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XiaoLan Li,1 Min Li,2 Juan Tian,1 Zi-Wei Shi,1 Ling-Zhi Wang,2 Kui Song1 1Department of Hematology, The First Affiliated Hospital of Jishou University, Jishou, Hunan, People’s Republic of China; 2Department of Pharmacy, The First Affiliated Hospital of Jishou University, Jishou, Hunan, People’s Republic of ChinaCorrespondence: Kui Song, Department of Hematology, The First Affiliated Hospital of Jishou University, 26 Century Avenue, Qianzhou, Jishou, Hunan, 416000, People’s Republic of China, Email js_hematology@163.comAbstract: Multiple myeloma (MM) is a malignancy of plasma cells that can cause anemia due to renal failure and bone marrow failure. Secondary polycythemia (SE) is a clinically rare disease that involves the overproduction of red blood cells. To our knowledge, the association of multiple myeloma and polycythemia has been reported, but the association of SE and multiple myeloma is rare and has been infrequently reported in literature. In contrast to anemia, the presence of polycythemia in multiple myeloma patients is a rare finding. A patient of IgA-λ multiple myeloma with secondary erythrocytosis recently admitted to our department is now reported as follows and relevant literature is reviewed to improve clinicians’ awareness of such rare comorbidities.Keywords: multiple myeloma, secondary erythrocytosis

Na Qu,1 Ke Song,2 Yating Ji,1 Mingxia Liu,1 Lijiang Chen,1 Robert J Lee,3,4 Lesheng Teng3,5 1School of Pharmacy, Liaoning University, Shenyang, 110036, People’s Republic of China; 2MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6229 ER, the Netherlands; 3School of Life Sciences, Jilin University, Changchun, 130023, People’s Republic of China; 4College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA; 5State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Yantai, 264000, People’s Republic of ChinaCorrespondence: Lesheng Teng, Email tenglesheng@jlu.edu.cnAbstract: Nanoparticle-based systems are extensively investigated for drug delivery. Among others, with superior biocompatibility and enhanced targeting capacity, albumin appears to be a promising carrier for drug delivery. Albumin nanoparticles are highly favored in many disease therapies, as they have the proper chemical groups for modification, cell-binding sites for cell adhesion, and affinity to protein drugs for nanocomplex generation. Herein, this review summarizes the recent fabrication techniques, modification strategies, and application of albumin nanoparticles. We first discuss various albumin nanoparticle fabrication methods, from both pros and cons. Then, we provide a comprehensive introduction to the modification section, including organic albumin nanoparticles, metal albumin nanoparticles, inorganic albumin nanoparticles, and albumin nanoparticle-based hybrids. We finally bring further perspectives on albumin nanoparticles used for various critical diseases.Plain Language Summary: Albumin appears to be a promising carrier for drug delivery with superior biocompatibility and enhanced targeting capacity. This review focuses on the importance of albumin nanoparticles in drug delivery and concludes the recent fabrication techniques to prepare albumin nanoparticles, the modification strategies to require functional albumin nanoparticles, and critical applications of albumin nanoparticles in various diseases. The aim of this review is to help readers understand the significant potential of albumin nanoparticles in drug delivery. Keywords: albumin nanoparticle, drug delivery, fabrication, modification, application

Feng Qiao,1,2 Hong Guo,1,2 Jing Zhang,1,2 Qing Zhang,3 Li Liu,3 Ge Meng,2 Hongmei Wu,2 Yeqing Gu,2 Kun Song,3 Changyi Li,1 Kaijun Niu2,3 1School of Dentistry, Stomatological Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 2Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 3Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Kaijun Niu, Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, People’s Republic of China, Email nkj0809@gmail.com; niukaijun@tmu.edu.cn Changyi Li, School of Dentistry, Stomatological Hospital, Tianjin Medical University, No. 12, Qixiangtai Road, Heping District, Tianjin, 300070, People’s Republic of China, Email lichangyi@tmu.edu.cnBackground: To explore the association between the number of missing teeth and the prevalence of hyperlipidemia in a Chinese adult population.Methods: 13,932 adults were investigated in the TCLSIH cohort study. The number of missing teeth was determined at baseline through a self-reported questionnaire, and then classified into three categories: 0, 1– 2, and ≥ 3. We defined hyperlipidemia as total cholesterol (TC) ≥ 5.17 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L or low-density lipoprotein (LDL) cholesterol ≥ 3.37 mmol/L or a self-report of physician-diagnosed hyperlipidemia during follow-up visits. Cox proportional-hazards regression models were employed to assess the relationship between the number of missing teeth and incident hyperlipidemia.Results: A total of 6756 first-incident cases of hyperlipidemia occurred during 42,048 person-years of follow-up (median follow-up, 4.2 years). After adjusted confounders, multivariable HRs and 95% CI for incident of hyperlipidemia across the categories of missing teeth were as follows: in male participants, 1.00 (reference), 1.10 (0.98, 1.22), and 1.03 (0.91, 1.16) (P for trend = 0.30); in female participants, 1.00 (reference), 1.09 (0.99, 1.19), and 1.18 (1.04, 1.33) (P for trend < 0.01).Conclusion: The number of missing teeth is associated with an increased risk of hyperlipidemia in female participants but not in male participants. Systemic chronic inflammation may potentially mediate this association.Keywords: tooth loss, dyslipidemia, epidemiological studies, population health, inflammation

Yiwen Zhang,1 Wei Wang,2,&ast; Lili Xu,1 Zhexun Lian,3 Jiale Huang,4 Yaowei Chang,5 Junjie Guo,3 Yangang Wang,1,&ast; Kexiu Song,6 Hongwei Ji7,8,&ast; 1Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Hematology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 3Department of Cardiology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Department of Cardiology, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 6Department of International Medicine, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 7Tsinghua Medicine, Tsinghua University, Beijing, People’s Republic of China; 8Department of Internal Medicine, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangang Wang, Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email wangyg@qdu.edu.cn Hongwei Ji, Tsinghua Medicine, Tsinghua University, Beijing, People’s Republic of China, Email hongweijicn@gmail.com

A relational database has been developed based on the original (n,n′γ) work carried out by A. M. Demidov et al., at the Nuclear Research Institute in Baghdad, Iraq (Demidov et al., 1978) for 105 independent measurements comprising 76 elemental samples of natural composition and 29 isotopically-enriched samples. The information from this Atlas includes: γ-ray energies and relative intensities; nuclide and level data corresponding to the residual nucleus and meta data associated with the target sample that allows for the extraction of the flux-weighted (n,n′γ) cross sections for a given transition relative to a defined value. The optimized angular-distribution-corrected fast-neutron flux-weighted partial γ-ray cross section for the production of the 846.8-keV 21+→0gs+γ-ray transition in 56Fe, determined to be 〈σγ〉=143(29) mb, is used for this purpose. However, different values for the adopted cross section can be readily implemented to accommodate user preference based on revised determinations of this quantity. The Atlas (n,n′γ) data has been compiled into a series of CSV-style ASCII data sets and a suite of Python scripts have been developed to build and install the database locally. The database can then be accessed directly through the SQLite engine, or using alternative methods such as the Jupyter Notebook Python-browser interface. Several examples exploiting different interaction methodologies are distributed with the complete software package.

A relational database has been developed based on the original (n,n′γ) work carried out by A. M. Demidov et al., at the Nuclear Research Institute in Baghdad, Iraq (Demidov et al., 1978) for 105 independent measurements comprising 76 elemental samples of natural composition and 29 isotopically-enriched samples. The information from this Atlas includes: γ-ray energies and relative intensities; nuclide and level data corresponding to the residual nucleus and meta data associated with the target sample that allows for the extraction of the flux-weighted (n,n′γ) cross sections for a given transition relative to a defined value. The optimized angular-distribution-corrected fast-neutron flux-weighted partial γ-ray cross section for the production of the 846.8-keV 21+→0gs+γ-ray transition in 56Fe, determined to be 〈σγ〉=143(29) mb, is used for this purpose. However, different values for the adopted cross section can be readily implemented to accommodate user preference based on revised determinations of this quantity. The Atlas (n,n′γ) data has been compiled into a series of CSV-style ASCII data sets and a suite of Python scripts have been developed to build and install the database locally. The database can then be accessed directly through the SQLite engine, or using alternative methods such as the Jupyter Notebook Python-browser interface. Several examples exploiting different interaction methodologies are distributed with the complete software package.

The interconversion of charge and spin currents via spin-Hall effect is essential for spintronics. Energy-efficient and deterministic switching of magnetization can be achieved when spin polarizations of these spin currents are collinear with the magnetization. However, symmetry conditions generally restrict spin polarizations to be orthogonal to both the charge and spin flows. Spin polarizations can deviate from such direction in nonmagnetic materials only when the crystalline symmetry is reduced. Here, we show control of the spin polarization direction by using a non-collinear antiferromagnet Mn3GaN, in which the triangular spin structure creates a low magnetic symmetry while maintaining a high crystalline symmetry. We demonstrate that epitaxial Mn3GaN/permalloy heterostructures can generate unconventional spin-orbit torques at room temperature corresponding to out-of-plane and Dresselhaus-like spin polarizations which are forbidden in any sample with two-fold rotational symmetry. Our results demonstrate an approach based on spin-structure design for controlling spin-orbit torque, enabling high-efficient antiferromagnetic spintronics.

The Cl35(n,p) and Cl35(n,α) cross sections at incident neutron energies between 2.42 and 2.74 MeV were measured using the Berkeley High Flux Neutron Generator. The cross sections for Cl35(n,p) were more than a factor of 3 to 5 less than all of the values in the neutron absorption data libraries, while the Cl35(n,α) cross sections are in reasonable agreement with the data libraries. The measured energy-differential cross section is consistent with a single resonance with a width of 293(46) keV. This result suggests that, despite the high incident neutron energy, any attempt to model (n,x) cross sections in the vicinity of the N=Z=20 shell gap requires a resolved resonance approach rather than a Hauser-Feshbach approach.

The Cl35(n,p) and Cl35(n,α) cross sections at incident neutron energies between 2.42 and 2.74 MeV were measured using the Berkeley High Flux Neutron Generator. The cross sections for Cl35(n,p) were more than a factor of 3 to 5 less than all of the values in the neutron absorption data libraries, while the Cl35(n,α) cross sections are in reasonable agreement with the data libraries. The measured energy-differential cross section is consistent with a single resonance with a width of 293(46) keV. This result suggests that, despite the high incident neutron energy, any attempt to model (n,x) cross sections in the vicinity of the N=Z=20 shell gap requires a resolved resonance approach rather than a Hauser-Feshbach approach.

Yuyu Lv,1,2 Ru Ren,1– 3 Chengxiang Tang,4 Kuimeng Song,5 Shunping Li,1– 3 Haipeng Wang1,2 1Center for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2NHC Key Laboratory of Health Economics and Policy Research (Shandong University), Jinan, People’s Republic of China; 3Center for Health Preference Research, Shandong University, Jinan, People’s Republic of China; 4Macquarie University Centre for the Health Economy, Macquarie University Business School & Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia; 5School of Health Care Security, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaCorrespondence: Shunping Li; Haipeng Wang, Centre for Health Management and Policy Research, Wenhua Xi Road 44, Jinan, Shandong Province, 250012, People’s Republic of China, Tel +86-131-8893-4998, +86-186-6899-6362, Email lishunping@sdu.edu.cn; wanghaipeng@sdu.edu.cnPurpose: To evaluate preferences for medications among patients with type 2 diabetes mellitus (T2DM) from urban community health stations or rural village clinics in Shandong province, China.Methods: We use a discrete choice experiment (DCE) to measure the medication preferences. Each patient completed six DCE choice sets. The attributes for the DCE questionnaire include mode of administration, out-of-pocket medication cost per month, fasting blood glucose control effect and frequency of hypoglycemia events. The conditional logit model (Clogit) and mixed logit model (MXL) were used to evaluate choice data.Results: A total of 887 patients with T2DM completed the survey. The mean age of participants was 64 years, 36.42% experienced complications, and the mean duration of diabetes was about 8 years. Overall, patients’ ideal medication would not have hypoglycemia events, provide normal fasting glucose levels, have oral medication three times a day and lower monthly medication cost. Patients prioritized the frequency of hypoglycemia events (β=15.055, P < 0.01) and were willing to spend CNY 393.10 per month to avoid hypoglycemia events. For patients with higher educational levels and with longer diagnosis time, the effect of fasting blood glucose was more relevant than all other outcomes.Conclusion: This study provides information on T2DM patients’ preference for medications. Our results suggest that clinical doctors should present patients with a variety of pharmaceutical characteristics and include their preference into medication decision, which will improve patient adherence and health outcomes.Keywords: type 2 diabetes mellitus, patients’ preference, medication, discrete choice experiment

Ke Song,1 Yiran Hu,1,2 Wei Chen,1 Wei Hua,2 Zening Jin1 1Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Zening Jin, Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Beijing, 100070, People’s Republic of China, Email zening_jin@126.com Wei Hua, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, North Lishi Road No.167, Beijing, 100073, People’s Republic of China, Tel +86 010-59975832, Email drhuaweifw@sina.comBackground: Not all patients with heart failure derive consistent benefit from prophylactic implantable cardioverter-defibrillator (ICD). We aimed to evaluate the role of MADIT-ICD benefit score in risk-stratifying in Asian patients with left ventricular ejection fraction (LVEF) ≤ 35%.Methods: In this two-center, retrospective study, a total of 136 patients with LVEF ≤ 35% who received an ICD for primary prevention were enrolled. The endpoints were defined as the ventricular tachycardia ≥ 200bpm (VT) or ventricular fibrillation (VF) and non-arrhythmic death. Based on the MADIT-ICD benefit score system, all patients were categorized into three groups: highest benefit group (n = 41), intermediate benefit group (n = 80), and lowest benefit group (n = 15).Results: Forty patients experienced VT/VF and seven died of non-arrhythmic causes during a median follow-up of 44.8 ± 28.9 months. Kaplan–Meier curves showed that patients in highest benefit group had a worse VT/VF occurrence compared to those in other groups. In the highest benefit group, the predicted risk of VT/VF was 17-fold higher than the risk of non-arrhythmic mortality (41.5% vs 2.4%, P < 0.001). In the intermediate benefit group, the predicted risk of VT/VF was 4.2-fold higher than the risk of non-arrhythmic mortality (26.3% vs 6.3%, P = 0.001). In the lowest benefit group, however, the difference in the corresponding predicted risks was attenuated without statistically significant (13.3% vs 5.1%, P = 0.56).Conclusion: We demonstrate that MADIT-ICD benefit score can be used for the assessment of ICD primary prevention benefits in Asian patients with LVEF ≤ 35%.Keywords: implantable cardioverter-defibrillator, primary prevention, risk score, risk stratification, heart failure with reduced ejection fraction

Atmospheric pressure nonequilibrium plasma holds significant potential in biomedical applications due to its ability to generate reactive species at low temperatures. However, accurately quantifying and controlling plasma dosage remains challenging. Although equivalent total oxidation potential (ETOP) has been proposed for defining dosage, previous methods required measurement of various reactive oxygen and nitrogen species (RONS) densities, which are impractical in diverse plasma settings. Efficient ETOP prediction across variable conditions is thus essential. To address this, we propose a machine learning-based ETOP modeling method. This study collected RONS density data under various conditions using laser-induced fluorescence and trained an artificial neural network to predict ETOP values based on input parameters like voltage, gas flow rate, oxygen concentration, and humidity. This approach enables efficient ETOP prediction across variable conditions, supporting the standardization and clinical application of plasma medicine. [ABSTRACT FROM AUTHOR]

Fu He,1,2 Kangjian Song,1,2 Ge Guan,3 Junyu Huo,1,2 Yang Xin,1 Tianxiang Li,3 Chao Liu,1 Qingwei Zhu,1,2 Ning Fan,1 Yuan Guo,1 Liqun Wu1 1Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People’s Republic of China; 2Department of Clinical Medicine, Qingdao University, Qingdao, 266071, Shandong, People’s Republic of China; 3Organ Transplant Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People’s Republic of ChinaCorrespondence: Liqun WuLiver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, 266003, Shandong Province, People’s Republic of ChinaTel +86 18661809789Email wulq5810@126.comPurpose: Gene rearrangements (GRs) have been reported to be related to adverse prognosis in some tumours, but the relationship in hepatocellular carcinoma (HCC) remains less studied. The objective of our study was to explore the clinicopathological characteristics and prognosis of HCC patients (HCCs) with GRs (GR-HCCs).Patients and Methods: This retrospective study included 297 HCCs who underwent hepatectomy and had their tumours sequenced by next-generation sequencing. Categorical variables between groups were compared by the chi-square test. The impact of variables on disease-free survival (DFS) and survival after relapse (SAR) was analysed by the Kaplan–Meier method and Cox regression.Results: We observed four repetitive GR events in 297 HCCs: BRD9/TERT, ARID2/intergenic, CDKN2A/intergenic and OBSCN truncation. GR-HCCs frequently presented with low tumour differentiation, tumour necrosis, microvascular invasion, elevated AFP and gene mutations (TP53, NTRK3 and BRD9). The 1-, 2-, and 3-year cumulative DFS rates in GR-HCCs were 45.1%, 31.9%, 31.9%, respectively, which were significantly lower than those of GR-negative HCCs (NGR-HCCs) (72.5%, 57.9%, and 49.0%, respectively; P = 0.001). GR was identified as an independent risk factor for inferior DFS in HCCs (HR = 1.980, 95% CI = 1.246– 3.147; P = 0.004). However, there was no significant difference in SAR between GR-HCCs and NGR-HCCs receiving targeted therapy or immunotherapy.Conclusion: GR is frequently associated with TP53 mutations and significantly affects DFS following radical resection for HCC. We recommend that GR-HCCs should be closely followed up as a high-risk group for postoperative recurrence.Keywords: hepatocellular carcinoma, gene rearrangement, next-generation sequencing, prognosis, risk factors

Radiation detection can provide a reliable means of detecting radiological material. Such capabilities can help to prevent nuclear and/or radiological attacks, but reliable detection in uncontrolled surroundings requires algorithms that account for environmental background radiation. The Berkeley Data Cloud (BDC) facilitates the development of such methods by providing a framework to capture, store, analyze, and share data sets. In the era of big data, both the size and variety of data make it difficult to explore and find data sets of interest and manage the data. Thus, in the context of big data, visualization is critical for checking data consistency and validity, identifying gaps in data coverage, searching for data relevant to an analyst's use cases, and choosing input parameters for analysis. Downloading the data and exploring it on an analyst's desktop using traditional tools are no longer feasible due to the size of the data. This paper describes the design and implementation of a visualization system that addresses the problems associated with data exploration within the context of the BDC. The visualization system is based on a JavaScript front end communicating via REST with a back end web server.

The lifespan of the guide rail is a bottleneck restricting the operational life of electromagnetic railguns. A well‐designed arc extinguishing device can reduce the arcing erosion caused by residual currents within the guide rail. The CuW alloy is widely used in the high‐pressure arc extinction field due to its excellent electrical and thermal conductivity, high strength, and hardness. Based on the theory of equilibrium state arc plasma, a finite element model of the air arc‐CuW electrode coupling in the arc extinction device was established to study millisecond‐level arc initiation, evolution, extinguishing characteristics, and distribution patterns under extreme and harsh operational conditions with a current input of 110 kA. The highest temperature in the arc column region was found to exceed 50,000 K. The study elucidated the influence of arc extinction device parameters on arc evolution, breakdown time, and breakdown voltage. Consequently, it established that the R70 spherical electrode exhibits optimal arc extinguishing characteristics. The aim of this research is to provide theoretical support for optimizing the arc suppression device. Additionally, experiments on high‐speed and high‐current arc extinction device discharges were conducted to validate the finite element analysis results regarding arc diffusion patterns and electrode erosion. [ABSTRACT FROM AUTHOR]

We present a high image quality head up display (HUD) based on the local dimming liquid crystal display (LCD). The proposed HUD provides high white luminance to improve day-time visibility and low black luminance to cope with the postcard effect during the night by the local dimming technique. To reduce the computational complexity, the pixel-based boosting values for the pixel compensation are computed by simple bi-linear interpolation, complex power functions are implemented by look-up tables, some multiplications are replaced with the sums of shifted values, and the numbers of look-up tables and multipliers are reduced by sequential process. The simulation results of the proposed local dimming algorithm for 640×1280 LCD panel and 10×22 LED backlight ensure higher peak signal-to-noise ratio than 40 dB and larger power reduction performance than 73% over 7 HUD images. In addition, the postcard effect improvement is verified over images on LCD panel as well as windshield. Maximum luminance and contrast ratio on the windshield of the prototype HUD system are measured as 16,088 cd/m $ ^2 $ 2 and $ 342\times {10^6} $ 342 × 10 6 :1. [ABSTRACT FROM AUTHOR]

Kangjian Song, Fu He, Yang Xin, Ge Guan, Junyu Huo, Qingwei Zhu, Ning Fan, Yuan Guo, Yunjin Zang, Liqun Wu Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of ChinaCorrespondence: Liqun WuLiver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao, Shandong, 266003, People’s Republic of ChinaTel +86 15315328331Email wulq5810@126.comPurpose: To explore the value of Tuberous sclerosis complex 2 (TSC2) mutations in evaluating the early recurrence of hepatocellular carcinoma (HCC) patients underwent hepatectomy.Patients and Methods: A total of 183 HCC patients were enrolled. Next-generation sequencing was performed on tumor tissues to analyze genomic alterations, tumor mutational burden and variant allele fraction (VAF). The associations between TSC2 mutations and recurrence rate within 1 year, RFS and OS after hepatectomy were analyzed.Results: Our results showed that TSC2 mutation frequency in HCC was 12.6%. Compared to patients without TSC2 mutation, the proportion of microvascular invasion (MVI) and Edmondson grade III–IV was significantly higher in patients with a TSC2 mutation (p< 0.05). The VAF of mutated TSC2 was higher in patients with maximum diameter of tumor > 5cm or MVI than that of other patients (p< 0.05). The frequency of TP53 mutation was significantly higher in patients with a TSC2 mutation than those without TSC2 mutation (p=0.003). Follow-up analysis showed that patients with a TSC2 mutation had significantly higher recurrence rate within 1 year (p=0.015) and poorer median recurrence-free survival (RFS) (p=0.010) than patients without TSC2 mutation. TSC2 mutations did not significantly affect overall survival of patients (p=0.480). The multivariate analysis results showed that the Barcelona Clinic Liver Cancer (BCLC) B-C stage, TSC2 mutations and preoperative serum alpha-fetoprotein level ≥ 400μg/L were independently associated with recurrence within 1 year after hepatectomy (HR=8.628, 95% CI: 3.836– 19.405, p=0.000; HR=3.885, 95% CI: 1.295– 11.653, p=0.015; HR=2.327, 95% CI: 1.018– 5.323, p=0.045; respectively), and poorer RFS after hepatectomy (HR=3.070, 95% CI: 1.971– 4.783, p=0.000; HR=1.861, 95% CI: 1.061– 3.267, p=0.030; HR=1.715, 95% CI: 1.093– 2.693, p=0.019; respectively).Conclusion: TSC2 mutations were significantly associated with MVI in liver para-carcinoma tissue and Edmondson grade III–IV in patients with HCC and were independently associated with recurrence within 1 year and poorer RFS after hepatectomy. The TSC2 mutation may be a potential predictor for early recurrence in HCC patients underwent hepatectomy.Keywords: hepatocellular carcinoma, tuberous sclerosis complex 2, next-generation sequencing, gene mutation, early recurrence

Xuan Qiu, Manjiang Li, Liqun Wu, Yang Xin, Siyu Mu, Tianxiang Li, Kangjian Song Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of ChinaCorrespondence: Liqun WuLiver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao, Shandong 266003, People’s Republic of ChinaTel +86 15315328331Email wulq5810@126.comObjective: To investigate the effects of fatigue on the survival of patients with advanced hepatocellular carcinoma treated with sorafenib.Patients and Methods: A retrospective analysis of 182 cases of patients with advanced hepatocellular carcinoma treated with sorafenib in our hospital from October 1, 2008, to October 31, 2017, showed clinical and pathological data and follow-up results. The clinical and pathological data as well as follow-up results of 182 patients with advanced hepatocellular carcinoma treated with sorafenib in our hospital from October 1, 2008, to October 31, 2018, were retrospectively analyzed. All patients were treated for at least 3 months. Patients were divided into three groups: fatigue grade I (n=74), fatigue grade II (n=62), and fatigue grade III (n=46), according to National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 5.0. Survival analysis between groups was performed by the Kaplan–Meier method (Log rank test), continuous variables were analyzed by t-test, and categorical variables were analyzed by chi-square test.Results: The overall survival (OS) of patients who were relieved of fatigue was 33.0± 9.3 months, whereas the OS of patients who were not relieved of fatigue was 15.0± 1.8 months (P< 0.000). Furthermore, the time to progress (TTP) of patients who were relieved of fatigue by resting was 20.3 ± 10.9 months compared to a TTP of 7.7 ± 1.0 months in patients who were not relieved of fatigue (P< 0.000).Conclusion: Patients, especially the elderly and infirm, were more susceptible to toxicity.Keywords: hepatocellular carcinoma, sorafenib, fatigue, survival