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Chang Su, Juan Tian, Xueqing He, Xiaona Chang, Guang Wang, Jia Liu Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaCorrespondence: Guang Wang; Jia Liu, Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, NO. 8, Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +8610-85231737 ; +8610-85231710, Email drwg6688@126.com; liujia0116@126.comBackground: Dyslipidemia has been implicated in the pathogenesis of several diseases, including thyroid dysfunction and immune disorders. However, whether circulating lipids and long-term use of lipid-lowering drugs influence the development of autoimmune thyroid disease (AITD) remains unclear. This study aims to evaluate the effects of lipid-lowering drugs on AITD and explore their potential mechanisms.Methods: Two-sample and two-step Mendelian randomization (MR) studies were performed to assess the causal relationships between circulating lipids (LDL-C, TC, TG, and ApoB) and seven lipid-lowering drug targets (ApoB, CETP, HMGCR, LDLR, NPC1L1, PCSK9, and PPARα) with AITD. Mediation analyses were conducted to explore potential mediating factors.Results: There was no clear causality between circulating lipids (ApoB, LDL-C, TC, and TG) and AITD (p > 0.05). ApoB inhibition is related to a reduced risk of autoimmune thyroiditis (AT) (OR = 0.462, p= 0.046), while PCSK9 inhibition is related to reduced Graves’ disease (GD) risk (OR = 0. 551, p = 0.033). Moreover, PCSK9 inhibition (OR = 0.735, p = 0.003), LDLR inhibition (OR = 0.779, p = 0.027), and NPC1L1 inhibition (OR = 0.599, p = 0.016) reduced the risk of autoimmune hypothyroidism (AIH). Mediation analysis showed that NPC1L1 inhibition and PCSK9 inhibition exerted effects on AIH through IL-4 and FGF-19 levels. And the effect of PCSK9 inhibition on GD through TNF-β levels.Conclusion: There was no clear causality between circulating lipids (ApoB, LDL-C, TC, and TG) and AITD. Lipid-lowering drug target gene inhibitors reduced the AITD risk by modulating inflammatory factors.Keywords: Mendelian randomization, drug targeting, thyroid autoimmune disease, lipid trait, inflammatory factors

Tiansu Lv,1,2,* Jie Tian,1,3,* Yaohuan Sun,1,3 Yujuan Zhang,1,2 Fang Qi,1,2 Liulan Xiang,1,2 Yutian Cao,1,2 Wenhui Zhang,1,2 Jiaxuan Huai,1,2 Yinfeng Dong,4 Xiqiao Zhou1,2 1Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3School of Nursing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 4Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiqiao Zhou; Yinfeng Dong, Email zhouxiqiao@njucm.edu.cn; dongyf@njucm.edu.cnBackground: Metabolic Associated Fatty Liver Disease (MAFLD) poses a significant threat to human health, as it can result in hepatic fibrosis and potentially progress to cirrhosis, in addition to causing a range of extrahepatic complications. The early detection of MAFLD is crucial, particularly during the initial stages when the condition may be amenable to reversal and the body composition could be vital importance.Methods: Data from participants at the Jiangsu Province Hospital of Traditional Chinese Medicine, covering the period from January 1 to December 31, 2022, were collected and subsequently randomized into training and validation cohorts. Independent risk factors for MAFLD were identified using statistical methodologies in conjunction with clinical relevance, and these factors were ultimately utilized to develop the nomogram.Results: In the training cohort, there were 356 cases of MAFLD out of a total of 513 patients, representing 71.2%, while in the validation cohort, 161 cases of MAFLD were identified out of 220 patients, accounting for 73.2%. In terms of statistical outcomes and clinical relevance, we identified a total of 12 closely related or significant variables. To enhance our understanding of the critical role of body composition parameters in predicting the incidence of MAFLD, we developed two distinct nomograms, one of which included body composition data. Notably, the nomogram that incorporated body composition demonstrated superior predictive performance, as evidenced by a well-fitted calibration curve and a C-index of 0.893 (with a range of 0.8625 to 0.9242). Furthermore, the decision curve analysis indicated that utilizing the nomogram that included body composition would yield greater benefits.Conclusion: The nomogram serves as an effective tool for predicting MAFLD. Its utility in early risk identification of MAFLD is of significant importance, as it facilitates timely intervention and treatment for patients affected by this condition.Keywords: Metabolic Associated Fatty Liver Disease, Body Composition, Nomogram

Abstract TBI-223, a novel oxazolidinone for tuberculosis, is designed to provide improved efficacy and safety compared to linezolid in combination with bedaquiline and pretomanid (BPaL). We aim to optimize the dosing of TBI-223 within the BPaL regimen for enhanced therapeutic outcomes. TBI-223 is investigated in preclinical monotherapy, multidrug therapy, and lesion penetration experiments to describe its efficacy and safety versus linezolid. A translational platform incorporating linezolid and BPaL data from preclinical experiments and 4 clinical trials (NCT00396084, NCT02333799, NCT03086486, NCT00816426) is developed, enabling validation of the framework. TBI-223 preclinical and Phase 1 data (NCT03758612) are applied to the translational framework to predict clinical outcomes and optimize TBI-223 dosing in combination with bedaquiline and pretomanid. Results indicate that daily doses of 1200–2400 mg TBI-223 may achieve efficacy comparable to the BPaL regimen, with >90% of patients predicted to reach culture conversion by two months.

Huizhen Yue,1– 3 Xiaolong Xu,1– 3 Bing Peng,1– 3 Xuanyu Wang,1 Shengnan Zhang,1 Jinhao Tian,4 Shuo Wang,1 Maifen Song,1 Qingquan Liu1– 3 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Chinese Medicine, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, People’s Republic of China; 4Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Qingquan Liu, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Gallery Backstreet, Dongcheng District, Beijing, People’s Republic of China, Email liuqingquan_2003@126.comPurpose: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of Candida-related infection. However, its antifungal mechanisms against the emerging fungal pathogen Candida auris remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against C. auris.Methods: The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against C. auris, including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a Galleria mellonella infection model.Results: First, 20 major compounds in CHGX-DME were detected and characterized. The MIC50% and MIC90% of CHGX-DME against C. auris isolates ranged from 50– 200 mg/L and 100– 400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of C. auris cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in C. auris. Importantly, it significantly improved the survival rate and reduced the fungal burden in G. mellonella infection models, suggesting a remarkable treatment effect against C. auris infection.Conclusion: CHGX-DME exhibited potent antifungal activity against C. auris and significantly ameliorated this fungal infection in the G. mellonella model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen C. auris.Keywords: Candida auris, multidrug resistance, CaoHuangGuiXiang formula, aggregative form, biofilm formation, antifungal efficiency

Wei Guo,1 Jing Tian,1 Yajing Wang,1 Yajing Zhang,1 Jingjing Yan,2 Yutao Du,2 Yanbo Zhang,2,3 Qinghua Han1,4 1Department of Cardiology, the 1st Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, People’s Republic of China; 2Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi Province, People’s Republic of China; 3Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, Shanxi Province, People’s Republic of China; 4Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan, Shanxi Province, People’s Republic of ChinaCorrespondence: Qinghua Han, Department of Cardiology, the 1st Hospital of Shanxi Medical University, No. 85 South JieFang Road, Yingze District, Taiyuan, Shanxi, People’s Republic of China, Email syhqh@sohu.com Yanbo Zhang, Department of Health Statistics, School of Public Health, Shanxi Medical University, No. 56 South XinJian Road, Yingze District, Taiyuan, Shanxi, People’s Republic of China, Email sxmuzyb@126.comPurpose: This study aimed to develop an integrative dynamic nomogram, including N-terminal pro-B type natural peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR), for predicting the risk of all-cause mortality in HFmrEF patients.Patients and Methods: 790 HFmrEF patients were prospectively enrolled in the development cohort for the model. The least absolute shrinkage and selection operator (LASSO) regression and Random Survival Forest (RSF) were employed to select predictors for all-cause mortality. Develop a nomogram based on the Cox proportional hazard model for predicting long-term mortality (1-, 3-, and 5-year) in HFmrEF. Internal validation was conducted using Bootstrap, and the final model was validated in an external cohort of 338 consecutive adult patients. Discrimination and predictive performance were evaluated by calculating the time-dependent concordance index (C-index), area under the ROC curve (AUC), and calibration curve, with clinical value assessed via decision curve analysis (DCA). Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to assess the contributions of NT-proBNP and eGFR to the nomogram. Finally, develop a dynamic nomogram using the “Dynnom” package.Results: The optimal independent predictors for all-cause mortality (APSELNH: A: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitor (ACEI/ARB/ARNI), P: percutaneous coronary intervention/coronary artery bypass graft (PCI/CABG), S: stroke, E: eGFR, L: lg of NT-proBNP, N: NYHA, H: healthcare) were incorporated into the dynamic nomogram. The C-index in the development cohort and validation cohort were 0.858 and 0.826, respectively, with AUCs exceeding 0.8, indicating good discrimination and predictive ability. DCA curves and calibration curves demonstrated clinical applicability and good consistency of the nomogram. NT-proBNP and eGFR provided significant net benefits to the nomogram.Conclusion: In this study, the dynamic APSELNH nomogram developed serves as an accessible, functional, and effective clinical decision support calculator, offering accurate prognostic assessment for patients with HFmrEF.Keywords: heart failure with mildly reduced ejection fraction, all-cause mortality, risk prediction model, risk strategy, dynamic nomogram

Jiaxin Zan,1,2 Xiaojing Dong,1,2 Hong Yang,1,2 Jingjing Yan,1,2 Zixuan He,3 Jing Tian,3 Yanbo Zhang1,2,4 1Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, People’s Republic of China; 3Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4School of Health Services and Management, Shanxi University of Chinese Medicine, Taiyuan, People’s Republic of ChinaCorrespondence: Jing Tian; Yanbo Zhang, School of Public health, Shanxi Medical University, 56 Xinjian Road, Taiyuan, Shanxi Province, People’s Republic of China, Tel/Fax +86 15535406059, Email 1105551933@qq.com; sxmuzyb@126.comPurpose: This study sought to develop an unbalanced-ensemble model that could accurately predict death outcomes of patients with comorbid coronary heart disease (CHD) and hypertension and evaluate the factors contributing to death.Patients and Methods: Medical records of 1058 patients with coronary heart disease combined with hypertension and excluding those acute coronary syndrome were collected. Patients were followed-up at the first, third, sixth, and twelfth months after discharge to record death events. Follow-up ended two years after discharge. Patients were divided into survival and nonsurvival groups. According to medical records, gender, smoking, drinking, COPD, cerebral stroke, diabetes, hyperhomocysteinemia, heart failure and renal insufficiency of the two groups were sorted and compared and other influencing factors of the two groups, feature selection was carried out to construct models. Owing to data unbalance, we developed four unbalanced-ensemble prediction models based on Balanced Random Forest (BRF), EasyEnsemble, RUSBoost, SMOTEBoost and the two base classification algorithms based on AdaBoost and Logistic. Each model was optimised using hyperparameters based on GridSearchCV and evaluated using area under the curve (AUC), sensitivity, recall, Brier score, and geometric mean (G-mean). Additionally, to understand the influence of variables on model performance, we constructed a SHapley Additive explanation (SHAP) model based on the optimal model.Results: There were significant differences in age, heart rate, COPD, cerebral stroke, heart failure and renal insufficiency in the nonsurvival group compared with the survival group. Among all models, BRF yielded the highest AUC (0.810; 95% CI, 0.778– 0.839), sensitivity (0.990; 95% CI, 0.981– 1.000), recall (0.990; 95% CI, 0.981– 1.000), and G-mean (0.806; 95% CI, 0.778– 0.827), and the lowest Brier score (0.181; 95% CI, 0.178– 0.185). Therefore, we identified BRF as the optimal model. Furthermore, red blood cell count (RBC), body mass index (BMI), and lactate dehydrogenase were found to be important mortality-associated risk factors.Conclusion: BRF combined with advanced machine learning methods and SHAP is highly effective and accurately predicts mortality in patients with CHD comorbid with hypertension. This model has the potential to assist clinicians in modifying treatment strategies to improve patient outcomes. Keywords: coronary heart disease comorbid with hypertension, ensemble learning, balanced random forest, SHAP, Prognosis

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

Pingyu An,1 Qiyue Zhao,2 Siyu Hao,3 Xiaodong Wang,4 Jiangtian Tian,5,6 Zhiqiang Ma3 1Basic Medical College, Harbin Medical University, Harbin, People’s Republic of China; 2School of Nursing, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Dermatology, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 5Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 6The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, People’s Republic of ChinaCorrespondence: Zhiqiang Ma, Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin, 150081, People’s Republic of China, Tel +86 18845139619, Email zhiqiangma@hrbmu.edu.cnAbstract: Psoriasis is an immune-mediated inflammatory skin disease where topical therapy is crucial. While various dosage forms have enhanced the efficacy of current treatments, their limited permeability and lack of targeted delivery to the dermis and epidermis remain challenges. We reviewed the evolution of topical therapies for psoriasis and conducted a bibliometric analysis from 1993 to 2023 using a predictive linear regression model. This included a comprehensive statistical and visual evaluation of each model’s validity, literature profiles, citation patterns, and collaborations, assessing R variance and mean squared error (MSE). Furthermore, we detailed the structural features and penetration pathways of emerging drug delivery systems for topical treatment, such as lipid-based, polymer-based, metallic nanocarriers, and nanocrystals, highlighting their advantages. This systematic overview indicates that future research should focus on developing novel drug delivery systems characterized by enhanced stability, biocompatibility, and drug-carrying capacity.Keywords: psoriasis, bibliometric, drug delivery, topical treatment, nanoparticle, nanocarriers

Wenxia Wu,1,2,* Jingwei Tian,1,* Lisha Xiao,1 Haochen Mai,1 Phei Er Saw,3– 5 Meng Zhang1,2 1Department of General Practice, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of General Practice, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Shanwei, Guangdong, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 4Guangzhou Key Laboratory of Medical Nanomaterials, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 5Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-Sen Memorial Hospital, Foshan, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Phei Er Saw; Meng Zhang, Email zhangm7@mail.sysu.edu.cn; caipeie@mail.sysu.edu.cnBackground: The incidence of cancer is increasing, and cancer survivors are also growing exponentially. Cancer is defined as a new chronic disease. Nevertheless, the management of cancer in the form of chronic diseases in China is still in its infancy, without a standardized care model.Objective: This study aimed to explore the current status of management of cancer care from the patient’s perspective.Methods: This cross-sectional study was a questionnaire survey of patients diagnosed with cancer, including information of the current situation of daily medical consultation, status of comorbidity, and expectations of seeking cancer care in future. Chi-square test and logistic regression analysis were used to explore the factors influencing patients’ choice of cancer management mode.Results: A total of 200 cancer patients were included in the study. The majority (n = 150) of cancer patients chose an oncologist in a tertiary hospital for cancer care. Difficulty in registration (45%), time-consuming (34.5%), repeated examinations (34.5%) and different treatment opinions (12.0%) were the main difficulties they encountered currently during tertiary hospital visits. In community hospital, lack of trust in general practitioners (n = 33) and the necessary drugs or testing items in community hospitals (n = 47) were the main difficulties during their visits. Logistic regression analysis showed that male (OR = 2.737, 95% CI, 1.332– 5.627, p = 0.006) and elderly patients (OR = 3.186, 95% CI, 1.172– 8.661, p = 0.023) were more likely to choose general practitioners (GPs) in community hospitals. Twenty-nine (14.5%) patients hope to have an integrated multidisciplinary management in tertiary and community hospitals with the active participation of GPs for cancer care.Conclusion: Improving drug availability, equipment and quality of cancer care services can help to increase cancer patients’ recognition of community hospital. In addition, the multidisciplinary management integrated tertiary hospitals and communities with the participation of GPs is a worth exploring mode that improves the management of cancer care.Keywords: cancer care, chronic disease management, general practitioners, GPs, multidisciplinary

Yanlei Li,1,&ast; Meng Ge,2,&ast; Jinlong Tian,1,&ast; Jinlei Zhou,1,3 Yao Kang,1 Chen Xia,1 Haiyu Shao,1 Yongguang Wang,4 Yazeng Huang,1 Tingxiao Zhao1 1Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 2Department of Orthopedics, Hospital of Traditional Chinese Medicine of Xiaoshan District, Hangzhou, Zhejiang, People’s Republic of China; 3Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Orthopedics, Linping Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingxiao Zhao; Yazeng Huang, Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Shangtang Road 158&num;, Hangzhou, Zhejiang, People’s Republic of China, Email spinezhaotingxiao@163.com; huangyazeng2007@163.comPurpose: Percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) has become one of the most popular minimally invasive surgeries today. However, the issue of hidden blood loss (HBL) in this surgery has received little attention. This study aims to examine the HBL in PE-TLIF surgery and the effect of tranexamic acid (TXA) on blood loss.Methods: In our research, We conducted a retrospective analysis of 300 patients who underwent PE-TLIF from September 2019 to August 2023. They were divided into 2 groups based on whether they received intravenous TXA injection before surgery. The variables compared included: demographic data, pre-and postoperative hemoglobin (HB), hematocrit (HCT), platelets (PLT), red blood cells (RBC), total blood loss (TBL), visible blood loss (VBL), HBL, operation time, postoperative hospital stay, inflammatory markers, coagulation parameters, and adverse events.Results: Regarding demographic characteristics, besides the operation time, no significant differences were observed between the two groups. Compared with the control group, the TXA group showed a significant reduction trend in TBL, HBL, and VBL (P < 0.05). On the first day after surgery, there were significant differences in prothrombin (PT), activated partial thromboplastin time (APTT), and D-dimer (D-D) levels between the two groups. Similarly, HCT also found similar results on the third day after surgery. No adverse events occurred in either group.Conclusion: Research has found that there is a significant amount of HBL in patients undergoing PE-TLIF. Intravenous injection of TXA can safely and effectively reduce perioperative HBL and VBL. Additionally, compared to the control group, the TXA group shows a significant reduction in operation time.Keywords: percutaneous endoscopic transforaminal lumbar interbody fusion, tranexamic acid, total blood loss, visible blood loss, hidden blood loss

Jue Li,1– 3,&ast; Yingxian Dong,1– 3,&ast; Jiawei Guo,4 Lei Wang,1 Jie Tian,1– 3 Li Wang,4 Guowei Che1– 3 1Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3West China Clinical Medical College, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guowei Che, Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China, Tel/Fax +86-28-86298113, Email cheguoweixw@126.comObjective: To evaluate whether using a cocktail of intercostal nerve blocks (TINB) during thoracoscopic surgery results in better clinical outcomes than patient-controlled analgesia (PCIA).Methods: Patients in two medical groups undergoing video-assisted thoracoscopic surgery (VATS) for pulmonary nodules in West China Hospital of Sichuan University were collected consecutively between March 2022 and December 2022. The groups were divided into two subgroups based on their analgesic program, which were TINB group and PCIA group. The primary outcome was the visual analogue scale (VAS) of the two groups at different stage after surgery and after discharge. Any analgesic related adverse events (ARAEs) were also recorded.Results: A total of 230 patients who underwent VATS were enrolled, in which 113 patients (49.1%) received a cocktail TINB after surgery, and 117 patients (50.9%) received a PCIA. After PSM, 62 patients in each group were selected. The difference of resting VAS (RVAS) and active VAS (AVAS) at different stage during hospitalization was only related to the change of period (p < 0.05, p < 0.05), and the two groups showed no significant differences in RVAS or AVAS during hospitalization (p = 0.271, p = 0.915). However, the rates of dizziness (4.84% vs 25.81%, p = 0.002), nausea and vomiting (0 vs 22.58%, p < 0.05), fatigue (14.52% vs 34.87%, p = 0.012), and insomnia (0 vs 58.06%, p < 0.05) in TINB group were lower than that in PCIA group. Besides, AVAS and RVAS at 7, 14, and 30 days after discharge in TINB group were both significantly lower than that in PCIA group (p < 0.05, p < 0.05).Conclusion: Cocktail TINB provided better analgesia after discharge and reduced the incidence of ARAEs in patients undergoing VATS. Keywords: analgesia, thoracoscopic intercostal nerve block, cocktail analgesia, video-assisted thoracoscopic surgery

Siyu Hao,1,2,&ast; Jiuyi Cong,1,&ast; Zhiqiang Ma,1,2 Yan Xia,3 Yu Zhang,1 Nannan Tong,1 Jiangtian Tian,2,4 Yuzhen Li1 1Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, People’s Republic of China; 3Scientific Research Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuzhen Li; Jiangtian Tian, Email liyuzhen@hrbum.edu.cn; tianjiangtian@126.comBackground: Psoriasis, a chronic inflammatory disorder with an unknown cause, significantly impacts the physical and psychological well-being of patients. However, current biomarkers related to psoriasis lack clinical specificity, sensitivity, and predictive ability.Methods: In this study, we collected skin lesion tissues from 20 psoriasis patients and 20 normal skin samples. Additionally, we obtained four datasets from the GEO database, which included human psoriasis and healthy specimens. We utilized SVM-RFE analysis and the LASSO regression model to identify potential biomarkers. Furthermore, we examined the composition of immune cell types in psoriasis and their correlation with specific genes.Results: Our investigation revealed 57 differentially expressed genes (DEGs), and we identified significantly enriched pathways through KEGG pathway analysis. The results of machine learning and WGCNA suggested that LCE3D and SPRR1B could potentially be used as marker genes for diagnosing psoriasis. RT-PCR and immunohistochemical detection confirmed the abnormally high expression of the SPRR1B gene in psoriasis. Analysis of immune cell infiltration revealed a strong positive correlation between SPRR1B and Macrophages M0 and T cells follicular helper, while showing the strongest negative correlation with resting Mast cells. In addition, we found that silencing SPRR1B in IFN-γ-treated HaCat cells could significantly reduce the increase in IL-17, IL-22, KRT6, and KRT16 caused by IFN-γ.Conclusion: These findings suggest that SPRR1B may have a significant role in the pathogenesis of psoriasis and could be employed as a novel immunomarker for its development.Keywords: psoriasis, SPRR1B, keratinocyte, immunomarkers, immunohistochemistry

Fangzhou Hu,1,&ast; Yunfei Zhu,1,&ast; Jingluan Tian,1 Hua Xu,1,2 Qun Xue1 1Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 2Department of Neurology, Affiliated Jintan Hospital of Jiangsu University, Changzhou Jintan First People’s Hospital, Changzhou, Jiangsu, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qun Xue, Email qxue_sz@163.comBackground: Multiple sclerosis (MS) causes chronic inflammation and demyelination of the central nervous system and comprises a class of neurodegenerative diseases in which interactions between multiple immune cell types mediate the involvement of MS development. However, the early diagnosis and treatment of MS remain challenging.Methods: Gene expression profiles of MS patients were obtained from the Gene Expression Omnibus (GEO) database. Single-cell and intercellular communication analyses were performed to identify candidate gene sets. Predictive models were constructed using LASSO regression. Relationships between genes and immune cells were analyzed by single sample gene set enrichment analysis (ssGSEA). The molecular mechanisms of key genes were explored using gene enrichment analysis. An miRNA network was constructed to search for target miRNAs related to key genes, and related transcription factors were searched by transcriptional regulation analysis. We utilized the GeneCard database to detect the correlations between disease-regulated genes and key genes. We verified the mRNA expression of 4 key genes by reverse transcription-quantitative PCR (RT‒qPCR).Results: Monocyte marker genes were selected as candidate gene sets. CD3D, IL2RG, MS4A6A, and NCF2 were found to be the key genes by LASSO regression. We constructed a prediction model with AUC values of 0.7569 and 0.719. The key genes were closely related to immune factors and immune cells. We explored the signaling pathways and molecular mechanisms involving the key genes by gene enrichment analysis. We obtained and visualized the miRNAs associated with the key genes using the miRcode database. We also predicted the transcription factors involved. We used validated key genes in MS patients, several of which were confirmed by RT‒qPCR.Conclusion: The prediction model constructed with the CD3D, IL2RG, MS4A6A, and NCF2 genes has good diagnostic efficacy and provides new ideas for the diagnosis and treatment of MS.Keywords: multiple sclerosis, biomarker, peripheral blood, prediction model

Yushen Jin,1 Zhongquan Cheng,2 Zhu Yuan,2 Yang Du,3 Jie Tian,3 Bing Shao1,4 1Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Centre for Disease Prevention and Control, Beijing, 100013, People’s Republic of China; 2Department of General Surgery, Capital Medical University, Beijing Friendship Hospital, Beijing, 100050, People’s Republic of China; 3CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China; 4College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People’s Republic of ChinaCorrespondence: Bing Shao; Jie Tian, Email shaobingch@sina.com; jietian@ia.ac.cnPurpose: Liver cancer is considered as the third leading cause of cancer-related deaths, with hepatocellular carcinoma (HCC) accounting for approximately 90% of liver cancers. Improving the treatment of HCC is a serious challenge today. The primary objective of this study was to construct SP94-Fe3O4@ICG&DOX nanoparticles and investigate their potential diagnosis and treatment effect benefits on HCC.Methods: Firstly, we synthesized and characterized SP94-Fe3O4@ICG&DOX nanoparticles and confirmed their in vitro release behavior, photothermal and photodynamic performance. Moreover, the in vivo imaging capability was also observed. Finally, the inhibitory effects on Hepa1-6 in vitro and in vivo were observed as well as biosafety.Results: SP94-Fe3O4@ICG&DOX nanoparticles have a size of ~22.1 nm, with an encapsulation efficiency of 45.2% for ICG and 42.7% for DOX, showing excellent in vivo MPI and fluorescence imaging capabilities for precise tumor localization, and synergistic photo-chemotherapy (pH- and thermal-sensitive drug release) against tumors under irradiation. With the assistance of a fluorescence molecular imaging system or MPI scanner, the location and contours of the tumor were clearly visible. Under a constant laser irradiation (808 nm, 0.6 W/cm2) and a set concentration (50 μg/mL), the temperature of the solution could rapidly increase to ~45 °C, which could effectively kill the tumor cells. It could be effectively uptaken by HCC cells and significantly inhibit their proliferation under the laser irradiation (100% inhibition rate for HCC tumors). And most importantly, our nanoparticles exhibited favorable biocompatibility with normal tissues and cells.Conclusion: This versatile agent can serve as an intelligent and promising nanoplatform that integrates multiple accurate diagnoses, precise positioning of cancer tissue, and effective coordination with synergistic tumor photodynamic therapy. Keywords: porous hollow structure, magnetic particle imaging, fluorescence imaging, synergistic treatment, theranostics

Ying Zhao, Jing Tian, Cuie Gao, Lu Liu, Linxin Pan, Zhiqiang Song Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Zhiqiang Song, Department of Dermatology, Southwest Hospital, Army Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email drsongzq@hotmail.comBackground: Blood eosinophilia is often associated with various dermatoses, such as atopic eczema, urticaria, drug eruption, bullous pemphigoid, and hypereosinophilic syndrome (HES). Differential diagnosis is very challenging due to the similarities of clinical and pathological characteristics.Purpose: To investigate and analyze the clinical characteristics of dermatoses associated with blood eosinophilia (DABE) to further optimize disease management.Patients and Methods: We conducted a retrospective analysis on 397 DABE patients with blood absolute eosinophil count (AEC) greater than or equal to 0.5× 109/L. Clinical characteristics, laboratory values, treatment course, and associated diagnoses were evaluated. All DABE patients were grouped based on the severity of eosinophilia as mild group (0.5 ≤ AEC× 109/L < 1.5), moderate group (1.5 ≤ AEC× 109/L < 3), and severe group (AEC× 109/L ≥ 3).Results: Our study revealed three distinct patterns: (1) Mild eosinophilia associated with localized skin lesions, atopic history, mildly elevated total serum IgE level, diagnosed with eczema/dermatitis, and frequent antihistamines use. (2) Moderate eosinophilia has the characteristics of both mild group and severe group. (3) The severe eosinophilia group had a high proportion of elderly people without atopic history, but with acute onset, generalized skin lesions, and high level of lactate dehydrogenase, and the majority of them were diagnosed with systemic diseases (HES or tumor).Conclusion: We summarize the clinical rules of dermatoses associated with blood eosinophilia, hoping to facilitate the diagnosis and treatment for patients.Keywords: eosinophilia, diagnosis, eczema, psoriasis, drug eruption

Jiaqi Tian,1,&ast; Zhengpu Han,1,2,&ast; Dandan Song,1 Yanjie Peng,1 Min Xiong,3 Zhen Chen,2 Shuyin Duan,4 Lin Zhang1,5 1Clinical Medical Research Center for Women and Children Diseases, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, People’s Republic of China; 2School of Public Health, Weifang Medical University, Weifang, People’s Republic of China; 3School of Public Health, North China University of Science and Technology, Tangshan, People’s Republic of China; 4School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 5Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Zhang, Clinical Medical Research Center for Women and Children Diseases, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250001, People’s Republic of China, Tel +86-531-68795046, Email zhanglin8901@163.com Shuyin Duan, School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250001, People’s Republic of China, Tel +86-13419581411, Email shuyinduan@126.comAbstract: Exosomes are nano-sized membrane vesicles that transfer bioactive molecules between cells and modulate various biological processes under physiological and pathological conditions. By applying bioengineering technologies, exosomes can be modified to express specific markers or carry therapeutic cargo and emerge as novel platforms for the treatment of cancer, neurological, cardiovascular, immune, and infectious diseases. However, there are many challenges and uncertainties in the clinical translation of exosomes. This review aims to provide an overview of the recent advances and challenges in the translation of engineered exosomes, with a special focus on the methods and strategies for loading drugs into exosomes, the pros and cons of different loading methods, and the optimization of exosome production based on the drugs to be encapsulated. Moreover, we also summarize the current clinical applications and prospects of engineered exosomes, as well as the potential risks and limitations that need to be addressed in exosome engineering, including the standardization of exosome preparation and engineering protocols, the quality and quantity of exosomes, the control of drug release, and the immunogenicity and cytotoxicity of exosomes. Overall, engineered exosomes represent an exciting frontier in nanomedicine, but they still face challenges in large-scale production, the maintenance of storage stability, and clinical translation. With continuous advances in this field, exosome-based drug formulation could offer great promise for the targeted treatment of human diseases.Keywords: engineered exosomes, drug delivery, clinical application, preparation strategy

Dan Han,1,2 Jing Tian,3 Junfeng Zhao,2 Shaoyu Hao4,5 1Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Radiation Oncology, Jinan Zhangqiu District People’s Hospital, Jinan, Shandong, People’s Republic of China; 4Department of Thoracic Surgery, Shandong University Cancer Center, Jinan, Shandong, People’s Republic of China; 5Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shaoyu Hao, Department of Thoracic Surgery, Shandong University Cancer Center, Jinan, Shandong, China; Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Tel +86 13188870730, Email hshaoyu1985@126.comPurpose: This study aims to identify the most effective treatment approach and compares the survival rates, along with complications, in patients with locally resectable esophageal squamous cell carcinoma (ESCC) who were treated with one of the three treatment patterns: neoadjuvant chemotherapy followed by surgery (NCT+S), neoadjuvant chemoradiotherapy followed by surgery (NCRT+S), or surgery followed by chemoradiotherapy (S+CRT).Methods: We conducted a retrospective analysis of the medical records of ESCC patients who received one of these treatments between March 2015 and March 2022. This analysis aimed to identify differences in long-term survival, pathological responses, and complications across the three treatment groups. To address potential confounding factors, propensity score matching (PSM) and Cox proportional hazards models were utilized.Results: This study included a cohort of 715 patients: 197 in the NCT+S group, 188 in the NCRT+S group, and 330 in the S+CRT group, all meeting the selection criteria. After PSM, the median disease-free survival (DFS) time was 38.9 months, 25.6 months, and 15.3 months for NCRT+S, NCT+S, and S+CRT groups, respectively. There were statistically significant differences in the 5-year DFS and 5-year OS among the three groups (P=0.04 and P=0.02, post-matching, respectively). Notably, neoadjuvant therapy showed a correlation with increased postoperative anastomotic leakage rates (17.5% in NCRT+S, 10% in NCT+S, and 5% in S+CRT; P=0.03, post-matching), regardless of the PSM adjustment.Conclusion: The findings indicate that neoadjuvant therapy before surgery offers a significant survival advantage over postoperative adjuvant therapy for patients with locally advanced resectable ESCC. Despite similar safety profiles, neoadjuvant therapy appears to be associated with a higher incidence of anastomotic leakage after surgery.Keywords: neoadjuvant therapy, esophageal squamous cell carcinoma, postoperative adjuvant therapy, prognosis

Lin Zhang,1,2 Yunyue Liu,2 Jinping Tian2,3 1Department of Infectious Diseases, The Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian, Jiangsu Province, People’s Republic of China; 2School of Nursing, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 3Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Jinping Tian, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Gulou District, Nanjing, Jiangsu Province, 210000, People’s Republic of China, Tel +86 13851550156, Email tianjp6@163.comAbstract: Chronic hepatitis B (CHB) is a common chronic viral infectious disease that requires long-term treatment to control the condition and prevent complications. To standardize treatment regimens for CHB, professional associations have established relevant guidelines, but they have often overlooked patient preferences. Historically, in the treatment process, medical decisions were predominantly made by physicians or health care administrators, with limited patient involvement, leading to the neglect of patient preferences. Patient attitudes, expectations, and needs are all influenced by their preferences, and patient preferences have a direct impact on treatment adherence. Understanding and respecting patient preferences are crucial to ensuring treatment effectiveness. This article will explore patient preferences in the treatment of CHB and elucidate the influence of patient preferences on treatment adherence, aiming to provide insights for the development of a more personalized and effective health care process.Keywords: CHB, treatment options, patient preferences, adherence

Ling Yang,1,2 Maolin Cao,3 Jing Tian,1 Peijin Cui,1 Ling Ai,3 Xue Li,4 Hua Li,5 Menghan Gao,1 Liang Fang,1,2,6 Libo Zhao,1,2 Fang Gong,2,6 Chanjuan Zhou1,3,4,6 1Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Cerebrovascular Disease Research, Chongqing, People’s Republic of China; 3Department of General Practice, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Central Laboratory, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Department of Ophthalmology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 6Chongqing Clinical Research Center for Geriatric Disease, Chongqing, People’s Republic of ChinaCorrespondence: Fang Gong; Chanjuan Zhou, Yongchuan Hospital of Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan, Chongqing, 402160, People’s Republic of China, Email 1512367841@qq.com; chanjuanzhou@hospital.cqmu.edu.cnPurpose: The quality of life of worldwide adolescents has been seriously affected by depression. Notably, the inflammatory response is closely associated with the pathophysiology of depression. The present study applied a novel targeted proteomics technology, Olink proximity extension assay (PEA), to profile circulating immune-related proteins in adolescents with depression.Methods: In the present study, the expression levels of 92 inflammation-related proteins were compared between adolescents with depression (ADs) (n=15) and healthy controls (HCs) (n=15), using the OLINK PEA inflammation panel. We further validated 5 top proteins that were identified through KEGG and GO analyses between 40 HCs and 50 ADs, including CCL4, CXCL5, CXCL6, CXCL11, and IL-18 using enzyme linked immunosorbent assay (ELISA).Results: We identified 13 differentially expressed proteins between the two cohorts, including 5 up-regulated and 8 down-regulated proteins. Among them, the TRAIL protein levels were significantly negatively correlated with the HAMA-14 score (r=− 0.538, p= 0.038), and the levels of transforming growth factor α (TGF-α) were significantly associated with a change in appetite (r = -0.658, p = 0.008). After validation by ELISA, CCL4, CXCL5, CXCL11, and IL-18 showed significant changes between ADs and HCs (p < 0.05), while CXCL6 showed an up-regulated tendency in ADs (p=0.0673). The pooled diagnostic efficacy (area under the curve [AUC]) of these five inflammation markers in clinical diagnosis for adolescent depression was 0.819 (95% CI: 0.735– 0.904).Conclusion: We report a number of inflammation-related plasma biomarkers, which uncover a potential involvement of chemokines, cytokines, and cytokine receptors in adolescent depression. Their roles in the pathophysiology of depression need to be further elucidated.Keywords: olink proximity extension assay, biomarkers, adolescent depression, inflammation

Xueqi Wan,&ast; Huan Zhang,&ast; Jinfan Tian,&ast; Peng Hao, Libo Liu, Yuquan Zhou, Jing Zhang, Xiantao Song, Changjiang Ge Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changjiang Ge; Xiantao Song, Email cjge1116@163.com; song0929@mail.ccmu.edu.cnAbstract: Atherosclerosis (AS), a category of cardiovascular disease (CVD) that can cause other more severe disabilities, increasingly jeopardizes human health. Owing to its imperceptible and chronic symptoms, it is hard to determine the pathogenesis and precise therapeutics for AS. A novel type of programmed cell death called ferroptosis was discovered in recent years that is distinctively different from other traditional cell death pathways in morphological and biochemical aspects. Characterized by iron overload, redox disequilibrium, and accumulation of lipid hydroperoxides (L-OOH), ferroptosis influences endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages, as well as inflammation, partaking in the pathology of many cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. The mechanisms behind ferroptosis are so sophisticated and interwoven that many molecules involved in this procedure are unknown. This review systematically depicts the initiation and modulation of ferroptosis and summarizes the contribution of ferroptosis to AS, which may open a feasible approach for target treatment in the alleviation of AS progression.Keywords: ferroptosis, iron overload, oxidation, lipid peroxidation, atherosclerosis

Junfeng Zhao,1,2,&ast; Shaoyu Hao,3,4,&ast; Jing Tian,5 Ying Li,6 Dan Han1,2 1Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Thoracic Surgery, Shandong University Cancer Center, Jinan, Shandong, People’s Republic of China; 4Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 5Department of Radiation Oncology, Jinan Zhangqiu District People’s Hospital, Jinan, Shandong, People’s Republic of China; 6Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan Han, Department of Radiation Oncology, Shandong University Cancer Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China, Tel +86-17862893373, Email echohandan@163.comPurpose: This study compares the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT) combined with radical esophagectomy in patients with resectable, locally advanced esophageal squamous cell cancer (ESCC).Patients and Methods: Patients with locally advanced ESCC treated with NICT or NCRT combined with esophagectomy between March 2016 and May 2022 were retrospectively analyzed and propensity score matched (PSM) in a 1:2 ratio to balance potential bias.Results: After PSM, 110 patients who received NCRT and 55 patients who received NICT were selected for the final analysis. The probability of tumor regression grade 0 and the rate of pathological complete remission (pCR) were significantly higher in the NCRT group than in the NICT group (57.3% vs 32.7%, P=0.003 and 48.2% vs 29.1%, P=0.030, respectively). The incidence of postoperative complications in the NCRT group was not significantly different from that in the NICT group (P=0.082). Patients in the NCRT group had significantly better disease-free survival (DFS) and overall survival (OS) than those in the NICT group (12-month DFS rate: 94.3% vs 81.8%, P=0.006; 12-month OS rate: 100.0% vs 95.4%, P=0.032). However, the results of the 24-month follow-up showed that there was also a statistically significant difference in DFS between the two groups. Patients with postoperative pCR had a longer DFS (P< 0.001).Conclusion: Short-term follow-up results show that NCRT has a significantly better pathologic response and prognosis than NICT in the treatment of patients with locally advanced ESCC. NCRT and NICT have similar safety profiles.Keywords: esophageal squamous cell carcinoma, neoadjuvant, chemoradiotherapy, immunotherapy, immune checkpoint inhibitor, esophagectomy

Jinlai Tian,1 Yun Zhou,1,2 Shenggang Yu1 1School of Educational Science, Beihua University, Jilin City, People’s Republic of China; 2Jilin Agricultural Science and Technology University, Jilin City, People’s Republic of ChinaCorrespondence: Shenggang Yu, School of Educational Science, Beihua University, Jilin Street 15, Jilin City, Jilin Province, 132013, People’s Republic of China, Tel/Fax +86-432-64602516, Email yusg445@126.comBackground/Objective: This mixed-methods research aimed to examine the impact of the Healthy Teachers Program (HTP) on special education teacher career resilience.Methods: Forty special education teachers recruited from Jilin, China, were randomly assigned to the intervention group (n =20) and the control (n =20) group. Data were collected using self-report questionnaires. The intervention group was taught eight program lessons by a school psychology teacher, which covered topics related to understanding career resilience, supporting self-awareness, changing career goals, and establishing interpersonal relationships. The researchers statistically analyzed the data collected at three-time points with repeated-measures analysis of variance and also conducted the focus group method to collect qualitative data for the social validity of HTP.Results: The HTP positively influences the career resilience of special education teachers and has a high degree of social validity in the social significance of the goals and the social importance of the effects but an insufficient degree in the social appropriateness of the procedures. The findings of this study indicate the feasibility and applicability of the HTP to enhance the career resilience of teachers and its limitations in Chinese special school settings.Conclusion: The health teachers program can effectively improve the career resilience of special education teachers and has a high degree of social validity.Keywords: career resilience, intervention program, Chinese special education school teachers, social validity

Le Zhuang,1– 6,&ast; Jie Tian,1– 4,7,&ast; Binbin Lai,1– 4,7 Guohong Zhang,1– 4 Hang Li1– 4 1Department of Dermatology, Peking University First Hospital, Beijing, People’s Republic of China; 2National Clinical Research Center for Skin and Immune Diseases, Peking University First Hospital, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Peking University First Hospital, Beijing, People’s Republic of China; 4NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Peking University First Hospital, Beijing, People’s Republic of China; 5Dermatology Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 6Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China; 7Institute of Medical Technology, Peking University Health Science Center, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hang Li, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China, Tel +8613693058190, Fax +861083572350, Email drlihang@126.comBackground: Anti-programmed cell death ligand-1 (anti-PD-L1) immunotherapy is often used for advanced urothelial carcinoma and melanoma, including amelanotic melanoma, a relatively rare subtype with little to no pigment in the tumor cells. However, cellular heterogeneity of amelanotic melanoma during or after anti-PD-L1 immunotherapy treatments has not been described.Purpose: To investigate cellular heterogeneity in acral amelanotic melanoma after immunotherapy exposure.Methods: We evaluated subtle visual changes of the melanoma by dermoscopy and performed a pathological examination to analyze the heterogeneity of microscopic morphological and immunohistochemistry changes. The cellular transcriptional heterogeneity and corresponding biological function profiles of the melanoma were determined by single-cell RNA sequencing (scRNA-seq).Results: The dermoscopic examination revealed black globules and scar-like depigmentation areas against a homogeneous red background. Pigmented and amelanotic melanoma cells were observed microscopically. The pigmented cells were large and contained melanin granules expressing Melan-A and HMB45; the amelanotic cells were small and did not express HMB45. Ki-67 immunohistochemical staining revealed that the pigmented melanoma cells had a higher proliferative ability than the amelanotic cells. scRNA-seq identified three cell clusters: amelanotic cell cluster 1, amelanotic cell cluster 2, and pigmented cell cluster. Furthermore, a pseudo-time trajectory analysis showed that amelanotic cell cluster 2 originated from amelanotic cell cluster 1 and transformed into the pigmented melanoma cell cluster. The expression pattern of melanin synthesis-related and lysosome-endosome-related genes in different cell clusters supported the cell cluster transformation results. Also, upregulated expression of cell cycle genes indicated that the pigmented melanoma cells had a high proliferative ability.Conclusion: Coexisting amelanotic and pigmented melanoma cells indicated cellular heterogeneity in an acral amelanotic melanoma from a patient who underwent immunotherapy treatment. Additionally, the pigmented melanoma cells acquired a higher proliferative ability than the amelanotic melanoma cells.Keywords: amelanotic, acral melanoma, cellular heterogeneity, immunotherapy, drug resistance

Yunyue Liu,1,* Mengyu Su,1,* Yang Lei,1 Jinping Tian,1,2 Leng Xue,1 Lin Zhang1 1School of Nursing, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Cardiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang Lei, School of Nursing, Nanjing Medical University, No. 101, Longmian Avenue, Jiangning District, Nanjing, Jiangsu Province, People’s Republic of China, Tel +86 19955062997, Fax +86 258 6869 555, Email nursleiyang@njmu.edu.cn Jinping Tian, The First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou Road, Gulou District, Nanjing, Jiangsu Province, People’s Republic of China, Tel +86 13851550156, Fax +86 519 6809 1881, Email tianjp6@163.comBackground: Although a large number of studies have demonstrated the effectiveness of cardiac rehabilitation(CR), patient preferences for CR remain unclear. Knowing patient preferences may contribute to increasing patient participation and adherence, thus improving patient prognosis.Methods: A systematic search was carried out using electronic databases and manual reference checks from inception until 15th June 2022. Quantitative studies, qualitative studies and mixed methods studies assessing patient preferences for CR were included. Two researchers independently conducted study selectionand data extraction. CR preferences were divided into three categories: CR settings, CR components, and CR contents. A narrative synthesis was applied to integrate the results of the included studies. The Mixed Methods Appraisal Tool (MMAT) was used to assess the quality of included studies.Results: Ultimately, 17 publications were included in this study. Regarding CR settings, most patients preferred the hospital to home, some considered both, and a few were willing to accept the local CR club as an alternative setting to the hospital. For CR components, regardless of age and gender, patients considered exercise training and nutrition counseling to be the most important and smoking cessation to be the least important. In exercise intervention of CR contents, progress discussion and encouragement were rated as most critical, and non-conflicting with other activities was rated as least critical. In psychological intervention of CR contents, most patients were willing to accept psychological intervention, and a few patients wanted to heal the trauma with the passage of time.Conclusion: This systematic review provides important insights into patient preferences for CR, clarifying patient preferences for CR settings, components, and contents, along with possible influencing factors. Patient preferences may change due to the COVID-19 epidemic, and there is still a need to focus on patient preferences for CR and conduct more relevant primary research to validate the findings of this paper in the future.Keywords: cardiac rehabilitation, patient preference, systematic review, COVID-19

Jingjing Yan,1 Jing Tian,1,2 Hong Yang,1 Gangfei Han,2 Yanling Liu,1 Hangzhi He,1 Qinghua Han,2 Yanbo Zhang3,4 1Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Shanxi University of Chinese Medicine, Taiyuan, People’s Republic of ChinaCorrespondence: Yanbo Zhang, Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Shanxi Medical University, No. 56 South Xinjian Road, Taiyuan, Shanxi Province, 030001, People’s Republic of China, Tel +86 3543985051, Email sxmuzyb@126.com Qinghua Han, Department of Cardiology, The First Hospital of Shanxi Medical University, No. 85 South Jiefang Road, Taiyuan, Shanxi Province, 030001, People’s Republic of China, Tel +86 3100113031, Fax +86 3514867146, Email syhqh@sohu.comBackground: Chronic heart failure (CHF) affects more than 3.8 million people worldwide. There is a paucity of studies focusing on psychosocial issues in CHF patients. This study aimed to investigate the association of social support, mental adjustment and death to exploring whether mental adjustment could mediate the relationship.Methods: From May 2017 to June 2021, we conducted a multicenter clinical study to collect 1552 patients data. The Patient Report Outcome (PRO) scale were disseminated to collect information in the physical, psychological, social and therapeutic domains of patients. Marginal structural model was used to investigate the association of social support and CHF death, and the role of mental adjustment in their mediation.Results: The direct effect of social support accounted for 44.76% of the total effect. High social support (≥ 14 points) reduced mortality by 46.3% (RR=0.537, P=0.027), medium social support (11– 14 points) reduced mortality by 45.3% (RR=0.547, P=0.042). Anxiety (effect percentage: 24.63%) and appetite-sleep quality (effect percentage: 30.61%) played a mediating role between social support and death in CHF patients. In women, aged > 75 years, divorced or widowed patients were most prone to anxiety due to inadequate support (RR=0.519, P=0.019; RR=0.403, P=0.002; RR=0.413, P=0.041). Family care and socioeconomic assistance significantly reduced the risk of death (RR=0.689, P=0.040; RR=0.584, P=0.012).Conclusion: Social support can reduce patient mortality, especially family care and social economic assistance. The elderly, female, divorced or widowed patients are more likely to cause mental illness due to inadequate social support.Keywords: chronic heart failure, social support, marginal structural model, mediation analysis

Jing Tian,1,2 Fengqin Ding,3 Ruoya Wang,3 Gangfei Han,1 Jingjing Yan,3 Na Yuan,3 Yutao Du,3 Qinghua Han,1 Yanbo Zhang2– 4 1Department of Cardiology, the 1st Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, People’s Republic of China; 3Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of ChinaCorrespondence: Yanbo Zhang, Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 3327518812, Email sxmuzyb@126.com Correspondence: Qinghua Han, Department of Cardiology, the 1st Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 3100113031, Email syhqh@sohu.comPurpose: This study aimed to identify subgroups of chronic heart failure (CHF) patients with distinct trajectories of quality of life (QOL) and to identify baseline characteristics associated with the trajectories.Patients and methods: Two-year, prospective, cohort study including 315 patients with CHF was conducted from July 2017. Information on QOL assessed by CHF-patient-reported outcomes measure (CHF-PROM) was collected at baseline, 6, 12, 18, and 24 months. Demographic and clinical variables were recorded at baseline. Growth mixture model was used to identify distinct trajectories of CHF-PROM and its physical, psychological, social, and therapeutic domains. Single factor analysis was employed to assess the factors associated with development of CHF-PROM over time.Results: Two classes of overall score of CHF-PROM were identified: poorer (14.0%) and better (86.0%). Poorer class tended to be aged, have low diastolic blood pressure, have concomitant atrial fibrillation, diabetes, chronic obstructive pulmonary disease, cancers, and central nervous system diseases, and used nitrates. Three classes of physical scores were identified: unstable-poorer (5.2%), stable-poorer (29.4%) and better (65.4%). Age, NYHA grade, chronic obstructive pulmonary disease, combined with cancers and central nervous system diseases were related to the grouping. Poorer (8.6%) and better (91.4%) classes of psychological scores were identified. Poorer class tended to be female and had concomitant atrial fibrillation. Degenerate class (34.6%) and meliorate class (65.4%) of therapeutic scores were identified. Degenerate class tended to have concomitant chronic obstructive pulmonary disease and use less angiotensin converting enzyme inhibitors.Conclusion: We identified different classes with distinct trajectories of QOL that may help proper evaluate QOL and further improve its status for patients CHF.Keywords: patient-reported outcome, chronic heart failure, growth mixture model, dynamic trajectory

Jianing Tian,1 Hongyan Yu,1 Larry Austin2 1Department of Physical Education, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2International Division, Shanghai Gezhi Middle School, Shanghai, People’s Republic of ChinaCorrespondence: Hongyan Yu, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Email yuhongyan@sjtu.edu.cnPurpose: To explore the role of subjective well-being in the relationship between physical activity (PA) and anxiety and whether the model is moderated by gender.Methods: We conducted a questionnaire survey by selecting 1153 college students from Shanghai Jiao Tong University in China, and data were analyzed using SPSS, Process, and AMOS.Results: 1) Correlation analysis showed that PA, subjective well-being, and anxiety were significantly related. Also, we found subjective well-being to differ significantly on the demographic variable registered residence. 2) Subjective well-being played a mediating role between PA and anxiety. 3) Gender played a moderating role in the direct effect of PA on anxiety, shown by the significant difference in the path coefficients between the male and female models (male: β = − 0.03, p > 0.05, female: β = 0.10, p < 0.05).Conclusion: Subjective well-being mediated the relationship between PA and anxiety, and gender moderated the mediating model. These findings highlight the importance of PA in reducing anxiety and increasing subjective well-being in the context of an epidemic.Keywords: subjective well-being, physical activity, anxiety, college students

Abstract To address the challenging task of effective sound absorption in the low and broad frequency band for underwater structures, we propose a novel grating‐like anechoic layer by filling rubber blocks and an air backing layer into metallic grating. The metallic gratings are incorporated into the anechoic layer as a skeleton for enhanced viscoelastic dissipation by promoting shear deformation between rubber and metal plates. The introduction of an air backing layer releases the bottom constraint of the rubber, thus intensifying its deformation under acoustic excitation. Based on the homogenization method and the transfer matrix method, a theoretical model is developed to evaluate the sound absorption performance of the proposed anechoic layer, which is validated against finite element simulation results. It is demonstrated that a sound absorption coefficient of the grating‐like anechoic layer of 0.8 can be achieved in the frequency range of 1294–10 000 Hz. Given the importance of sound absorption at varying frequencies, the weighted average method is subsequently used to comprehensively evaluate the performance of the anechoic layer. Then, with structural density taken into consideration, an integrated index is proposed to further evaluate the acoustic properties of the proposed anechoic layer. Finally, the backing conditions and the boundary conditions of finite‐size structures are discussed. The results provide helpful theoretical guidance for designing novel acoustic metamaterials with broadband low‐frequency underwater sound absorption.

Teng Zhu,&ast; Jing Sun,&ast; Lin Ma, Jing Tian Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Ma, Department of Dermatology, Beijing Children’s hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China, Tel/Fax +8601059616161, Email bch_maleen@aliyun.comPurpose: Exosomes are important regulators of keratinocytes (KCs) that have been implicated in a variety of skin disorders. The effect of circulatory exosomes on KCs in pediatric atopic dermatitis (AD) has not been well studied. This study aims to explore the effect of plasma exosomes on KC activation, apoptosis and inflammation in pediatric AD patients.Patients and Methods: Exosomes were extracted from plasma collected from 20 pediatric AD patients and 20 age-matched healthy controls. AD-exosomes were added with KCs at concentrations of 0 g/L, 10 g/L, 20 g/L and 30 g/L. Proliferation of KCs in each group was measured using Ki67 staining flow cytometry. Apoptosis was measured using Annexin V-FITC/PI double staining flow cytometry. KCs were divided into three groups according to the source of the exosomes they were cultured with: patients with AD, healthy controls and blank controls. Q-PCR was used to detect the activation (K6) and differentiation (K10) of cells, as well as inflammatory indicators (thymic stromal lymphopoietin (TSLP) and IL-33).Results: The proliferation rate of KCs treated with 20 g/L exosomes from AD patients was significantly lower than that of other groups, while the apoptosis rate was significantly increased. Additionally, expression levels of K6, K10, TSLP and IL-33 were all up-regulated compared to keratinocytes treated with exosomes from healthy controls.Conclusion: Exosomes from the peripheral blood of pediatric AD patients can regulate the activation, apoptosis and inflammatory cytokine secretion of KCs in vivo, which may participate in the pathogenesis of AD.Keywords: atopic dermatitis, children, plasma, exosome, keratinocyte

Yanlei Li,1,2,&ast; Jinlong Tian,1,2,&ast; Meng Ge,1,2,&ast; Lichen Ji,1,3 Yao Kang,1 Chen Xia,1 Jun Zhang,1,2 Yazeng Huang,1,2 Fabo Feng,1 Tingxiao Zhao,1,2 Haiyu Shao1 1Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, People’s Republic of China; 2Bengbu Medical College, Bengbu, People’s Republic of China; 3Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyu Shao; Tingxiao Zhao, Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Shangtang Road 158#, Hangzhou, 310014, People’s Republic of China, Email shaohaiyu@163.com; spinezhaotingxiao@163.comBackground: With the aging population growth in the world, the prevalence of osteoporotic vertebral compression fracture (OVCF) is rapidly increasing and receiving widespread attention. Although there are numerous articles on the topic, the research status and hotspot analysis are unclear.Objective: The goal of this study is to identify trends in the OVCF field and to analyze the most highly cited original articles published in the Web of Science Index on OVCF using bibliometric analysis.Methods: All OVCF data were obtained from the Web of Science Core Collection, and the number of citations, institutions, journals, countries, and years of publication in this field were visually analyzed using VOSviewer, the bibliometrics online analysis platform, and Excel software. Simultaneously, the top 100 most cited articles were extracted and analyzed.Results: A total of 756 publications were related to OVCF were included from 1900 to 2022. In recent years, the number of articles on OVCF significantly increased. They are mainly from 41 countries/regions and 202 journals, led by China and the United States. Among all countries, China had the most significant contribution on OVCF (n = 363), and it also was cited most often (n = 3337). The institution with the most articles was Soochow University (n = 40). Osteoporosis International was the journal with most studies and has published 50 on this field. The journal of Spine was cited most often (n = 1968). The most productive periods were from 2016 to 2020, which received 294 articles and 4868 citations. After the analysis, the “vertebroplasty” and “kyphoplasty” of OVCF have been the most common research hotspots.Conclusion: This study represents an updated bibliometric analysis of OVCF. The aim is to identify current research hotspots and future trends to guide clinicians and researchers in this field.Keywords: osteoporotic vertebral compression fracture, OVCF, bibliometric analysis, VOSviewer, Web of Science, research trends

Lan Ma,1,2 Zhengpu Han,1,2 Haoyu Yin,1,2 Jiaqi Tian,1,2 Jing Zhang,3 Ning Li,3 Chunjie Ding,4 Lin Zhang2 1School of Public Health, Weifang Medical University, Weifang, 261053, People’s Republic of China; 2Clinical Medical Research Center for Women and Children Diseases, Maternal and Child Health Care Hospital of Shandong Province, Shandong University, Jinan, 250001, People’s Republic of China; 3School of Public Health, North China University of Science and Technology, Tangshan, 063210, People’s Republic of China; 4School of Public Health, Xinxiang Medical University, Xinxiang, 453000, People’s Republic of ChinaCorrespondence: Lin Zhang, Clinical Medical Research Center for Women and Children Diseases, Maternal and Child Health Care Hospital of Shandong Province, Shandong University, Jinan, 250001, People’s Republic of China, Tel +86-531-68795046, Email zhanglin8901@163.comIntroduction: Silica nanoparticles (SiNPs) are one of the most widely used inorganic nanomaterials, and exposure to SiNP has been demonstrated to induce pulmonary inflammation, primarily promoted by the NLRP3-mediated macrophage pyroptosis. However, mechanisms underlying the activation of NLRP3 signaling are complex, and whether cathepsin B (CTSB), an enzyme released by the ruptured lysosome, could trigger NLRP3 assembly is controversial.Methods: To further characterize the role of CTSB in silica-induced pyroptosis, we conducted this study by establishing SiNP exposure models in vitro. The morphological features of SiNPs were exhibited by the SEM and TEM, and the effects of SiNPs’ internalization on macrophages were examined by the TEM and immunofluorescent staining. Moreover, Western blot was performed to detect the expression of proteins related to pyroptosis and CTSB after blocking the expression of NLRP3 and CTSB.Results: We found that SiNPs internalization caused the rupture of macrophage membrane and promoted the aging of cells with increased intracellular vacuoles. Also, the expression of NLRP3, ASC, Caspase-1, GSDMD, Pro-IL-1β, IL-1β, and CTSB increased under the stimulation of SiNP, which could be suppressed by additional treatment with MCC950, an NLRP3-specific inhibitor. Besides, we found SiNP joint treatment with leupeptin, a CTSB inhibitor, could inhibit the expression of CTSB, but it had no effect on the expression of NLRP3, ASC, and Caspase-1, and the process of macrophage pyroptosis was also not affected.Conclusion: SiNP exposure induces rupture of macrophages and the release of lysosomal CTSB, but CTSB fails to specifically act on the NLRP3 inflammasome to induce pyroptosis which is causally linked to lung inflammation and fibrosis.Keywords: silica nanoparticles, NLRP3 inflammasome, cathepsin B, pyroptosis, macrophage

Lei Zhang,1,&ast; Bing Wang,2,&ast; Guo Yin,2 Jue Wang,2 Ming He,3 Yuqi Yang,4 Tiejie Wang,2 Ting Tang,3 Xie-An Yu,2 Jiangwei Tian1 1State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 211198, People’s Republic of China; 2NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen, Guangdong Province, 518057, People’s Republic of China; 3Dermatology Department, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, 550002, People’s Republic of China; 4School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, 550002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xie-An Yu; Jiangwei Tian, Email yuxieanalj@126.com; jwtian@cpu.edu.cnIntroduction: Urinary tract infections (UTI) are one of the most serious human bacterial infections affecting millions of people every year. Therefore, simple and reliable identification of the urinary tract pathogenic bacteria within a few minutes would be of great significance for diagnosis and treatment of clinical patients with UTIs. In this study, the fluorescence sensor was reported to guide the detection of urinary tract bacterial infections rapidly.Methods: The Ami-AuNPs-DNAs sensor was fabricated by the amino-modified Au nanoparticles (Ami-AuNPs) and six DNAs signal molecules, which bound to the urinary tract pathogenic bacteria and generated corresponding response signals. Further, based on the collected response signals, identification was performed by principal component analysis (PCA) and linear discriminant analysis (LDA). The Ami-AuNPs and Ami-AuNPs-DNAs were characterized by transmission electron microscopy, UV−vis absorption spectrum, Fourier transform infrared spectrum, dynamic light scattering and zeta potentials. Thereafter, the Ami-AuNPs-DNAs sensor was used to discriminate and identify five kinds of urinary tract pathogenic bacteria. Moreover, the quantitative analysis performance towards individual bacteria at different concentrations were also evaluated.Results: The Ami-AuNPs-DNAs sensor were synthesized successfully in terms of spherical, well-dispersed and uniform in size, which could well discriminate five main urinary tract pathogenic bacteria with unique fingerprint-like patterns and was sufficiently sensitive to determine individual bacteria with a detection limit to 1× 107 cfu/mL. Furthermore, the sensor had also been successfully applied to identify bacteria in urine samples collected from clinical UTIs.Conclusion: The developed fluorescence sensor could be applied to rapid and accurate discrimination of urinary tract pathogenic bacteria and holds great promise for the diagnosis of the disease caused by bacterial infection.Keywords: fluorescence sensor, rapid and accurate identification, point-of-care testing, bacterial infection, urinary tract infections

Shoujun Xu,1,&ast; Meng Li,2,&ast; Chunlan Yang,3 Xiangling Fang,4 Miaoting Ye,4 Yunfan Wu,2 Binrang Yang,4 Wenxian Huang,4 Peng Li,1 Xiaofen Ma,2 Shishun Fu,2 Yi Yin,2 Junzhang Tian,2 Yungen Gan,1 Guihua Jiang2 1Department of Radiology, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 2Department of Medical Imaging, Guangdong Second Provincial General Hospital, Guangzhou, People’s Republic of China; 3Department of Hematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 4Department of Department of Children Healthcare, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Guihua Jiang; Yungen Gan, Email jianggh@gd2h.org.cn; gdszgyg-1@126.comPurpose: This study used the graph-theory approach, degree centrality (DC) to analyze whole-brain functional networks at the voxel level in children with ASD, and investigated whether DC changes were correlated with any clinical variables in ASD children.Methods: The current study included 86 children with ASD and 54 matched healthy subjects Aged 2– 5.5 years. Next, chloral hydrate induced sleeping-state functional magnetic resonance imaging (ss-fMRI) datasets were acquired from these ASD and healthy subjects. For a given voxel, the DC was calculated by calculating the number of functional connections with significantly positive correlations at the individual level. Group differences were tested using two-sample t-tests (p < 0.01, AlphaSim corrected). Finally, relationships between abnormal DCs and clinical variables were investigated via Pearson’s correlation analysis.Results: Children with ASD exhibited low DC values in the right middle frontal gyrus (MFG) (p

Haohan Zhou,1,2,&ast; Jiayi Tian,3,&ast; Hongyu Sun,1 Jiaying Fu,1 Nan Lin,1 Danni Yuan,1 Li Zhou,3 Meihui Xia,3 Liankun Sun1 1Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, 200000, People’s Republic of China; 3First Hospital, Jilin University, Changchun, 130021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liankun Sun, Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, People’s Republic of China, Email sunlk@jlu.edu.cn Meihui Xia, First Hospital, Jilin University, Changchun, 130021, People’s Republic of China, Email xiamh@jlu.edu.cnPurpose: Magnetic iron oxide nanoparticle (MNP) drug delivery system is a novel promising therapeutic option for cancer treatment. Material issues such as fabrication and functionalized modification have been investigated; however, pharmacologic mechanisms of bare MNPs inside cancer cells remain obscure. This study aimed to explore a systems pharmacology approach to understand the reaction of the whole cell to MNPs and suggest drug selection in MNP delivery systems to exert synergetic or additive anti-cancer effects.Methods: HeLa and SiHa cell lines were used to estimate the properties of bare MNPs in cervical cancer through 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and enzyme activity assays and cellular fluorescence imaging. A systems pharmacology approach was utilized by combining bioinformatics data mining with clinical data analysis and without a predefined hypothesis. Key genes of the MNP onco-pharmacologic mechanism in cervical cancer were identified and further validated through transcriptome analysis with quantitative reverse transcription PCR (qRT-PCR).Results: Low cytotoxic activity and cell internalization of MNP in HeLa and SiHa cells were observed. Lysosomal function was found to be impaired after MNP treatment. Protein tyrosine kinase 2 beta (PTK2B), liprin-alpha-4 (PPFIA4), mothers against decapentaplegic homolog 7 (SMAD7), and interleukin (IL) 1B were identified as key genes relevant for MNP pharmacology, clinical features, somatic mutation, and immune infiltration. The four key genes also exhibited significant correlations with the lysosome gene set. The qRT-PCR results showed significant alterations in the expression of the four key genes after MNP treatment in HeLa and SiHa cells.Conclusion: Our research suggests that treatment of bare MNPs in HeLa and SiHa cells induced significant expression changes in PTK2B, PPFIA4, SMAD7, and IL1B, which play crucial roles in cervical cancer development and progression. Interactions of the key genes with specific anti-cancer drugs must be considered in the rational design of MNP drug delivery systems.Keywords: drug delivery, anti-cancer drugs, PTK2B, PPFIA4, SMAD7, IL1B

Luoyang Ma,1,2 Xiaoyan Zheng,1,3 Rui Lin,1 Antonia RuJia Sun,4 Jintong Song,1 Zhiqiang Ye,1 Dahong Liang,1 Min Zhang,1 Jia Tian,1 Xin Zhou,2 Liao Cui,1 Yuyu Liu,1 Yanzhi Liu1,3,5 1Guangdong Provincial Key Laboratory for Research and Development of Natural Drug, School of Pharmacy, Guangdong Medical University, Zhanjiang City, Guangdong Province, 524023, People’s Republic of China; 2Marine Medical Research Institute of Zhanjiang, Zhanjiang City, Guangdong Province, 524023, People’s Republic of China; 3Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang city, Guangdong province, 524045, People’s Republic of China; 4Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen City, Guangdong Province, 518055, People’s Republic of China; 5Shenzhen Osteomore Biotechnology Co., Ltd., Shenzhen city, Guangdong Province, 518118, People’s Republic of ChinaCorrespondence: Yanzhi Liu; Yuyu Liu, Tel +86-759-2388405 ; +86-759-2388588, Email liuyanzhi02@163.com; liuyuyu77@163.comAbstract: Drug delivery for osteoarthritis (OA) treatment is a continuous challenge because of their poor bioavailability and rapid clearance in joints. Intra-articular (IA) drug delivery is a common strategy and its therapeutic effects depend mainly on the efficacy of the drug-delivery system used for OA therapy. Different types of IA drug-delivery systems, such as microspheres, nanoparticles, and hydrogels, have been rapidly developed over the past decade to improve their therapeutic effects. With the continuous advancement in OA mechanism research, new drugs targeting specific cell/signaling pathways in OA are rapidly evolving and effective drug delivery is critical for treating OA. In this review, recent advances in various IA drug-delivery systems for OA treatment, OA targeted strategies, and related signaling pathways in OA treatment are summarized and analyzed based on current publications.Keywords: osteoarthritis, knee, drug delivery, intra-articular

Shasha Duan,1– 3,&ast; Chao Wang,1,2,&ast; Xiangli Xu,4 Xiaoshan Zhang,3 Gaofeng Su,1,2 You Li,1,2 Shuai Fu,1,2 Ping Sun,1,2 Jiawei Tian1 1Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, People’s Republic of China; 3Department of Ultrasound, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, People’s Republic of China; 4Department of Ultrasound, the Second Hospital of Harbin city, Harbin, Heilongjiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiawei Tian; Ping Sun, Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150086, People’s Republic of China, Tel +86 451-86605811, Fax +86 451-86605745, Email jwtian2004@163.com; sunpinghmu@163.comPurpose: Angiogenesis is required for improving myocardial function and is a key factor in long-term prognosis after an acute myocardial infarction (AMI). Although exosomes are known to play a crucial role in angiogenesis, the role of peripheral exosomes in angiogenic signal transduction in patients with AMI remains unclear. Here, we explored the effect of exosomes extracted from the peripheral serum of AMI patients on angiogenesis and elucidated the downstream pathways.Patients and Methods: Serum exosomes were obtained from patients with AMI (AMI-Exo) and healthy individuals (Con-Exo). The exosomes were cocultured with human umbilical vein endothelial cells (HUVECs) in vitro, with aortic rings ex vivo, and were used to treat mouse hind-limb ischemia and mouse AMI model in vivo.Results: AMI-Exo raised HUVEC proliferation, tube formation, and migration, and enhanced microvessel sprouting from aortic rings compared to Con-Exo, both in vitro and ex vivo. Quantitative reverse transcription-polymerase chain reaction revealed that the abundance of miR-126-3p, a crucial regulator of angiogenesis, was increased in AMI-Exo. The inhibition of miR-126-3p decreased the benefits of AMI-Exo treatment, and miR-126-3p upregulation enhanced the benefits of Con-Exo treatment in HUVECs, aortic rings, the mouse hind-limb ischemia model, and the mouse AMI model. Knockdown and overexpression analyses revealed that miR-126-3p regulated angiogenesis in HUVECs by directly targeting tuberous sclerosis complex 1 (TSC1). Moreover, we found that miR-126-3p could inhibit TSC1 expression, which further activated mTORC1 signaling and increased HIF-1α and VEGFA expression, ultimately promoting angiogenesis.Conclusion: Collectively, our results provide a novel understanding of the function of exosomes in angiogenesis post AMI. We demonstrated that exosomes from the peripheral serum of AMI patients promote angiogenesis via the miR-126-3p/TSC1/mTORC1/HIF-1α signaling pathway.Keywords: acute myocardial infarction, angiogenesis, exosomes, miR-126-3p, tuberous sclerosis complex 1

Wei Cheng, Fen Li, Jing Tian, Xi Xie, Jin-Wei Chen, Xiao-Fei Peng, Qi Tang, Yan Ge Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaCorrespondence: Yan Ge, Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China, Email geyan2003@csu.edu.cnAbstract: Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare autoinflammatory disease characterized by dermatological disorders and osteoarticular inflammatory lesions. This article reviews the application of biologics and other treatments based on the therapeutic target and the size of molecules in SAPHO syndrome. We found that drugs, especially biologics, have different effects on bone, joint, and skin damage. This may relate to the different inflammatory pathways involved in the osteoarticular and cutaneous symptoms in SAPHO patients. In this study, we provide stratified medication recommendations for SAPHO syndrome. Patients with osteoarticular symptoms can consider tumor necrosis factor blockers, JAK inhibitor, interleukin (IL)-1 inhibitor, and IL-17 inhibitor. Patients with cutaneous symptoms should consider IL-17 and JAK inhibitors. Apremilast, Tripterygium wilfordii Hook F, and bisphosphonates are other effective treatments.Keywords: SAPHO, osteoarticular symptoms, cutaneous symptoms, immune pathway pathways, biologics, targeted small molecule compounds

Meng Ge,1,2,&ast; Yuan Zhang,2,3,&ast; Yanlei Li,1,2,&ast; Chenchen Feng,1,2,&ast; Jinlong Tian,1,2 Yazeng Huang,1,2 Tingxiao Zhao1 1Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Bengbu Medical College, Bengbu, People’s Republic of China; 3Center for General Practice Medicine, Department of Rheumatology and Immunology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingxiao Zhao; Yazeng Huang, Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Shangtang Road 158#, Hangzhou, Zhejiang, 310014, People’s Republic of China, Email spinezhaotingxiao@163.com; huangyazeng2007@163.comBackground: In recent years, the research on subacromial impingement syndrome (SIS) has gradually increased. Although the research directions are diverse, the overall research status and trend are not clear.Objective: The aim of our study was to use bibliometric analysis to identify the trends in SIS-related research and to analyze the most highly cited scientific publications on SIS.Methods: All data were retrieved from the Web of Science Core Collection database, and the year of publications, countries, journals, institutions and total number of citations were extracted and analyzed. The results related to countries, institutions and keywords were then analyzed using VOSviewer software and bibliometrics online analysis platform. And, we also identified the 100 most cited articles on SIS.Results: A total of 548 articles related to AIS were identified. The frequency of publication on SIS has increased substantially over time. Among all countries, Turkey has contributed the most publications on SIS (n=118). The institution with the most articles was Istanbul University (n=17). Journal of Shoulder and Elbow Surgery topped the list of journals and has published 19 SIS-related publications. The hotspot of research changed from the former arthroscopic surgery to physical therapy and rehabilitation.Conclusion: The scientific research on SIS has rapidly expanded in recent years. This study represents the first bibliometric analysis of SIS, gives us a systematic and comprehensive summary into the development of SIS.Keywords: subacromial impingement syndrome, SIS, bibliometric analysis, research trends, VOSviewer, Web of Science

Shijiao Ma,1 Chenchen Gu,1 Junjie Xu,1 Jinxin He,2 Shuli Li,1 Haolan Zheng,1 Bo Pang,1 Ying Wen,1 Qiaojun Fang,3 Weiquan Liu,1 Jiesheng Tian1 1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, People’s Republic of China; 2College of Veterinary Medicine, Shanxi Agriculture University, Taigu, Shanxi, 030801, People’s Republic of China; 3CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, People’s Republic of ChinaCorrespondence: Weiquan Liu; Jiesheng Tian, Tel/Fax +8610-62732676 ; +8610-62731440, Email weiquan8@cau.edu.cn; tianhome@cau.edu.cnPurpose: Nanoparticles (NPs) decorated with functional ligands are promising candidates for cancer diagnosis and treatment. However, numerous studies have shown that chemically coupled targeting moieties on NPs lose their targeting capability in the biological milieu because they are shielded or covered by a “protein corona”. Herein, we construct a functional magnetosome that recognizes and targets cancer cells even in the presence of protein corona.Methods: Magnetosomes (BMPs) were extracted from magnetotactic bacteria, M. gryphiswaldense (MSR-1), and decorated with trastuzumab (TZ) via affibody (RA) and glutaraldehyde (GA). The engineered BMPs are referred to as BMP-RA-TZ and BMP-GA-TZ. Their capacities to combine HER2 were detected by ELISA, the quantity of plasma corona proteins was analyzed using LC-MS. The efficiencies of targeting SK-BR-3 were demonstrated by confocal laser scanning microscopy and flow cytometry.Results: Both engineered BMPs contain up to ∼ 0.2 mg TZ per mg of BMP, while the quantity of HER2 binding to BMP-RA-TZ is three times higher than that binding to BMP-GA-TZ. After incubation with normal human plasma or IgG-supplemented plasma, GA-TZ-containing BMPs have larger hydrated radii and more surface proteins in comparison with RA-TZ-containing BMPs. The TZ-containing BMPs all can be targeted to and internalized in the HER2-overexpressing breast cancer cell line SK-BR-3; however, their targeting efficiencies vary considerably: 50– 75% for RA-TZ-containing BMPs and 9– 19% for GA-TZ-containing BMPs. BMPs were incubated with plasma (100%) and cancer cells to simulate human in vivo environment. In this milieu, BMP-RA-TZ uptake efficiency of SK-BR-3 reaches nearly 80% (slightly lower than for direct interaction with BMP-RA-TZ), whereas the BMP-GA-TZ uptake efficiency is < 17%.Conclusion: Application of the RA scaffold promotes and orients the arrangement of targeting ligands and reduces the shielding effect of corona proteins. This strategy improves the targeting capability and drug delivery of NP in a simulated in vivo milieu.Keywords: affibody, protein corona, magnetosomes, human epidermal growth factor receptor 2, HER2

Nickel smelting produces a large amount of nickel slag which contains a lot of Fe in the form of FeO. The effect of FeO content on the melting properties and structure of nickel slag is investigated by thermodynamic calculations and experiments, using the nickel slag of water quenching furnace as raw material, which is simplified to CaO-SiO2-FeO-MgO slag system. The results are as follows: with increasing FeO content, the precipitated primary phase changes from melilite to olivine. The liquidus temperature, softening temperature, hemispherical temperature, flow temperature, viscosity, and critical viscosity temperature of the slag system tend to decrease gradually, but the solid phase temperature tends to decrease first and then increase. The centre of the symmetric stretching vibration band of the [SiO4]4 tetrahedron -in the slag system shifts to the low wavenumber region. The mole fraction of O0 in the slag continuously decreases, and the mole fraction of O- and O2- increases. The complex silicon-oxygen tetrahedron structure gradually disintegrates and the structural unit tends to be simple.

Pretomanid is a nitroimidazooxazine antimycobacterial drug that was approved in more than 10 countries as part of a three-drug, all oral regimen, consisting of bedaquiline, pretomanid, and linezolid (BPaL) for 6-months treatment of adults with pulmonary extensively drug-resistant tuberculosis (XDR-TB) or with complicated forms of multidrug-resistant tuberculosis (MDR-TB). The toxicological profile of pretomanid was thoroughly evaluated in repeat-dose oral toxicity studies up to 39 weeks long in cynomolgus monkeys. Exposures up to 10-fold higher than in humans at the approved pretomanid dose (200 mg) were achieved in acute studies allowing for characterization of dose-limiting toxicity. Target organs and processes identified in acute and chronic toxicity studies included QT prolongation, nervous system effects, and liver effects (minimal hepatocellular hypertrophy without elevations in liver enzymes). In a 13-week study, no cataracts were present at the end of dosing, but 2 of 12 monkeys had cataracts at the end of a 13-week recovery period. No cataracts related to pretomanid administration were observed in subsequent 13-week or 39-week studies. No male reproductive toxicity was observed in these studies. No-observed-adverse-effect levels (NOAELs) were identified in all studies. Exposures at the NOAELs equaled, or exceeded, human exposure at the approved pretomanid dose with the exception of female monkeys in a 39-week chronic toxicity study. These data support the use of pretomanid as part of the 6-month BPaL regimen for treating XDR-TB and MDR-TB.

Jianpeng Li,1– 3,&ast; Jinlong Cao,1– 3,&ast; Pan Li,1– 3 Ran Deng,1– 3 Zhiqiang Yao,1– 3 Lijun Ying,1– 3 Junqiang Tian1– 3 1Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, People’s Republic of China; 2Key Laboratory of Gansu Province for Urological Diseases, The Second Hospital of Lanzhou University, Lanzhou, People’s Republic of China; 3Clinical Center of Gansu Province for Nephron-Urology, The Second Hospital of Lanzhou University, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junqiang TianDepartment of Urology, The Second Hospital of Lanzhou University, Lanzhou, 730030, People’s Republic of ChinaEmail ery_tianjq@lzu.edu.cnBackground: Clear cell renal cell carcinoma (ccRCC) is a commonly occurring tumor. Through a deeper understanding of the immune regulatory mechanisms in the tumor microenvironment, immunotherapy may serve as a potential treatment for cancer patients. This study aimed at identifying the survival-related immune cells and hub genes, which could be potential targets for immunotherapy in ccRCC.Methods: The gene expression profiles and clinical data of ccRCC patients were extracted from UCSC Xena and Gene Expression Omnibus (GEO) databases. Kaplan–Meier (KM) survival and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were utilized to select the survival-related tumor-infiltrating immune cells. Multivariate Cox regression was utilized to develop a signature based on the tumor-infiltrating immune cells (TIICs). Based on the signature, the risk score was calculated, following which the samples were divided into high-risk and low-risk groups. Differentially expressed genes (DEGs) between the two risk groups were identified. Functional enrichment analysis was performed and cytoHubba plug-in of Cytoscape was used to identify the hub genes. Multiple datasets were utilized to validate these hub genes, including the Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and the Human Protein Atlas (HPA), and the GEO datasets. Finally, a correlation analysis was performed to evaluate the relationship between the hub genes and TIICs.Results: Four immune survival-related cells, including T cell CD4 memory-activated, T cell regulatory (Tregs), eosinophils, and mast cell resting were identified. Nine immune-specific hub genes were identified, which included APOE, CASR, CTLA4, CXCL8, EGF, F2, KNG1, MMP9, and IL6. Furthermore, these hub genes were significantly correlated with clinical traits and closely associated with some TIICs.Conclusion: A total of four survival-related immune cell types and nine hub genes were found to be closely associated with ccRCC. These findings may have implications for the development of novel potential immunotherapeutic targets for ccRCC.Keywords: ccRCC, tumor-infiltrating immune cells, hub genes, TCGA, tumor microenvironment

Lin Mei,1,&ast; Xiaodan Li,1,&ast; Shengcai Wang,1,&ast; Run Si,2 Tingting Ji,1 Zhifei Xu,3 Yun Peng,4 Yue Liu,4 Hongbin Li,1 Jie Zhang,1 Yongli Guo,5 Jinghong Tian,6 Guifei Zhou,2 Huifang Huang,2 Jun Tai,1,7,&ast; Jiangang Liu,8,9 Xin Ni1 1Department of Otolaryngology, Head and Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2School of Computer and Information Technology, Beijing Jiaotong University, Beijing, People’s Republic of China; 3Department of Respiration, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing, People’s Republic of China; 4Department of Radiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 5Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, People’s Republic of China; 6Department of Neurorehabilitation, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 7Department of Otorhinolaryngology, Children’s Hospital, Capital Institute of Pediatrics, Beijing, People’s Republic of China; 8Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China; 9Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People’s Republic of China, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiangang LiuBeijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, 100191, People’s Republic of ChinaEmail jgliu@buaa.edu.cnXin NiDepartment of Otolaryngology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56 Nanlishilu, Beijing, People’s Republic of ChinaTel +86-139-1011-1999Email nixin@bch.com.cnObjective: To investigate the impacts of obstructive sleep apnea (OSA) on white matter (WM) integrity and cognitive functions of pediatric patients with different levels of OSA severity.Methods: Fifty-eight children with OSA and thirty-four healthy controls (HC) were recruited. All participants underwent diffusion tensor imaging (DTI) examination, polysomnography (PSG), and neurocognitive assessments. Patients were divided into mild OSA (MG) and moderate-severe OSA (SG) groups. WM integrity, PSG data, and neurocognitive assessment scores were compared among those groups.Results: For apnea hypopnea index (AHI), obstructive apnea hypopnea index (OAHI), arousal index, SpO2 nadir, and attention, SG was worse than both MG and HC with MG worse than HC. For baseline SpO2 and intelligence, SG was worse than both MG and HC with no significant difference between MG and HC. Impaired WM integrity was observed in bilateral anterior thalamic radiation, bilateral inferior fronto-occipital fasciculus, bilateral inferior longitudinal fasciculus, right superior longitudinal fasciculus, right hippocampus, left cingulate gyrus, right uncinate fasciculus, callosum forceps major, and callosum forceps minor only for SG than for HC. WM integrity was significantly correlated with OSA severity and neurocognitive assessment scores only for SG, but not for MG.Conclusion: Decreased baseline SpO2, WM impairment, and intelligence decline were all observed only for SG, but not for MG, implying an associated relationship among decreased SpO2, WM impairment and WM impairment. Thus, for SG, additional assessments of brain damage and cognitive function decline are needed for prognostic evaluation of OSA.Keywords: diffusion tensor imaging, obstructive sleep apnoea, children, tract-based spatial statistics, white matter

Jian Chen, Shu Li, Yan Ge, Jin Kang, Jia-fen Liao, Jin-feng Du, Jing Tian, Xi Xie, Fen Li Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Fen LiDepartment of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University, No. 139 Ren Min Middle Road, Changsha, 410011, People’s Republic of ChinaEmail lifen0731@csu.edu.cnBackground: Approximately 30% of patients with rheumatoid arthritis (RA) respond poorly to combination therapy of multiple drugs. The molecular mechanisms of different responses to methotrexate + leflunomide + infliximab therapy in patients with RA were explored in this study.Methods: Infliximab was administered to patients with RA whose disease activity score was higher than 5.1 after 1 month of combination therapy with methotrexate and leflunomide. After 14 weeks of undergoing triple therapy, patients with RA were classified as responders and non-responders. Protein profiles at baseline and 14th week were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and proteins with significant differences ≥ 1.2 folds change or ≤ 0.8 folds change were defined as differentially expressed proteins (DEPs). Overlapping DEPs between responders and non-responders were confirmed by parallel reaction monitoring (PRM). Bioinformatic analyses were performed for DEPs.Results: The results revealed 5 non-responders (NRs) and 15 responders (Rs). iTRAQ analysis indicated 13 overlapping DEPs and included 6 opposite change DEPs such as testicular tissue protein Li 70, cofilin 1, fibrinogen beta chain, galectin-10, serotransferrin (TF) and albumin. The difference in serotransferrin between responders and non-responders confirmed by PRM was significant. Verification by PRM indicated that TF was elevated in the Rs group and was reduced in the NRs group. Bioinformatic analysis indicated that serotransferrin was involved in the hypoxia-inducible factor-1 pathway and ferroptosis.Conclusion: Serotransferrin-related molecular mechanism may be a new direction to study refractory RA.Keywords: rheumatoid arthritis, proteomics, effectiveness, disease modifying antirheumatic drugs, serotransferrin

Xiaohua Zhang,1,&ast; Xinguo Liu,2,&ast; Qiongxiang Ye,2 Xunbao Wang,2 Jinjun Chen,2 Zhiyong Wang,2 Pengfei Zhao,2 Baozhou Tao,2 Guoping Xu,2 Wanfeng Xu,2 Kan Wu,2 Yao Xiao,3 Li Yang,1 Junqiang Tian,1 Juan Wang,1 Zhilong Dong,1 Zhiping Wang1 1Institute of Urology, Lanzhou University Second Hospital; Key Laboratory of Gansu Province for Urological Diseases; Gansu Nephro-Urological Clinical Center, Lanzhou, Gansu Province, People’s Republic of China; 2Department of Urology, Susong County People’s Hospital, Susong, Anhui Province, People’s Republic of China; 3Department of Pediatrics, Lanzhou University Second Hospital, Lanzhou, Gansu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiping Wang Email wangzplzu@163.comObjective: To compare the analgesic efficacy and safety of acupuncture and lornoxicam in acute renal colic (ARC).Design, Setting, Participant: A randomized, double-blind, parallel-controlled, single-centered trial was conducted at Susong County People’s Hospital from October 2019 to November 2020. Eighty-four patients with ARC were randomly divided into lornoxicam group (Group L) and acupuncture group (Group A). Group A was treated with acupuncture at Sanyinjiao (SP6), Yinlingquan (SP9) and normal saline, and Group L was treated with sham acupuncture at SP6, SP9 and lornoxicam.Main Outcome Measures: Visual analogue scale (VAS) scores and adverse reactions such as nausea and dizziness were recorded within 5, 10, 15, 20 and 40 minutes after treatment. The main outcome of this study was the short-term effective (STE) rate, the secondary outcome was the onset time, and the safety index was incidence of adverse reactions.Results: A total of 80 patients completed this study, including 41 patients (21 males and 20 females) in Group L and 39 patients (21 males and 18 females) in Group A. Group A exhibited lower scores versus group L after treatment (P < 0.05). The overall STE of group L was 61.00% (25/41), significantly lower than group A [84.62% (33/39)] (P < 0.001). There was no difference in the incidence of adverse reactions between group A [2.6% (1/39)] and group L [7.3% (3/41)] (P = 0.616). The ordered logistic regression analysis showed patients receiving acupuncture therapy are more likely to be cured [OR = 2.887, 95% CI: (1.190, 7.000), P = 0.019].Conclusion: Acupuncture at SP6, SP9 and intramuscular injection of lornoxicam can effectively and safely relieve ARC, but the former has faster and better analgesic effect. Moreover, the incidence of adverse reactions was similar between the two treatments. This acupuncture therapy is recommended as a complementary therapy for ARC.Keywords: acupuncture, lornoxicam, renal colic, analgesia

Abstract Big Data in the area of Remote Sensing has been growing rapidly. Remote sensors are used in surveillance, security, traffic, environmental monitoring, and autonomous sensing. Real-time detection of small moving targets using a remote sensor is an ongoing, challenging problem. Since the object is located far away from the sensor, the object often appears too small. The object’s signal-to-noise-ratio (SNR) is often very low. Occurrences such as camera motion, moving backgrounds (e.g., rustling leaves), low contrast and resolution of foreground objects makes it difficult to segment out the targeted moving objects of interest. Due to the limited appearance of the target, it is tough to obtain the target’s characteristics such as its shape and texture. Without these characteristics, filtering out false detections can be a difficult task. Detecting these targets, would often require the detector to operate under a low detection threshold. However, lowering the detection threshold could lead to an increase of false alarms. In this paper, the author will introduce a new method that improves the probability to detect low SNR objects, while decreasing the number of false alarms as compared to using the traditional baseline detection technique.

Sirui Fu,1,2,&ast; Meiqing Pan,2,3,&ast; Jie Zhang,4,&ast; Hui Zhang,2,3,5,&ast; Zhenchao Tang,2,3,5 Yong Li,1 Wei Mu,2,3,5 Jianwen Huang,1 Di Dong,3 Chongyang Duan,6 Xiaoqun Li,7 Shuo Wang,2,3 Xudong Chen,8 Xiaofeng He,9 Jianfeng Yan,10 Ligong Lu,1 Jie Tian2,3,5,11 1Zhuhai Interventional Medical Centre, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People’s Republic of China; 2Beijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China; 3CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Department of Radiology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People’s Republic of China; 5Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, People’s Republic of China; 6Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of China; 7Department of Interventional Treatment, Zhongshan City People’s Hospital, Zhongshan, People’s Republic of China; 8Department of Radiology, Shenzhen People’s Hospital, Shenzhen, People’s Republic of China; 9Interventional Diagnosis and Treatment Department, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 10Department of Radiology, Yangjiang People’s Hospital, Yangjiang, People’s Republic of China; 11University of Chinese Academy of Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie TianBeijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, People’s Republic of ChinaEmail tian@ieee.orgLigong LuZhuhai Interventional Medical Centre, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Zhuhai, 519000, Guangdong Province, People’s Republic of ChinaEmail llg0902@sina.comPurpose: For timely treatment of extrahepatic metastasis and macrovascular invasion (aggressive progressive disease [PD]) in hepatocellular carcinoma, models aimed at stratifying the risks of subsequent aggressive PD should be constructed.Patients and Methods: After dividing 332 patients from five hospitals into training (n = 236) and validation (n = 96) datasets, non-invasive models, including clinical/semantic factors (ModelCS), deep learning radiomics (ModelD), and both (ModelCSD), were constructed to stratify patients according to the risk of aggressive PD. We examined the discrimination and calibration; similarly, we plotted a decision curve and devised a nomogram. Furthermore, we performed analyses of subgroups who received different treatments or those in different disease stages and compared time to aggressive PD and overall survival in the high- and low-risk subgroups.Results: Among the constructed models, ModelCSD, combining clinical/semantic factors and deep learning radiomics, outperformed ModelCS and ModelD (areas under the curve [AUCs] for the training dataset: 0.741, 0.815, and 0.856; validation dataset: 0.780, 0.836, and 0.862), with statistical difference per the net reclassification improvement, the integrated discrimination improvement, and/or the DeLong test in both datasets. Besides, ModelCSD had the best calibration and decision curves. The performance of ModelCSD was not affected by treatment types (AUC: resection = 0.839; transarterial chemoembolization = 0.895; p = 0.183) or disease stages (AUC: BCLC [Barcelona Clinic Liver Cancer] stage 0 and A = 0.827; BCLC stage AB &B = 0.861; p = 0.537). Moreover, the high-risk group had a significantly shorter median time to aggressive PD than the low-risk group (training dataset hazard ratio [HR] = 0.108, p < 0.001; validation dataset HR = 0.058, p < 0.001) and poorer overall survival (training dataset HR = 0.357, p < 0.001; validation dataset HR = 0.204, p < 0.001).Conclusion: Our deep learning-based model successfully stratified the risks of aggressive PD. In the high-risk population, current guideline indicates that first-line treatments are insufficient to prevent extrahepatic metastasis and macrovascular invasion and ensure survival benefits, so more therapies may be explored for these patients.Keywords: aggressive disease progression, deep learning radiomics, clinical factors, high-risk, risk prediction

Qian Zhang,1 ZheMin Duan,1 Dan Xiang,1 Yue Yu,1 JingJin Tian2 1Center for Studies of Education and Psychology of Minorities in Southwest Area & Faculty of Education, Chongqing, People’s Republic of China; 2Dawn Innovation Kindergarten, Chongqing, People’s Republic of ChinaCorrespondence: Qian ZhangDivision of Early Childhood Education, Faculty of Education, Southwest University, Chongqing, 400715, People’s Republic of ChinaEmail zhq@swu.edu.cnPurpose: In this study, we examined whether prosocial cartoons could inspire children to donate toys to others immediately upon exposure.Participants and Methods: Cartoons were rated as prosocial or control via 80 adults. One hundred and fifty-six children participated in the study (Mage = 5.29, SD = 0.79). Children in the experimental group were exposed to cartoons in which the main character had a large number of donating behaviors, while children in the control group watched cartoons without donating behaviors (randomized controlled study). They watched these cartoons for 4 consecutive days. Afterwards, children’s donating behaviors toward their peers were assessed in the Toy Donation Task (TDT). An analytic method of 2 (cartoon: prosocial vs control) × 2 (gender: male vs female) × 3 (age: 4 vs 5 vs 6) analysis of variance (ANOVA) was used to make result analyses.Results: The empirical results indicated that watching cartoons specifically depicting charitable donations (and not cartoons with other prosocial content) increased donations for charitable causes, whilst watching the control cartoons (cartoons without prosocial content) which did not depict characters acting in an antisocial way did not increase donating behavior. Specifically, 5-year-old female children reported more donating behavior than 6-year-old female children and 4-year-old female children, whilst no significant age effects were found among male children. Here, 4– 6-year-old female children and 4– 5-year-old male children in the prosocial cartoon condition reported more donating behavior than those in the control cartoon condition.Conclusion: These findings indicated an accumulating positive effect of watching cartoons with donating content on children’s donating behavior, especially for 4– 6-year-old female children and 4– 5-year-old male children.Keywords: prosocial cartoons, donating behavior, toy donation task, children

Yilan Xing,1,2 Shishun Fu,3 Meng Li,3 Xiaofen Ma,3 Mengchen Liu,3 Xintong Liu,2 Yan Huang,2 Guang Xu,2 Yonggang Jiao,2 Hong Wu,2 Guihua Jiang,1,3 Junzhang Tian1,3 1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Neurology of Guangdong Second Provincial General Hospital, Guangzhou, People’s Republic of China; 3Department of Medical Imaging of Guangdong Second Provincial General Hospital, Guangzhou, People’s Republic of ChinaCorrespondence: Junzhang Tian; Guihua JiangDepartment of Medical Imaging of Guangdong Second Provincial General Hospital, No. 466, Xingang Road, Guangzhou, People’s Republic of ChinaTel +86 20 89168701; +86 18620120333Email tianjunzhang2015@163.com; GH.jiang2002@163.comPurpose: The aim of this study was to compare regional homogeneity (ReHo) changes in Parkinson’s disease mild cognitive impairment (PD-MCI) patients with respect to normal controls (NC) and those with cognitively normal PD (PD-CN). Further, the study investigated the relationship between ReHo changes in PD patients and neuropsychological variation.Patients and Methods: Thirty PD-MCI, 19 PD-CN, and 21 NC subjects were enrolled. Resting state functional magnetic resonance imaging data of all subjects were collected, and regional brain activity was measured for ReHo. Analysis of covariance for ReHo was determined between the PD-MCI, PD-CN, and NC groups. Spearman rank correlations were assessed using the ReHo maps and data from the neuropsychological tests.Results: In comparison with NC, PD-CN patients showed significantly higher ReHo values in the right middle frontal gyrus (MFG) and lower ReHo values in the left supramarginal gyrus, bilateral inferior parietal lobule (IPL), and the right postcentral gyrus (PCG). In comparison with PD-CN patients, PD-MCI patients displayed significantly higher ReHo values in the right PCG, left middle occipital gyrus (MOG) and IPL. No significant correlation between ReHo indices and the neuropsychological scales was observed.Conclusion: Our finding revealed that decreases in ReHo in the default mode network (DMN) may appear before PD-related cognitive impairment. In order to preserve executive attention capacity, ReHo in the right MFG in PD patients lacking cognition impairment increased for compensation. PD-MCI showed increased ReHo in the left MOG, which might have been caused by visual and visual-spatial dysfunction, and increased ReHo in the left IPL, which might reflect network disturbance and induce cognition deficits.Keywords: Parkinson’s disease, mild cognitive impairment, ReHo, fMRI, DMN

Yue Yang,1,&ast; Taya Tang,1,&ast; Bo Liu,1 Jijing Tian,1 Haiyan Wu,1 Zhongjie Liu,1 Zhaoping Liu,2 Lei Zhang,2 Huihui Bao,2 Tianlong Liu1 1Laboratory of Veterinary Pathology and Nanopathology, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 2China National Center for Food Safety Risk Assessment, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianlong LiuLaboratory of Veterinary Pathology and Nanopathology, College of Veterinary Medicine, China Agricultural University, No. 2 West Road Yuanmingyuan, Beijing, 100193, People’s Republic of ChinaTel/Fax +86 010 62732843Email liutianlong@cau.edu.cnHuihui BaoChina National Center for Food Safety Risk Assessment, No. 37, Guangqu Road, Chaoyang District, Beijing, 100022, People’s Republic of ChinaTel +86 010 52165564Fax +86 010 52165561Email baohuihui@cfsa.net.cnBackground: Phototherapy has significant potential as an effective treatment for cancer. However, the application of a multifunctional nanoplatform for photodynamic therapy (PDT) and photothermal therapy (PTT) at a single excitation wavelength remains a challenge.Materials and Methods: The double emulsion solvent evaporation method was used to prepare toluidine blue@poly lactic-co-glycolic acid (TB@PLGA) nanoparticles (NPs). The biocompatibility of TB@PLGA NPs was evaluated, and a 660 nm luminescence was used as the light source. The photothermal effect, photothermal stability, and singlet oxygen yield of NPs in an aqueous solution verified the feasibility of NPs as a PTT/PDT synergistic therapy drug.Results: TB@PLGA NPs were successfully prepared and characterized. In vitro experiments demonstrated that TB@PLGA NPs can cause massive necrosis of tumor cells and induce apoptosis through a photodynamic mechanism under 660 nm laser irradiation. The TB@PLGA NPs also achieved optimal tumor inhibition effect in vivo.Conclusion: The TB@PLGA NPs prepared in this study were applied as a dual-mode phototherapeutic agent under single laser irradiation. Both in vitro and in vivo experiments demonstrated the good potential of PTT/PDT for tumor inhibitors.Keywords: toluidine blue, single irradiation, antitumor, 660 nm, phototherapy