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Jingmei Huang,1,* Lianshan Guo,1,* Xiaoxiao Huang,1 Xiaoping Yu,2 Liqiao Lin,1 Xinlin Jiang,3 Zhihao Bai,4 Zhengzhao Li1 1Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China; 2Department of Radiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China; 3Department of General Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China; 4College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengzhao Li, Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China, Email lizhengzhao7680@163.com Zhihao Bai, College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, People’s Republic of China, Email zhihao_bai@163.comPurpose: The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6, co-loaded into carbonized Zn/Co bimetallic organic frameworks. The goal was to achieve controlled CTX release and synergistic photodynamic therapy, with a focus on evaluating anti-tumor activity against human liver cancer cell lines (Hep G2).Methods: Purified cobra cytotoxin (CTX) and photosensitizer Ce6 were co-loaded into carbonized Zn/Co bimetallic organic frameworks, resulting in RGD-PDA@C-ZIF@(CTX+Ce6). The formulation was designed with surface-functionalization using polydopamine and tumor-penetrating peptide RGD. This approach aimed to facilitate controlled CTX release and enhance the synergistic effect of photodynamic therapy. The accumulation of RGD-PDA@C-ZIF@(CTX+Ce6) at tumor sites was achieved through RGD’s active targeting and the enhanced permeability and retention (EPR) effect. In the acidic tumor microenvironment, the porous structure of the metal-organic framework disintegrated, releasing CTX and Ce6 into tumor cells.Results: Experiments demonstrated that RGD-PDA@C-ZIF@(CTX+Ce6) nanoparticles, combined with near-infrared laser irradiation, exhibited optimal anti-tumor effects against human liver cancer cells. The formulation showcased heightened anti-tumor activity without discernible systemic toxicity.Conclusion: The study underscores the potential of utilizing metal-organic frameworks as an efficient nanoplatform for co-loading cytotoxins and photodynamic therapy in liver cancer treatment. The developed formulation, RGD-PDA@C-ZIF@(CTX+Ce6), offers a promising avenue for advancing the clinical application of cytotoxins in oncology, providing a solid theoretical foundation for future research and development.Keywords: metal-organic frameworks, cytotoxins, photodynamic therapy, liver cancer

Qian Fan,1,&ast; Zhongmei Bai,2,&ast; Fabrice Yves Ndjana Lessomo,3,&ast; Bingqing Dong,1 Weiqin Zhong,1 Fenglin Jin,1 Zhiquan Wang3 1Department of Cardiology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province, People’s Republic of China; 2Department of Cardiology, The People’s Hospital of Huangmei, Huanggang, Hubei Province, People’s Republic of China; 3Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiquan Wang; Fenglin Jin, Email 2839515516@qq.com; cardio7788@163.comBackground: Low volume change and minimal trauma observed during angiography are the reason why physicians often overlook any changes affecting pre-operative electrolytes levels after coronary intervention. However, few studies have addressed the issue of electrolyte changes after the coronary intervention. Therefore, our study investigates coronary angiography’s effect on electrolytes and provides the quick identification of groups more prone to electrolyte changes.Methods: From the department of cardiology of the second affiliated hospital of Shandong’s first medical university, 374 patients undergoing coronary angiography were selected. Pre-intervention and post-intervention serums, sodium (Na+), potassium (K+), chloride (Cl−), magnesium (Mg2+) and renal function were analyzed. The correlation between influential factors was also assessed. The association of hypokalemia with short-major adverse cardiac events (MACE) and arrhythmia was evaluated.Results: Among the 374 subjects including 264 patients who had a simple angiography and 110 patients who received coronary artery interventional therapy. A decrease in potassium levels was found in 81.8% of the patients, and post-interventional hypokalemia was observed in 15.0%. After the intervention, the hypokalemia among males was 2.18 times than that of females, and the pre-operative serum potassium level was 3.5mmol/L≤K+< 4.0mmol/L and was 2.09 times than that of K+≥ 4.0 mmol/L, but was not associated with age and either simple coronary angiography or PCI (percutaneous coronary intervention). Hypernatremia was also prevalent in males under 60 years and with pre-operative hypernatremia. Significant variations were found between hypokalemia and influential factors like hypertension, diabetes, and gastrointestinal disease. We also found that there was no obvious correlation between hypokalemia and recurrent angina, heart failure and death, but significantly increased the risk of some arrhythmias.Conclusion: Male patients are more likely to suffer from electrolyte disturbance after coronary intervention. There is a need to emphasize monitoring and managing electrolyte changes to prevent severe complications in the peri-operative period.Keywords: coronary angiography, electrolytes, hypokalemia, hypernatremia, risk factors

Zhengzhao Li,1,&ast; Lianshan Guo,1,&ast; Liqiao Lin,1 Tongting Wang,1 Yanqiu Jiang,1 Jin Song,1 Jihua Feng,1 Jianfeng Huang,2 Haoyu Li,2 Zhihao Bai,3 Wenqi Liu,4 Jianfeng Zhang1 1Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China; 2Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China; 3College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, China; 4Department of Radiation Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China&ast;These authors contributed equally to this workCorrespondence: Zhihao Bai, College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, China, Tel/Fax +86 771-3237584, Email zhihao_bai@163.com Jianfeng Zhang, Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China, Tel +86 771- 3277068, Fax +86 771- 3277277, Email zhangjianfeng@gxmu.edu.cnPurpose: Although the combined photo-thermal (PTT) and photodynamic therapy (PDT) of tumors have demonstrated promise as effective cancer therapy, the hypoxic and insufficient H2O2 supply of tumors seriously limits the efficacy of PDT, and the acidic environment reduces the catalytic activity of nanomaterial in the tumor microenvironment. To develop a platform for efficiently addressing these challenges, we constructed a nanomaterial of Aptamer@dox/GOD-MnO2-SiO2@HGNs-Fc@Ce6 (AMS) for combination tumor therapy. The treatment effects of AMS were evaluated both in vitro and in vivo.Methods: In this work, Ce6 and hemin were loaded on graphene (GO) through π-π conjugation, and Fc was connected to GO via amide bond. The HGNs-Fc@Ce6 was loaded into SiO2, and coated with dopamine. Then, MnO2 was modified on the SiO2. Finally, AS1411-aptamer@dox and GOD were fixed to gain AMS. We characterized the morphology, size, and zeta potential of AMS. The oxygen and reactive oxygen species (ROS) production properties of AMS were analyzed. The cytotoxicity of AMS was detected by MTT and calcein-AM/PI assays. The apoptosis of AMS to a tumor cell was estimated with a JC-1 probe, and the ROS level was detected with a 2’,7’-Dichlorodihydrofluorescein diacetate (DCFH-DA) probe. The anticancer efficacy in vivo was analyzed by the changes in the tumor size in different treatment groups.Results: AMS was targeted to the tumor cell and released doxorubicin. It decomposed glucose to produce H2O2 in the GOD-mediated reaction. The generated sufficient H2O2 was catalyzed by MnO2 and HGNs-Fc@Ce6 to produce O2 and free radicals (•OH), respectively. The increased oxygen content improved the hypoxic environment of the tumor and effectively reduced the resistance to PDT. The generated •OH enhanced the ROS treatment. Moreover, AMS depicted a good photo-thermal effect.Conclusion: The results revealed that AMS had an excellent enhanced therapy effect by combining synergistic PTT and PDT.Keywords: nanomaterial, photo-thermal therapy, photodynamic therapy, hypoxia

Zixing Bai1 &ast;, Xuhan Cao1 &ast;, Yanjun Yang,1 Xudong Sun,1 Yongli Dong,2 Jianmin Wen,1 Weidong Sun1 1Second Department of Orthopedics, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Scientific Research Department, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Sun, Wangjing Hospital of China Academy of Chinese Medical Sciences, No. 6 Central South Road, Wangjing, Chaoyang District, Beijing, 100102, People’s Republic of China, Tel +86-84739140, Email sunweidong8239@aliyun.comObjective: To investigate the risk factors for hallux valgus complicated with pain under the second metatarsal and construct an effective model and method for predicting hallux valgus complicated with pain under the second metatarsal based on risk factors.Methods: A total of 545 patients with hallux valgus who were admitted to our hospital were divided randomly into a training set and a validation set. The demographic characteristics, imaging indices and gait test indices of the patients were collected. The risk factors were identified by univariate and multivariate logistic regression analyses. A risk prediction model for hallux valgus with pain under the second metatarsal was established, and the area under the curve (AUC) of the receiver operating characteristic and a decision curve analysis were used for verification and identification. The value of the model was tested in the verification group.Results: Second metatarsal length, second metatarsal peak pressure, hallux valgus angle (HVA), intermetatarsal angle 1– 2 (IMA1– 2) and weight were the risk factors for hallux valgus complicated with pain under the second metatarsal. Based on the weighting of these seven risk factors, a prediction model was established. The AUC of the prediction model was 0.84 (95% confidence interval [CI]: 0.802~0.898, P < 0.05), and the results of a Hosmer–Lemeshow test showed a good degree of calibration (χ2 = 10.62, P > 0.05). The internal validation of the AUC was 0.83 (95% CI: 0.737– 0.885, P < 0.05). The model had obvious net benefits when the threshold probability was 10%– 70%.Conclusion: Second metatarsal length, second metatarsal peak pressure, HVA, IMA1– 2 and weight were the risk factors for hallux valgus combined with second metatarsal pain. The risk prediction model for hallux valgus complicated with pain under the second metatarsal based on these seven variables was proven effective.Level of Evidence: Level III, retrospective comparative study.Keywords: hallux valgus, metatarsalgia, nomogram, predictive model, risk factors

Jing Li,1 Peng Li,2 Hong Su,1 Haonan Feng,3 Zhongyuan Bai,4 Yanfeng Xi1 1Department of Pathology, Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, Shanxi, 030013, People’s Republic of China; 2Department of Breast Surgery, Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, Shanxi, 030013, People’s Republic of China; 3Department of Pathology, Chengdu Second People’s Hospital, Chengdu, Sichuan, 610000, People’s Republic of China; 4Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of ChinaCorrespondence: Yanfeng Xi, Department of Pathology, Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, 3 Workers’ New Village Street, Xing Hua Ling, Taiyuan, Shanxi, 030013, People’s Republic of China, Email xiyanfeng1998@163.comObjective: To study the relationship between cyclin-dependent protein kinase 6 (CDK6) expression in diffuse large B-cell lymphoma (DLBCL) and the clinical biological behavior and prognosis.Methods: Data mining was performed using the Oncomine and The Cancer Genome Atlas (TCGA) databases to analyze the expression level of CDK6 in DLBCL. CDK6 alterations in DLBCL and related functional networks were analyzed with c-BioPortal and the Gene Set Enrichment Analysis was performed by using DAVID and FunRich software. In addition, screening for differential gene expression of CDK6 was done and enriched by using LinkedOmics. Finally, formalin-fixed and paraffin-embedded (FFPE) tissue samples from 102 patients with DLBCL were collected from the Department of Pathology, Shanxi Cancer Hospital (Taiyuan, Shanxi, China) from January 2015 through December 2020. All cases had complete clinical course records. Thirty cases of lymph node reactive hyperplasia tissues were used as controls. The expression of CDK6 in DLBCL tissues was detected by qRT‑PCR and immunohistochemistry.Results: Bioinformatics analysis: The data showed that mRNA expression level and DNA copy number variations (CNVs) of CDK6 were significantly higher in DLBCL as compared to normal tissue (P ˂ 0.05). Based on C-BioPortal analysis, we speculated that amplification was the most common copy of CDK6 CNV in DLBCL. Through Gene Ontology (GO) analysis of these genes, it was found that the proteins were mainly located in the nucleus and cytoplasm. The biological interaction network of CDK6 alterations were found to participate primarily in the G1-S phase of the process. Analysis of LinkedOmics mRNA sequencing data showed that three genes were positively correlated with CDK6 expression: PSMD1, C2orf29 and ASB1. Through experimental verification, we found that CDK6 was overexpressed in DLBCL, and the expression of CDK6 mRNA and protein in DLBCL were positively correlated with Ann Arbor staging and IPI score (P< 0.05), and negatively correlated with overall survival (P< 0.001).Conclusion: Data mining results and experiments revealed and confirmed multi-level evidence for the importance of CDK6 in DLBCL; hence, CDK6 may be a potential marker in DLBCL. Thus, our study will perhaps lay the foundation for further research on the role of CDK6 in the genesis and development of DLBCL.Keywords: cyclin-dependent protein kinase 6, diffuse large B-cell lymphoma, bioinformatics analysis, prognosis

Huiting Zhou,1,&ast; Xiaying Lu,2,3,&ast; Jie Huang,1,&ast; Patrick Jordan,2 Shurong Ma,1 Lingqi Xu,1 Fangjie Hu,1 Huan Gui,1 He Zhao,1 Zhenjiang Bai,1 H Paul Redmond,2 Jiang Huai Wang,2 Jian Wang1 1Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland; 3Department of Physiology, Gannan Medical University, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Wang, Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of China, Email wj196312@vip.163.com Jiang Huai Wang, Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland, Email jh.wang@ucc.ieBackground: Neonates are susceptible to a wide range of microbial infection and at a high risk to develop severe sepsis and septic shock. Emerged evidence has shown that induction of trained immunity triggers a much stronger inflammatory response in adult monocytes/macrophages, thereby conferring protection against microbial infection.Methods: This study was carried out to examine whether trained immunity is inducible and exerts its protection against microbial sepsis in neonates.Results: Induction of trained immunity by Bacillus Calmette-Guerin (BCG) plus bacterial lipoprotein (BLP) protected neonatal mice against cecal slurry peritonitis-induced polymicrobial sepsis, and this protection is associated with elevated circulating inflammatory cytokines, increased neutrophil recruitment, and accelerated bacterial clearance. In vitro stimulation of neonatal murine macrophages with BCG+BLP augmented both inflammatory response and antimicrobial activity. Notably, BCG+BLP stimulation resulted in epigenetic remodeling characterized by histone modifications with enhanced H3K4me3, H3K27Ac, and suppressed H3K9me3 at the promoters of the targeted inflammatory and antimicrobial genes. Critically, BCG+BLP stimulation led to a shift in cellular metabolism with increased glycolysis, which is the prerequisite for subsequent BCG+BLP-triggered epigenetic reprogramming and augmented inflammatory response and antimicrobial capacity.Conclusion: These results illustrate that BCG+BLP induces trained immunity in neonates, thereby protecting against microbial infection by boosting both inflammatory and antimicrobial responses.Keywords: trained immunity, inflammatory response, antimicrobial activity, epigenetic reprogramming, intracellular metabolic rewiring, neonatal sepsis

Rong Chen,1 Wenbin Yang,2 Jing Sun,3 Yuan Liu,4 Qing An,2 Feijuan Zhang,2 Zhuanli Bai,5 Qi Luan2 1College of Life Sciences, Northwest University, Xi’an, 710069, People’s Republic of China; 2Department of Dermatology, Xi’an No.3 Hospital, the Affiliated Hospital of Northwest University, Northwest University, Xi’an, 710069, People’s Republic of China; 3Department of Anesthesiology, Northwest Women’s and Children’s Hospital, Xi’an, 710061, People’s Republic of China; 4Center of Medical Genetics, Northwest Women’s and Children’s Hospital, Xi’an, 710061, People’s Republic of China; 5Department of Plastic and Aesthetic Maxillofacial Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Qi Luan, Department of Dermatology, Xi’an No.3 Hospital, the Affiliated Hospital of Northwest University, Northwest University, Xi’an, 710069, People’s Republic of China, Tel/Fax +86-29-61816090, Email luanq@sina.com Zhuanli Bai, Department of Plastic and Aesthetic Maxillofacial Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Email zhuanlibai@xjtu.ecu.cnBackground: Hyaluronic acid (HA)-based fillers are applied to treat facial wrinkles and volume loss. Many efforts have been made to improve properties of HA to prolong the duration in aesthetic indications. A new cross-linking technique called “Tri-Hyal”, could make HAs to achieve desired rheological characteristics. HAs synthesized by Tri-Hyal are triple cross-linked and sustained-release, which could increase duration of promoting skin rejuvenation after injection.Purpose: To evaluate the efficiency and persistence of HAs with Tri-Hyal on skin rejuvenation and further investigate underlying mechanisms, we compared the performances of cross-linked HA (AF) based on Tri-Hyal with another highly acceptable HA filler (Res) in vivo and in vitro.Methods: Male BALB/c mice were divided into three groups, treated with AF, Res and vehicle, respectively. Skin biopsies were taken on day 0, 30, 90 and 180 after injection and hematoxylin and eosin (H&E), Masson’s trichrome (MT), immunohistochemical (IHC) stainings for CD31, TGF-β and MMP9 were performed. EdU incorporation, cell counting kit-8 (CCK-8), SA-β-Gal staining and activity were measured by biochemical analysis. RFP-GFP-LC3 adeno virus was used for autophagic flux detection. Protein levels of CD44, P62 and LC3I/II were detected by Western blot. Reactive oxygen species (ROS) level was detected by flow cytometry with DCFH-DA probe.Results: The AF synthesized by Tri-Hyal showed persistent dermal structural correction without attenuation up to 6 months, which was illustrated by skin thickness, formation of elastic fibers and vascular density. Consistently, in fibroblasts the AF improved cell proliferation and slowed the senescent in vitro. Furthermore, it promoted cellular autophagy to reduce ROS level, which would account for its function in skin renewal.Conclusion: The HA with Tri-Hyal could stimulate the production of extracellular matrix components more persistently than traditional HA fillers. In terms of mechanisms, it delayed senescence in dermal fibroblasts through reducing oxidative stress mediated by induction of autophagy.Keywords: skin rejuvenation, fibroblasts, senescence, ROS, autophagy

Yu Shi,1 Hai Wang,2 Li Zhang,1 Ming Zhang,1 Xiaoyan Shi,1 Honghong Pei,1 Zhenghai Bai1 1Emergency Department & EICU, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaan Xi, 710004, Peoples’ Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an, Shaan Xi, 710061, Peoples’ Republic of ChinaCorrespondence: Honghong Pei; Zhenghai Bai, The Emergency Department &EICU, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi ‘an, Shaanxi, Peoples’ Republic of China, Email peihhjz@163.com; baizhenghaijz2021@163.comBackground: Intensive care unit (ICU) delirium is one of the most common clinical syndromes that results in many adverse events that affect patients, families, and hospitals. To date, there has been no tool for effectively predicting the occurrence of delirium in emergency intensive care unit (EICU) patients.Methods: We conducted a retrospective cohort study and constructed a prediction model for 319 patients in EICU, who met our inclusion criteria. We analyzed the relationship between patients’ clinical data within 24 hours of admission and delirium, applied univariate and multivariate logistic regression analyses to select the most relevant variables for construction of nomogram models, then applied bootstrapping for internal validation.Results: A total of five variables, namely stomach and urinary tubes, as well as sedative, mechanical ventilation and APACHE-II scores, were selected for model construction. We generated a total of five sets of models (three sets of construction models and two sets of internal verification models), with similar predictive value. The optimal model was selected, and together with the 5 variables used to construct a nomogram. The AUC of the MFP model in all patients was 0.76 (0.70, 0.82), whereas that in non-elderly patients (< 60 years old) for the full model was 0.83 (0.74, 0.91). In elderly patients (≥ 60 years old), the AUC of the MFP model was 0.82 (0.73, 0.91).Conclusion: Overall, the five-marker-based prognostic tool, established herein, can effectively predict the occurrence of delirium in EICU patients.Keywords: area under curve, delirium, emergency intensive care unit, model, prediction

Zhixun Bai,1– 4,&ast; Yi Ma,2,3,5,&ast; Zhiyun Shi,2,3,6,&ast; Ting Li,2,3,7 Shan Hu,2– 4,8 Bei Shi2– 4 1Department of Internal Medicine, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 2Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 3Affiliated Hospital of Zunyi Medical University Cross-Regional Specialized Alliance, Zunyi, Guizhou, People’s Republic of China; 4College of Medicine, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 5Department of Cardiology, Affiliated Yinjiang County People’s Hospital of Zunyi Medical University, Tongren, Guizhou, People’s Republic of China; 6Department of Cardiology, Affiliated Qianxi County People’s Hospital of Zunyi Medical University, Bijie, Guizhou, People’s Republic of China; 7Department of Cardiology, Affiliated Dafang County People’s Hospital of Zunyi Medical University, Bijie, Guizhou, People’s Republic of China; 8Department of Cardiology, Affiliated Tongzi County People’s Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bei ShiDepartment of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of ChinaEmail shibei2147@163.comPurpose: This study aimed to establish an accurate and easy predictive model for ST-segment elevation myocardial infarction (STEMI) patients with hyperuricemia, using readily available features to estimate intrahospital mortality risk.Patients and Methods: This was a multicenter retrospective study involving the development of risk prediction models for intrahospital mortality among all STEMI patients with hyperuricemia from Zunyi Medical University Chest Pain Center’s specialized alliance between January 1, 2016 and June 30, 2020. The primary outcome was intrahospital mortality. A total of 48 candidate variables were considered from demographic and clinical data. The least absolute shrinkage and selection operator (LASSO) was used to develop a nomogram. Concordance index values, decision curve analysis, the area under the curve (AUC), and clinical impact curves were examined. In this study, 489 patients with STEMI were included in the training dataset and an additional 209 patients from the 44 chest pain centers were included in the test cohort. B-type natriuretic peptides, α-hydroxybutyrate dehydrogenase (α-HBDH), cystatin C, out-of-hospital cardiac arrest (OHCA), shock index, and neutrophil-to-lymphocyte ratio were associated with intrahospital mortality and included in the nomogram.Results: The model showed good discrimination power, and the AUC generated to predict survival in the training set was 0.875 (95% confidence interval, 0.825– 0.925). In the validation set, the AUC of survival predictions was 0.87 (95% confidence interval, 0.792– 0.947). Calibration plots and decision curve analysis showed good model performance in both datasets. A web-based calculator (https://bzxzmu.shinyapps.io/STEMI-with-Hyperuricemia-intrahospital-mortality/) was established based on the nomogram model, which was used to measure the levels of OHCA, neutrophil-to-lymphocyte ratio, shock index, α-HBDH, cystatin C, and B-type natriuretic peptides.Conclusion: For practical applications, this model may prove clinically useful for personalized therapy management in patients with STEMI with hyperuricemia.Keywords: hyperuricemia, STEMI, nomogram, mortality

Dong Wang,* Jinghui Zhang,* Zhigang Bai, Yingchi Yang, Tingting Wang, Lan Jin, Jin Wang, Guocong Wu, Tiankuo Kou, Zhongtao Zhang Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center of Digestive Diseases, Beijing 100050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhongtao Zhang; Yingchi YangDepartment of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center of Digestive Diseases, 95 Yongan Road, Xi-Cheng District, Beijing 100050, People’s Republic of ChinaTel +86-134-6668-0330; +86-158-1015-2032 Email zhangzht@ccmu.edu.cn; yangyingchi@ccmu.edu.cnBackground: Advancing age is associated with high incidence of colorectal cancer (CRC) and high rates of postoperative complications (POCs). However, the impact of of POC severity — evaluated by Clavien–Dindo classification (CDC) or comprehensive complication index (CCI) — on long-term overall survival (OS) in elderly patients after radical CRC resection is not clear.Methods: Elderly patients aged 65 years or more with CRC undergoing radical resection were retrospectively recruited. POC details were collected and evaluated using CDC grades and the CCI, blinded to patients’ other information. Risk factors for CDC grade ≥II POCs were analyzed by multivariate logistic regression. Effects of CDC grade II–IV POCs on long-term OS were analyzed via propensity-score matching (PSM) analysis followed by Kaplan–Meier curve plotting and multivariate Cox proportional-hazard regression adjusted for all potential confounders. The prognostic value of the CCI was also explored and compared with CDC grades.Results: A total of 614 elderly patients were identified, of which 20, 106, 25, 11, and 13 cases experienced CDC grade I, II, III, IV, and V POCs, respectively. Higher age, female sex, coronary heart diseases, family history of tumors, preoperative anemia, high amount of bleeding during operation, and high positive dissected lymph–node ratio were found to be risk factors for CDC grade II–V POCs. After PSM analyses, CDC grade II–IV POCs were identified to be associated with poor long-term OS, which was also verified in the entire cohort. The CCI was also found to be significantly associated with decreased long-term OS and showed prognostic values similar to CDC grades.Conclusion: Both CDC grades and the CCI can be used to evaluate POCs and are associated with long-term OS in elderly patients undergoing radical CRC resection.Keywords: elderly, colorectal cancer, postoperative complications, Clavien–Dindo classification, comprehensive complication index, overall survival

Abstract: A real-time capable core ICRF heating model on NSTX and WEST is developed. The model is based on two nonlinear regression algorithms, the random forest ensemble of decision trees and the multilayer perceptron neural network. The algorithms are trained on TORIC ICRF spectrum solver simulations of the expected flat-top operation scenarios in NSTX and WEST assuming Maxwellian plasmas. The surrogate models are shown to successfully capture the multi-species core ICRF power absorption predicted by the original model for the high harmonic fast wave and the ion cyclotron minority heating schemes while reducing the computational time by six orders of magnitude. Although these models can be expanded, the achieved regression scoring, computational efficiency and increased model robustness suggest these strategies can be implemented into integrated modeling frameworks for real-time control applications.

Xiao-nan Zhao,* Zhen-zi Bai,* Cheng-hua Li, Chuan-lun Sheng, Hong-yan Li Department of Infectious, The Third Hospital of Jilin University, Changchun City, Jilin Province 130033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-yan LiDepartment of Infectious, The Third Hospital of Jilin University, No. 126, Sendai Avenue, Changchun City, Jilin Province 130033, People’s Republic of ChinaTel +86-431-84995690Email hongyanl234@163.comBackground: The macrophage is one of the most important types of immune cells that protect against harmful stimuli. Macrophage activation plays a pivotal role in the progression and development of various inflammatory diseases. The neurokinin 1 receptor (NK-1R) is a G protein-coupled receptor that plays an important role in inflammatory diseases. Aprepitant is a kind of NK-1R antagonist. The purpose of this study is to determine the protective effect of aprepitant in lipopolysaccharide (LPS)-induced inflammatory responses in macrophages.Methods: We examined the anti-inflammatory and anti-oxidant effects of aprepitant in LPS-treated RAW264.7 macrophages by using real-time PCR, ELISA, and Western blot analysis. We also assessed cellular oxidative stress signaling by measuring the levels of cellular MDA, total ROS, and NADPH oxidase expression. Cellular NO production was measured by DAF-FM DA staining. The inhibitory effect of aprepitant against NF-κB signaling was evaluated by luciferase assay and Western blot analysis.Results: The expression of NK-1R is increased in LPS-induced macrophages, suggesting a potential role of the receptor in the inflammatory response. We show that aprepitant protects macrophages against oxidative stress by reducing the generation of ROS and the expression of NOX-4. Furthermore, aprepitant inhibits the secretion of pro-inflammatory cytokines and chemotactic factors by mediating the NF-κB signaling pathway.Conclusion: The NK-1R receptor antagonist aprepitant acts as an anti-inflammatory agent, indicating that the blockage of the NK-1R pathway in macrophages has the potential to suppress inflammation.Keywords: aprepitant, NK-1R, inflammation, NF-κB, oxidative stress

Wenhao Man,* Huajun Lin,* Zhao Liu, Lei Jin, Jin Wang, Jun Zhang, Zhigang Bai, Hongwei Yao, Zhongtao Zhang, Wei Deng Department of General Surgery, Beijing Friendship Hospital, Capital Medical University and National Clinical Research Center for Digestive Diseases, Beijing 100050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei DengDepartment of General Surgery, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing 100050, People’s Republic of ChinaTel +86 134 2613 6152Email dengweiwei@126.comPurpose: We aimed to investigate the value of inflammation-based prognostic scores for predicting early complications after radical surgery for colorectal carcinoma.Methods: We retrospectively analyzed data of 154 patients who underwent elective resection of colorectal carcinoma between January 2017 and December 2018 at Beijing Friendship Hospital. Univariate, multivariate, and receiver operating characteristic curve analyses were conducted. As inflammation indices, we evaluated the preoperative modified Glasgow Prognostic Score (GPS), as well as the C-reactive protein/albumin ratio (CAR), postoperative GPS, and C-reactive protein levels on postoperative day 3 (POD3).Results: Within 30 days postoperatively, complications occurred in 80 patients (51.9%). And high levels of preoperative mGPS (P=0.002), preoperative CAR (P=0.019), POD3 CAR (P< 0.001) and POD3 poGPS (P< 0.001) can significantly affect postoperative complications after surgery for colorectal cancer, with CRP on POD3 (odds ratio, 1.015; 95% confidence interval, 1.006– 1.024; P=0.001) as independent risk factors. Among all inflammation-based indicators, POD3 CAR had the highest area under the curve (0.711) and positive predictive value (83.2%). Higher CAR (≥ 2.6) on POD3 was associated with a higher rate of complications (92.9% vs 36.6%, P< 0.001), especially of infectious nature (54.8% vs 16.1%, P< 0.001).Conclusion: CAR≥ 2.6 on POD3 reflects sustained systemic inflammation and represents a useful predictor of complications after surgery for colorectal carcinoma, facilitating early detection, timely intervention, and enhanced recovery.Keywords: C-reactive protein, albumin, Glasgow Prognostic Score, colorectal carcinoma, surgery, postoperative complications, risk prediction

Hongyan Li, Xiaonan Zhao, Chenghua Li, Chuanlun Sheng, Zhenzi Bai Infectious Department, China-Japan Union Hospital, Jilin University, Changchun 130033, China Background: There is evidence that abnormal expression of lncRNAs is associated with hepatitis B virus (HBV) infection-induced hepatocellular carcinoma (HCC). However, the mechanisms remain not fully elucidated. The study aimed to identify novel lncRNAs and explore their underlying mechanisms based on the ceRNA hypothesis. Methods: The RNA and miRNA expression profiling in 20 tumor and matched adjacent tissues from HBV–HCC patients were retrieved from the Gene Expression Omnibus database under accession numbers GSE77509 and GSE76903, respectively. Differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) were identified using the EdgeR package. Protein–protein interaction (PPI) network was constructed for DEGs followed by module analysis. The ceRNA network was constructed based on interaction relationships between miRNAs and mRNAs/lncRNAs. The functions of DEGs were predicted using DAVID and BinGO databases. The prognosis values (overall survival [OS] and recurrence-free survival [RFS]) of ceRNA network genes were determined using The Cancer Genome Atlas (TCGA) data with Cox regression analysis and Kaplan–Meier method. Results: The present study screened 643 DELs, 83 DEMs, and 1,187 DEGs. PPI network analysis demonstrated that CDK1 and CCNE1 were hub genes and extracted in functionally related modules. E2F2, CDK1, and CCNE1 were significantly enriched into cell cycle pathway. FAM182B-miR-125b-5p-E2F2 and LINC00346-miR-10a-5p-CDK1/CCNE1 ceRNA axes were obtained by constructing the ceRNA network. Patients with high expressions of DELs and DEGs in the above ceRNA axes had poor OS, while patients with the high expression of DEMs possessed excellent OS. CDK1 was also an RFS-related biomarker, with its high expression predicting poor RFS. The upregulation of LINC00346 and CDK1 but the downregulation of miR-10a-5p in HCC was validated in other microarray datasets and TCGA database. Conclusion: The LINC00346-miR-10a-5p-CDK1 axis may be an important mechanism for HBV-related HCC, and genes in this ceRNA axis may be potential prognostic biomarkers and therapeutic targets. Keywords: hepatocellular carcinoma, hepatitis B virus, ceRNA, lncRNA, miRNA, prognosis, bioinformatics analysis, TCGA

Yingchi Yang, Dong Wang, Lan Jin, Guocong Wu, Zhigang Bai, Jin Wang, Hongwei Yao, Zhongtao Zhang Department of General Surgery, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China Purpose: The aim of this study was to investigate the prognostic value of the combination of microsatellite instability (MSI) and BRAF V600E mutation in colorectal cancer (CRC).Materials and methods: We compare the prognosis difference among CRC patients with four subtypes according to MSI and BRAF mutation, ie, microsatellite stable/BRAF wild type (MSS/BRAFwt), MSS/BRAF mutation (MSS/BRAFmut), MSI/BRAFwt, and MSI/BRAFmut, by pooling the previous related reports and public available data sets till December 2017 for the first time.Results: Twenty-seven independent studies comprising 24,067 CRC patients were included. Meta-analysis suggested that, compared with MSS/BRAFwt subtype, MSS/BRAFmut was associated with shorter overall survival (OS) (N=25, HR = 2.018, 95% CI = 1.706–2.388, P=2.220E-16), while there was a trend of association of MSI/BRAFmut with OS (N=13, HR = 1.324, 95% CI = 0.938–1.868, P=1.096E-01) and no association of MSI/BRAFwt with OS (N=17, HR = 0.996, 95% CI = 0.801–1.240, P=9.761E-01). Compared with MSI/BRAFwt subtype, MSI/BRAFmut was a poor factor for OS (N=22, HR = 1.470, 95% CI = 1.243–1.740, P=7.122E-06). Compared with MSS/BRAFmut subtype, both MSI/BRAFwt (N=11, HR = 0.560, 95% CI = 0.433–0.725, P=1.034E-05) and MSI/BRAFmut (N=16, HR = 0.741, 95% CI = 0.567–0.968, P=2.781E-02) were favorable for OS. Subgroup analysis revealed similar results in all subgroups except the subgroup of stage IV cancer, in which MSI showed poor effects on OS in BRAF wild-type patients (N=6, HR = 1.493, 95% CI = 1.187–1.879, P=6.262E-04) but not in BRAF-mutated patients (N=5, HR = 1.143, 95% CI = 0.789–1.655, P=4.839E-01). Meta-analysis regression and test of interaction revealed no interaction of MSI with BRAF mutation when evaluating the associations of MSI/BRAF mutation subtypes with OS in CRC.Conclusion: Among the four subtypes according to MSI and BRAF mutation, MSS/BRAFmut was a poor prognostic factor, while MSS/BRAFwt and MSI/BRAFwt were comparable and favorable and MSI/BRAFmut was moderate in CRC. The combination of MSI/BRAF mutations could facilitate the planning of individualized treatment strategies and prognosis improvement in CRC. Keywords: meta-analysis, microsatellite instability, colorectal cancer, BRAF mutation, prognosis

Zhengliang Zhang,1 Jiangli Sun,1 Zhenghai Bai,1 Haijun Li,2 Shicai He,2 Rui Chen,2 Xiangming Che21Department of Emergency, Second Affiliated Hospital of Xi’an Jiaotong University, 2Department of General Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaAbstract: MicroRNA (miRNA)-153 (miR-153) has been considered as a novel tumor-related miRNA and is found to be significantly deregulated in human cancers. In this study, we found that the expression levels of miR-153 were obviously lower in gastric cancer tissues than those in matched adjacent nontumor tissues. Otherwise, miR-153 was expressed at significantly lower levels in aggressive tumor tissues. Clinical association analysis indicated that low expression of miR-153 was prominently correlated with poor prognostic features in gastric cancer. Furthermore, we demonstrated that the low expression of miR-153 was correlated with short 5-year survival of gastric cancer patients. Multivariate Cox regression analysis indicated that miR-153 was an independent prognostic marker in gastric cancer. Our in vitro studies showed that upregulation of miR-153 reduced cell migration and invasion in MKN-45 cells. Meanwhile, downregulation of miR-153 promoted SGC-7901 cell migration and invasion. An inverse correlation between miR-153 and SNAI1 expression was observed in gastric cancer tissues. In addition, upregulation of miR-153 reduced SNAI1 expression and subsequently suppressed epithelial–mesenchymal transition (EMT) with elevated expression of E-cadherin and reduced expression of vimentin in MKN-45 cells. Furthermore, downregulation of miR-153 increased SNAI1 expression and promoted EMT in SGC-7901 cells. In conclusion, miR-153 is an independent prognostic marker for predicting survival of gastric cancer patients and may promote gastric cancer cell migration and invasion, by inhibiting SNAI1-induced EMT.Keywords: miR-153, prognosis, SNAI1, EMT, tumor metastasis

Three machine learning techniques (multilayer perceptron, random forest, and Gaussian process) provide fast surrogate models for lower hybrid current drive (LHCD) simulations. A single GENRAY/CQL3D simulation without radial diffusion of fast electrons requires several minutes of wall-clock time to complete, which is acceptable for many purposes, but too slow for integrated modeling and real-time control applications. More accurate simulations with fast electron diffusion are even slower, requiring multiple hours of run time with parallel processing. The machine learning models use a database of 16,000+ GEN-RAY/CQL3D simulations for training, validation, and testing. Latin hypercube sampling methods implemented in πScope ensure that the database covers the range of 9 input parameters (ne0, Te0, Ip, Bt, R0, n∥︀, Ze f f, Vloop, PLHCD) with sufficient density in all regions of parameter space. The surrogate models reduce the computation time from minutes-hours to ms with high accuracy across the input parameter space. Data-driven surrogate models also allow for solving inverse and "lateral"problems. A surrogate model for the inverse problem maps from a desired current drive or power deposition profile to a set of input parameters that would result in such a profile, while a surrogate model for the lateral problem maps from a measured experimental quantity such as hard x-ray emission to a current drive or power deposition profile. The πScope database creation workflow is flexible and applicable to other RF simulation codes such as TORIC.

Three machine learning techniques (multilayer perceptron, random forest and Gaussian process) provide fast surrogate models for lower hybrid current drive (LHCD) simulations. A single GENRAY/CQL3D simulation without radial diffusion of fast electrons requires several minutes of wall-clock time to complete, which is acceptable for many purposes, but too slow for integrated modelling and real-Time control applications. The machine learning models use a database of more than 16Â 000 GENRAY/CQL3D simulations for training, validation and testing. Latin hypercube sampling methods ensure that the database covers the range of nine input parameters (, and) with sufficient density in all regions of parameter space. The surrogate models reduce the inference time from minutes to ms with high accuracy across the input parameter space.

22Na is an important isotope for the study of extinct radioactivity, meanwhile its sufficiently long half life provides the possibility to observe live 22Na in nearby nova explosions. The 22Na(p,γ) 23Mg is one of the key reactions that influence the 22Na abundance in nova ejecta. To study the proton resonant states in 23Mg relevant to the astrophysical 22Na(p,γ) 23Mg reaction rates, two measurements have been carried out at the CRIB separator of University of Tokyo, and the RIBLL secondary beamline in Lanzhou, respectively. The 22Na secondary beam was produced via the 1H(22Ne, 22Na)n charge exchange reaction. Thick-target inverse-kinematics method is applied to obtain the excitation function of 22Na+p elastic scattering. Extended gas target and solid state polyethylene foil were used in the two measurements, respectively, to map the different excitation energy region of the compound nucleus 23Mg. Several new resonant levels are observed and their contribution to the 22Na(p,γ) 23Mg reaction rate is evaluated.

We present an efficient and reliable algorithm for solving a class of nonlinear eigenvalue problems arising from the modeling of particle accelerator cavities. The eigenvalue nonlinearity in these problems results from the use of waveguides to couple external power sources or to allow certain excited electromagnetic modes to exit the cavity. We use a rational approximation to reduce the nonlinear eigenvalue problem first to a rational eigenvalue problem. We then apply a special linearization procedure to turn the rational eigenvalue problem into a larger linear eigenvalue problem with the same eigenvalues, which can be solved by existing iterative methods. By using a compact scheme to represent both the linearized operator and the eigenvectors to be computed, we obtain a numerical method that only involves solving linear systems of equations of the same dimension as the original nonlinear eigenvalue problem. We refer to this method as a compact rational Krylov (CORK) method. We implemented the CORK method in the Omega3P module of the Advanced Computational Electromagnetic 3D Parallel (ACE3P) simulation suite and validated it by comparing the computed cavity resonant frequencies and damping Q factors of a small model problem to those obtained from a fitting procedure that uses frequency responses computed by another ACE3P module called S3P. We also used the CORK method to compute trapped modes damped in an ideal eight 9-cell SRF cavity cryomodule. This was the first time it was possible to compute these modes directly. The damping Q factors of the computed modes match well with those measured in experiments and the difference in resonant frequencies is within the range introduced by cavity imperfection. Therefore, the CORK method is an extremely valuable tool for computational cavity design.