded that a brief virtual visual experience of campus street trees in autumn has stress recovery effects on graduate students, and the different levels of stress recovery are associated with different types of street trees., Competing Interests: The authors declare no conflict of interest.

Purpose: In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results., Methods: Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m 2 , fluorouracil 400 mg/m 2 , and fluorouracil 2.4 g/m 2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m 2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS)., Results: In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% ( P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% ( P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% ( P = .971 by log-rank test), respectively., Conclusion: mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts' clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

Objectives: Interventional treatment of patients with acute coronary syndrome (ACS) is surging dramatically in China in recent years, whereas nationwide assessments of the quality of percutaneous coronary intervention (PCI) procedural performance and outcomes are scarce. We aimed to provide an updated and real-world overview of the performance of PCI in patients with ACS since 2011 in China after the China PEACE study from 2001 to 2011., Methods: In this cross-sectional study, data were extracted from the National Registry of Cardiovascular Intervention in Military Hospitals database to create a national sample of 144 659 patients with ACS undergoing PCI at 117 military hospitals in all regions of China from calendar years 2011-2014. Patient characteristics, procedural performance, PCI outcomes and adverse events and temporal changes were analysed., Results: During 2011-2014, patients with ACS undergoing PCI increased dramatically. Small numbers of high-volume hospitals performed the majority of PCI procedures. However, only half of these patients were adequately covered and proportions for the use of assisted devices and novel medications were relatively small. Radial artery access was still increasing with time. Primary PCIs were performed on 45.4% ST-segment elevation myocardial infarction patients with PCI procedures. 3.8% lesion vessels involve left main artery. Implanted stents, the overall complications and in-hospital mortality were decreasing remarkably., Conclusions: In Chinese military hospitals, interventional resources were limited with great regional disparities, there are still gaps to be filled to better serve patients with ACS. Our findings can serve as an indispensable supplement to a more comprehensive understanding of the practice of contemporary cardiac intervention in China., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To better define the effect of JAK2V617F mutant allele burden on clinical presentation of patients with essential thrombo cythamia (ET), especially thrombosis., Methods: Two ml of heparin anti-coagulated bone marrow was collected from 229 ET cases, who were diagnosed and treated in the First People's Hospital of Yunnan Province during 2013.10 to 2016.12. and then the mononuclear cells were separated by Red Blood Cell Lysis Buffer, genomic DNA was extracted from mononuclear cells by using a commercial DNA isolation kit and amplified by allele specific polymerase chain reaction (PCR). According to the size of molecular weight, the amplified products were separated by electrophoresis on a 2% agarose gel to screen the JAK2V617F mutation, then the JAK2V617F mutation burden was detected by real-time polymerase chain reaction (RT-PCR) in 120 patients with JAK2V617F mutation. Meanwhile, these samples were sequenced in order to verify the accuracy of the PCR screewing., Results: ET patients with thrombotic events had significantly higher JAK2V617F allele burden than those without thrombosis (23.2% vs 14.2%) ( P<0.05). Meanwhile, ET patients showed increased JAK2V617F allele burden in the group with higher leukocytosis (WBC > 10×10 9 /L) (P<0.001) and hemoglobin (> 150 g/L) (P<0.05). JAK2V617F mutation burden in 17 patients with splenomegaly was higher than that in 45 patients without splenomegaly (28.1% vs 11.8%) (P<0.05). but the JAK2V617F mutation burden was regatively correlated with platelet count (P<0.05). On the other hand, no correlation was found between JAK2V617F mutation burden and sex (P > 0.05). Univariate analysis showed that the JAK2V617F allele burden did not affect survival. Multivariable analysis showed that prognostic variable including WBC counts, hemoglobin level, age, sex, and splenomegaly not affected survival, (P > 0.05)., Conclusion: The clinical presentations of ET patients, such as WBC counts, hemoglobin level and splenomegaly, are influenced by the JAK2V617F mutation burden. ET patients with thrombotic events has significantly higher JAK2V617F allele burden than those in ET palients without thrombosis.JAK2V617F mutation burden has no relations with sex and age..