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Yitong Cai,1 Ming Liu,2 Weixiang Luo,3 Jingping Zhang,1 Chaoran Qu4 1Xiangya School of Nursing, Central South University, Changsha, Hunan, People’s Republic of China; 2Evidence-Based Medicine Center, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 3Department of Nursing, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 4Department of Operating Room, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Jingping Zhang, Xiangya School of Nursing, Central South University, No. 172, Tong-Zi-Po Road, Yue Lu District, Changsha, Hunan, People’s Republic of China, Email jpzhang1965@csu.edu.cn Chaoran Qu, Department of Operating Room, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China, Email qvchaoran@outlook.comBackground: Nurses frequently experience both direct and indirect trauma, leading to significant psychological challenges. While much research has focused on the negative impacts of such trauma, less attention has been given to vicarious post-traumatic growth (VPTG). Given the high levels of indirect trauma that nurses face, understanding VPTG is crucial for mitigating its adverse effects and enhancing mental health and work efficiency.Objective: To map and synthesize the literature on vicarious post-traumatic growth and identify key knowledge gaps in vicarious post-traumatic growth research.Methods: This scoping review follows the approach proposed by Arksey and O’Malley. We conducted this scoping review using the methodology recommended by the Joanna Briggs Institute, supported by the PAGER framework. We searched 7 databases and gray literature on May 19, 2023 to obtain relevant research.Results: Finally, we included 29 studies from 9 countries. There are currently no reliable data on the incidence of vicarious post-traumatic growth among nurses worldwide. There are multiple instruments available to investigate vicarious post-traumatic growth in nurses, and the vicarious post-traumatic growth inventory is more recommended. Factors affecting nurses’ vicarious post-traumatic growth include coping styles, psychological factors, and social support. Indirect trauma exposure and vicarious post-traumatic growth coexist. There are currently three intervention strategies for vicarious post-traumatic growth, but none have been proven in clinical trials.Conclusion: This is the first scoping review on vicarious post-traumatic growth, there are a lot of research deficiencies and gaps in current research on vicarious post-traumatic growth for nurses. In view of the impact of secondary traumatic events on nurses, future research should pay more attention to nurses’ vicarious post-traumatic growth and promote the development of vicarious post-traumatic growth.Plain Language Summary: What is already known about the topic?Nurses are exposed to secondary traumatic events as part of their every-day work.Nurses experiencing these different secondary trauma exposures experience both positive and negative outcomes, but there has been less research on vicarious post-traumatic growth.The influencing factors of nurses’ vicarious post-traumatic growth and its related survey tools are not clear yet.What this paper addsGender, trauma type, and nurses’ core beliefs, self-efficacy, coping styles, and social support are influencing factors of vicarious post-traumatic growth.Currently, vicarious post-traumatic growth -related survey tools are roughly divided into three types, among which secondary posttraumatic growth inventory and vicarious post-traumatic growth inventory tools are specific survey tools.There are various relationships between indirect exposure to trauma and vicarious post-traumatic growth, and there are differences between different types of indirect trauma exposure. However, there is basically a consensus that indirect exposure to trauma and vicarious post-traumatic growth coexist. There are currently no targeted, scalable, and repeatable interventions for vicarious post-traumatic growth.Keywords: nurse, vicarious post-traumatic growth, secondary traumatic, scoping review

Shuai Guo,1,* Zhaoting Gong,1,* Xiaona Sun,2 Fei Gao,1 Xiang Li,1 Xiaolin Zu,1 Chao Qu,1 Hongliang Zhang,3 Hai Gao1 1Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Laizhou City People’s Hospital, Laizhou, People’s Republic of China; 3Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hai Gao, Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China, Email gaohai1221@mail.ccmu.edu.cn Hongliang Zhang, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, People’s Republic of China, Email 13810694497@163.comBackground: Ischemic cardiomyopathy (ICM) significantly contributes to global disease burden, while the role of ferroptosis in ICM remains underexplored.Methods: We identified differentially expressed ferroptosis-related genes (DEFRGs) by analyzing the GSE57338 dataset and cross-referencing with FerrDb. Consensus clustering was then used to identify ferroptosis-associated clusters within the ICM samples. A ferroptosis-specific predictive signature was developed using the least absolute shrinkage and selection operator (LASSO) method and validated with the GSE5406 dataset. Additionally, quantitative real-time PCR (qRT-PCR) experiments were performed to validate the 11 feature genes in a rat ICM model.Results: We identified 15 DEFRGs in GSE57338, which distinguished two patient clusters with distinct ferroptosis gene expression, pathway enrichment profiles, and metabolic characteristics. All DEFRGs were upregulated in cluster 2. Potential therapeutic targets were also identified for different ICM patient clusters. The 11-gene predictive signature (TXNRD1, STEAP3, STAT3, SCL2A1, PLIN2, NQO1, NNMT, IL33, ENPP2, ARRDC3, ALOX5) showed robust predictive power in both training and validation sets. High-risk patients exhibited increased infiltration of CD8+ T cells, CD4+ naïve T cells, M0/M1 macrophages, and resting mast cells, along with significant enrichment in epithelial mesenchymal transition and interferon responses. Low-risk patients had higher infiltration of regulatory T cells and monocytes. Results of qPCR analysis confirmed the bioinformatic analysis, validating the expression of the 11 feature genes in the rat ICM model.Conclusion: We identified two ferroptosis-related clusters in ICM patients and developed a predictive signature based on ferroptosis-related genes. Our findings highlight the importance of ferroptosis in ICM and offer new insights for its diagnosis and treatment.Keywords: ischemic cardiomyopathy, ferroptosis, bioinformatics analysis, predictive signature

Chen Qu,1,&ast; Fei Xia,2,&ast; Ling Chen,1 Hong-Jian Li,2 Wei-Min Li1 1Department of Ultrasonography, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 2Department of Ultrasonography, Huai’an Cancer Hospital, Huai’an, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-Jian Li, Department of Ultrasonography, Huai’an Cancer Hospital, Huai’an, Jiangsu, 223232, People’s Republic of China, Tel +8613511507565, Email 492938595@qq.com Wei-Min Li, Department of Ultrasonography, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, People’s Republic of China, Tel +8613912362309, Email 1005342597@qq.comPurpose: : To explore the diagnostic value of artificial intelligence (AI)-based on real-time dynamic ultrasound imaging system for minimal breast lesions.Patients and Methods: Minimal breast lesions with a maximum diameter of ≤ 10mm were selected in this prospective study. The ultrasound equipment and AI system were activated Simultaneously. The ultrasound imaging video is connected to the server of AI system to achieve simultaneous output of AI and ultrasound scanning. Dynamic observation of breast lesions was conducted via ultrasound. And these lesions were evaluated and graded according to the Breast Imaging Reporting and Data System (BI-RADS) classification system through deep learning (DL) algorithms in AI. Surgical pathology was taken as the gold standard, and ROC curves were drawn to determine the area under the curve (AUC) and the optimal threshold values of BI-RADS. The diagnostic efficacy was compared with the use of a BI-RADS category > 3 as the threshold for clinically intervening in diagnosing minimal breast cancers.Results: 291 minimal breast lesions were enrolled in the study, of which 228 were benign (78.35%) and 63 were malignant (21.65%). The AUC of the ROC curve was 0.833, with the best threshold value > 4A. When using >BI-RADS 3 and >BI-RADS 4A as threshold values, the sensitivity and negative predictive value for minimal breast cancers were higher for >BI-RADS 3 than >BI-RADS 4A (100% vs 65.08%, 100% vs 89.91%, P values < 0.001). However, the corresponding specificity, positive predictive value, and accuracy were lower than those for >BI-RADS 4A (42.11% vs 85.96%, 32.31% vs 56.16%, and 54.64% vs 81.44%, P values < 0.001).Conclusion: The AI-based real-time dynamic ultrasound imaging system shows good capacity in diagnosing minimal breast lesions, which is helpful for early diagnosis and treatment of breast cancer, and improves the prognosis of patients. However, it still results in some missed diagnoses and misdiagnoses of minimal breast cancers.Keywords: Breast cancer, ultrasound, artificial intelligence, diagnostic

Xiangdong Gongye,1,2,&ast; Peng Xia,1,2,&ast; Tianyin Ma,1,2,&ast; Yibo Chai,1,2 Zhang Chen,1,2 Yimin Zhu,1,2 Chengming Qu,1,2 Jie Liu,1,2 Wing Wa Guo,1,2 Minghe Zhang,1,2 Yingyi Liu,1,2 Ming Tian,1,2 Yufeng Yuan1– 3 1Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, People’s Republic of China; 3Taikang Center for Life and Medical Sciences of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Tian; Yufeng Yuan, Email dr.med.mingtian@whu.edu.cn; yuanyf1971@whu.edu.cnBackground: The liver’s regenerative capacity allows it to repair itself after injury. Extracellular vesicles and particles (EVPs) in the liver’s interstitial space are crucial for signal transduction, metabolism, and immune regulation. Understanding the role and mechanism of liver-derived EVPs in regeneration is significant, particularly after partial hepatectomy, where the mechanisms remain unclear.Methods: A 70% hepatectomy model was established in mice, and EVPs were isolated and characterized using electron microscopy, nanocharacterization, and Western blot analysis. Combined metabolomic and transcriptomic analyses revealed β-sitosterol enrichment in EVPs and activation of the Hedgehog signaling pathway during regeneration. The role of β-sitosterol in EVPs on the Hedgehog pathway and its targets were identified using qRT-PCR, Western blot analysis. The regulation of carnitine synthesis by this pathway was determined using a dual luciferase assay. The effect of a β-sitosterol diet on liver regeneration was verified in mice.Results: After 70% hepatectomy, the liver successfully regenerated without liver failure or death. At 24 hours post-surgery, tissue staining showed transient regeneration-associated steatosis (TRAS), with increased Ki67 positivity at 48 hours. EVPs displayed a spherical lipid bilayer structure with particle sizes of 70– 130 nm. CD9, CD63, and CD81 in liver-derived EVPs were confirmed. Transcriptomic and metabolomic analyses showed EVPs supplementation significantly promoted carnitine synthesis and fatty acid oxidation. Tissue staining confirmed accelerated TRAS resolution and enhanced liver regeneration with EVP supplementation. Mass spectrometry identified β-sitosterol in EVPs, which binds to Smo protein, activating the Hedgehog pathway. This led to the nuclear transport of Gli3, stimulating Setd5 transcription and inducing carnitine synthesis, thereby accelerating fatty acid oxidation. Mice with increased β-sitosterol intake showed faster TRAS resolution and liver regeneration compared to controls.Conclusion: Liver-derived EVPs promote regeneration after partial hepatectomy. β-sitosterol from EVPs accelerates fatty acid oxidation and promotes liver regeneration by activating Hedgehog signaling pathway. Keywords: liver regeneration, extracellular vesicles and particles, β-sitosterol, carnitine synthesis, hedgehog signaling pathway

Chen Qu,1,&ast; Hong-jian Li,2,&ast; Qi Gao,3 Jun-chao Zhang,1 Wei-min Li1 1Department of Ultrasonography, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 2Department of Ultrasonography, Huai’an Cancer Hospital, Huai’an, Jiangsu, People’s Republic of China; 3Department of Ultrasonography, Zhongda Hospital Southeast University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-min Li, Department of Ultrasonography, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, People’s Republic of China, Tel +8613912362309, Email 1005342597@qq.comPurpose: This study aimed to investigate the alteration trends and overlaps of positive features in benign and malignant thyroid nodules of different sizes based on the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS).Patients and Methods: 1337 patients with 1558 thyroid nodules were retrospectively recruited from November 2021 to December 2023. These nodules were divided into three groups according to maximum diameter: A (≤ 10 mm), B (10– 20 mm), and C (≥ 20 mm). C-TIRADS positive features were compared between benign and malignant thyroid nodules of different sizes. In addition, the trends of positive features with changes in nodule size among malignant thyroid nodules were analyzed.Results: The incidence of positive features in malignant thyroid nodules was higher than that in benign. As benign nodules grow, the incidence of all positive features showed a linear decreasing trend (Z values were 72.103, 101.081, 17.344, 33.909, and 129.304, P values < 0.001). With the size of malignant thyroid nodules increased, vertical orientation, solid, marked hypoechogenicity, and ill-defined/irregular margins/extrathyroidal extension showed a linear decreasing trend (Z = 148.854, 135.378, 8.590, and 69.239, respectively; P values < 0.05), while suspicious microcalcifications showed a linear increasing trend (Z = 34.699, P< 0.001). In terms of overlapping characteristics, group A had a significantly higher overlapping rate than the other two groups, and the overlapping rate of solid indicators remained the highest among all three groups (P < 0.05).Conclusion: Differences in positive features were observed between thyroid nodules of different sizes. Except for suspicious microcalcifications, the incidence of other four positive features decreased with increasing nodule size. In addition, a negative correlation was observed between the overlap rate and nodule size. These results may provide a basis for sonographers to upgrade or downgrade thyroid nodules based on their own experience.Keywords: size, thyroid, C-TIRADS, ultrasound

Guanming Shao,&ast; Yonghui Ma,&ast; Chao Qu, Ruiqian Gao, Chengzhan Zhu, Linlin Qu, Kui Liu, Na Li, Peng Sun, Jingyu Cao Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Sun; Jingyu Cao, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China, Email psun1@qdu.edu.cn; cjy7027@163.comBackground: Circulating eosinophils are associated with tumor development. An eosinophil-related index, the neutrophil to eosinophil ratio (NER), can be used to predict the prognosis of patients with tumors. However, there is still a lack of efficient prognostic biomarkers for HCC. In this study, we aimed to investigate the predictive value of the NER and develop an optimal machine learning model for the recurrence of HCC patients. Patients and methods: A retrospective collection of 562 patients who underwent hepatectomy with a pathologic diagnosis of HCC was performed. The relationship between NER and progression-free survival (PFS) was investigated. We developed a new machine learning framework with 10 machine learning algorithms and their 101 combinations to select the best model for predicting recurrence after hepatectomy. The performance of the model was assessed by the area under the curve (AUC) of characteristics and calibration curves, and clinical utility was evaluated by decision curve analysis (DCA).Results: Kaplan‒Meier curves showed that the PFS in the low NER group was significantly better than that in the high NER group. Multivariate Cox regression analysis showed that NER was an independent risk factor for recurrence after surgery. The random survival forests (RSF) model was selected as the best model that had good predictive efficacy and outperformed the TNM, BCLC, and CNLC staging systems.Conclusion: The NER has good predictive value for postoperative recurrence in patients with hepatocellular carcinoma. Machine learning model based on NER can be used for accurate predictions.Keywords: hepatocellular carcinoma, liver resection, recurrence, machine learning, neutrophil-to-eosinophil ratio

Zehui Qin,1 Minhua Li,1,2 Juanjuan Cheng,1,2 Ziwei Huang,1,2 Gaoxiang Ai,1,2 Chang Qu,3 Youliang Xie,1 Yucui Li,1 Huijun Liao,4 Jianhui Xie,5– 7 Ziren Su1,2 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, People’s Republic of China; 3College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou, 510006, People’s Republic of China; 4Department of Clinical Pharmacy and Pharmaceutical Services, Huazhong University of Science and Technology Union Shenzhen Hospital (the 6th affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, People’s Republic of ChinaCorrespondence: Ziren Su, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China, Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, People’s Republic of China, Email suziren@gzucm.edu.cn Huijun Liao, Department of Clinical Pharmacy and Pharmaceutical Services, Huazhong University of Science and Technology Union Shenzhen Hospital (the 6th affiliated hospital of Shenzhen University), Shenzhen, People’s Republic of China, Email liaohuijun1016@163.comPropose: Berberine (BBR) is extensively studied as an outstanding anti-hyperuricemia drug. However, the clinical application of BBR was limited due to its poor absorption and low bioavailability. Therefore, there is an urgent necessity to find a novel drug formulation to address the issues of BBR in clinical application.Methods: Herein, we conducted the solubility, characterization experiments to verify whether BBR and sodium taurocholate (STC) self-assembled nanoparticles (STC@BBR-SANPs) could form. Furthermore, we proceeded the release experiment in vitro and in vivo to investigate the drug release effect. Finally, we explored the therapeutic effect of STC@BBR-SANPs on hyperuricemia (HUA) through morphological observation of organs and measurement of related indicators.Results: The solubility, particle size, scanning electron microscopy (SEM), and stability studies showed that the stable STC@BBR-SANPs could be formed in the BBR-STC system at ratio of 1:4. Meanwhile, the tissue distribution experiments revealed that the STC@BBR-SANPs could accelerate the absorption and distribution of BBR. In addition, the pharmacology study demonstrated that both BBR and STC@BBR-SANPs exhibited favorable anti-HUA effects and nephroprotective effects, while STC@BBR-SANPs showed better therapeutic action than that of BBR.Conclusion: This work indicated that STC@BBR-SANPs can be self-assembly formed, and exerts excellent uric acid-lowering effect. STC@BBR-SANPs can help to solve the problems of poor solubility and low absorption rate of BBR in clinical use, and provide a new perspective for the future development of BBR.Graphical Abstract: Keywords: berberine, sodium taurocholate, intermolecular interactions, self-assembled, nanoparticles, hyperuricemia

Jiongdi Lu,1,2,&ast; Zhi Zheng,3,&ast; Yixuan Ding,1,2 Yuanxu Qu,1,2 Wentong Mei,1,2 Zhen Fang,1,2 Chang Qu,1,2,&ast; Yulu Feng,4 Yulin Guo,1,2 Chongchong Gao,1,2 Feng Cao,1,2 Fei Li1,2 1Clinical Center of Acute Pancreatitis, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Chui Yang Liu Hospital Affiliated Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Clinical Center of Acute Pancreatitis, Department of General Surgery, Department of Surgery, Xuanwu Hospital of Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-10-83198731, Fax +86-10-83198868, Email feili36@ccmu.edu.cn Feng Cao, Clinical Center of Acute Pancreatitis, Department of General Surgery, Xuanwu Hospital of Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Email f.cao@xwhosp.orgObjective: To clarify the incidence of colonic complications in patients with NP and their impact on prognosis.Methods: The clinical data of NP patients admitted to the Department of General Surgery of Xuanwu Hospital, Capital Medical University from January 2014 to December 2020 were retrospectively analyzed. Patients were grouped according to the presence or absence of colonic complications, and the clinical prognosis of the two groups was analyzed after matching using a 1:1 propensity score, The primary study endpoint was patient mortality during hospitalization. Data are reported as median (range) or percentage of patients (%).Results: A total of 306 patients with NP were included in this study, and the incidence of colonic complications was 12.4%, including 15 cases of colonic obstruction, 17 cases of colonic fistula, and 9 cases of colonic hemorrhage. Before matching, patients in the colonic group had severe admissions and poor clinical outcomes (P< 0.05). After matching, the baseline data and clinical characteristics at admission were comparable between the two groups of patients. In terms of clinical outcomes, although the mortality was similar in the two groups (P> 0.05), but patients in the colonic group were more likely to have multiorgan failure, length of nutrition support, number of minimally invasive interventions, number of extra-pancreatic infections, length of ICU stay and total length of stay were significantly higher than those of patients in the group without colonic complications (P< 0.05). During long-term follow-up, patients in the colonic group were more likely to develop recurrent pancreatitis.Conclusion: About 12.4% of NP patients developed colonic complications, and after PSM it was found that colonic complications only led to a longer hospital stay and an increased number of clinical interventions in NP patients and did not increase the mortality.Keywords: necrotizing pancreatitis, colon involvement, propensity score match

Jiongdi Lu,1,2 Yixuan Ding,1,2 Yuanxu Qu,1,2 Wentong Mei,1,2 Yulin Guo,1,2 Zhen Fang,1,2 Chang Qu,1,2 Chongchong Gao,1,2 Feng Cao,1,2,&ast; Fei Li,1,2,&ast; Yulu Feng3 1Clinical Center of Acute Pancreatitis, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pediatric, Chui Yang Liu Hospital Affiliated Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li; Feng Cao, Clinical Center of Acute Pancreatitis, Capital Medical University, Department of General Surgery, Department of Surgery, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-10-83198731, Fax +86-10-83198868, Email feili36@ccmu.edu.cn; f.cao@xwhosp.orgObjective: The incidence of acute pancreatitis (AP) is increasing. Twenty percent of AP patients with developing necrotizing pancreatitis (NP), while ~40– 70% of NP patients develop potentially fatal infectious complications. When patients are suspected or confirmed infected pancreatic necrosis (IPN), antibiotics should be administered timeously to control the infection, but long-term use of antibiotics can lead to multidrug-resistant bacteria (MDRB) infection and eventually to increased mortality. Our study aimed to determine the incidence of MDRB infection and evaluate the risk factors for MDRB infection in IPN patients.Methods: Clinical data of IPN patients admitted to the general surgery department of Xuanwu Hospital of Capital Medical University between January 1, 2014, and December 31, 2021, were retrospectively analyzed.Results: IPN patients (n = 267) were assigned to MDRB infection (n = 124) and non-MDRB infection (n = 143) groups. On admission, patients in the MDRB group had a higher modified computer tomography severity index (CTSI) score (P < 0.05), pancreatic necrosis degree, and PCT level (P < 0.05) than those in the non-MDRB group, and the prognosis of patients in MDRB group was poor. The most common gram-negative bacteria were Acinetobacter baumannii (n = 117), the most common gram-positive bacteria were Enterococcus faecium (n = 98), and the most common fungal infection was Candida albicans (n = 47). Multivariable analysis showed that complications of EPI (OR: 4.116, 95% CI: 1.381– 12.271, P = 0.011), procalcitonin (PCT) level at admission (OR: 2.728, 95% CI: 1.502– 4.954, P = 0.001), and degree of pancreatic necrosis (OR: 2.741, 95% CI: 1.109– 6.775, P = 0.029) were independent risk factors for MDRB infection in IPN patients.Conclusion: We identified common infectious strains and risk factors for MDRB infection in IPN patients.Keywords: infected pancreatic necrosis, extra-pancreatic infection, multidrug-resistant bacteria, risk factor analysis

Jian Yang,&ast; Bin Zhang,&ast; Chengliang Qu,&ast; Li Liu,&ast; Yanyan Song Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanyan Song, Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004, People’s Republic of China, Tel +86 951-6743014, Fax +86 951-6744302, Email songyanyanyys60@126.comObjective: To investigate the risk factors of deep sternal wound infection (DSWI) after off-pump coronary artery bypass grafting and its prevention and treatment strategy.Methods: The clinical data of 465 patients who underwent OPCABG with a median chest incision were retrospectively analyzed. The patients were divided into the observation group (with DSWI, 32 cases) and the control group (without DSWI, 433 cases) according to the occurrence of DSWI. The preoperative, intraoperative, and postoperative clinical data relevant to DSWI were collected in both groups. The univariate and multivariate logistic regression analyses were adopted to analyze the risk factors for DSWI after OPCABG and investigateand its prevention and treatment strategy.Results: DSWI occurred in 32 cases with an incidence of infection of 6.89%. There were 5 cases died in the observation group (with DSWI), the overall mortality rate was 1.07% and the intra-group mortality rate was 15.6%. There were 16 cases died in the control group (without DSWI) because of low cardiac output syndrome and multiple organ failure, the overall and intra-group mortality rates were 3.44% and 3.69% respectively. By analyzing the risk factors of DSWI between the two groups, the differences in age, body mass index (BMI), history of diabetes mellitus (DM), operation time, tracheal intubation time, time of stay in thecardiac care unit, blood transfusion (blood plasma)> 800mL, blood transfusion (erythrocyte suspension)> 6um, secondary thoracotomy were statistically significant between the observation and control groups (P < 0.05 in all).Conclusion: Obesity, history of DM, prolonged operation time and tracheal intubation time, time of stay in CCU, utilization of blood product and secondary thoracotomy were DSWI independent risk factors after OPCABG.Some preventive measure should been implemented to reduce the incidence of DSWI, such as shorter operation time and tracheal intubation time, reducing the utilization of blood product.Keywords: off-pump coronary artery bypass grafting, sternal wound infection, risk factor

Xianqiang Yu,1,&ast; Cheng Qu,2,&ast; Lu Ke,2 Zhihui Tong,2 Weiqin Li1,2 1Medical School, Southeast University, Nanjing, People’s Republic of China; 2Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiqin Li Email liweiqindr@nju.edu.cnBackground: Sepsis is the leading cause of death in critically ill patients. Although it is well known that the immune system plays a key role in sepsis, exactly how it works remains unknown.Methods: In our study, we used weighted gene co-expression network analysis (WGCNA) to screen out the immune-related genes that may play a critical role in the process of sepsis.Results: A total of three sepsis-related hub genes were screened for further verification. Subsequent analysis of immune subtypes suggested their potential predictive effect in the clinic.Conclusion: Our study shows that three immune-related genes CHMP1A, MED15 and MGAT1 are important biomarkers of sepsis. The screened genes may help to distinguish normal individuals from patients with different degrees of sepsis.Keywords: sepsis, gene co-expression network, biomarker, immune cell

Baorui Ma,* Linnuo Pang,* Pingqing Huang, Jie Bai, Zhiqin Zhang, Huimin Wu, Mengru Cai, Jin Yang, Yuchen Xu, Xingbin Yin, Changhai Qu, Jian Ni School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changhai Qu; Jian NiSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Higher Education Zone, Fangshan District, Beijing, 102488, People’s Republic of ChinaEmail quchanghai@bucm.edu.cn; njtcm@263.netPurpose: To prepare the levocarnitine thermosensitive in situ gel (LCTG) and evaluate its effect on dry eye disease (DED).Methods: Draize eye irritation test and other examinations were used to evaluate the eye irritation after multiple administration of LCTG. The Schirmer test, fluorescein sodium staining, HE staining and TUNEL staining were used to detect the tear secretion, corneal injury, histopathological changes of the cornea and lacrimal gland, and the apoptosis rate of cornea epithelial cells after 3 days of the administration. The conjunctival goblet cell density was detected by PAS staining, and the expression levels of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) of corneal epithelial cells were detected by immunofluorescence staining after 7 days of the administration.Results: LCTG is non-irritating to rabbit eyes and has good biocompatibility. LCTG administration for 3 days can significantly increase the amount of tear secretion in mice with DED, promote corneal epithelial integrity and central corneal epithelium thickness recovery, and improve the pathological morphology and structure of corneal and lacrimal gland tissues, and reduce the apoptosis rate of the corneal epithelial cells. After 7 days of the administration, the preparation can promote the proliferation of conjunctival goblet cells and down-regulate the cornea expression levels of MMP-3 and MMP-9 in epithelial cells.Conclusion: The LCTG has a good curative effect on mice with DED, and the overall curative effect is better than that of levocarnitine solution.Keywords: levocarnitine, cornea, in situ gel, delivery, dry eye disease

Cheng-hao Qu,1,2 Tong Li,1,2 Zhan-peng Tang,1,2 Xi-Rui Zhu,1,2 Jing-yi Han,1,2 Hui Tian2 1Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of ChinaCorrespondence: Hui TianDepartment of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of ChinaTel +86 18560080016Email tianhuiql@126.comPurpose: Emerging studies have revealed that platelets are involved in tumor metastasis in lung adenocarcinoma (ADC). The solid pathological subtype of lung ADC is associated with metastasis, recurrence, and poor prognosis. However, there is no study exploring the relationship between platelets and different lung pathological subtypes.Patients and Methods: The association between platelet counts and lymph node metastasis was analyzed in 852 patients with lung ADC who underwent surgery and lymph node dissection. Multivariate logistic analysis was conducted to identify the risk factors of lymph node metastasis. Then, lymph node metastasis and other factors were analyzed to determine their correlation with platelet count and histological subtype.Results: We found that the platelet count was associated with lymph node metastasis (P = 0.01) in multivariable analysis, independent of tumor size, predominant subtype, visceral pleural invasion, and microvessel invasion. In patients with a platelet count ≥ 300 × 109/L, the rate of lymph node metastasis was 38.5%, almost twice as high as that in patients with a platelet count < 300 × 109/L (23.2%). Additionally, elevated platelet counts, even those within the normal range, were significantly associated with a higher rate of lymph node metastasis. The mean platelet count in patients with solid-predominant histology (269.70 ± 69.38 × 109/L) was significantly higher than that in patients with other histologies (P < 0.001).Conclusion: Elevated platelet counts are significantly associated with a higher rate of lymph node metastasis, even if the platelet counts are within the reference range. Platelet counts were significantly higher in patients with solid-predominant histology than in patients with other histologies. In addition, VEGF-C may play an important role in lymphatic metastasis in patients with lung ADC. We hypothesize that antiplatelet therapy may reduce lymph node metastasis in lung ADC patients.Keywords: lung adenocarcinoma, platelets, lymph node, solid-predominant, pathological subtype

Yanhong Liu, Yuanyuan Jiang, Lidong Xu, Chongxing Qu, Lei Zhang, Xingguo Xiao, Wenxia Chen, Kunkun Li, Qianping Liang, Huili Wu Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, People’s Republic of ChinaCorrespondence: Huili WuDepartment of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, No. 124, Funiu Road, Zhongyuan District, Zhengzhou City, Henan Province 450007, People’s Republic of ChinaTel +86-0371-67690972Email wuhuili00965@163.comBackground: Gastric cancer (GC) is a severe threat to human life, with high incidence and mortality. Circular RNAs (circRNAs) play crucial roles in the progression of GC. This study attempted to investigate the potential role of circ-NRIP1 and associated action mechanisms in GC cells.Methods: The expression of circ-NRIP1 and miR-186-5p was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, apoptosis, and migration were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometry assay, and transwell assay, respectively. Cellular glycolysis, including cellular glucose uptake, lactate, and ATP/ADP ratios, was also detected by commercial assay kits. The protein levels of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) were quantified by Western blot. The relationship between miR-186-5p and circ-NRIP1 or myosin heavy chain 9 (MYH9) was predicted by the online bioinformatics tool, starBase, and verified by dual-luciferase reporter assay. Xenograft tumor model was used to evaluate biological function in vivo.Results: The expression of circ-NRIP1 was up-regulated in tissues of GC patients and cells, as well as negatively associated with that of miR-186-5p in tissues. circ-NRIP1 knockdown inhibited cell proliferation, migration, and glycolysis, but induced apoptosis in HGC-27 and AGS cells. circ-NRIP1 competitively targeted miR-186-5p, and MYH9 was a target of miR-186-5p. miR-186-5p knockdown inverted the bio-function effects and glycolytic activation from circ-NRIP1 silencing in HGC-27 and AGS cells. Meanwhile, MYH9 overexpression could rescue the effects of miR-186-5p. Besides, miR-186-5p knockdown inverted the expression pattern of si-circ-NRIP1 transfection in GC cells. Additionally, in vivo experiments confirmed that sh-circ-NRIP1 inhibited tumor growth.Conclusion: circ-NRIP1 accelerated the glycolysis and GC progression by modulating MYH9 via miR-186-5p, suggesting that circ-NRIP1 was a promising biomarker for the treatment of GC.Keywords: GC, circ-NRIP1, miR-186-5p, glycolysis, MYH9

Feng-Li Deng,1–4,* Jun-Xi Pan,2,3,5,* Peng Zheng,2,3,6 Jin-Jun Xia,2,3 Bang-Min Yin,1–3 Wei-Wei Liang,1–3 Yi-Fan Li,2,3,6 Jing Wu,2,3 Fan Xu,2,3 Qing-Yuan Wu,2,3,7 Chao-Hua Qu,2,3 Wei Li,2,3 Hai-Yang Wang,2,3 Peng Xie1–31Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, People’s Republic of China; 2Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China; 3Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 4School of Public Health and Management, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 5The First Affiliated Hospital of Kunming Medical University, Kunming 650032, People’s Republic of China; 6Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 7Department of Neurology, Three Gorges Central Hospital, Chongqing Medical University, Chongqing 400016, People’s Republic of China *These authors contributed equally to this work Purpose: Depression is a complex psychiatric disorder. Various depressive rodent models are usually constructed based on different pathogenesis hypotheses.Materials and methods: Herein, using our previously established naturally occurring depressive (NOD) model in a non-human primate (cynomolgus monkey, Macaca fascularis), we performed metabolomics analysis of cerebrospinal fluid (CSF) from NOD female macaques (N=10) and age- and gender-matched healthy controls (HCs) (N=12). Multivariate statistical analysis was used to identify the differentially expressed metabolites between the two groups. Ingenuity Pathways Analysis and MetaboAnalyst were applied for predicted pathways and biological functions analysis.Results: Totally, 37 metabolites responsible for discriminating the two groups were identified. The NOD macaques were mainly characterized by perturbations of fatty acid biosynthesis, ABC transport system, and amino acid metabolism (eg, aspartate, glycine, serine, and threonine metabolism). Interestingly, we found that eight altered CSF metabolites belonging to short-chain fatty acids and amino acids were also observed in the serum of NOD macaques (N=13 per group).Conclusion: Our findings suggest that peripheral and central short-chain fatty acids and amino acids are implicated in the onset of depression.Keywords: naturally occurring depressive, depression, non-human primate, metabonomics, cerebrospinal fluid, short-chain fatty acid

Dawei Wang,1,* Zhuoxin Cheng,2,3,* Ming Zhao,1,* Chengbin Jiao,2 Qinghui Meng,1 Huayang Pan,1 Yu Xie,1 Long Li,1 Yexing Zhu,1 Wei Wang,1 Chunlei Qu,1 Deshen Liang1 1Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People’s Republic of China; 2Department of General Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi 154002, People’s Republic of China; 3Heilongjiang Provincial Key Laboratory of Metabolic Disease, Jiamusi 154002, People’s Republic of China *These authors contributed equally to this work Background: Accumulating evidence has shown that protein tyrosine phosphatases (PTPs) are involved in regulating the transduction of many signaling pathways and play important roles in modulating the progression of some cancers, but the functions of PTPs in cancers have not been well elucidated until now. Here, we aimed to identify the roles of protein tyrosine phosphatase nonreceptor type 9 (PTPN9), a cytoplasmic PTP, in the development of colorectal cancer and elucidate the regulatory mechanism involved.Materials and methods: Cell viability assessment, colony formation assay, caspase-3 and caspase-9 activity assay, real-time PCR, and Western blot analysis were applied.Results: Our results showed that PTPN9 expression was frequently downregulated in colorectal cancer tissues compared with adjacent normal tissues. Overexpression of PTPN9 mitigated cell growth and colony formation and induced cell apoptosis in colorectal cancer. Conversely, PTPN9 knockdown promoted cell growth and survival. Moreover, PTPN9 negatively regulated the activation of Stat3 and depressed its nuclear translocation in colorectal cancer. The effects of PTPN9 knockdown on cell apoptosis were attenuated by inhibition of the Stat3 pathway.Conclusion: These results indicate that PTPN9 inhibits cell growth and survival by repressing the activation of Stat3 in colorectal cancer, which suggests an important underlying mechanism of regulating cell growth and provides a novel candidate therapeutic target for colorectal cancer. Keywords: PTPN9, apoptosis, colorectal cancer, Stat3, cell survival, PTPMeg2

Jinlong Wei,1 Lingbin Meng,2 Xue Hou,1 Chao Qu,1 Bin Wang,1 Ying Xin,3 Xin Jiang1 1Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; 2Department of Internal Medicine, Florida Hospital, Orlando, FL 32803, USA; 3Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China Abstract: Radiotherapy (RT) is a major treatment for malignant tumors. The latest data show that >70% of patients with malignant tumors need RT at different periods. Skin changes can be experienced by up to 95% of patients who underwent RT. Inflammation and oxidative stress (OS) have been shown to be generally associated with radiation-induced skin reactions (RISRs). Inflammatory response and OS interact and promote each other during RISRs. Severe skin reactions often have a great impact on the progress of RT. The treatment of RISRs is particularly critical because advanced RT technology can also lead to skin reactions. RISRs are classified into acute and chronic reactions. The treatment methods for acute RISRs include steroid treatment, creams, ointments, and hydrocolloid dressings, depending on the reaction grading. Chronic RISRs includes chronic ulcerations, telangiectasias, and fibrosis of the skin, and advanced ­treatments such as mesenchymal stem cells, hyperbaric oxygen therapy, superoxide dismutase, and low-intensity laser therapy can be considered. Here, we review and summarize the ­important mechanisms that cause RISRs as well as the standard and advanced treatments for RISRs. Keywords: radiation-induced skin reactions, inflammatory response, oxidative stress, treatment

Hongda Chen,1,* Yue Zhang,1,2,* Siwen Li,3,* Ni Li,1 Yuhan Chen,4 Bei Zhang,3 Chunfeng Qu,1 Huiguo Ding,4 Jian Huang,3,5 Min Dai1 1National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 2Office of Scientific Research, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China; 3Liver Research Center, Experimental Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing, China; 4Department of Gastrointestinal and Hepatology, Beijing You’ An Hospital Affiliated to Capital Medical University, Beijing, China; 5National Clinical Research Center of Digestive Diseases, Beijing, China *These authors contributed equally to this work Background: Although a number of serum biomarkers for detection of hepatocellular carcinoma (HCC) have been explored, their exact diagnostic value remains unclear. We aimed to conduct a direct comparison of five representative serum biomarkers for detecting HCC and to derive multi-marker prediction algorithms. Patients and methods: In total, 846 patients were recruited from three hospitals in China, including 202 HCC patients, 226 liver cirrhosis patients, 215 chronic hepatitis B virus-infected patients, and 203 healthy volunteers. Serum levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), des-gamma-carboxyprothrombin (DCP), squamous cell carcinoma antigen, and centromere protein F autoantibody were measured by ELISA. The diagnostic performances of individual biomarkers and multi-marker combinations were evaluated by receiver operating characteristics analysis. The bootstrapping method was adopted to adjust for potential overfitting of all diagnostic indicators. Results: DCP exhibited the best diagnostic performance, with areas under the curve (AUC) for detecting HCC of 0.82 (95% CI 0.64–0.80) and sensitivity of 65.2% (95% CI 63.3–82.1%) at 90% specificity. Of note, DCP showed similar diagnostic efficacy for detecting AFP-positive and AFP-negative HCC. After a comprehensive search for multi-marker combinations, a two-marker prediction algorithm including AFP and DCP was constructed and yielded an AUC of 0.87 (95% CI 0.68–0.84) for detecting HCC. In addition, the combination showed good ability in discriminating early-stage HCC and decompensated liver cirrhosis, with an AUC of 0.81 (95% CI 0.75–0.86). Conclusion: DCP could be a complementary biomarker in the early diagnosis of HCC. The constructed multi-marker prediction algorithms could contribute toward distinguishing HCC from non-malignant chronic liver diseases. Keywords: early detection, liver cirrhosis, prediction model

Dan Shi,1,* Yan Liu,1,* Ronggang Xi,1 Wei Zou,2 Lijun Wu,3 Zhiran Zhang,1 Zhongyang Liu,1 Chao Qu,1 Baoli Xu,1 Xiaobo Wang1 1Department of Pharmacy, The 210th Hospital of People’s Liberation Army, 2College of Life Science, Liaoning Normal University, Dalian, Liaoning, 3Department of Pharmaceutics, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Chronic myelogenous leukemia (CML) is characterized by the t(9;22) (q34;q11)-associated Bcr-Abl fusion gene, which is an essential element of clinical diagnosis. As a traditional Chinese medicine, realgar has been widely used for the treatment of various diseases for >1,500 years. Inspired by nano-drug, realgar nanoparticles (NPs) have been prepared with an average particle size of

Jinjun Liang,1,2 Xiaoran Yuan,1,2 Shaobo Shi,1,2 Fang Wang,1,2 Yingying Chen,1,2 Chuan Qu,1,2 Jingjing Chen,1,2 Dan Hu,1–3 Yang Bo1,2 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China; 3Masonic Medical Research Laboratory, Utica, NY, USA Background: Major depression is diagnosed in 18% of patients following myocardial infarction (MI), and the antidepressant fluoxetine is shown to effectively decrease depressive symptoms and improve coronary heart disease prognosis. We observed the effect of fluoxetine on cardiac electrophysiology in vivo in a rat model of post-MI depression and the potential mechanism. Methods and results: Eighty adult male Sprague Dawley rats (200–250 g) were randomly assigned to five groups: normal control (control group), MI (MI group), depression (depression group), post-MI depression (model group), and post-MI depression treated with intragastric administration of 10 mg/kg fluoxetine (fluoxetine group). MI was induced by left anterior descending coronary artery ligation. Depression was developed by 4-week chronic mild stress (CMS). Behavior measurement was done before and during the experiment. Electrophysiology study in vivo and Western blot analysis were carried on after 4 weeks of CMS. After 4 weeks of CMS, depression-like behaviors were observed in the MI, depression, and model groups, and chronic fluoxetine administration could significantly improve those behaviors (P

Building "happy schools" has been one of the key concerns by many countries in recent years with an aim to create a friendly, safe, and happy teaching and learning environment so that teachers and students can have more motivation in improving their teaching and learning achievements, thus bringing forth more happiness to the involved individuals and organizations. The article introduces the concept of a "happy school", outlined the perspectives on building happy schools by the world and Vietnamese political, cultural leaders, educational researchers as well as organizations so that they can be applied in the process of educational innovation. Thereby, the authors identify the key elements and criteria for such a "happy school" model, clarify the roles of the schools' headmasters as well as summarize a set of ten messages for a happy school to prepare under the current situation of school innovation.

Activating mutations, such as E76K and D61Y, in PTPN11 (SHP2), a protein tyrosine phosphatase implicated in multiple cell signaling processes, are associated with 35% of patients with juvenile myelomonocytic leukemia (JMML), an aggressive childhood myeloproliferative neoplasm (MPN). Here we show that the interaction between leukemia-associated mutant Shp2 and Gab2, a scaffolding protein important for cytokine-induced PI3K/Akt signaling, was enhanced, and that the mTOR pathway was elevated in Ptpn11E76K/+ leukemic cells. Importantly, MPN induced by the Ptpn11E76K/+ mutation was markedly attenuated in Ptpn11E76K/+/Gab2-/- double mutant mice-overproduction of myeloid cells was alleviated, splenomegaly was diminished and myeloid cell infiltration in nonhematopoietic organs was decreased in these double mutants. Excessive myeloid differentiation of stem cells was also normalized by depletion of Gab2. Acute leukemia progression of MPN was reduced in the double mutant mice and, as such, their survival was much prolonged. Furthermore, treatment of Ptpn11E76K/+ mice with Rapamycin, a specific and potent mTOR inhibitor, mitigated MPN phenotypes. Collectively, this study reveals an important role of the Gab2/PI3K/mTOR pathway in mediating the pathogenic signaling of the PTPN11 gain-of-function mutations and a therapeutic potential of Rapamycin for PTPN11 mutation-associated JMML.

We present in situ measurements of spectrally resolved X-ray scattering and X-ray diffraction from monocrystalline diamond samples heated with an intense pulse of heavy ions. In this way, we determine the samples' heating dynamics and their microscopic and macroscopic structural integrity over a timespan of several microseconds. Connecting the ratio of elastic to inelastic scattering with state-of-the-art density functional theory molecular dynamics simulations allows the inference of average temperatures around 1300 K, in agreement with predictions from stopping power calculations. The simultaneous diffraction measurements show no hints of any volumetric graphitization of the material, but do indicate the onset of fracture in the diamond sample. Our experiments pave the way for future studies at the Facility for Antiproton and Ion Research, where a substantially increased intensity of the heavy ion beam will be available. [ABSTRACT FROM AUTHOR]

Macrocystis sp. isolate 501 is a brown algae in the family Laminariaceae. Here, we sequenced, assembled, and annotated the complete chloroplast (cp) genome of Macrocystis sp. isolate 501. The cp genome of Macrocystis sp. isolate 501 is 130 103 bp in length with a GC content of 30.86%. The assembled genome has a typical cyclic structure, containing a large single-copy (LSC) region of 76 397 bp, a small single-copy (SSC) region of 42 856 bp, and a pairof inverted repeatregions(IRs) of 10 850 bp. The cp genome contains 140 unique genes, including 105 protein-codinggenes, six rRNA genes, and 29 tRNA genes. Phylogenetic analysis showed that Macrocystis sp. isolate 501 was closely related to Phaeophyceae. The chloroplast sequence of this species was aligned on NCBI, and the highest coverage was Macrocystis pyrifera (99.18%). Macrocystis pyrifera, also known as the giant brown algae, was first described by the French naturalist Nicolas Duclos in 1750. However, the first detailed description and name of the species was given by the French naturalist Adolphe-Francois Le Jolis in 1863, an article entitled "Étude des Algues littorales de la Manche." We named the algae we get "Macrocystis sp. isolate 501," which is the first time that this species has been mentioned. Herein we present the first report on Macrocystis sp. isolate 501 with published genomic information. [ABSTRACT FROM AUTHOR]