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Yong-Yao Wu,1,&ast; Jun-Yuan Li,1,&ast; Qiao-Jing Xia,1 Yi-Yi Gao,1 Chao Zhang,1 Peng-Jie Xu,1 Jiang Liu,1 Hao-Jie Zhang,1 Ri-Zhen Yu2 1Department of Nephrology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang Province, 315099, People’s Republic of China; 2Urology & Nephrology Center, Department of Nephrology, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao-Jie Zhang, Department of Nephrology, Ningbo Medical Center Lihuili Hospital, No. 1111 Jiangnan Road, Yinzhou District, Ningbo City, Zhejiang Province, 315099, People’s Republic of China, Email zhang_haojie843@outlook.com Ri-Zhen Yu, Urology & Nephrology Center, Department of Nephrology, Affiliated People’s Hospital, Hangzhou Medical College, No. 158 Shangtang Road, Gongshu District, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86 571-85893889, Fax +86 571-85131448, Email rizhen_3180yu83@126.comObjective: Sarcopenia is more common in maintenance hemodialysis (MHD) patients, and the aim of this study is to analyze the risk factors associated with sarcopenia in MHD patients, along with its correlation to emotional status and quality of life.Methods: This is a cross-sectional cohort study. A total of 111 MHD patients who were treated in the Department of Nephrology of our hospital were selected as the study subjects by convenience sampling. The quality of life and emotional status were evaluated by health survey scale (SF-36), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Regression analysis was used to explore the influencing factors of sarcopenia. Correlation analysis was used to investigate the correlation between sarcopenia and quality of life and emotional status.Results: The prevalence of sarcopenia was 59.8%. The results showed that age, gender, body mass index (BMI), dialysis time, economic status, marital status and pre-dialysis creatinine were significant factors affecting the development of sarcopenia in hemodialysis patients (p< 0.05). The SF-36 total score was significantly lower in the sarcopenia group (72.05± 12.28 vs 78.03± 10.55) than in the non-sarcopenia group, but the anxiety scale score (52.97± 4.67 vs 36.2± 3.36) and depression scale score (57.67± 4.58 vs 38.71± 3.77) were significantly higher than those in the non-sarcopenia group (p< 0.001). Correlation analysis showed that sarcopenia was positively correlated with SAS and SDS scores and negatively correlated with SF-36 total score (p < 0.05).Conclusion: The risk of sarcopenia was higher among MHD patients who were older, male, single, with a longer MHD duration, lower economic status, lower BMI, comorbid diabetes and lower levels of creatinine.Keywords: maintenance hemodialysis, sarcopenia, quality of life, risk factors, cross-sectional studies

Yuan Gao,1,2,&ast; Ting-Lin Zhang,3,&ast; Hong-Jian Zhang,1,2,&ast; Jie Gao,3 Peng-Fei Yang1,2,4 1Oriental Pan-Vascular Devices Innovation College, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 2School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 4Neurovascular Center, Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng-Fei Yang, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China, Tel +86-15921196312, Fax +86-2131161784, Email 15921196312@163.com Jie Gao, Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China, Tel/Fax +86-21-31162092, Email gaojiehighclea@smmu.edu.cnAbstract: Ischemic stroke, a condition that often leads to severe nerve damage, induces complex pathological and physiological changes in nerve tissue. The mature central nervous system (CNS) lacks intrinsic regenerative capacity, resulting in a poor prognosis and long-term neurological impairments. There is no available therapy that can fully restore CNS functionality. However, the utilization of injectable hydrogels has emerged as a promising strategy for nerve repair and regeneration. Injectable hydrogels possess exceptional properties, such as biocompatibility, tunable mechanical properties, and the ability to provide a supportive environment for cell growth and tissue regeneration. Recently, various hydrogel-based tissue engineering approaches, including cell encapsulation, controlled release of therapeutic factors, and incorporation of bioactive molecules, have demonstrated great potential in the treatment of CNS injuries caused by ischemic stroke. This article aims to provide a comprehensive review of the application and development of injectable hydrogels for the treatment of ischemic stroke-induced CNS injuries, shedding light on their therapeutic prospects, challenges, recent advancements, and future directions. Additionally, it will discuss the underlying mechanisms involved in hydrogel-mediated nerve repair and regeneration, as well as the need for further preclinical and clinical studies to validate their efficacy and safety.Keywords: ischemic stroke, central nervous system, hydrogels, neural restoration, nerve regeneration

Lu Liu,1,&ast; Ling Zhou,1,&ast; Ling-Ling Wang,1 Peng-Dou Zheng,1 Feng-Qin Zhang,1 Zhen-Yu Mao,1 Huo-Jun Zhang,2 Hui-Guo Liu1 1Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui-Guo Liu; Huo-Jun Zhang, Email huiguol@163.com; hjzhang@whu.edu.cnAbstract: Bronchial asthma is a complex heterogeneous airway disease, which has emerged as a global health issue. A comprehensive understanding of the different molecular mechanisms of bronchial asthma may be an efficient means to improve its clinical efficacy in the future. Increasing research evidence indicates that some types of programmed cell death (PCD), including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis, contributed to asthma pathogenesis, and may become new targets for future asthma treatment. This review briefly discusses the molecular mechanism and signaling pathway of these forms of PCD focuses on summarizing their roles in the pathogenesis and treatment strategies of asthma and offers some efficient means to improve clinical efficacy of therapeutics for asthma in the near future.Keywords: asthma, bronchial asthma, programmed cell death

Ning Li,1 Ju-hua He,2 Chao Song,3 Li-chun Yang,4 Hong-jiang Zhang,1 Zhi-hai Li1 1Department of Ultrasound, Yunnan Kungang Hospital, Kunming, Yunnan Province, People’s Republic of China; 2Department of Function Examination, Yunnan Provincial Hospital of Traditional Chinese Medicine, Kunming, Yunnan Province, People’s Republic of China; 3Department of Radiology, Yunnan Kungang Hospital, Kunming, Yunnan Province, People’s Republic of China; 4Department of Ultrasound, Yunnan Cancer Hospital, Kunming, Yunnan Province, People’s Republic of ChinaCorrespondence: Chao SongDepartment of Radiology, Yunnan Kungang Hospital, Kunming, Yunnan Province 650302, People’s Republic of ChinaTel +86-13908848395Email songchaodr@aliyun.comLi-chun YangDepartment of Ultrasound, Yunnan Cancer Hospital, Kunming, Yunnan Province 650118, People’s Republic of ChinaTel +86-13888087336Email yangchunli321@126.comBackground: It is controversial whether contralateral prophylactic central neck dissection (PCND) should be performed for patients with solitary and clinical lymph node negative (cN0) papillary thyroid carcinoma (PTC) although routine ipsilateral PCND is required.Objective: The aim of this study was to develop an improved nomogram including clinical features, ultrasound, and acoustic radiation force impulse (ARFI) elastography for the prediction of contralateral central lymph node metastasis (CLNM) in patients with solitary and cN0 PTC in the preoperative period.Materials and Methods: A total of 340 patients were retrospectively included as the training cohort and 170 patients as the external validation cohort. Patients were grouped according to the pathological results of contralateral CLNM. The association between the clinical characteristics, ultrasound, and ARFI elastography and the risk for contralateral CLNM were analyzed. A nomogram was established based on the result of multivariable logistic analysis to predict the risk of contralateral CLNM, which was assessed by internal and external validation.Results: CLNM was found in 213 patients (41.8%), among whom 142 (27.8%) had ipsilateral CLNM and 95 (18.6%) had contralateral CLNM (including 68 (13.3%) with bilateral CLNM). Multivariable analysis revealed that patients with younger age, male gender, larger tumor size, closer distance from the capsule, microcalcification, and larger SWVmean were independent predictors associated with the contralateral CLNM (P < 0.05), which was served as the basis of the nomogram. It showed good discrimination (C-index: 0.856) and calibration (χ2 = 9.028, P = 0.340, Hosmer–Lemeshow test) in the training cohort, and good discrimination was maintained in the external validation cohort (C-index: 0.792).Conclusion: The nomogram utilizing the features of ultrasound combined with ARFI elastography in preoperatively predicting the risk of contralateral CLNM in patients with solitary and cN0 PTC was established, which showed superior performance both in internal and external validation.Keywords: prophylactic central neck dissection, papillary thyroid carcinoma, central lymph node metastasis, acoustic radiation force impulse, nomogram

Shao-Ang Cheng,1,* Li-Zhong Liang,2,* Qi-Lian Liang,1 Zhen-Yi Huang,3 Xiao-Xia Peng,1 Xiao-Cui Hong,1 Xing-Bo Luo,1 Gao-Le Yuan,1 Hui-Jie Zhang,1 Liang Jiang4 1Oncology Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; 2Medical Insurance Office, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; 3Department of Finance, Central Hospital of Guangdong Agriculture Reclamation, Zhanjiang 524002, China; 4Interventional Ward, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China *These authors contributed equally to this work Background: To investigate the epidemiological features of breast cancer laterality and molecular subtypes in southern China.Materials and methods: A total of 2,049 cases who were diagnosed with unilateral breast cancer in the past 5 years were classified based on laterality and molecular subtypes. Molecular subtypes were defined in accordance with the 2013 St. Gallen recommendations.Results: Breast cancer was more likely to be diagnosed in the left breast than in the right at a rate of around 5%. In the case of invasive carcinomas, the right breast was more commonly affected than the left in young (

Liang Jiang,1,* Qi-Lian Liang,2 Wei-Ming Liang,1,* Hui-Jie Zhang,2 Jie Huang,2 Gao-Le Yuan,2 Xiao-Xia Peng,2 Shao-Ang Cheng,2 Zhi-Gang Huang,3 Xiang-Ning Zhang4 1Interventional Ward, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; 2Oncology Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; 3Department of Epidemiology, School of Public Health, Guangdong Medical University, Dongguan 523808, China; 4Department of Pathophysiology, School of Basic Medical Science, Guangdong Medical University, Dongguan 523808, China *These authors contributed equally to this work Introduction: Dynamin 3 (DNM3) is a large GTPase that possesses mechanochemical properties and has been shown to be involved in malignancies. However, most studies about DNM3 are observational, and knowledge of the precise molecular mechanism of DNM3 remains limited.Materials and methods: We constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, which was then transfected into SW620 and LoVo cells. One cell line was divided into three groups. DNM3 mRNA and protein expression was analyzed by quantitative real-time PCR and Western blot assay. To investigate DNM3 biological activity in colon cancer SW620 and LoVo cell line, we performed cell proliferation, transwell migration, and invasion assay. Matrix metalloproteinase (MMP)-2 and MMP-9 protein expressions were detected by Western blot.Result: We successfully constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, and stable DNM3 expression was observed in SW620 and LoVo cell lines. The vector overexpressing DNM3 inhibited the proliferation, weak invasion, and migration ability of colon cancer SW620 and LoVo cells relative to those in the control group (all P

Shini Feng,1 Huijie Zhang,2 Chunyi Zhi,3 Xiao-Dong Gao,1 Hideki Nakanishi1 1Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People’s Republic of China; 2School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People’s Republic of China; 3Department of Physics and Materials Science, City University of Hong Kong, Kowloon, Hong Kong SAR, People’s Republic of China Background: Anticancer drug-delivery systems (DDSs) capable of responding to the physiological stimuli and efficiently releasing drugs inside tumor cells are highly desirable for effective cancer therapy. Herein, pH-responsive, charge-reversal poly(allylamine hydrochlorid)-citraconic anhydride (PAH-cit) functionalized boron nitride nanospheres (BNNS) were fabricated and used as a carrier for the delivery and controlled release of doxorubicin (DOX) into cancer cells.Methods: BNNS was synthesized through a chemical vapor deposition method and then functionalized with synthesized charge-reversal PAH-cit polymer. DOX@PAH-cit–BNNS complexes were prepared via step-by-step electrostatic interactions and were fully characterized. The cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release inside cancer cells were visualized by confocal laser scanning microscopy. The in vitro anticancer activity of DOX@PAH-cit–BNNS was examined using CCK-8 and live/dead viability/cytotoxicity assay. Results: The PAH-cit–BNNS complexes were nontoxic to normal and cancer cells up to a concentration of 100 µg/mL. DOX was loaded on PAH-cit–BNNS complexes with high efficiency. In a neutral environment, the DOX@PAH-cit–BNNS was stable, whereas the loaded DOX was effectively released from these complexes at low pH condition due to amide hydrolysis of PAH-cit. Enhanced cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release in the nucleus of cancer cells were revealed by confocal microscopy. Additionally, the effective delivery and release of DOX into the nucleus of cancer cells led to high therapeutic efficiency.Conclusion: Our findings indicated that the newly developed PAH-cit–BNNS complexes are promising as an efficient pH-responsive DDS for cancer therapy. Keywords: boron nitride nanospheres, drug delivery, doxorubicin, pH-responsive charge-reversal, controlled release

Xiaojie Liu,1,* Yongchun Song,1,* Ping Liang,2 Tingshi Su,2 Huojun Zhang,3 Xianzhi Zhao,3 Zhiyong Yuan,1 Ping Wang1 1Department of Radiotherapy,Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 2Cyberknife Center, Ruikang Hospital, Guangxi Traditional Chinese Medical University, Nanning, 3Department of Radiotherapy, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Objective: The objective of this study was to investigate the safety of robotic stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) patients and its related factors.Methods: A total of 74 HCC patients with Child–Turcotte–Pugh (CTP) Class A were included in a multi-institutional, single-arm Phase II trial (NCT 02363218) between February 2013 and August 2016. All patients received SBRT treatment at a dose of 45 Gy/3f. The liver function was compared before and after SBRT treatment by the analysis of adverse hepatic reactions and changes in CTP classification.Results: After SBRT treatment, eight patients presented with decreases in CTP classification and 13 patients presented with ≥ grade 2 hepatic adverse reactions. For patients presenting with ≥ grade 2 hepatic adverse reactions, the total liver volume of ≤1,162 mL and a normal liver volume (total liver volume – gross tumor volume [GTV]) of ≤1,148 mL were found to be independent risk factors and statistically significant (P1,162 mL and a normal liver volume >1,148 mL should be ensured to improve therapeutic safety. Keywords: hepatocellular carcinoma, robotic stereotactic body radiation therapy, CyberKnife, Child–Turcotte–Pugh class, adverse hepatic reactions

Jin-Hua Zhang,1,2,* Zhao-Shui Shangguan,3,* Chao Chen,4 Hui-Jie Zhang,4 Yi Lin1 1College of Chemical Engineering, Huaqiao University, 2Department of Pharmacy, Xiamen Medical College, 3Central Laboratory, The First Affiliated Hospital of Xiamen University, 4Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China *These authors contributed equally to this work Abstract: The present study was aimed to investigate the effects of guggulsterone (GS) on proinflammatory responses as well as the underlying molecular mechanisms in macrophage upon lipopolysaccharide (LPS) stimulation. Effects of GS on viability of Raw264.7 cells were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (PCR) was employed to examine the mRNA expression of cytokines, including interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS). Phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (p38), and inhibitor of nuclear factor kappaB (IκB) were determined using immunoblotting. The results revealed that GS was not toxic to Raw264.7 cells at designated concentrations. We demonstrated that GS significantly suppressed the elevated mRNA expression of proinflammatory cytokines, including IL-1β, TNF-α, and iNOS in a dose-dependent manner. GS treatment reduced the level of IκB phosphorylation in LPS-stimulated macrophages in a dose-dependent manner. Use of BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-κB), led to significantly suppressing effects on IL-1β and TNF-α expression similar as that of GS-treated cells. Our findings suggest that GS possesses anti-inflammatory activity, which may be attributed to downregulation of iNOS and inhibition of NF-κB activity in LPS-stimulated Raw264.7 cells. Keywords: Anti-inflammatory effects, guggulsterone, lipopolysaccharides, NF-κB, IL-1β, TNF-α

Han Wu,1,* Xue-Liang Shi,1,* Hai-Jian Zhang,2 Qing-Jie Song,1 Xiao-Bing Yang,1 Wei-Dong Hu,1 Guang-Lin Mei,1 Xi Chen,1 Qin-Sheng Mao,1 Zhong Chen1 1Department of General Surgery, The Affiliated Hospital of Nantong University, 2Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong, People’s Republic of China *These authors contributed equally to this work Purpose: Excessive ST3Gal-I levels predict a poor outcome for patients with several types of tumors. This study aims to investigate the role of ST3Gal-I in determining the invasive and metastatic potential of human hepatocellular carcinoma (HCC) and clinical prognosis for patients with HCC.Methods: We compared the expression of ST3Gal-I in various HCC cell lines and in 20 pairs of tumor and peritumor tissue samples using Western blot analysis. Changes in the degree of invasiveness and migration were determined before and after small interfering RNA-induced knockdown of ST3Gal-I using a Transwell matrigel invasion assay and scratch wound assay. The correlation between ST3Gal-I expression and prognosis was determined in a large HCC patient cohort (n=273).Results: ST3Gal-I expression was higher in metastatic HCCLM3 cells and tumor tissue compared with normal adjacent tissue. Following the ST3Gal-I knockdown, the invasiveness and migration of HCCLM3 cells were markedly reduced. ST3Gal-I expression in HCC correlated closely with tumor thrombus (P5.0 cm, P=0.032), tumor node metastasis stages II–III (P=0.002), and Barcelona Clinic Liver Cancer stages B–C (P

Hao-jie Zhang,1,2 Jing Tao,1 Lu Sheng,1 Xin Hu,3 Rui-ming Rong,2 Ming Xu,2 Tong-yu Zhu2 1Department of Urology, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China Abstract: Twist2 is a member of the basic helix-loop-helix (bHLH) family and plays a critical role in tumorigenesis. Growing evidence has proven that Twist2 is involved in tumor progression; however, the role of Twist2 in human kidney cancer and its underlying mechanisms remain unclear. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of Twist2 in kidney cancer cells and tissues. Cell proliferation, cell cycle, apoptosis, migration, and invasion assay were analyzed using the Cell Count Kit-8, flow cytometry, wound healing, and Transwell analysis, respectively. In this study, we showed that Twist2 was upregulated in human kidney cancer tissues compared with normal kidney tissues. Twist2 promoted cell proliferation, inhibited cell apoptosis, and augmented cell migration and invasion in human kidney-cancer-derived cells in vitro. Twist2 also promoted tumor growth in vivo. Moreover, we found that the knockdown of Twist2 decreased the levels of ITGA6 and CD44 expression. This result indicates that Twist2 may promote migration and invasion of kidney cancer cells by regulating ITGA6 and CD44 expression. Therefore, our data demonstrated that Twist2 is involved in kidney cancer progression. The identification of the role of Twist2 in the migration and invasion of kidney cancer provides a potential appropriate treatment for human kidney cancer. Keywords: kidney cancer, Twist2, ITGA6, CD44

Huijie Zhang,1 Shini Feng,1 Ting Yan,1 Chunyi Zhi,2 Xiao-Dong Gao,1 Nobutaka Hanagata3,41The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Physics and Materials Science, City University of Hong Kong, Kowlong, Hong Kong SAR, People’s Republic of China; 3Biomaterials Unit, International Center for Materials Nanoarchitectonics, National Institute for Materials Science, Ibaraki, Japan; 4Nanotechnology Innovation Station, National Institute for Materials Science, Ibaraki, JapanAbstract: CpG oligodeoxynucleotides (ODNs) stimulate innate and adaptive immune responses. Thus, these molecules are promising therapeutic agents and vaccine adjuvants against various diseases. In this study, we developed a novel CpG ODNs delivery system based on polyethyleneimine (PEI)-functionalized boron nitride nanospheres (BNNS). PEI was coated on the surface of BNNS via electrostatic interactions. The prepared BNNS–PEI complexes had positive zeta potential and exhibited enhanced dispersity and stability in aqueous solution. In vitro cytotoxicity assays revealed that the BNNS–PEI complexes with concentrations up to 100 µg/mL exhibited no obvious cytotoxicity. Furthermore, the positively charged surface of the BNNS–PEI complexes greatly improved the loading capacity and cellular uptake efficiency of CpG ODNs. Class B CpG ODNs loaded on the BNNS–PEI complexes enhanced the production of interleukin-6 and tumor necrosis factor-α from peripheral blood mononuclear cells compared with CpG ODNs directly loaded on BNNS. Contrary to the free CpG ODNs or CpG ODNs directly loaded on BNNS, class B CpG ODNs loaded on the BNNS–PEI complexes induced interferon-α simultaneously. PEI coating may have changed the physical form of class B CpG ODNs on BNNS, which further affected their interaction with Toll-like receptor 9 and induced interferon-α. Therefore, BNNS–PEI complexes can be used to enhance the immunostimulatory effect and therapeutic activity of CpG ODNs and the treatment of diseases requiring interleukin-6, tumor necrosis factor-α, and interferon-α.Keywords: CpG oligodeoxynucleotide, boron nitride nanosphere, polyethyleneimine, immunostimulatory effect, cytokine

Wen Bao,1 Ran Liu,1 Yonglu Wang,1,2 Fei Wang,1 Guohua Xia,1 Haijun Zhang,1 Xueming Li,2 Haixiang Yin,2 Baoan Chen11Department of Hematology and Oncology, Key Medical Disciplines of Jiangsu Province, Zhongda Hospital, Medical School of Southeast University, 2College of Pharmacy, Nanjing University of Technology, Nanjing, People’s Republic of ChinaAbstract: Chemotherapy offers a systemic cancer treatment; however, it is limited in clinical administration due to its serious side effects. In cancer medicine, the use of nanoparticles (NPs) drug delivery system (DDS) can sustainedly release anticancer drug at the specific site and reduce the incidence of toxicity in normal tissues. In the present study, we aimed to evaluate the benefit of a novel chemotherapeutic DDS and its underlying mechanisms. Daunorubicin (DNR) was loaded into poly (lactic-co-glycolic acid) (PLGA)-poly-l-lysine (PLL)-polyethylene glycol (PEG)-transferrin (Tf) NPs to construct DNR-PLGA-PLL-PEG-Tf-NPs (DNR-loaded NPs) as a DDS. After incubating with PLGA-PLL-PEG-Tf-NPs, DNR, and DNR-loaded NPs, the leukemia K562 cells were collected and the intracellular concentration of DNR was detected by flow cytometry, respectively. Furthermore, the effect of drugs on the growth of tumors in K562 xenografts was observed and the relevant toxicity of therapeutic drugs on organs was investigated in vivo. Meanwhile, cell apoptosis in the excised xenografts was measured by transferase-mediated dUTP nick-end labeling assay, and the expression of apoptosis-related proteins, including Bcl-2, Bax, Caspase-9, Caspase-3, and cleaved-PARP, was determined by Western blotting analysis. Results showed that DNR-loaded NPs increased intracellular concentration of DNR in K562 cells in vitro and induced a remarkable improvement in anticancer activity in the xenografts in vivo. The expression of Bcl-2 protein was downregulated and that of Bax, Caspase-9, Caspase-3, and cleaved-PARP proteins were obviously upregulated in the DNR-loaded NPs group than that in other ones. Interestingly, pathological assessment showed no apparent damage to the main organs. In summary, the results obtained from this study showed that the novel NPs DDS could improve the efficacy of DNR in the treatment of leukemia and induce apoptosis via intrinsic pathway. Thus, it can be inferred that the new drug delivery may be a useful clinical tool.Keywords: PLGA-PLL-PEG, daunorubicin, transferrin, K562 cells, apoptosis

Lei Wang1,2,*, Haijun Zhang1,2,*, Baoan Chen1,2, Guohua Xia1,2, Shuai Wang1,2, Jian Cheng1,2, Zeye Shao1,2, Chong Gao1,2, Wen Bao1,2, Liang Tian1,2, Yanyan Ren1,2, Peipei Xu1,2, Xiaohui Cai1,2, Ran Liu1,2, Xuemei Wang3 1Department of Hematology and Oncology, Zhongda Hospital, Medical School, 2Faculty of Oncology, Medical School, 3State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing, China*These authors contributed equally to this workAbstract: Traditional Chinese medicine is gradually becoming a new source of anticancer drugs. One such example is wogonin, which is cytotoxic to various cancer cell lines in vitro. However, due to its low water solubility, wogonin is restricted to clinical administration. Recently, the application of drug-coated magnetic nanoparticles (MNPs) to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. In this study, wogonin was conjugated with the drug delivery system of MNPs by mechanical absorption polymerization to fabricate wogonin-loaded MNPs. It was demonstrated that MNPs could strengthen wogonin-induced cell inhibition, apoptosis, and cell cycle arrest in Raji cells by methylthiazol tetrazolium assay, flow cytometer assay, and nuclear 4',6-diamidino-2-phenylindole staining. Furthermore, the molecular mechanisms of these phenomena were explored by western blot, in which the protein levels of caspase 8 and caspase 3 were increased significantly while those of survivin and cyclin E were decreased significantly in wogonin-MNPs group. These findings suggest that the combination of wogonin and MNPs provides a promising strategy for lymphoma therapy.Keywords: wogonin, magnetic nanoparticles, Raji cell, apoptosis, cell cycle, caspase 8, caspase 3, survivin, cyclin E

Topological superconductors (TSCs) are unconventional superconductors with bulk superconducting gap and in-gap Majorana states on the boundary that may be used as topological qubits for quantum computation. Despite their importance in both fundamental research and applications, natural TSCs are very rare. Here, combining state of the art synchrotron and laser-based angle-resolved photoemission spectroscopy, we investigated a stoichiometric transition metal dichalcogenide (TMD), 2M-WS2 with a superconducting transition temperature of 8.8 K (the highest among all TMDs in the natural form up to date) and observed distinctive topological surface states (TSSs). Furthermore, in the superconducting state, we found that the TSSs acquired a nodeless superconducting gap with similar magnitude as that of the bulk states. These discoveries not only evidence 2M-WS2 as an intrinsic TSC without the need of sensitive composition tuning or sophisticated heterostructures fabrication, but also provide an ideal platform for device applications thanks to its van der Waals layered structure.

Rationale: The etiology of hepatopulmonary syndrome (HPS), a common complication of cirrhosis, is unknown. Inflammation and macrophage accumulation occur in HPS; however, their importance is unclear. Common bile duct ligation (CBDL) creates an accepted model of HPS, allowing us to investigate the cause of HPS.Objectives: We hypothesized that macrophages are central to HPS and investigated the therapeutic potential of macrophage depletion.Methods: Hemodynamics, alveolar-arterial gradient, vascular reactivity, and histology were assessed in CBDL versus sham rats (n = 21 per group). The effects of plasma on smooth muscle cell proliferation and endothelial tube formation were measured. Macrophage depletion was used to prevent (gadolinium) or regress (clodronate) HPS. CD68(+) macrophages and capillary density were measured in the lungs of patients with cirrhosis versus control patients (n = 10 per group).Measurements and Main Results: CBDL increased cardiac output and alveolar-arterial gradient by causing capillary dilatation and arteriovenous malformations. Activated CD68(+)macrophages (nuclear factor-κB+) accumulated in HPS pulmonary arteries, drawn by elevated levels of plasma endotoxin and lung monocyte chemoattractant protein-1. These macrophages expressed inducible nitric oxide synthase, vascular endothelial growth factor, and platelet-derived growth factor. HPS plasma increased endothelial tube formation and pulmonary artery smooth muscle cell proliferation. Macrophage depletion prevented and reversed the histological and hemodynamic features of HPS. CBDL lungs demonstrated increased medial thickness and obstruction of small pulmonary arteries. Nitric oxide synthase inhibition unmasked exaggerated pulmonary vasoconstrictor responses in HPS. Patients with cirrhosis had increased pulmonary intravascular macrophage accumulation and capillary density.Conclusions: HPS results from intravascular accumulation of CD68(+)macrophages. An occult proliferative vasculopathy may explain the occasional transition to portopulmonary hypertension. Macrophage depletion may have therapeutic potential in HPS. [ABSTRACT FROM AUTHOR]

Extraskeletal osteosarcoma (EOS) is an uncommon and usually highly aggressive mesenchymal tumor. Retroperitoneal extraskeletal osteosarma (REOS) is exceedingly rare. Due to the rare nature of the disease, both the diagnosis and the management of REOS can be challenging. We present the clinical history, CT findings, angiographic manifestations, and use of transarterial chemoembolization for treatment in a case of REOS. To our knowledge, the angiographic features of and attempt at transarterial treatment of REOS have not been reported in the literature. [ABSTRACT FROM AUTHOR]

Traditional continuing medical education (CME) depended primarily on periodic courses and conferences. The cost-effectiveness of these courses has not been established, and often the content is not tailored to best meet the needs of the students. Internet training has the potential to accomplish these goals. Over the last 10 years, we have developed a Web site entitled "Orthochina.org," based upon the wiki concept, which uses an interactive, case-based format. We describe the development of online case discussions, and various technical and administrative requirements. As of December 31, 2007, there were 33,984 registered users, 9,759 of which passed the confirmation procedures. In 2007, an average of 211 registrants visited daily. The average number of first page clicks was 4,248 per day, and the average number of posts was 70 per day. All cases submitted for discussion include the patient's complaint, physical examination findings, and relevant images based on specific criteria for case discussion. The case discussions develop well professionally. No spam posting or unauthorized personal advertisement is permitted. In conclusion, online academic discussions proceed well when the orthopaedic surgeons who participate have established their identities. [ABSTRACT FROM AUTHOR]

No diploma for orthopaedic surgery is available in the current medical education and licensing system in China. The orthopaedist generally receives on-the-job training in a clinical practice after getting a license to practice surgery. There are multiple training pathways to and opportunities in orthopaedic surgery, and these vary from hospital to hospital and from region to region. These include on-the-job training, academic visits, rotation through different departments based on local medical needs, fellowship training in large general or teaching hospitals (locally, regionally, nationally, or internationally), English language training, postgraduate diploma training, and Internet CME. Due to the current training system, orthopaedic techniques and skill levels vary greatly from hospital to hospital. [ABSTRACT FROM AUTHOR]

China is a developing country with a population over 1.3 billion with the second largest group of people in poverty next to India. There are about 159 million motor vehicles, with 163,887,372 drivers. From 2001 to 2004 over 100,000 people died each year in traffic accidents. With law enforcement and public education, traffic accidents have decreased, and the death rate is now less than 100,000 each year. [ABSTRACT FROM AUTHOR]

Background: Acute aortic dissection (AD) in pregnancy poses a lethal risk to both mother and fetus. However, well-established therapeutic guidelines are lacking. This study aimed to investigate clinical features, outcomes and optimal management strategies for pregnancy-related AD., Methods: We conducted a retrospective multicentre cohort study including 67 women with acute AD during pregnancy or within 12 weeks postpartum from three major cardiovascular centres in China between 2003 and 2021. Patient characteristics, management strategies and short-term outcomes were analysed., Results: Median age was 31 years, with AD onset at median 32 weeks gestation. Forty-six patients (68.7%) had type A AD, of which 41 underwent immediate surgery. Overall maternal mortality was 10.4% (7/67) and fetal mortality was 26.9% (18/67). Compared with immediate surgery, selective surgery was associated with higher risk of composite maternal and fetal death (adjusted RR: 12.47 (95% CI 3.26 to 47.73); p=0.0002) and fetal death (adjusted RR: 8.77 (95% CI 2.33 to 33.09); p=0.001)., Conclusions: Immediate aortic surgery should be considered for type A AD at any stage of pregnancy or postpartum. For pregnant women with AD before fetal viability, surgical treatment with the fetus in utero should be considered. Management strategies should account for dissection type, gestational age, and fetal viability., Trial Registration Number: NCT05501145., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Seven undescribed abietane diterpenoids [abietamethinols A-G (1-7)] were isolated from the twigs and leaves of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic methods including 2D NMR, and they were further confirmed by X-ray crystallographic data. Lophanic acid was considered as the precursor of 1-7 in the biosynthesis pathway hypothesis. These compounds were evaluated for their cytotoxic, anti-bacterial and anti-AIV (avian influenza virus) activities. Compound 5 showed 42.9% inhibitory activity against the cancer cell line SMMC-7721 at the concentration of 40 μM, 3 and 4 could inhibit the bacterial growth of Streptococcus sobrinus by 55.3% and 63.2% at the concentrations of 148.6 and 141.9 μM, respectively, and 4 was demonstrated with antiviral activity against AIV with the inhibitory effect of 68.4% at 25 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Severe burns related to fires and explosions of lithium-ion batteries of electric motorcycles have not been reported to date. We retrospectively studied 419 patients admitted to our burn intensive care unit from January 2016 to December 2021. Of these 419 patients, 26 (22 male, 4 female; median age, 42 years) had burns related to lithium-ion battery fires and explosions, and all of their injury characteristics were similar to those of traditional flame burns. Lithium-ion battery-related burns were the eighth most common cause of burn injuries among all hospitalized patients. The 26 patients comprised 10 unemployed and 16 employed individuals. Twenty-three patients were injured at home during the battery charging process, and three were injured outdoors (one by a fire while the electric motorcycle was stationary and the others two by a fire while riding the motorcycle). The burn sites were distributed over the whole body; the burn area ranged from 10 % to 100 % of the total body surface area, and the burn depth ranged from superficial second-degree burns to third-degree burns. Twenty-three patients had inhalation injuries, and ten underwent prophylactic tracheostomy and intubation. Multiple operations were required for wound repair. Although convenient, lithium-ion electric motorcycles can also cause severe burns. To prevent these injuries, we must increase public safety awareness and education, develop new battery energy storage systems and battery management systems, and ensure the safety of batteries. Consumers should be aware of the potential dangers of lithium-ion batteries and comply with related security measures., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Acute lung injury (ALI) is a serious adverse event in the management of acute type A aortic dissection (ATAAD). Using a large-scale cohort, we applied artificial intelligence-driven approach to stratify patients with different outcomes and treatment responses. A total of 2,499 patients from China 5A study database (2016-2022) from 10 cardiovascular centers were divided into 70% for derivation cohort and 30% for validation cohort, in which extreme gradient boosting algorithm was used to develop ALI risk model. Logistic regression was used to assess the risk under anti-inflammatory strategies in different risk probability. Eight top features of importance (leukocyte, platelet, hemoglobin, base excess, age, creatinine, glucose, and left ventricular end-diastolic dimension) were used to develop and validate an ALI risk model, with adequate discrimination ability regarding area under the receiver operating characteristic curve of 0.844 and 0.799 in the derivation and validation cohort, respectively. By the individualized treatment effect prediction, ulinastatin use was significantly associated with significantly lower risk of developing ALI (odds ratio [OR] 0.623 [95% CI 0.456, 0.851]; P = 0.003) in patients with a predicted ALI risk of 32.5-73.0%, rather than in pooled patients with a risk of <32.5 and >73.0% (OR 0.929 [0.682, 1.267], P = 0.642) (Pinteraction = 0.075). An artificial intelligence-driven risk stratification of ALI following ATAAD surgery were developed and validated, and subgroup analysis showed the heterogeneity of anti-inflammatory pharmacotherapy, which suggested individualized anti-inflammatory strategies in different risk probability of ALI., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: Parkinson's disease (PD) demonstrates considerable heterogeneity in the manifestation of clinical symptoms and disease progression. Recently, six clinical milestones have been proposed to evaluate disease severity in PD. However, the identification of PD progression subtypes based on these milestone events has not yet been performed., Methods: Latent class analysis (LCA) was employed to identify subtypes of PD progression based on the timing of the first occurrence of six milestones within a 6-year follow-up period in Parkinson's Progression Markers Initiative (PPMI) database., Results: The study cohort consisted of 354 early PD patients, of whom 42.9% experienced at least one milestone within six years. LCA identified two distinct subtypes of PD progression: slow progression (83%) and rapid progression (17%). The total number of milestones over six years was significantly higher in the rapid progression subtype compared to the slow progression subtype (median: 3.00 vs. 0.00, p < 0.001). At baseline, the rapid progression subtype, compared to the slow progression subtype, was characterized by an older age at onset and more severe motor and non-motor symptoms. On biomarkers, the rapid progression subtype demonstrated elevated CSF p-tau and serum NFL, but decreased mean striatal DAT uptake. Five clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, and RBD) were selected to construct the predictive model. The original predictive model achieved an AUC of 0.82. In internal validation using bootstrap resampling, the model achieved an AUC of 0.82, with a 95%CI ranging from 0.76 to 0.87. The model's performance was acceptable regarding both calibration and clinical utility., Conclusion: Approximately 17% of early PD patients exhibited the rapid progression subtype, characterized by the occurrence of more and earlier-onset milestones. The nomogram predictive model, incorporating five baseline clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, RBD), serves as a valuable tool for prognostic counseling and patient selection in PD clinical trials., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The intrapapillary capillary loop (IPCL) characteristics, visualized using magnifying endoscopy, are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma (ESCC). Japan Esophageal Society (JES) classification is the most widely used classification. Microvascular structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor: tortuosity, dilatation, irregular caliber, and different shapes. However, the pathological characteristics of IPCLs have not been thoroughly investigated, especially the microvascular structures corresponding to the deepest parts of the lesions' infiltration., Aim: To investigate differences in pathological microvascular structures of ESCC, which correspond to the deepest parts of the lesions' infiltration., Methods: Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April 2023. Patients first underwent magnified endoscopic examination, followed by endoscopic submucosal dissection or surgical treatment. Pathological images were scanned using a three-dimensional slice scanner, and the pathological structural differences in different types, according to the JES classification, were analyzed using nonparametric tests and t -tests., Results: The 35 lesions were divided into four groups according to the JES classification: A, B1, B2, and B3. Statistical analyses revealed significant differences ( a P < 0.05) in the short and long calibers, area, location, and density between types A and B. Notably, there were no significant differences in these parameters between types B1 and B2 and between types B2 and B3 ( P > 0.05). However, significant differences in the short calibers, long calibers, and area of IPCL were observed between types B1 and B3 ( a P < 0.05); no significant differences were found in the density or location ( P > 0.05)., Conclusion: Pathological structures of IPCLs in the deepest infiltrating regions differ among various IPCL types classified by the JES classification under magnifying endoscopy, especially between the types A and B., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Continuous dynamic recrystallization (CDRX) is widely acknowledged to occur during hot forming and plays a significant role in microstructure development in alloys with moderate to high stacking fault energy. In this work, the flow stress and CDRX behaviors of the TC18 alloy subjected to hot deformation across a wide range of processing conditions are studied. It is observed that deformation leads to the formation of new low-angle grain boundaries (LAGBs). Subgrains rotate by absorbing dislocations, resulting in an increase in LAGB misorientation and the transition of some LAGBs into high-angle grain boundaries (HAGBs). The HAGBs migrate within the material, assimilating the (sub)grain boundaries. Subsequently, an internal state variable (ISV)-based CDRX model is developed, incorporating parameters such as the dislocation density, adiabatic temperature rise, subgrain rotation, LAGB area, HAGB area, and LAGB misorientation angle distribution. The values of the correlation coefficient (R), relative average absolute error (RAAE), and root-mean-square error (RMSE) between the anticipated true stress and measured stress are 0.989, 6.69%, and 4.78 MPa, respectively. The predicted outcomes demonstrate good agreement with experimental findings. The evolving trends of the subgrain boundary area under various conditions are quantitatively analyzed by assessing the changes in dynamic recovery (DRV)-eliminated dislocations and misorientation angles. Moreover, the ISV-based model accurately predicts the decreases in grain and crystallite sizes with higher strain rates and lower temperatures. The projected outcomes also indicate a transition from a stable and coarse-grained microstructure to a continuously recrystallized substructure.

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of TFE3-rearranged perivascular epithelioid cell tumor (PEComa). Methods: Eight cases of PEComa with TFE3 rearrangement diagnosed in the First Affiliated Hospital of Air Force Medical University from January 2014 to July 2022 were collected. Three were consultation cases and 5 were collected from our hospital; 7 cases were resection specimens and 1 case was a needle biopsy specimen. Routine histolopathological analysis, immunohistochemical staining, fluorescence in situ hybridization (FISH) and the next-generation sequencing were performed. Clinical data were collected and the prognosis was assessed. Results: The 8 patients consisted of 5 females and 3 males with a median age of 45 years (ranged from 25 to 65 years). The tumor location included 1 uterus, 1 liver, 1 urachus, 2 kidneys, 1 abdominal cavity, 1 colon, and 1 retroperitoneum (3 subsequent recurrences in the abdominal cavity, pelvis and ovary, and abdominal cavity, respectively). Morphologically, the tumor cells were uniform and epithelioid with translucent or eosinophilic cytoplasm. They were arranged in nests or sheets, most of which were separated by thin-walled blood vessels. There were no papillary structures, and no overt smooth muscle or fat components. Atypical features were seen in 3 cases, with bizarre nuclei and tumor giant cells. Large areas of necrosis were visible, and mitosis was common (up to 28/50 HPF). Melanin deposition was present in 3 cases. Immunohistochemical staining showed diffuse and strong positivity for TFE3 in 8/8 cases and for HMB45 in 6/8 cases; focal positivity for Cathepsin K and Melan-A in 6/8 cases and for SMA in 2/8 of cases. All cases were negative for CKpan, PAX8 and Desmin. TFE3 gene break-apart was detected by FISH in all 8 cases, 4 of which underwent next-generation sequencing, and it revealed that 2 cases presented with SFPQ::TFE3 fusion, 1 case with ASPSCR1::TFE3 fusion, and 1 case with no chimeric fusion. Seven cases were followed up for 4-94 months. All cases were alive; 4 cases were disease-free, 2 cases showed recurrence, and 1 case had metastasis at initial diagnosis. Conclusions: TFE3-rearranged PEComa has unique histomorphological, immunohistochemical and molecular characteristics. The biological behavior is aggressive, which could lead to recurrence and metastasis, and warrants close clinical follow-up.

Objective: Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B 1 (AFB 1 ), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB 1 -induced hepatocyte injury and the mechanisms underlying those effects were investigated., Methods: Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB 1 -induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB 1 was used to evaluate the effects of baicalin., Results: In vitro, baicalin significantly attenuated AFB 1 -induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB 1 -induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB 1 -treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin., Conclusions: Baicalin can alleviate AFB 1 -induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB 1 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)