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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

We report the first measurement of discrimination between low-energy helium recoils and electron recoils in liquid xenon. This result is relevant to proposed low-mass dark matter searches which seek to dissolve light target nuclei in the active volume of liquid-xenon time projection chambers. Low-energy helium recoils were produced by degrading α particles from ^{210}Po with a gold foil situated on the cathode of a liquid xenon time-projection chamber. The resulting population of helium recoil events is well separated from electron recoils and is also offset from the expected position of xenon nuclear recoil events.

Silicon photomultipliers (SiPMs) are solid-state, single-photon sensitive, pixelated sensors whose usage for scintillation detection has rapidly increased over the past decade. It is known that the avalanche process within the device, which renders a single photon detectable, can also generate secondary photons which may be detected by a separate device. This effect, known as external crosstalk, could potentially degrade the science goals of future xenon dark matter experiments. In this article, we measure the effect of external crosstalk in a dual-phase, liquid xenon time projection chamber fully instrumented with SiPMs. We then consider the implications for a future xenon dark matter experiment utilizing SiPMs and discuss possible solutions.

We have built and operated a crystalline/vapor xenon TPC, with the goal of improving searches for dark matter. The motivation for this instrument is the fact that beta decays from the radon decay chain to the ground state presently limit the state-of-the-art liquid/vapor xenon experiments. In contrast, a crystalline xenon target has the potential to exclude, or tag and reject radon-chain backgrounds. As a preamble to demonstrating such capabilities, the present article makes a first demonstration of the operation of a crystalline/vapor xenon TPC with electroluminescence (gas gain) for the electron signal readout. It also shows that the scintillation yield in crystalline xenon appears to be identical to that in liquid xenon, in contrast to previous results.