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Ya-ru Liu,1,2,* Jie-Quan Wang,3– 5,* Ling Fang,1,2 Quan Xia1,2 1Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, 230022, People’s Republic of China; 3Department of Pharmacy, Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of China; 4Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, 230000, People’s Republic of China; 5Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, 230000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Fang; Quan Xia, Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Email fangling@ahmu.edu.cn; xiaquan2010@163.comAbstract: Rheumatoid arthritis (RA) is a systemic inflammatory disease whose precise pathogenesis remains mysterious. The involvement of epigenetic regulation in the pathogenesis of RA is one of the most anticipated findings, among which non-coding RNAs (ncRNAs) hold great application promise as diagnostic and therapeutic biomarkers for RA. Extracellular vesicles (EVs) are a heterogeneous group of nano-sized, membrane-enclosed vesicles that mediate intercellular communication and substance exchange, especially the transfer of ncRNAs from donor cells, thereby regulating the functional activities and biological processes of recipient cells. In light of the significant correlation between EVs, ncRNAs, and RA, we first documented expression levels of EVs and their-encapsulated ncRNAs in RA individuals, and methodically discussed their-implicated signaling pathways and phenotypic changes. The last but not least, we paied special attention to the therapeutic benefits of gene therapy reagents specifically imitating or silencing candidate ncRNAs with exosomes as carriers on RA animal models, and briefly highlighted their clinical application advantage and foreground. In conclusion, the present review may be conducive to a deeper comprehension of the diagnostic and therapeutic roles of EVs-enwrapped ncRNAs in RA, with special emphasis on exosomal ncRNAs, which may offer hints for the monitoring and treatment of RA. Keywords: rheumatoid arthritis, extracellular vesicles, non-coding RNAs, diagnostic and therapeutic role

Yin Cao,1– 4 Qingrong Xia,1– 4 Jun Liang,1– 4 Jiequan Wang,1– 4 Feng Shan,1– 4 Biao Dai1– 4 1Department of Pharmacy, Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 3Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, People’s Republic of China; 4Department of Clinical Pharmacy, Anhui Clinical Research Center for Mental Disorders, Hefei, People’s Republic of ChinaCorrespondence: Jun Liang, Department of Pharmacy, Hefei Fourth People’s Hospital, 316 Huangshan Road, Hefei, 230000, People’s Republic of China, Email amhcliangj@163.comObjective: The present study aims to investigate the effect of common cold on the serum clozapine concentrations in hospitalized patients with schizophrenia.Methods: A total of 65 schizophrenic patients with common cold receiving clozapine treatment were retrospectively enrolled. The demographic data, medication situation, clozapine concentration, and parameters of routine haematological and biochemical laboratory tests were obtained from the medical record system. The serum clozapine concentration and clozapine concentration/dose (C/D) ratios between the baseline period and cold period were compared by paired-sample t tests. Association between the changes in serum concentration and C/D ratios of clozapine and changes in white blood cell (WBC) and neutrophil (NE) counts was evaluated using Pearson correlation analysis.Results: The serum clozapine concentration (t = − 9.856, P < 0.001) and clozapine C/D ratios (t = − 10.071, P < 0.001) were found to be significantly elevated in the cold period compared to the baseline period. Moreover, the changes in the serum clozapine concentration were found to be significantly elevated in female patients compared to male patients (t = − 2.483, P = 0.017). Furthermore, changes in the serum clozapine concentration were positively correlated to the changes in WBC (r = 0.303, P = 0.014) and NE (r = 0.315, P = 0.011) counts. Similarly, changes in clozapine C/D ratios were positively correlated to the changes in WBC (r = 0.275, P = 0.027) and NE (r = 0.328, P = 0.008) counts.Conclusion: The serum clozapine concentrations in patients with schizophrenia during the common cold period were increased, which might by related to the elevated WBC and NE counts.Keywords: clozapine, blood drug concentration, schizophrenia, white blood cell count, neutrophil count, common cold

Jing Shang,1,&ast; Qi Xia,1,&ast; Yuji Sun,2 Hongtao Wang,2 Jia Chen,1 Yue Li,1 Feng Gao,2 Peihao Yin,1,3,4 Zeting Yuan1– 4 1Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China; 2Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China; 3Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, Shanghai, 200062, People’s Republic of China; 4The Fifth School of Clinical Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zeting Yuan; Peihao Yin, Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China, Email yuan340202@163.com; yinpeihao@shutcm.edu.cnPurpose: Compared with traditional photothermal therapy (PTT, > 50°C), mild PTT (≤ 45°C) is a promising strategy for tumor therapy with fewer adverse effects. Unfortunately, its anti-tumor efficacy is hampered by thermoresistance induced by overexpression of heat shock proteins (HSPs). In our previous study, we found bufalin (BU) is a glycolysis inhibitor that depletes HSPs, which is expected to overcome thermotolerance of tumor cells. In this study, BU-loaded multifunctional nanoparticles (NPs) were developed for enhancing the mild PTT of colorectal cancer (CRC).Methods: Fe3O4 NPs coated with the polydopamine (PDA) shell modified with polyethylene glycol (PEG) and cyclic arginine-glycyl-aspartic peptide (cRGD) for loading BU (Fe3O4@PDA-PEG-cRGD/BU NPs) were developed. The thermal variations in Fe3O4@PDA-PEG-cRGD/BU NPs solution under different conditions were measured. Glycolysis inhibition was evaluated by measuring the glucose uptake, extracellular lactate, and intracellular adenosine triphosphate (ATP) levels. The cellular cytotoxicity of Fe3O4@PDA-PEG-cRGD/BU NPs was analyzed using a cell counting kit-8 assay, Calcein-AM/PI double staining, and flow cytometry in HCT116 cells. The magnetic resonance imaging (MRI) performance and anti-tumor therapeutic efficacy of Fe3O4@PDA-PEG-cRGD/BU NPs were evaluated in HCT116-tumor bearing mice.Results: Fe3O4@PDA-PEG-cRGD/BU NPs had an average diameter of 260.4± 3.5 nm, the zeta potential of – 23.8± 1.6 mV, the drug loading rate of 1.1%, which had good thermal stability, photothermal conversion efficiencies and MRI performance. In addition, the released BU not only killed tumor cells but also interfered with glycolysis by targeting the steroid receptor coactivator 3 (SRC-3)/HIF-1α pathway, preventing intracellular ATP synthesis, and combating HSP-dependent tumor thermoresistance, ultimately strengthening the thermal sensitivity toward mild PTT both in vitro and in vivo.Conclusion: This study provides a highly effective strategy for enhancing the therapeutic effects of mild PTT toward tumors. Keywords: mild photothermal therapy, glycolysis metabolism, bufalin, HIF-1α, SRC-3

Menghong Wan, Chen Wang, Jiamin Cui, Qing Xia, Lei Zhang Caoyang Community Health Service Center, Shanghai, 200063, People’s Republic of ChinaCorrespondence: Lei Zhang, Caoyang Community Health Service Center, No. 121 Lanxi Street, Putuo District, Shanghai, 200063, People’s Republic of China, Email Zhanglei_871007@163.comBackground: The incidence of chronic obstructive pulmonary disease (COPD) is increasing year by year. Kruppel-like factor 6 (KLF6) plays an important role in inflammatory diseases. However, the regulatory role of KLF6 in COPD has not been reported so far.Methods: The viability of human bronchial epithelial cells BEAS-2B induced by cigarette smoke extract (CSE) was detected by CCK-8 assay. The protein expression of KLF6 and sirtuin 4 (SIRT4) was appraised with Western blot. RT-qPCR and Western blot were applied to examine the transfection efficacy of sh-KLF6 and Oe-KLF6. Cell apoptosis was detected using flow cytometry. The levels of inflammatory factors IL-6, TNF-α and IL-1β were assessed with ELISA assay. DCFH-DA staining was employed for the detection of ROS activity and the levels of oxidative stress markers SOD, CAT and MDA were estimated with corresponding assay kits. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content and Complex I activity were evaluated with JC-1 staining, ATP colorimetric/fluorometric assay kit and Complex I enzyme activity microplate assay kit. With the application of mitochondrial permeability transition pore detection kit, mPTP opening was measured. Luciferase report assay was employed to evaluate the activity of SIRT4 promoter and chromatin immunoprecipitation (ChIP) to verify the binding ability of KLF6 and SIRT4 promoter.Results: KLF6 expression was significantly elevated in CSE-induced cells. KLF6 was confirmed to suppress SIRT4 transcription. Interference with KLF6 expression significantly inhibited cell viability damage, cell apoptosis, inflammatory response, oxidative stress and mitochondrial dysfunction in CSE-induced BEAS-2B cells, which were all reversed by SIRT4 overexpression.Conclusion: Silencing KLF6 alleviated CSE-induced mitochondrial dysfunction in bronchial epithelial cells by SIRT4 upregulation.Keywords: KLF6, SIRT4, COPD, CSE, mitochondrial dysfunction

Yin Cao,1– 4 Yayun Xu,5– 7 Qingrong Xia,1– 4 Feng Shan,1– 4 Jun Liang1– 4 1Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 3Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, People’s Republic of China; 4Anhui Clinical Research Center for Mental Disorders, Hefei, People’s Republic of China; 5Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 6Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, People’s Republic of China; 7The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei, People’s Republic of ChinaCorrespondence: Jun Liang, Department of Pharmacy, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, Anhui Mental Health Center, 316 Huangshan Road, Hefei, 230000, People’s Republic of China, Email amhcliangj@163.comObjective: Schizophrenia (SCZ) is a severe, protracted neurological disorder that causes disruptive conduct in millions of individuals globally. Discovery of potential biomarkers in clinical settings would lead to the development of efficient diagnostic techniques and an awareness of the disease’s pathogenesis and prognosis. The aim of the present study was to discover and identify serum complement factor-based biomarkers in discriminating patients with first-episode SCZ from healthy controls.Methods: Eighty-nine patients with first-episode SCZ and 89 healthy controls were included in this study. Psychiatric symptom severity of patients with SCZ was measured with the Brief Psychiatric Rating Scale-18 Item Version (BPRS) and the Scales for the Assessment of Negative/Positive Symptoms (SANS/SAPS). A total of 5 complement factors including complement component 1 (C1), C2, C3, C4, and 50% hemolytic complement (CH50) were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. The levels of serum complement factors in the SCZ and control groups were compared, and the receiver operating characteristic (ROC) curve method was used to assess the diagnostic values of various complement factors for separating SCZ patients from healthy controls. Pearson’s correlation test was used to assess the relationships between serum complement factor concentrations and the psychiatric symptom severity.Results: There was an increase in serum levels of C1, C2, C3, C4, and CH50 among patients with SCZ. Moreover, based on ROC curve analysis, the AUC value of a combined panel of C1, C2, C3, C4, and CH50 was 0.857 when used to discriminate patients with SCZ from healthy controls. Furthermore, serum C2, C3, and CH50 levels were positively correlated to the scores of SANS, SAPS, and BPRS in patients with SCZ, respectively.Conclusion: These results suggested that circulating complement factors including C1, C2, C3, C4, and CH50 may have potential in discovering biomarkers for diagnosing first-episode SCZ.Keywords: complement factors, biomarker, diagnosis, serum, schizophrenia

Shenglan Ma,1– 3,&ast; Peijun Ju,4,&ast; Qingrong Xia,1– 3 Zhongde Pan,5 Jianliang Gao,1– 3 Loufeng Zhang,1– 3 Hua Gao,1– 3 Junwei Yan,1– 3 Jie Zhang,1– 3 Keming Wang,1– 3 Chao Li,1– 3 Wen Xie,1– 3,&ast; Cuizhen Zhu1– 3,&ast; 1Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Clinical Center for Psychiatry and Mental Health, Hefei Fourth People’s Hospital, Hefei, 230022, People’s Republic of China; 3Anhui Mental Health Center, Hefei, People’s Republic of China; 4Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Traditional Chinese Medicine for Mental Health, Shanghai, People’s Republic of China; 5Shanghai Key Laboratory of Forensic Medicine, Academy of Forensic Science, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Xie; Cuizhen Zhu, Affiliated Psychological Hospital of Anhui Medical University, No. 316 Huangshan Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86 13339102285 ; +86 13705535258, Fax +86 055163616000, Email xiewen0808@sina.com; zhucuizhen88@126.comPurpose: The study aims to clarify the negative psychological state and resilience impairments of schizophrenia (SCZ) with metabolic syndrome (MetS) while evaluating their potential as risk factors.Patients and Methods: We recruited 143 individuals and divided them into three groups. Participants were evaluated using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD)-24, Hamilton Anxiety Rating Scale (HAMA)-14, Automatic Thoughts Questionnaire (ATQ), Stigma of Mental Illness scale and Connor–Davidson Resilience Scale (CD-RISC). Serum biochemical parameters were measured by automatic biochemistry analyzer.Results: The score of ATQ was highest in the MetS group (F = 14.5, p < 0.001), and the total score of CD-RISC, subscale tenacity score and subscale strength score of CD-RISC were lowest in the MetS group (F = 8.54, p < 0.001; F = 5.79, p = 0.004; F = 10.9, p < 0.001). A stepwise regression analysis demonstrated that a negative correlation was observed among the ATQ with employment status, high-density lipoprotein (HDL-C), and CD-RISC (β=− 0.190, t=− 2.297, p = 0.023; β=− 0.278, t=− 3.437, p = 0.001; β=− 0.238, t=− 2.904, p = 0.004). A positive correlation was observed among the ATQ with waist, TG, WBC, and stigma (β=0.271, t = 3.340, p = 0.001; β=0.283, t = 3.509, p = 0.001; β=0.231, t = 2.815, p = 0.006; β=0.251, t=− 2.504, p = 0.014). The area under the receiver-operating characteristic curve analysis showed that among all independent predictors of ATQ, the TG, waist, HDL-C, CD-RISC, and stigma presented excellent specificity at 0.918, 0.852, 0.759, 0.633, and 0.605, respectively.Conclusion: Results suggested that the non-MetS and MetS groups had grievous sense of stigma, particularly, high degree of ATQ and resilience impairment was shown by the MetS group. The TG, waist, HDL-C of metabolic parameters, CD-RISC, and stigma presented excellent specificity to predict ATQ, and the waist showed excellent specificity to predict low resilience level.Keywords: years of education, negative symptoms, waist circumstance

Yilin Hou,1,2 Xiaoyu Hou,1,2 Qian Nie,3 Qiuyang Xia,1,2 Rui Hu,1,2 Xiaoyue Yang,1,2 Guangyao Song,2,4 Luping Ren2,4 1Graduate School, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 3Health Examination Center, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 4Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of ChinaCorrespondence: Guangyao Song; Luping Ren, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email sguangyao2@163.com; renluping1122@163.comPurpose: The aim of this study was to evaluate the association of bone turnover markers (BTMs) with type 2 diabetes mellitus (T2DM) and microvascular complications.Methods: A total of 166 T2DM patients and 166 non-diabetic controls matched by gender and age were enrolled. T2DM patients were sub-classified into groups based on whether they had diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). Clinical data including demographic characteristics and blood test results [serum levels of osteocalcin (OC), N-terminal propeptide of type 1 procollagen (P1NP), and β-crosslaps (β-CTX)] were collected. Logistic regression and restrictive cubic spline curves were performed to examine the association of BTMs with the risk of T2DM and microvascular complications.Results: After adjusting for family history of diabetes, sex and age, an inverse association was observed between elevated serum OC levels [O, p < 0.001] and increased serum P1NP levels , p < 0.001] with the risk of T2DM. Moreover, there was an inverse linear association of serum OC and P1NP levels with the risk of T2DM. However, β-CTX was not associated with T2DM. Further analysis showed a nonlinear association between OC and the risk of DR, while P1NP and β-CTX were not correlated with DR. Serum concentrations of BTMs were not associated with the risks of DPN and DKD.Conclusion: Serum OC and P1NP levels were negatively correlated with T2DM risk. Particularly, serum OC levels were associated with DR risk. Given that BTMs are widely used as markers of bone remodeling, the present finding provides a new perspective for estimating the risk of diabetic microvascular complications.Keywords: bone turnover markers, type 2 diabetes mellitus, microvascular complications

Qing Xia,&ast; Yue Tang,&ast; Wang Li, Tingting Liang, Yue Zhou, Jun Liu, Feila Liu School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feila Liu, School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, People’s Republic of China, Tel +86-15123002638, Fax +86 2362563190, Email liufeila@cqut.edu.cnIntroduction: The immunosuppressive tumor microenvironment (TME) of solid tumors inhibits most drug delivery system-based nanomaterials from achieving deep penetration in tumor tissue and interferes with T cell activity in terms of differentiation and exhaustion, which is becoming a critical therapy hurdle for solid tumors. Therefore, developing a therapeutic strategy with abilities of rapid establishment of tumor-targeted cells, elimination of immune obstacles, and enhanced active immunization is very important, while is still a big challenge.Methods: A new strategy was explored to enhance immune therapy via the conjugation of microRNA155 (miR) to the surface of therapeutic monocyte with graphene quantum dots (GQDs).Results: TME was reversed using surface-engineered monocyte immunotherapy via reprogramming pro-tumoral M2 TAMs into antitumor M1, and thus tumor elimination was dramatically enhanced.Conclusion: Such a surface-engineered monocyte immunotherapy has been demonstrated to be well tolerated to intravenous administration and bio-compatible, showing the potential to be extended for the solid tumor treatment.Graphical Abstract: Keywords: solid tumor, surface-engineered monocyte, GQDs, miR155, immunotherapy

Mina Wang,1,2,&ast; Xiaobai Xu,1,&ast; Bingcong Zhao,1 Lu Liu,1 Luopeng Zhao,1 Fan Zhang,1 Xu Ji,1 Fang Yuan,1 Qiuyu Xia,1 Shaosong Wang,1 Wei Tian,1 Linpeng Wang,1 Bin Li1 1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Li; Xiaobai Xu, Email libin@bjzhongyi.com; xu_xiaobai1990@sina.comPurpose: Knee osteoarthritis (KOA) is regarded as one of the leading musculoskeletal diseases. Although the efficacy is under exploration, fire needling therapy is considered an effective alternative for KOA. This trial aims to investigate the effectiveness of different frequencies of fire needling therapy in attenuating pain and promoting function in KOA patients.Methods: This is a study protocol for a pilot, three-arm, single-center, randomized controlled trial. A total of 90 participants with KOA will be recruited and randomly assigned to the high-frequency fire needling group (3 sessions per week, for 6 weeks), the low-frequency fire needling group (1 session per week, for 6 weeks) or the positive control group (Diclofenac Diethylamine Emulgel, 3 times per day, for 6 weeks) in a 1:1:1 ratio. Participants will accomplish the trial at Week 14 after a follow-up evaluation. The response rate will be set as the primary outcome that the proportion of participants obtaining a minimal clinically important difference, which is identified as ≥ 2 units on the numerical rating scale (NRS) and ≥ 6 units on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at Week 6 compared with Week 0. Secondary outcomes are NRS, WOMAC, Brief Pain Inventory, Short-Form Health Survey-12, Timed Up and Go Test, and pain threshold.Discussion: This is the first standardized protocol comparing fire needling therapy and positive control drugs. This trial may provide reliable evidence for the effectiveness of fire needling therapy and dose–effect property of it in KOA. Trial registration: The trial has been registered on Chinese Clinical Trial Registry (Registered number: ChiCTR2100043041), registered on 4 February 2021.Keywords: knee osteoarthritis, fire needling therapy, different frequencies, dose–effect property

Bangju Li, Xizhen Fan, Qun Xia Day Surgery Ward, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001 People’s Republic of ChinaCorrespondence: Xizhen Fan, Day Surgery Ward The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China, Tel +86-0551-62283316, Email 1014958512@qq.comObjective: To investigate the effect of changing the normal appointment mode on day surgery.Methods: From December 2020 to December 2021, 302 patients with day surgery admitted to the hospital by using the unified reservation mode of the intelligent bed system were selected as the experimental group, while 302 patients with day surgery admitted to the hospital by using the decentralised bed reservation mode were randomly selected as the control group. The same-day surgery cancellation rate, bed utilisation rate and patient satisfaction were analysed and compared between the two groups.Results: The treatment experience of the patients in the experimental group was higher than that in the control group. The same-day surgery cancellation rate was lower than that of the control group, with a statistically significant difference (P < 0.05).Conclusion: The unified computer reservation mode of the intelligent bed reservation system is superior to the decentralised reservation mode across departments. A daytime intelligent bed reservation mode was adopted for unifying bed appointments, which could effectively reduce the same-day cancellation rate of day surgery, improve bed utilisation and improve patient satisfaction.Keywords: COVID-19, day surgery, surgical cancellation rate, patient satisfaction, evaluation

Wenfan Gao,1– 4,&ast; Yayun Xu,5– 7,&ast; Jun Liang,1– 4 Yanhong Sun,1– 4 Yuanyuan Zhang,1– 4 Feng Shan,1– 4 Jinfang Ge,6– 8 Qingrong Xia1– 4 1Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 3Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, People’s Republic of China; 4Anhui Clinical Research Center for Mental Disorders, Hefei, People’s Republic of China; 5Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 6Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, People’s Republic of China; 7The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei, People’s Republic of China; 8School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinfang Ge, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230000, People’s Republic of China, Email gejinfang@ahmu.edu.cn Qingrong Xia, Department of Science and Education, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, Anhui Mental Health Center, 316 Huangshan Road, Hefei, 230000, People’s Republic of China, Email ahmcxqr@163.comObjective: Evidence indicates a potential role of chemokines in depression-like behavior and depression-related pathophysiological processes. In the present study, we examined the serum levels of multiple chemokines, focusing on CC chemokines, in patients with major depressive disorder (MDD), with the aim to discover and identify serum chemokines-based biomarkers for MDD diagnosis.Methods: Participants included 24 patients with MDD and 24 healthy controls. The 24-item Hamilton Depression Rating Scale (HAMD-24) was administered to assess the disease severity of patients with MDD. A total of 9 serum CC chemokines including MCP-1 (CCL-2), MIP-1α (CCL-3), MIP-1β (CCL-4), eotaxin-1 (CCL-11), MCP-4 (CCL-13), TARC (CCL-17), MIP-3α (CCL-20), MDC (CCL-22), and Eotaxin-3 (CCL-26) were measured using electrochemiluminescence immunoassays. The levels of serum CC chemokines between MDD group and control group were compared, and diagnostic values of different CC chemokines were evaluated using the receiver operating characteristic (ROC) curve method for discriminating MDD patients from healthy controls. Correlations between the levels of serum CC chemokines and depression severity (HAMD-24 scores) were evaluated using Pearson’s correlation test.Results: Patients with MDD had higher levels of serum MIP-1α and MIP-1β and lower levels of serum MCP-1, MCP-4, TARC, MDC, and Eotaxin-3 compared to controls (all P < 0.05). Moreover, ROC curve analysis showed that the Area Under Curve (AUC) values of MIP-1α, MCP-4, TARC, and Eotaxin-3 were > 0.7 in discriminating patients with MDD from healthy controls. Furthermore, no significant relationship was found between the levels of serum CC chemokines and HAMD-24 scores in MDD group.Conclusion: These results suggested that circulating CC chemokines may hold promise in the discovery of biomarkers for diagnosing MDD.Keywords: chemokines, biomarker, diagnosis, serum, major depressive disorder

Fenfen Gu,1,&ast; Chuling Hu,2,&ast; Wei Cao,3,&ast; Chao Li,1 Qingming Xia,4 Yuan Gao,4 Yan Liu,1 Shen Gao1,4 1Department of Clinical Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Jiaxing Maternity and Child Health Care Hospital, Jiaxing, People’s Republic of China; 3Department of Neurovascular Disease, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shen Gao; Yan Liu, Tel/Fax +86 21 81873715 ; +86 21 25077156, Email liullk@126.com; liuyan03@xinhuamed.com.cnIntroduction: Currently, the main treatment for advanced breast cancer is still chemotherapy. Immunological and chemical combination therapy has a coordinated therapeutic effect and achieves some efficacy. However, the immunosuppressive tumor microenvironment is a major cause for the failure of immunotherapy in breast cancer. CpG oligodeoxynucleotides can activate the tumor immune microenvironment to reverse the failure of immunotherapy.Methods: In this study, we designed an amphiphilic peptide micelle system (Co-LMs), which can targeted delivery of the immune adjuvant CpG and the chemotherapeutic drug doxorubicin to breast cancer tumors simultaneously. The peptide micelle system achieved tumor microenvironment pH and redox-sensitive drug release.Results and Discussion: Co-LMs showed 2.3 times the antitumor efficacy of chemotherapy alone and 5.1 times the antitumor efficacy of immunotherapy alone in triple-negative breast cancer mice. Co-LMs activated cytotoxic CD8+ T lymphocytes and CD4+ T cells in mice to a greater extent than single treatments. We also found that Co-LMs inhibited the metastasis of circulating tumor cells in the bloodstream to some extent. These results indicate that the Co-LMs offer a promising therapeutic strategy against triple-negative breast cancer.Keywords: chemo-immunotherapy, tumor microenvironment, CpG, nanoparticles, triple-negative breast cancer

Yanqiu He,1,&ast; Cheng Hu,1,&ast; Shiyu Liu,1 Mingjie Xu,1 Ge Liang,2 Dan Du,3 Tingting Liu,1 Fei Cai,1 Zhiyao Chen,1 Qingyuan Tan,1 Lihui Deng,1 Qing Xia1 1Pancreatitis Centre, Department and Laboratory of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Clinical Proteomics and Metabolomics, Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihui Deng, Pancreatitis Centre, Department and Laboratory of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China, Email denglihui@scu.edu.cnBackground: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas without specific treatment. Shenmai injection (SMI) was reported to eliminate the severity of experimental AP. This study aimed to explore the mechanisms underlying the synergistic protective effects of SMI on AP based on network pharmacology and experimental validation.Methods: Network pharmacology analysis and molecular docking based on identified components were performed to construct the potential therapeutic targets and pathways. The principal components of SMI were detected via ultra-high-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Effect of SMI and the identified components on cellular injury and IL6/STAT3 signaling was assessed on mouse pancreatic acinar cell line 266– 6 cells. Finally, 4% sodium taurocholate (NaT) was used to induce AP model to assess the effects of SMI in treating AP and validate the potential molecular mechanisms.Results: By searching the TCMSP and ETCM databases, 119 candidate components of SMI were obtained. UHPLC-QTOF/MS analysis successfully determined the representative components of SMI: ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D. Fifteen hub targets and eight related pathways were obtained to establish the main pharmacology network. Subnetwork analysis and molecular docking indicated that the effects of these four main SMI components were mostly related to the interleukin (IL) 6/STAT3 pathway. In vitro, SMI, ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D increased the cell viability of NaT-stimulated mouse pancreatic acinar 266– 6 cells and decreased IL6 and STAT3 expression. In vivo, 10 mL/kg SMI significantly alleviated the pancreatic histopathological changes and the expression of IL6 and STAT3 in the AP mice.Conclusion: This study demonstrated SMI may exert anti-inflammatory effects against AP by suppressing IL6/STAT3 activation, thus providing a basis for its potential use in clinical practice and further study in treating AP.Keywords: acute pancreatitis, Shenmai injection, network pharmacology, molecular docking, IL6/STAT3 signaling pathway

Xueying Zhang,1– 3,* Chen He,1– 3,* Peijun Ju,4,* Qingrong Xia,1– 3 Jianliang Gao,1– 3 Loufeng Zhang,1– 3 Xuequan Chen,1– 3 Hui Yuan,1– 3 Hua Gao,1– 3 Yang Zhang,1– 3 Junwei Yan,1– 3 Wen Xie,1– 3,* Cuizhen Zhu1– 3,* 1Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Clinical Center for Psychiatry and Mental Health, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 3Anhui Mental Health Center, Hefei, People’s Republic of China; 4Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen Xie; Cuizhen Zhu, Affiliated Psychological Hospital of Anhui Medical University, No. 316 Huangshan Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86 13339102285 ; +86 13705535258, Fax +86 055163616000, Email xiewen0808@sina.com; zhucuizhen88@126.comPurpose: The study aimed to clarify the cognitive impairments of schizophrenia with metabolic syndrome while evaluating their potential as risk factors.Patients and Methods: We recruited 153 participants and divided them into three groups according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria and the guideline standards for the prevention and treatment of dyslipidemia in Chinese adults in 2007 for metabolic syndrome, as follows: healthy control group (n = 47); nonmetabolic syndrome group (n = 58); and metabolic syndrome group (n = 48). Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale. Cognitive function and automatic thinking were estimated using the Montreal Cognitive Assessment Scale, Verbal Fluency Test, and Automatic Thoughts Questionnaire. Serum biochemical parameters were measured by automatic biochemistry analyzer.Results: One-way ANOVA analysis revealed that differential cognition impairments in schizophrenia patients compared to controls. Furthermore, results of multiple comparisons showed that more serious barriers in orientation, language fluency, and negative automatic thinking existed in the metabolic syndrome group than in the healthy and non-metabolic syndrome groups. Spearman correlation and stepwise linear regression analyses showed that psychopathological symptoms, high waist circumference, and high triglyceride were the predictive factors for negative automatic thoughts, orientation, and language fluency. Those results collectively revealed that high waist circumference, high triglyceride and negative automatic thinking had validity and effectiveness in predicting the cognitive function impairments of the metabolic syndrome group.Conclusion: The present findings strongly supported the notion that aberrant parameters of high waist circumference, high triglyceride and high negative automatic thoughts had validity and effectiveness predictive role for cognitive impairments in the schizophrenics with metabolic syndrome. The schizophrenia patients with metabolic syndrome should receive regular monitoring and adequate treatment for metabolic and psychological risk factors.Keywords: second-generation antipsychotics, negative symptoms, diet, Montreal Cognitive Assessment Scale, Verbal Fluency Test

Shuyue Jiao,1 Xin Zhang,2 Dapeng Wang,3 Hongyong Fu,3 Qingxin Xia3 1Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Pathology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 3Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University; Henan Medical Key Laboratory of Tumor Pathology and Artificial Intelligence Diagnosis, Zhengzhou, People’s Republic of ChinaCorrespondence: Qingxin Xia; Hongyong Fu, Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University; Henan Medical Key Laboratory of Tumor Pathology and Artificial Intelligence Diagnosis, Zhengzhou Key Laboratory of Accurate Pathological Diagnosis of Intractable Tumors, Zhengzhou, 450000, People’s Republic of China, Email tudou414135404@163.com; dlxiaoyong@126.comIntroduction: Small cell lung cancer (SCLC), an aggressive subtype of lung cancer characterized by the development of neuroendocrine tumors, is prone to distant metastasis, resistant to platinum-based drugs and has a poor prognosis. The development of next-generation sequencing technology (NGS) has led to the identification of many genetic alterations in SCLC. Few druggable targeted molecules can be used in clinical practice. Currently, NGS is widely employed in routine clinical practice of non-small cell lung cancer to assist in therapeutic options and prognosis evaluation. This study aims to investigate genes involved in small cell lung cancer (SCLC), their occurrence and their significance in clinical events.Methods: Tumor tissue specimens from 18 Chinese SCLC patients were collected through a 520 cancer‐related genes panel for next-generation sequencing. First, the association between sequence results and clinical outcomes was examined. Subsequently, data on clinical pathology and sequencing results were analyzed.Results: The Kaplan–Meier curve displayed a significant reduction in PFS for SCLC patients with LRP1B or MAP3K13 mutations. Overall survival (OS) of SCLC patients with MSH6 mutation was significantly higher than those with SPEN mutation.Conclusion: Next-generation sequencing demonstrates that the genetic landscape of SCLC. Mutation status of LRP1B, MAP3K13, MSH6 and SPEN has prognostic significance, which might be potential therapeutic targets. We found possible genes and related signaling pathways that affect metastasis. These results can improve our understanding of the mutation characteristics of SCLC and identify potential biomarkers to guide targeted therapies.Keywords: small cell lung cancer, next-generation sequencing, genetic alteration, tumor mutation burden, clinical significance

Xiaoping Wu,1,2,&ast; Biao Dai,2,3,&ast; Fanfan Yan,1,2 Yang Chen,2,4 Yayun Xu,5 Qingrong Xia,2,6 Xulai Zhang1,2 1Department of Geriatric Psychology, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Medical Education and Research, Anhui Mental Health Center, Hefei, People’s Republic of China; 3Department of Pharmacy, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Modified Electroconvulsive Therapy Room, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230032, People’s Republic of China; 5Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 6Department of Science and Education, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xulai Zhang, Department of Geriatric Psychology, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, No. 316 Huangshan Road, Hefei, 230032, People’s Republic of China, Tel +86 551 63616022, Fax +86 551 63616022, Email Xulaizhang@ahmhcentre.comAim: Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder (MDD), especially elderly patients. As individuals with TRD are at an increased risk of committing suicide and pose a higher risk of relapse, early diagnostic biomarkers of TRD and a better understanding of the resistance mechanism are highly needed. This study aimed to determine whether serum cortisol, nesfatin-1, and pro-inflammatory cytokines can be used as biomarkers for the diagnosis of elderly patients with TRD.Methods: Thirty elderly patients with TRD were selected as the TRD group. Thirty elderly patients with MDD who were effectively treated with conventional antidepressants were selected as the non-TRD group. The baseline levels of serum cortisol, nesfatin-1, and pro-inflammatory cytokines were measured and compared, and their diagnostic values were evaluated using the receiver operating characteristic (ROC) curve method for discriminating patients with TRD from those without TRD.Results: Serum cortisol, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were significantly higher in the non-TRD and TRD groups than in the control group. Moreover, serum cortisol, CRP, TNF-α, and IL-6 levels in the TRD group were significantly lower than those in the non-TRD group. Furthermore, serum nesfatin-1 levels in the non-TRD group were significantly lower than those in the control and TRD groups, while the serum IL-1β levels in the non-TRD group were significantly higher than those in the control and TRD groups. Additionally, an ROC analysis revealed an area under the curve (AUC) of 0.929 for the combination of nesfatin-1 and IL-1β and an AUC of 0.956 for the combination of cortisol, nesfatin-1, and IL-1β in discriminating elderly patients with TRD from those without non-TRD.Conclusion: Serum cortisol, nesfatin-1, and IL-1β may be potential diagnostic biomarkers for discriminating elderly patients with TRD from those without TRD.Keywords: treatment-resistant depression, nesfatin-1, cortisol, pro-inflammatory cytokine, diagnosis, elderly

Qiyun Jiang,1,2 Dan Gong,1,2 Huiqi Li,3 Donglan Zhang,4 Suzhen Hu,5 Qinghua Xia,6 Hong Yuan,7 Peng Zhou,6 Yiying Zhang,7 Xing Liu,8 Mei Sun,1,2 Jun Lv,1,2 Chengyue Li1,2 1Department of Health Policy and Management, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Research Institute of Health Development Strategies, Fudan University, Shanghai, People’s Republic of China; 3School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 4Department of Health Policy and Management, College of Public Health, University of Georgia, Athens, GA, USA; 5Department of Medical Affairs, Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 6Department of Chronic Disease Prevention and Control, Changning District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 7Department of Chronic Disease Prevention and Control, Jiading District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 8Department of Epidemiology, School of Public Health, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Chengyue Li; Jun Lv, Department of Health Policy and Management, School of Public Health, Fudan University, P.O. Box 177, 130 Dong’an Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-33561022 ; +86-21-33563953, Fax +86-21-33563380, Email lichengyue@fudan.edu.cn; lujun@shmu.edu.cnPurpose: This study aimed to develop a screening tool based on a risk scoring approach that could identify individuals at high risk for hypertension in Shanghai, China.Methods: A total of 3147 respondents from the 2013 Shanghai Chronic Disease and Risk Factor Surveillance were randomly divided into the derivation group and validation group. The coefficients obtained from multivariable logistic regression were used to assign a score to each variable category. The receiver operating characteristic (ROC) curve was used to find the optimal cut-off point and to evaluate the screening performance.Results: Age, family history of hypertension, having diabetes, having dyslipidemia, body mass index, and having abdominal obesity contributed to the risk score. The area under the ROC curve was 0.817 (95% CI: 0.797– 0.836). The optimal cut-off value of 20 had a sensitivity of 83.4%, and a specificity of 64.3%, demonstrating good performance.Conclusion: We developed a simple and valid screening tool to identify individuals at risk for hypertension. Early detection could be beneficial for high-risk groups to better manage their conditions and delay the progression of hypertension and related complications.Keywords: Eastern China, high-risk population, hypertension, risk scoring method, screening tool

Hao Yang,1,&ast; Qing Xia,2,&ast; Yan Shen,2 Ting-Li Chen,3 Jing Wang,3 Ya-Yun Lu2 1Department of Stomatology, Huadong Sanatorium, Wuxi, 214065, People’s Republic of China; 2Health Examination Center, Huadong Sanatorium, Wuxi, 214065, People’s Republic of China; 3Department of Ophthalmology, Huadong Sanatorium, Wuxi, 214065, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ya-Yun LuHealth Examination Center, Huadong Sanatorium, Wuxi, 214065, People’s Republic of China, Tel +86 13763384379, Email luyy28@163.comBackground: Hashimoto’s thyroiditis (HT) is recognized as the most common autoimmune thyroid disease, often accompanied by the diffuse enlargement of thyroid with abundant blood flow and elevated level of thyroid autoantibodies. As obesity had a positive association with the risk of HT. Thus, this retrospective study was established to further explore the gender relationship between metabolic obesity phenotypes and the risk of Hashimoto’s thyroiditis (HT).Materials and Methods: Data for 3697 subjects aged ≥ 18 years were randomly collected from a Health check-up database from April to December 2019. Obesity was defined by general obesity (GO; body mass index [BMI] ≥ 28 kg/m2) and abdominal obesity (AO; waist circumstance, male ≥ 90 cm, female ≥ 85 cm). Metabolic unhealthy was defined as having at least one metabolic syndrome component and a homeostasis model assessment of insulin resistance ≥ 2.5. Obesity phenotypes were divided into three groups: GO, AO, compound obesity (GO+AO). After adjustment for potential confounding factors, multivariate logistic regression was used to assess the association between metabolic obesity phenotypes and risk of HT by sex and explore the correlation between different obesity patterns and HT risk by metabolic health status.Results: The incidence of HT was 23.5% and significantly higher among females than males with different metabolic phenotypes (26.2% vs 20.5%, p< 0.05), except metabolically healthy AO. Compared with non-obese subjects, different metabolic obesity phenotypes were independent risk factors among males (p< 0.05). Among females, unhealthy metabolic status with GO (adjusted odds ratio [OR]=2.62) or AO (adjusted OR=2.87) and metabolically healthy non-GO (adjusted OR=2.05) were risk factors of HT (p< 0.05). Increasing BMI categories and waist circumstance quartiles were positively correlated with HT risk (p for trend < 0.05). Subgroup analyses indicated that GO+AO (adjusted OR=2.52) or only AO (adjusted OR=2.41) were risk factors for HT for those with unhealthy metabolic status. Moreover, GO+AO (adjusted OR=2.37) was an independent risk factor for HT under healthy metabolic status.Conclusion: GO+AO was associated with an increased risk of HT, identifying higher BMI/WC as a significant risk factor for HT. Males with unhealthy metabolic state or obesity and metabolically unhealthy females with obesity are high-risk group for HT. Additionally, only AO and GO+AO conferred increased risk of HT for individuals with metabolic abnormalities.Keywords: Hashimoto’s thyroiditis, metabolic obesity phenotypes, general obesity, abdominal obesity, retrospective data

Ni Zeng,1,2 Liwen Ma,3 Yuxin Cheng,1 Qingyue Xia,1 Yueyue Li,1 Yihe Chen,1 Zhiyu Lu,1 Qian Lu,1 Feng Jiang,4 Dan Luo1 1Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 3Department of Dermatology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 4Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of ChinaCorrespondence: Dan LuoDepartment of Dermatology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, People’s Republic of ChinaEmail daniluo2005@163.comFeng JiangDepartment of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, No. 419, Fangxie Road, Shanghai, 200011, People’s Republic of ChinaEmail dxyjiang@163.comObjective: In this research, we studied the genes associated with ferroptosis to develop a prognostic model and find out an association with tumor immune microenvironment in skin cutaneous melanoma (SKCM) patients.Methods: To find SKCM-related ferroptosis genes, we used Cox regression and LASSO approach on 60 genes related to ferroptosis and SKCM-related RNA-seq. Following that, a ferroptosis-related gene signature was created. Time-dependent ROC curve and Kaplan–Meier analysis were calculated to determine its capability of prediction. Besides, several assessments were used to evaluate overall survival (OS), accompanied by the creation of a nomogram for the clinicopathologic factors and the ferroptosis-related gene signature we established. We also investigated the relationship between ferroptosis-related gene signature with three immune checkpoints and immune cell infiltration.Results: Our prognostic model included two genes (ALOX5, CHAC1). In both TCGA and GEO cohorts, OS was lower in high-risk category. Using our gene signature, we can reliably predict OS. Additionally, our gene signature can predict immune cell infiltration and SKCM immunotherapy response.Conclusion: Our gene signature has shown to be a reliable predictor of OS, reflect the immune microenvironment, and predict the effectiveness of immunotherapy for SKCM patients.Keywords: skin cutaneous melanoma, SKCM, ferroptosis, immune microenvironment, immune checkpoint

Ke Rong,1 Xiaoliu Li,2 Weimin Jiang,1 Xuhua Wu,1 Qingquan Xia,2 Jie Chen,1 Xiaofan Yin2 1Department of Orthopedics, The First Affiliated Hospital of Soochow University, Soochow, 215006, People’s Republic of China; 2Department of Orthopedics, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of ChinaCorrespondence: Weimin JiangDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Soochow, 215006, People’s Republic of ChinaTel +86-512-65223637Email min_jw@21cn.comBackground: Osteonecrosis of the femoral head (ONFH) seriously affects the quality of life and labor ability of patients. It is urgent and vital to find the methods for necrosis clinical treatment.Objective: This study aims to study the potential protective effects of Alendronate in the early stage of femur head necrosis.Methods: Ten clinal ONFH tissue samples were employed. H&E staining was employed for the observation of the pathological characteristics of ONFH. The rat model (n=12) was established by the treatment of liquid nitrogen and then treated with Alendronate. The protein expression of BMP2, EIF2AK3, EIF2A and ATF4 were detected via Western blotting and IHC.Results: Fibrin and necrotizing granulation tissue were observed in ONFH tissues with lymphocytes and plasma cells infiltrating in the necrotic area, exhibiting the inflammatory muscle with abnormal shape and color. In the Model group, the BMP2 and ATF4 were mainly distributed in the cell boundaries. The relative protein expression of BMP2, EIF2AK3, EIF2A, ATF4 was decreased in the Model group, compared to the NC group, which was partially recovered by the Alendronate application.Conclusion: Alendronate application partially reversed the suppression of expression of BMP2, EIF2AK3, EIF2A, ATF4 caused by liquid nitrogen. Alendronate could be a promising strategy of curing ONFH via targeting BMP2/EIF2AK3/EIF2A/ATF4 pathway.Keywords: femoral head necrosis, alendronate, BMP2, ATF4

Xiangtian Ling,1 Xinqi Ma,1 Xielan Kuang,1 Yuxiu Zou,1 Han Zhang,1 Han Tang,1 Han Du,1 Binbin Zhu,1 Hao Huang,1 Qing Xia,1 Minghao Chen,1 Danyi Mao,1 Dongli Chen,1 Huangxuan Shen,1,2 Jianhua Yan1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, People’s Republic of China; 2Biobank of Eye, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Huangxuan Shen; Jianhua YanZhongshan Ophthalmic Center, Sun Yat-Sen University, 54 Xianlie Road, Guangzhou, 510060, People’s Republic of ChinaTel +8620-8733-5261; +8620-8733-0484Fax +8620-8733-3271Email shenhx@mail.sysu.edu.cn; yanjh2011@126.comPurpose: To assess the cellular and molecular effects of lidocaine on muscles/myoblasts.Methods: Cultured myogenic precursor (C2C12) cells were treated with varying concentrations of lidocaine.Results: Cell viability of C2C12 cells was inhibited by lidocaine in a concentration-dependent manner, with concentrations ≥ 0.08%, producing a dramatic reduction in cell viability. These ≥ 0.08% concentrations of lidocaine arrested cell cycles of C2C12 cells in the G0/G1 phase. Moreover, lidocaine inhibited cell migration and myogenic processes in C2C12 cells at low concentrations. Results from QRT-PCR assays revealed that following treatment with lidocaine, Notch1, Notch2, Hes1, Csl and Dll4 all showed higher levels of expression, while no changes were observed in Mmal1, Hey1, Dll1 and Jag1.Conclusion: This work provides the first description of the effects of lidocaine upon the regeneration of muscles and maintenance of satellite cells at the cellular and molecular levels. In specific, we found that the Dll4-Notch-Csl-Hes1 axis was up-regulated suggesting that the Notch signaling pathway was involved in producing these effects of lidocaine. These findings provide a new and important foundation for future investigations into the effects of drug therapies in muscle diseases.Keywords: local anesthetics, C2C12 cells, myogenic differentiation, strabismus, Notch signaling pathway

Ying Liu,1,* Xiaojie Li,1,* Shuwen Xiao,1 Xinyi Liu,1 Xuanming Chen,1 Qiyue Xia,1 Song Lei,2 Hongxia Li,1 Zhihui Zhong,3 Kai Xiao1 1National Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 3Laboratory of Non-Human Primate Disease Model Research, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kai Xiao Tel +86-28-83326313Email xiaokaikaixiao@scu.edu.cnBackground: Gold nanoparticles (AuNPs) have shown great promise in various biomedical applications, but their effects on male reproductive function remain to be ascertained. The aim of this study was to investigate the uptake, cytotoxicity and testosterone production inhibition of AuNPs in mouse Leydig cells, as well as their accumulation in the testes of male mice and their effects on male reproductive function.Results: AuNPs (5 nm) were able to be internalized into the endosomes/lysosomes of TM3 Leydig cells, induce the formation of autophagosomes, increase the production of reactive oxygen species (ROS), and disrupt the cell cycle in S phase, resulting in concentration-dependent cytotoxicity and DNA damage. Interestingly, AuNPs significantly reduced testosterone production in TM3 cells by inhibiting the expression of 17α-hydroxylase, an important enzyme in androgen synthesis. After repeated intravenous injection, AuNPs gradually accumulated and retained in the testes of male BALB/c mice in a dose-dependent manner. One week after withdrawal, the level of plasma testosterone in the 0.5 mg/kg AuNPs group was significantly reduced compared to that in the PBS control group, accompanied by the decreased expression of 17α-hydroxylase in the testes. In addition, AuNPs treatment significantly increased the rate of epididymal sperm malformation, but without affecting fertility.Conclusion: Our results suggest that AuNPs can accumulate in the testes and reduce testosterone production in Leydig cells by down-regulating the expression of 17α-hydroxylase, thus affecting the quality of epididymal sperm.Keywords: gold nanoparticles, Leydig cells, testosterone, reproductive toxicity, fertility

Yang Liu,1,2,* Jun Liang,2,* Qingrong Xia,2 Xin Zhou,1 Xuefeng Xie1 1Department of Basic and Clinical Pharmacology, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, Anhui, People’s Republic of China; 2Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei 230000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuefeng XieDepartment of Basic and Clinical Pharmacology, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, People’s Republic of ChinaTel/Fax +86 551 65172137Email xiexuefeng@ahmu.edu.cnObjective: To explore the therapeutic effects of lithium combined with second-generation antipsychotics (SGAs) of quetiapine, clozapine, olanzapine, and risperidone for the treatment of manic episodes in patients with bipolar disorder (BD) to guide the selection of medications.Methods: We examined the case data of patients with BD who experienced manic episodes and were hospitalized in a Class 3A Psychiatric Hospital in Anhui Province from January 2015 to October 2019. The enrolled patients were rated using the Bech–Rafaelsen Mania Rating Scale (BRMS) before and after treatment, and relevant adverse effects were monitored.Results: Analysis of the collected case data of 182 patients showed significant differences in the BRMS scores on admission and at discharge of patients treated with lithium combined with each SGA. The chi-square test showed no obvious difference in the final therapeutic effects of lithium combined with each of the four SGAs (χ2 = 7.365, P = 0.146). However, there were differences in the incidence of adverse effects (χ2 = 10.604, P = 0.014) and remission rate after 2 weeks of treatment (χ2 = 10.174, P = 0.017). Logistic regression analysis revealed that the incidence of adverse effects was related to the length of stay in hospital and clozapine treatment. The remission rate after 2 weeks was associated with the length of stay in hospital, clozapine treatment, and age of onset.Conclusion: Lithium combined with SGAs (quetiapine, clozapine, olanzapine, and risperidone) effectively improves the manic symptoms of patients with BD who experience manic episodes. Lithium combined with quetiapine for the treatment of bipolar manic episode has advantages with respect to the speed of effective and incidence of adverse effects.Keywords: bipolar mania, atypical antipsychotic, mood stabilizers, remission rate

Jianfeng Bao,1,2 Xiangyang Zu,2 Xiao Wang,1 Jinghua Li,2 Dandan Fan,3 Yupeng Shi,1 Qingchun Xia,4 Jingliang Cheng1 1Functional Magnetic Resonance and Molecular Imaging Key Laboratory of Henan Province, Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, Henan, People’s Republic of China; 3Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Henan Key Laboratory of Boron Chemistry and Advanced Energy Materials, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan, People’s Republic of ChinaCorrespondence: Jingliang ChengThe First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaTel +86-13603863860Fax +86-37166964992Email cjr.chjl@vip.163.comQingchun XiaHenan Normal University, Xinxiang, Henan, People’s Republic of ChinaTel +86-13353679807Fax +86-3733329030Email xiaqingchun@htu.edu.cnBackground: Recent studies have validated and confirmed the great potential of nanoscale metal-organic framework (NMOF) in the biomedical field, especially in improving the efficiency of cancer diagnosis and therapy. However, most previous studies only utilized either the metal cluster or the organic ligand of the NMOF for cancer treatments and merely reported limited theranostic functions, which may not be optimized. As a highly designable and easily functionalized material, prospective rational design offers a powerful way to extract the maximum benefit from NMOF for cancer theranostic applications.Materials and Methods: A NMOF based on hafnium (Hf) cluster and Mn(III)-porphyrin ligand was rational designed and synthesized as a high-performance multifunctional theranostic agent. The folic acid (FA) was modified on the NMOF surface to enhance the cancer targeting efficacy. The proposed “all-in-one” FA-Hf-Mn-NMOF (fHMNM) was characterized and identified using various analytical techniques. Then, in vitro and in vivo studies were performed to further explore the effects of fHMNM both as the magnetic resonance imaging (MRI)/computed tomography (CT)/photoacoustic imaging (PAI) contrast agent and as the photothermal therapy (PTT)/radiotherapy (RT) agent.Results: A tumour targeting multifunctional fHMNM was successfully synthesized with high performance for MRI/CT/PAI enhancements and image-guided PTT/RT synergistic therapy properties. Compared with the current clinical CT and MR contrast agents, the X-ray attenuation and T1 relaxation rate of this integrated nanosystem increased 1.7-fold and 3– 5-fold, respectively. More importantly, the catalase-like Mn(III)-porphyrin ligand can decompose H2O2 into O2 in tumour microenvironments to improve the synergistic treatment efficiency of PTT and RT. Significant tumour growth inhibition was achieved in mouse cancer models without obvious damage to the other organs.Conclusion: This work highlights the potential of fHMNM as an easily designable material for biomedical applications, could be an effective tool for in vivo detection and subsequent treatment of tumour.Keywords: metal-organic framework, theranostics, multimodality imaging, radiotherapy, photothermal therapy

Tengteng Wang, Qinghua Xia, Xiude Chen, Xunbo Jin Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Xiude ChenDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250014, People’s Republic of ChinaTel +86 15168863866Email scistone_2019@163.comBackground and Aim: Baidu, currently the top online search tool in China, has developed an internet search trends gathering and analysis tool called the Baidu Index. The aim of this study was to explore the value of the Baidu Index for monitoring online kidney stones-related information-seeking behavior and understanding of population features and priorities in China.Materials and Methods: The Baidu Index was queried using the term “kidney stones” for the period 2014– 2018. The search volume was recorded as well as a demand graph, with a geographic and demographic distribution. For surgical treatment modalities, the medical term “extracorporeal shock wave lithotripsy (ESWL)” was analyzed and then compared to the term “kidney stone surgery” to assess changes.Results: The search trend for the term “kidney stones” remained sustained growth over time. Searches were mostly presented by the age 20– 49, in males in the south of China. The demand graph indicated that the diagnosis, followed by the treatment, and dietary control of kidney stones had received the most attention. The search volume related to ESWL showed a similar increasing trend, but was searched with a greater volume than the term “kidney stone surgery” for most of the last 5 years.Conclusion: The Baidu Index is a useful tool to track online health information-seeking behavior of internet users in China. The geographic and demographic characteristics in kidney stones seem to be reflected in online search trend data to some extent.Keywords: search engine, Baidu Index, kidney stones, kidney stone surgery, extracorporeal shock wave lithotripsy

Xi Cao,1,2 Tingfei Tan,1,2 Dongchun Zhu,1,2 Haixia Yu,1,2 Yaru Liu,1,2 Haiyun Zhou,1,2 Yong Jin,3,4 Quan Xia1,2 1Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, People’s Republic of China; 3Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of China; 4The Key Laboratory of Major Autoimmune Diseases, Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Quan Xia Tel +86 551 62922154Email xiaquan2010@163.comBackground: Melanoma is the most common symptom of aggressive skin cancer, and it has become a serious health concern worldwide in recent years. The metastasis rate of malignant melanoma remains high, and it is highly difficult to cure with the currently available treatment options. Effective yet safe therapeutic options are still lacking. Alternative treatment options are in great demand to improve the therapeutic outcome against advanced melanoma. This study aimed to develop albumin nanoparticles (ANPs) coated with macrophage plasma membranes (RANPs) loaded with paclitaxel (PTX) to achieve targeted therapy against malignant melanoma.Methods: Membrane derivations were achieved by using a combination of hypotonic lysis, mechanical membrane fragmentation, and differential centrifugation to empty the harvested cells of their intracellular contents. The collected membrane was then physically extruded through a 400 nm porous polycarbonate membrane to form macrophage cell membrane vesicles. Albumin nanoparticles were prepared through a well-studied nanoprecipitation process. At last, the two components were then coextruded through a 200 nm porous polycarbonate membrane.Results: Using paclitaxel as the model drug, PTX-loaded RANPs displayed significantly enhanced cytotoxicity and apoptosis rates compared to albumin nanoparticles without membrane coating in the murine melanoma cell line B16F10. RANPs also exhibited significantly higher internalization efficiency in B16F10 cells than albumin nanoparticles without a membrane coating. Next, a B16F10 tumor xenograft mouse model was established to explore the biodistribution profiles of RANPs, which showed prolonged blood circulation and selective accumulation at the tumor site. PTX-loaded RANPs also demonstrated greatly improved antitumor efficacy in B16F10 tumor-bearing mouse xenografts.Conclusion: Albumin-based nanoscale delivery systems coated with macrophage plasma membranes offer a highly promising approach to achieve tumor-targeted therapy following systemic administration.Keywords: macrophage membrane, albumin nanoparticles, melanoma, paclitaxel, tumor-targeted therapy

Qian-qian Chen,1–3 Jia-min Shi,1,2 Zhou Ding,1,2 Qing Xia,1,2 Tian-sheng Zheng,1,2 Yan-bei Ren,1,2 Ming Li,1,2 Li-hong Fan1,2 1Department of Respiratory Medicine, Shanghai 10th People’s Hospital, Tongji University, Shanghai 200072, People’s Republic of China; 2Institute of Energy Metabolism and Health, Tongji University School of Medicine, Shanghai 200072, People’s Republic of China; 3Medical School of Nantong University, Nantong, Jiangsu 22601, People’s Republic of ChinaCorrespondence: Li-hong Fan; Ming LiDepartment of Respiratory Medicine, Shanghai 10th People’s Hospital, Tongji University, #301 Mid Yianchang Road, Shanghai 200072, People’s Republic of ChinaTel/fax +86 1 800 176 3288; +86 1 339 135 8760Email 18260626371@163.com; mlid163@163.comBackground: Berberine (BBR) from the widely used Chinese herbal medicine Huanglian has an array of pharmacological and biochemical properties, including anti-neoplastic activity. However, the specific mechanisms underlying these properties are unknown. The aim of this study was to explore the anti-tumor mechanisms of BBR in non-small cell lung cancer (NSCLC).Methods: The effects of BBR on NSCLC tumor development and programmed cell death were investigated both in vivo and in vitro. Luciferase reporter assays were used to determine whether tissue factor (TF) was a target of miR-19a.Results: BBR suppressed NSCLC growth and promoted apoptosis in NSCLC cells by modulating miR-19a and TF expression. Luciferase assays showed that TF was a direct inhibitory target of miR-19a in NSCLC cells. BBR induced apoptosis through the miR-19a/TF/MAPK axis.Conclusion: The results suggest that BBR induces apoptosis of NSCLC cells via the miR-19a/TF/MAPK signaling pathway.Keywords: non-small-cell lung carcinoma, NSCLC, berberine, miR-19a, tissue factor, TF, MAPK

Qiyue Xia,1,2,* Jinxing Huang,1,* Qiyi Feng,1 Xuanming Chen,1 Xinyi Liu,1 Xiaojie Li,1 Ting Zhang,3 Shuwen Xiao,1 Hongxia Li,1 Zhihui Zhong,3,4 Kai Xiao1,41National Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China; 2Toxicology Department, Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan Province, China; 3Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; 4Sichuan Kangcheng Biotech Co., Ltd, Chengdu, Sichuan Province, ChinaCorrespondence: Kai XiaoNational Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, 28 Gaopeng Ave, High-Tech Development Zone, Chengdu 610041, Sichuan Province, People’s Republic of ChinaTel +86 288 332 6313Fax +86 288 517 3043Email xiaokaikaixiao@scu.edu.cn*These authors contributed equally to this workBackground: Gold nanoparticles (AuNPs) have shown great promise in biomedical applications. However, the interaction of AuNPs with biological systems, its underlying mechanisms and influencing factors need to be further elucidated.Purpose: The aim of this study was to systematically investigate the effects of particle size on the uptake and cytotoxicity of AuNPs in normal cells and cancer cells as well as their biological distribution in vivo.Results: Our data demonstrated that the uptake of AuNPs increased in HepG2 cancer cells but decreased in L02 normal cells, with the increase of particle size (5-50 nm). In both cancer cells and normal cells, small (5 nm) AuNPs exhibited greater cytotoxicity than large ones (20 and 50 nm). Interestingly, 5 nm AuNPs induced both apoptosis and necrosis in HepG2 cells through the production of reactive oxygen species (ROS) and the activation of pro-caspase3, whereas it mainly induced necrosis in L02 cells through the overexpression of TLR2 and the release of IL-6 and IL-1a cytokines. Among them, 50 nm AuNPs showed the longest blood circulation and highest distribution in liver and spleen, and the treatment of 5 nm AuNPs but not 20 nm and 50 nm AuNPs resulted in the increase of neutrophils and slight hepatotoxicity in mice.Conclusion: Our results indicate that the particle size of AuNPs and target cell type are critical determinants of cellular uptake, cytotoxicity and underlying mechanisms, and biological distribution in vivo, which deserves careful consideration in the future biomedical applications.Keywords: gold nanoparticles, particle size, uptake, toxicity, biodistribution

Yuhuan Yang,1,* Shuna Yao,1,* Jiuyang Zhang,1 Zheng Yan,1 Junfeng Chu,1 Haiying Wang,1 Zhihua Yao,1 Fan Zhang,2 Qingxin Xia,3 Yanyan Liu11Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Central Laboratory, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Yanyan LiuDepartment of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, 127 Dong Ming Road, Zhengzhou, Henan 450008, People’s Republic of ChinaEmail yyliu@zzu.edu.cnQingxin XiaDepartment of Pathology, Affiliated Cancer Hospital of Zhengzhou University, 127 Dong Ming Road, Zhengzhou, Henan 450008, People’s Republic of ChinaEmail 13838173710@139.com*These authors contributed equally to this workAbstract: Early T-cell precursor (ETP) leukemia represents a new subtype of T-lymphoblastic leukemia/lymphoma with unique immunophenotypes expressing T-cell and one or more of the myeloid/stem cell markers. Here, we report a young patient who had primary mediastinal mass and pleural effusion without bone marrow involvement. A CT-guided mediastinal biopsy and flow cytometry analysis of the pleural effusion revealed the blast cells to have complicated immunophenotypes: strongly expressed T-cell antigen CD7, myeloid-lineage antigens CD33 and CD13 and stem cell markers cTdT, CD34, and HLA-DR; dimly expressed myeloid-lineage specific antigen cMPO and B-cell antigen cCD79a; but did not express T-cell specific antigen cytoplasmic CD3 and B-cell specific antigen CD19. Clonal T-cell receptor rearrangement eventually determined the cell of origin from ETPs, not myeloblasts. The patient showed primary resistance to lymphoid and myeloid-directed induction therapy. Finally, low-dose decitabine combined with modified-CAG regimen induced a complete remission and allogeneic stem cell transplantation was performed as consolidation. The case indicates a primary mediastinal neoplasm from ETP with distinctive immunophenotype from leukemia type. Low-dose decitabine and modified-CAG regimen in combination with allogeneic stem cell transplantation may improve the outcome of patient.Keywords: early T-cell precursor, decitabine, G-CSF priming, T-lymphoblastic lymphoma

Shuang-xiang Tan,1,2 Rui-cheng Hu,1,2 Qian Xia,2 Yong-li Tan,1 Jing-jing Liu,1 Gui-xiang Gan,1 Li-le Wang1 1Hunan Province Institute of Gerontology, Hunan Provincial People’s Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, China; 2Department of Respiratory Medicine, Hunan Provincial People’s Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, China Background: Non–small cell lung cancer (NSCLC) is one of the leading malignant tumors worldwide. Aberrant gene promoter methylation contributes to NSCLC, and PRDM is a tumor suppressor gene family that possesses histone methyltransferase activity. This study aimed to investigate whether aberrant methylation of PRDM promoter is involved in NSCLC. Materials and methods: Primary tumor tissues, adjacent nontumorous tissues, and distant lung tissues were collected from 75 NSCLC patients including 52 lung squamous cell carcinoma (LSCC) patients and 23 lung adenocarcinoma patients. The expression of PRDMs was detected by polymerase chain reaction (PCR), Western blot, and immunohistochemical analysis. The methylation of PRDM promoters was detected by methylation-specific PCR. The correlation of methylation and expression of PRDMs with clinicopathological characteristics of patients were analyzed. Results: mRNA expression of PRDM2, PRDM5, and PRDM16 was low or absent in tumor tissues compared to distant lung tissues. The methylation frequencies of PRDM2, PRDM5, and PRDM16 in tumor tissues were significantly higher than those in distal lung tissues. In LSCC patients, methylation of PRDM2 and PRDM16 was correlated with smoking status and methylation of PRDM5 was correlated with tumor differentiation. Conclusion: The expression of PRDM2, PRDM5, and PRDM16 is low or absent in NSCLC, and this is mainly due to gene promoter methylation. Smoking may be an important cause of PRDM2 and PRDM16 methylation in NSCLC. Keywords: lung tumor, PR domain zinc finger protein, epigenetics, methylation, gene expression

Quansong Xia,1,* Wei Wang,2,* Juan Xu,3 Xue Chen,2 Zhaoming Zhong,2 Chuanzheng Sun2 1Department of Clinical Laboratory, 2Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, 3Department of Internal Medicine, The People’s Hospital of Guandu District, Kunming, People’s Republic of China *These authors contributed equally to this work Background: Radiotherapy and chemotherapy are the two important postoperative management approaches for anaplastic thyroid carcinoma (ATC), and several studies have suggested that postoperative radiotherapy and chemotherapy can prolong the survival of patients with ATC. However, the results remain inconsistent. Objective: A meta-analysis was performed to address whether postoperative radiotherapy and chemotherapy could prolong the survival of patients with ATC. Methods: Relevant studies were included, and pooled hazard ratios (HRs) together with 95% confidence intervals (CIs) were calculated. Results: Ten relevant studies on factors that affect the prognosis for ATC were included in this meta-analysis, evaluating a total of 1,163 patients. The pooled HR for overall survival (OS) was calculated using a random-effects model. The pooled results demonstrated that for all patients with resectable ATC, the combination of surgery and radiotherapy significantly reduced the risk of death compared with surgery alone (HR =0.51, 95% CI: 0.36–0.73, Z=3.66, P=0.0002). To investigate the prognostic impacts of chemotherapy in patients with ATC, we also calculated the pooled HR of chemotherapy for OS using a random-effects model; however, the pooled results suggested that chemotherapy did not prolong the survival of ATC patients compared with controls (HR =0.63, 95% CI: 0.33–1.21, Z=1.39, P=0.17). Conclusion: This study provided evidence that currently, for patients with ATC, postoperative radiotherapy may prolong survival; in contrast, chemotherapy did not improve long-term survival. Keywords: anaplastic thyroid carcinoma, postoperative radiotherapy, chemotherapy, prognosis, meta-analysis

Danting Cui,1 Xiaodan Lu,1 Chenggong Yan,1 Xiang Liu,1 Meirong Hou,1 Qi Xia,2 Yikai Xu,1 Ruiyuan Liu2,3 1Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 3School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of China Abstract: Bombesin (BBN), an analog of gastrin-releasing peptide (GRP), specifically binds to GRP receptors, which are overexpressed in human prostate cancer (PC). Here, we synthesized a BBN-modified gadolinium oxide (Gd2O3) nanoprobe containing fluorescein (Gd2O3-5(6)-carboxyfluorescein [FI]-polyethylene glycol [PEG]-BBN) for targeted magnetic resonance (MR)/optical dual-modality imaging of PC. The Gd2O3-FI-PEG-BBN nanoparticles exhibited a relatively uniform particle size with an average diameter of 52.3 nm and spherical morphology as depicted by transmission electron microscopy. The longitudinal relaxivity (r1) of Gd2O3-FI-PEG-BBN (r1 =4.23 mM–1s–1) is comparable to that of clinically used Magnevist (Gd-DTPA). Fluorescence microscopy and in vitro cellular MRI demonstrated GRP receptor-specific and enhanced cellular uptake of the Gd2O3-FI-PEG-BBN in PC-3 tumor cells. Moreover, Gd2O3-FI-PEG-BBN showed more remarkable contrast enhancement than the corresponding nontargeted Gd2O3-FI-PEG according to in vivo MRI and fluorescent imaging. Tumor immunohistochemical analysis further demonstrated improved accumulation of the targeted nanoprobe in tumors. BBN-conjugated Gd2O3 may be a promising nanoplatform for simultaneous GRP receptor-targeted molecular cancer diagnosis and antitumor drug delivery in future clinical applications. Keywords: magnetic resonance imaging, gadolinium oxide, bombesin, gastrin-releasing peptide receptor, molecular imaging

The emergence of graphene (GR) has recently opened up an exciting new field in the science and technology of two-dimensional (2D) nanomaterials with continuously growing academic and technological impetus. GR exhibits unique electronic, optical, magnetic, thermal, and mechanical properties arising from its strictly 2D structure and, thus, has many important technical applications. In the last 2 years, GR, as novel sensing material has attracted tremendous attention and research interest. To further improve electrochemical property, large numbers of GR-based hybride materials have been well designed, synthesized, and investigated for sensing application. The hybridization can be an effective strategy to enhance functionality of the materials, and the integration of nanomaterials on GR potentially paves a new way to enhance their electronic, chemical, and electrochemical properties. As a result, the GR composites often offer better analytical characteristics than GR materials alone. However, the immobilizations of GR-based material and enzyme are important to enhance electrochemical properties and use of the biosensor. Classical coating method results in poor stability due to loss of the enzyme/antibody. To resolve the problem, we developed a green and controllable strategy to fabricate well-dispersed GR-metal nanocomposite modified functional conducting polymer film containing carbonyl groups with electrochemical deposition. Horseradish peroxidase was finally connected covalently to the film with 1-ethyl-3-(3-dimethylaminepropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) as activator. The as-prepared GR/gold nanocomposite offers remarkable catalysis performance to the redox of hydrogen peroxide on the electrode surface. In this review, from the viewpoint of chemistry and materials, we will cover recent significant advances in hybrids, design, and synthesis of GR-based film, as well as immobilization of enzyme/antibody on the electrode, and analytical application together with discussion on the major challenges and opportunities for future GR research.

Anthocyanins and selenium (Se) have antioxidant properties and are crucial to human health. Previous works have well studied the role of exogenous Se fertilization in grain quality and anthocyanin formation in colored crops, whereas few reports on naturally Se-enriched colored grains exist. In this study, the quality, anthocyanin accumulation, and metabolism of natural Se-enriched purple waxy corn and common purple waxy corn were compared during kernel development. Natural Se-enriched purple waxy corn had higher concentrations of total Se, anthocyanins, flavones, starch (branched- and straight-chain), and sugar than common purple waxy corn, and the optimum eating date was 28 days after pollination. Genes related to anthocyanin biosynthesis were significantly upregulated in natural Se-enriched purple waxy corn, resulting in enriched anthocyanin metabolites (6-O-malonyl-beta-D-glu and 3-O-glu in Cy, Pn, and Pg). Most importantly, genetic alterations were observed which several genes and transcription factors were downregulated some branch pathways of lignin synthesis and accelerated anthocyanin synthesis. Our results profiled anthocyanin metabolism in naturally Se-enriched purple waxy corn to promote harvesting. [ABSTRACT FROM AUTHOR]