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Apart from northern and central China, the fossil record of the latest Miocene and Early Pliocene of Asia is not well documented and the record of South China during this interval is especially poor. Shuitangba, a site in Yunnan Province, offers a rare window into the paleoenvironment of the latest Miocene in southwestern China. Over 2400 vertebrate and macrobotanical specimens have been recovered from the site. The faunal assemblage is dominated by aquatic avian taxa and many of the mammalian taxa are those that indicate densely vegetated, water-margin habitats. Pollen and carpological remains indicate a temperate to subtropical, broad-leaved/coniferous forest around standing water, with more open areas containing grasses and herbs. Analyses of clay minerals, chemical weathering, and enamel stable isotopes suggest that Shuitangba was warmer and more humid than today, possibly with more pronounced seasonality. Results of community structure analysis indicate that the Shuitangba mammalian community was different from those of other Late Miocene Chinese sites in the high proportions of aquatic-dependent mammalian taxa. While Shuitangba shared mammalian faunal elements with other Late Miocene sites in Yunnan, it was still faunally distinct. Further, Shuitangba was depauperate in its mammalian fauna, which may have been a result of the depositional setting rather than a true reflection of regional faunal diversity.

Zhenghua Cao,1 Shengkun Zhao,1 Shaodan Hu,2 Tong Wu,3 Feng Sun,2 LI Shi2 1Changchun University of Traditional Chinese Medicine, Changchun, Jilin, People’s Republic of China; 2Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin, People’s Republic of China; 3Geriatric Department, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of ChinaCorrespondence: LI Shi, Email shili0648@163.comPurpose: To employ bioinformatics and machine learning to predict the characteristics of immune cells and genes associated with the inflammatory response and ferroptosis in chronic obstructive pulmonary disease (COPD) patients and to aid in the development of targeted traditional Chinese medicine (TCM). Mendelian randomization analysis elucidates the causal relationships among immune cells, genes, and COPD, offering novel insights for the early diagnosis, prevention, and treatment of COPD. This approach also provides a fresh perspective on the use of traditional Chinese medicine for treating COPD.Methods: R software was used to extract COPD-related data from the Gene Expression Omnibus (GEO) database, differentially expressed genes were identified for enrichment analysis, and WGCNA was used to pinpoint genes within relevant modules associated with COPD. This analysis included determining genes linked to the inflammatory response in COPD patients and analyzing their correlation with ferroptosis. Further steps involved filtering core genes, constructing TF-miRNA‒mRNA network diagrams, and employing three types of machine learning to predict the core miRNAs, key immune cells, and characteristic genes of COPD patients. This process also delves into their correlations, single-gene GSEA, and diagnostic model predictions. Reverse inference complemented by molecular docking was used to predict compounds and traditional Chinese medicines for treating COPD; Mendelian randomization was applied to explore the causal relationships among immune cells, genes, and COPD.Results: We identified 2443 differential genes associated with COPD through the GEO database, along with 8435 genes relevant to WGCNA and 1226 inflammation-related genes. A total of 141 genes related to the inflammatory response in COPD patients were identified, and 37 core genes related to ferroptosis were selected for further enrichment analysis and analysis. The core miRNAs predicted for COPD include hsa-miR-543, hsa-miR-181c, and hsa-miR-200a, among others. The key immune cells identified were plasma cells, activated memory CD4 T cells, gamma delta T cells, activated NK cells, M2 macrophages, and eosinophils. Characteristic genes included EGF, PLG, PTPN22, and NR4A1. A total of 78 compounds and 437 traditional Chinese medicines were predicted. Mendelian randomization analysis revealed a causal relationship between 36 types of immune cells and COPD, whereas no causal relationship was found between the core genes and COPD.Conclusion: A definitive causal relationship exists between immune cells and COPD, while the prediction of core miRNAs, key immune cells, characteristic genes, and targeted traditional Chinese medicines offers novel insights for the early diagnosis, prevention, and treatment of COPD.Keywords: bioinformatics analysis, Mendelian randomization, machine learning, COPD, characteristic genes, targeted traditional Chinese medicine, early diagnosis

Ming-Ming Li,* Yi Zhang,* Fang Sun, Man-Xiu Huai, Fei-Yu Zhang, Jia-Xing Pan, Chun-Ying Qu, Feng Shen, Zheng-Hong Li, Lei-Ming Xu Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei-Ming Xu; Yi Zhang, Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai, People’s Republic of China, 200092, Tel/Fax +86 21 2507 8999, Email xuleiming@xinhuamed.com.cn; zhangyi02@xinhuamed.com.cnPurpose: Photodynamic therapy (PDT) induces anti-tumor immune responses by triggering immunogenic cell death in tumor cells. Previously, we demonstrated that novel QDs-RGD nanoparticles exhibited high efficiency as photosensitizers in the treatment of pancreatic cancer. However, the underlying mechanism of the anti-tumor immune effects induced by the photosensitizer remains unknown. This study assessed the anticancer immune effect of QDs-RGD, as well as the conventional photosensitizer chlorine derivative, YLG-1, for comparison, against pancreatic cancer in support of superior therapeutic efficacy.Methods: The pancreatic cancer cell line, Panc02, was used for in vitro studies. C57BL/6 mice bearing pancreatic cancer cell-derived xenografts were generated for in vivo studies to assess the anti-tumor effects of QDs-RGD-PDT and YLG-1-PDT. The immunostimulatory ability of both photosensitizers was examined by measuring the expression of damage-associated molecular patterns (DAMP), such as calreticulin (CRT), assessing dendritic cell (DC) maturation, and analyzing cytokine expression. The specific immunity of QDs-RGD and YLG-1-PDT on distant tumor were determined by combining PDT with anti-CTLA-4 antibody.Results: QDs-RGD-PDT and YLG-1-PDT significantly inhibited pancreatic cancer cell growth in a dose- and time-dependent manner. While both photosensitizers significantly promoted CRT release, DC maturation, and interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) expression, QDs-RGD exerted a stronger immunostimulatory effect than YLG-1. Combination treatment with QDs-RGD and CTLA-4 blockade was able to significantly inhibit the growth of distant tumors.Conclusion: QDs-RGD is a novel and effective PDT strategy for treating pancreatic tumors by inducing anti-tumor immune responses.Keywords: quantum dots, RGD peptides, cancer immunotherapy, pancreatic neoplasm

Lijie Ma, Fang Sun, Kaiyi Zhu, Qiuxia Han, Qianmei Sun Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaCorrespondence: Qianmei Sun; Qiuxia Han, Email sunqianmei5825@126.com; qiuxiahanamy@163.comPurpose: The serum lipid level is strongly associated with atherosclerosis. However, research on the relationship between lipid-derived indices and acute ischemic stroke (AIS) occurrence in hemodialysis populations is limited. This study aimed to explore the predictive value of lipid-derived indices, including atherogenic index of plasma (AIP), Non- high density lipoprotein cholesterol (Non-HDL-C), Non-HDL-C/HDL-C, and lipoprotein combine index (LCI) in clinical practice for the occurrence and prognosis of AIS in hemodialysis patients.Methods: A total of 451 patients undergoing maintenance hemodialysis were screened and 350 were enrolled in this study. The lipid parameters exhibit a progressive increase across the tertiles, with values rising from Q1 through Q3. Enrolled patients were divided into three groups (Q1, Q2, and Q3) based on tertiles of AIP, Non-HDL-C, Non-HDL-C/HDL-C, and LCI values. Kaplan-Meier curves were performed to investigate the association between the AIP, Non-HDL-C, Non-HDL-C/HDL-C, LCI and AIS-free survival in hemodialysis patients. Chi-square analysis was used to explore the association between the AIP, Non-HDL-C, Non-HDL-C/HDL-C, LCI and AIS outcomes in hemodialysis patients. AIS outcomes were assessed using the modified Rankin Scale (mRS).Results: Kaplan-Meier analysis revealed that the AIS-free survival rates were significantly higher in the Q1 group compared to Q2 and Q3 groups for AIP, Non-HDL-C, Non-HDL-C/HDL-C, and LCI. Log rank tests showed statistically significant differences between the Q1 group and the Q2 and Q3 groups (p < 0.05 for all). The proportion of patients with a good outcome mRS was higher in the Q1 group compared to the Q2-Q3 groups (AIP: 0.818 vs 0.792; Non- HDL-C: 0.866 vs 0.767; Non- HDL-C/HDL-C: 0.867 vs 0.767; LCI: 0.938 vs 0.750).Conclusion: The four lipid-derived parameters are effective predictors of AIS in patients undergoing hemodialysis, and AIP has a strongest correlation with the risk of AIS. Hemodialysis patients with elevated levels of the four lipid-derived indices had a higher incidence of AIS and poorer functional outcomes compared to those with lower levels. Our conclusions may require confirmation by further research in the future.Keywords: hemodialysis, acute ischemic stroke, atherogenic index of plasma, non-high density lipoprotein cholesterol, lipoprotein combine index

Jiao Zhang,1,2 Yi Yin,3,4 Jiliang Tang,5 Yingrong Zhang,1,2 Yanan Tian,1,2 Fengkai Sun1,2,6 1Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Department of Paediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 4Department of Paediatrics, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 5Emergency Department, Rizhao Central Hospital, Rizhao, People’s Republic of China; 6College of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of ChinaCorrespondence: Fengkai Sun, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jingwu Road 324&num;, Jinan, 250021, People’s Republic of China, Tel +86-531-68776902, Fax +86-531-68776072, Email sunfengkai2016@126.com; sunfengkai@sdfmu.edu.cnBackground: Effective biomarkers are needed to predict the efficacy of immune checkpoint inhibitors (ICIs) therapy in hepatocellular carcinoma (HCC). We evaluated the early changes in serum interleukin-8 (IL-8) levels as a biomarker of response to ICIs in patients with unresectable HCC.Methods: Eighty patients who received ICIs therapy alone or in combination with other treatments for unresectable HCC were included. Serum was collected at baseline and 2– 4 weeks after the first dose. Serum IL-8 levels were measured using by ELISA.Results: In the progressive disease (PD) group, serum IL-8 levels increased significantly before the second dose of ICIs therapy compared with baseline levels (P < 0.001). Early changes in serum IL-8 levels were significantly associated with the response to ICIs therapy (P < 0.001). A cutoff value of 8.1% increase over the baseline most effectively predicted the response to ICIs. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy in patients with unresectable HCC. Patients with increases in serum IL-8 levels > 8.1% had significantly shorter overall survival (OS) and progression-free survival (PFS) than those with increases in serum IL-8 levels ≤ 8.1% (P < 0.001). Increases in serum IL-8 levels > 8.1% were independent prognosticators of worse OS (P = 0.003) and PFS (P < 0.001).Conclusion: Early changes in serum IL-8 levels, measured only 2– 4 weeks after starting therapy, could predict the response to ICIs therapy, as well as OS and PFS of patients with unresectable HCC. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy and predicted worse OS and PFS.Keywords: interleukin-8, immune checkpoint inhibitor, response, serum biomarker, hepatocellular carcinoma

Yujie Xie,1 Fanglin Shao,1 Yuxiu Ji,1 Dechao Feng,1,2 Ling Wang,3 Zonghai Huang,3 Shengjian Wu,1 Fuhua Sun,1 Hong Jiang,4 Akira Miyamoto,5 Haiming Wang,6 Chi Zhang1 1Rehabilitation Medicine Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3School of Information and Communication Engineering, University of Electronic Science and Technology, Chengdu, Sichuan, People’s Republic of China; 4Rehabilitation Medicine Department, Xichong County People’s hospital, Nanchong, Sichuan, People’s Republic of China; 5Faculty of Rehabilitation, Nishikyushu University, Kansaitama, Japan; 6Department of Rehabilitation Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Haiming Wang, Department of Rehabilitation Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China, Tel +868950771, Fax +86 830 8950771, Email wanghaiming866@163.com Chi Zhang, Rehabilitation Medicine Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Email chizhang_swmu@126.comPurpose: To provide a comprehensive analysis of associated genes with osteoarthritis (OA). Here, we reported a network analysis of OA progression by using a Steiner minimal tree algorithm.Methods: We collected the OA-related genes through screening the publications in MEDLINE. We performed functional analysis to analyze the associated biochemical pathways of the OA-related genes. Pathway crosstalk analysis was constructed to explore interactions of the enriched pathways. Steiner minimal tree algorithm was used to analyze molecular pathway networks. The average clustering coefficient was compared with the corresponding values of the Osteoarthritis-specific network. The new finding RNA was compared with former single-cell RNA-seq analysis results.Results: A gene set with 177 members reported to be significantly associated with Osteoarthritis was collected from 187 studies. Functional enrichment analysis revealed a specific related-OA gene including skeletal system development, cytokine-mediated signaling pathway, inflammatory response, cartilage development, and extracellular matrix organization. We performed a pathway crosstalk analysis among the 72 significantly enriched pathways. A total of 151 of the 177 genes in the Osteoarthritis gene set were included in the human interactome network. There were 31 genes in the former single-cell RNA-seq analysis results. The CLU, ENO1, SRRM1, UBC, HMGB1, NR3C1, NOTCH2NL, and CBX5 have significantly increased expression in seven molecularly defined populations of OA cartilage.Conclusion: The Steiner tree-based approach finds new biological molecules associated with OA genes.Keywords: network analysis, Steiner minimal tree, osteoarthritis, bioinformatics, osteoarthritis genes

Hao Yang,1– 3,&ast; Guanglin Lei,2,&ast; Zhuoya Deng,1 Fang Sun,1 Yuying Tian,1 Jinxia Cheng,1 Hongyu Yu,1 Cong Li,1 Changqing Bai,4 Shaogeng Zhang,2 Guangwen An,5 Penghui Yang1 1Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Hepatological Surgery, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Surgery, Taian City Central Hospital, Taian, People’s Republic of China; 4Department of Respiratory, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Guangdong, People’s Republic of China; 5Department of Pharmacy, No. 984 Hospital of the PLA, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Penghui Yang; Guangwen An, Email ypenghuiamms@hotmail.com; anchen337722@163.comBackground: Oncolytic virus (OV) therapy has emerged as a promising novel form of immunotherapy. Moreover, an increasing number of studies have shown that the therapeutic efficacy of OV can be further improved by arming OVs with immune-stimulating molecules.Methods: In this study, we used reverse genetics to produce a novel influenza A virus, termed IAV-OX40L, which contained the immune-stimulating molecule OX40L gene in the influenza virus nonstructural (NS1) protein gene. The oncolytic effect of IAV-OX40L was explored on hepatocellular carcinoma (HCC)HCC cells in vitro and in vivo.Results: Hemagglutination titers of the IAV-OX40L virus were stably 27– 28 in specific-pathogen-free chicken embryos. The morphology and size distribution of IAV-OX40L are similar to those of the wild-type influenza. Expression of OX40L protein was confirmed by Western blot and immunofluorescence. MTS assays showed that the cytotoxicity of IAV-OX40L was higher in HCC cells (HepG2 and Huh7) than in normal liver cells (MIHA) in a time- and dose-dependent manner in vitro. We found that intratumoral injection of IAV-OX40L reduced tumor growth and increased the survival rate of mice compared with PR8-treated controls in vivo. In addition, the pathological results showed that IAV-OX40L selectively destroyed tumor tissues without harming liver and lung tissues. CD4+ and CD8+ T cells of the IAV-OX40L group were significantly increased in the splenic lymphocytes of mice. Further validation confirmed that IAV-OX40L enhanced the immune response mainly by activating Th1-dominant immune cells, releasing interferon-γ and interleukin-2.Conclusion: Taken together, our findings demonstrate the novel chimeric influenza OV could provide a potential therapeutic strategy for combating HCC and improve the effectiveness of virotherapy for cancer therapy.Keywords: OVs, OX40L, IAV, HCC

Feifei Sun,1,&ast; Chenjing Wang,1,&ast; Yi Xu,1 Pingping Lin,1 Yaozhong Cao,2 Jiahui Zhang,3 Xin Li,1 Xin Jiang,1 Yao Fu,1 Yu Cao1 1Clinical Trials Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Clinical Medical Center, Xiuzheng Pharmaceutical Group, Hangzhou, Zhejiang, People’s Republic of China; 3Xiuzheng Bio-Medicine Research Institute, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Cao, Clinical Trials Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China, Tel +86 532 82911767, Email caoyu@qdu.edu.cnIntroduction: Hyperuricemia is a disease with abnormal purine metabolism, which leads to the increase of urate concentration. It is an independent risk factor for the occurrence and development of metabolic syndrome, type 2 diabetes, hypertension, cardiovascular disease, chronic kidney disease, and gout. The enzyme urate oxidase can metabolize urate to allantoin, resulting in decreased urate concentrations. Pegylated the urate oxidase can extend half-life and decrease immunogenicity of the protein. This trial aims to evaluate the safety, tolerability, pharmacokinetics(PK), pharmacodynamics(PD) and immunogenicity of a new intravenous PEGylated urate oxidase produced by Xiuzheng Bio-Medicine Research Institute Co., Ltd.Methods and Analysis: A randomized, double-blind, placebo-controlled, phase I, dose escalation study will be conducted in China. In total, 56 subjects will be enrolled in the study, with 24 healthy subjects in the low dose-escalation stage and 32 patients with hyperuricemia in the high dose-escalation stage. There is a bridging between the two stages. Subjects are randomized to PEGylated urate oxidase or the placebo in a 3:1 ratio in each group and followed up for 71 days observation. The primary outcomes include PK, PD, tolerability; the secondary outcomes include safety and immunogenicity.Ethics and Dissemination: The trial is performed abiding by the Declaration of Helsinki, Good clinical practice (GCP) and the guidelines of China National Medical Products Administration (NMPA). Relevant documents, including protocol, informed consent and drug inspection report, are all approved independently by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University. The first subject was enrolled on January 17, 2022.Trial Registration: Clinicaltrials, NCT05226013 (Registered April 2, 2022, Retrospectively registered). ChinaDrugTrials, CTR20211801(Registered July 27, 2021).Keywords: PEGylated urate oxidase, healthy volunteers, patients with hyperuricemia, study protocol

Shu Cui,1,&ast; Zhiwei Liu,1,&ast; Yun Liu,1 Gaofeng Yao,1 Yanhai Wu,1 Juanjuan Li,1 Feng Sun,1,2 Liang Sun,1,2 Longlong Sun1,2 1Department of Psychiatry, Third People’s Hospital of Fuyang, Fuyang, Anhui, 236000, People’s Republic of China; 2School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, 238000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gaofeng Yao; Yanhai Wu, Department of Psychiatry, Third People’s Hospital of Fuyang, Wenxing Road, Fuyang, Anhui, 236000, People’s Republic of China, Email yao_gaofeng@126.com; wyh0387@163.comObjective: This study aims to investigate the association between the systemic immune-inflammatory index (SII) and suicide attempt (SA) in children and adolescents with first-episode, drug-naïve Major Depressive Disorder (MDD) during the COVID-19 pandemic.Methods: A retrospective study was conducted on 263 MDD patients hospitalized at the Third Hospital of Fuyang City between 2020 and 2022. Patients were categorized into two groups based on the presence of previous SA. The study compared the differences in SII and clinical characteristics between the two groups and used the receiver operating characteristic (ROC) curve to determine the optimal critical value of SII and the area under the curve. Binary logistic regression was used to analyze the independent risk factors for SA.Results: Compared with the patients without SA history, the patients with a personal history of SA had a higher mean HDRS scores (Z=− 2.369, p=0.018), higher mean neutrophil count (Z=− 2.870, p=0.004), higher mean platelet count (Z=− 2.155, p=0.031), and higher mean SII (Z=− 3.170, p=0.002). The optimal critical SII determined by the ROC curve was 548.15 (sensitivity = 63.2%, specificity = 83.1%), and the area under the curve was 0.661. After adjusting for gender, age, BMI, illness duration and HDRS score, the risk of total SA in patients with high SII was 8.296 times higher than in those with low SII (OR = 8.296, 95% CI: 3.803– 18.095, P < 0.001), The risk of recent SA was 13.922 times higher in patients with high SII than in those with low SII (OR = 13.922, 95% CI: 5.587– 34.693, p < 0.001). However, high SII was not a risk factor for past SA (OR = 0.547, 95% CI: 0.062– 4.842, P=0.587).Conclusion: SII may be an inexpensive, easily accessible strategy that can assist in determining suicide risk in adolescents with MDD.Keywords: major depressive disorder, suicide attempt, children and adolescents, systemic immune-inflammation index, first-episode

Lijie Ma,&ast; Qiuxia Han,&ast; Fang Sun, Kaiyi Zhu, Qianmei Sun Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianmei Sun, Email sunqianmei5825@126.comPurpose: This study aimed to explore whether the mean platelet volume/platelet count ratio (MPR) has predictive value for the occurrence and prognosis of acute ischemic stroke (AIS) in hemodialysis patients.Patients and Methods: A total of 402 patients undergoing maintenance hemodialysis were screened and 259 were enrolled in this study. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the predictive power of the models. The patients enrolled in this study were divided into three groups based on the tertiles of the MPR value (Q1, Q2, and Q3). Kaplan-Meier curves were used to investigate the association between the MPR and AIS-free survival in hemodialysis patients. Chi-square analysis was performed to explore the association between the MPR and AIS outcomes in hemodialysis patients. And the AIS outcome was assessed using the modified Rankin Scale (mRS).Results: MPR had a predictive value for the occurrence of AIS (AUC=0.814) in hemodialysis patients with a high sensitivity and specificity. AIS-free survival rates in the MPR Q1, MPR Q2, and MPR Q3 groups were 0.930, 0.701, and 0.360, respectively. The proportion of patients with good outcomes (mRS 0– 2) was significantly greater among patients in the MPR Q1-Q2 group than in the MPR Q3 group (0.844 vs 0.745, p < 0.001).Conclusion: The MPR can be used as a good predictor of AIS in patients undergoing hemodialysis. Patients on hemodialysis with increased MPR levels had a higher incidence of AIS and poorer functional outcomes than those with low MPR levels.Keywords: acute ischemic stroke, hemodialysis, mean platelet volume/ platelet count ratio, predictor, prognosis

Guojian Yang,&ast; Le Li,&ast; Xi Peng, Guodong Tang, Naixin Zheng, Ying Zhao, Hui Li, Huiping Zhang, Fucheng Sun, Hu Ai Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hu Ai, Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 DaHua Road, Dong Dan, Beijing, 100730, People’s Republic of China, Tel +86 18601025086, Email aihumd@aliyun.comPurpose: Coronary angiography-derived fractional flow reserve (caFFR) is a novel computational flow dynamics (CFD)-derived assessment of coronary vessel flow with good diagnostic performance. Herein, we performed a retrospective study to evaluate the reproducibility of caFFR findings between observers and investigate the diagnostic performance of caFFR for coronary stenosis defined as FFR ≤ 0.80, especially in the grey zone (0.75≤caFFR ≤ 0.80).Patients and Methods: A total of 150 patients (167 coronary vessels) underwent caFFR (with FlashAngio used for calculation of flow variables) and subsequent invasive fractional flow reserve (FFR) measurements. Outcomes, including reproducibility, were compared for vessels in and outside the grey zone.Results: The correlation of caFFR findings was good between the two laboratories (r = 0.723, p< 0.001). The AUC of ROC were both high for caFFR-CoreLab1 and caFFR-CoreLab2 (0.975 and 0.883). The diagnostic accuracy, sensitivity, specificity, and negative and positive predictive values were not significantly different between the two laboratories (p> 0.05). caFFR had a strong correlation with measures to FFR (r=0.911, p

Ren F, Shrestha C, Shi H, et al. Onco Targets Ther. 2020;13;9419-9428. At the authors request, we, the Editor and Publisher of the journal OncoTargets and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from another article authored by the first author, Fang Ren. Specifically, The image for Figure 4H, OVCAR-8, miR-421 mimics, has been duplicated with an image for Figure 4F, MDA-MB-231, anti-miR-374a, from Zhang J, He Y, Yu Y, et al. Upregulation of miR-374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer. Cancer Med. 2018;7:3351–3362. https://doi.org/10.1002/cam4.1576. In addition, images for Figure 5D, Lenti-NC group and Lenti-miR-421, Ki-67 have been duplicated. The authors responded to our queries but were unable to provide a satisfactory explanation for the duplicated images or provide satisfactory data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and we, the editor and publisher, agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Wenzhe Zhao,1 Haiqin Zhu,1 Xiaoqing Zhao,1 Xinyi Wu,1 Fei Sun,1 Meng Pan,1,&ast; Shengru Zhou2,&ast; 1Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), Suzhou, 215123, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengru Zhou, Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University, (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), No. 9, Chongwen Road, Suzhou, 215123, People’s Republic of China, Tel +86-17717453465, Fax +86-2164669691, Email zhoushengru1989@foxmail.comPurpose: Direct immunofluorescence (DIF) on frozen sections (DIF-F) plays a key role in the identification and differential diagnosis of bullous dermatoses, which are a group of critical autoimmune diseases that include pemphigus, bullous pemphigoid (BP), and epidermolysis bullosa acquisita (EBA). However, this technique requires specialized laboratory equipment conditions, sample acquisition and sample preservation. In this study, the application value of DIF on paraffin-embedded tissue sections (DIF-P) detecting IgG using heat-induced antigen retrieval (HIAR) in the diagnosis of bullous dermatosis was explored.Patients and Methods: Samples from 12 patients with pemphigus vulgaris (PV), 10 patients with pemphigus foliaceus (PF), 17 patients with BP, and 4 patients with EBA were retrospectively studied for DIF-P IgG detection. Formalin-fixed, paraffin-embedded tissue (FFPE) was used, and the antigen retrieval method used in the experiment was HIAR. All patients were diagnosed with the autoimmune bullous disease (AIBD) based on clinical presentation, histopathology, DIF-F, and enzyme-linked immunosorbent assay (ELISA).Results: Intercellular staining for IgG in the epidermis was successful in paraffin-embedded tissue sections in 11 of 12 PV samples and in all 10 PF samples. IgG at the basement membrane zone (BMZ) was not detected by immunofluorescent staining in 17 BP samples and 4 EBA samples.Conclusion: The detection of IgG by DIF-P using HIAR can be used for the diagnosis of pemphigus as an alternative method to DIF-F.Keywords: pemphigus, bullous dermatoses, direct immunofluorescence, IgG, paraffin-embedded section, heat-induced antigen retrieval

Zhongbao Wang,1 Yunshao Zheng,2 Yunli Fan,2 Yunming Fan,2 Xianbiao Su,2 Bingrui Wang,2 Jing Li,2 Diancai Chen,2 Fengxia Sun,2 Shen Li,2 Jiashu Ma,1 Xianwei Li,2 Ludong Bai,2 Ranran Li2 1Department of Psychiatry, Jining Medical University, Jining, People’s Republic of China; 2Department of Psychiatry, Shandong Mental Health Center, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Ranran Li, Department of Psychiatry, Shandong Mental Health Center, Shandong University, 49 East Wenhua Road, Jinan, Shandong, 250014, People’s Republic of China, Tel +86 18678777190, Email dtlrr113@126.comBackground: Most antipsychotic drugs are dopamine receptor antagonists that usually lead to abnormal increases in prolactin concentrations and the development of hyperprolactinemia (HPRL), which in turn causes sexual dysfunction in patients. Peony-Glycyrrhiza Decoction (PGD) enhanced dopamine D2 receptors (DRD2) and dopamine transporter (DAT) and significantly reversed the expression of DRD2 and DAT. Therefore, we hypothesized that PGD might effectively improve hyperprolactinemia and alleviate sexual dysfunction in patients.Methods: We performed an 8-week randomized controlled study on 62 subjects with schizophrenia who were randomized into two groups. The experimental group was treated with the PGD intervention, and the control group did not receive treatment. The primary outcome indicators were the levels of sex hormones and the total Arizona Sexual Experience Scale (ASEX) score.Results: There was a significant difference in PRL levels between the two groups at weeks 4 and 8. From the beginning to the end of the experiment, there was a significant increase in PRL levels in the control group, while there was no significant change in the experimental group. The ASEX scale assessed sexual function in both groups, and patients in the experimental group showed an improvement in sexual function at week 8. During the experiment, the two groups found no differences between Positive and Negative Syndrome Scale (PANSS) scores and Treatment Emergent Symptom Scale (TESS) scores.Conclusion: PGD significantly improved the patient’s sexual function but was less effective in reducing prolactin levels and may prevent further increases in prolactin levels.Keywords: hyperprolactinemia, antipsychotics, Peony-Glycyrrhiza Decoction, schizophrenia, sexual function, adverse effects