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Decheng Meng,1 Fengxia Zhang,2 Wenfei Yu,1 Xin Zhang,1 Guoliang Yin,1 Pengpeng Liang,3 Yanan Feng,1 Suwen Chen,1 Hongshuai Liu1 1The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China; 3Shenzhen Hospital, Shanghai University of Traditional Chinese Medicine, Shenzhen, 518001, People’s Republic of ChinaCorrespondence: Fengxia Zhang, Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China, Tel +86-131-5317-5246, Email fxzhang0987@163.comAbstract: Non-alcoholic fatty liver disease(NAFLD) is an umbrella term for a range of diseases ranging from hepatic fat accumulation and steatosis to non-alcoholic steatohepatitis (NASH) in the absence of excessive alcohol consumption and other definite liver damage factors. The incidence of NAFLD has increased significantly in recent years and will continue to grow in the coming decades. NAFLD has become a huge health problem and economic burden. SIRT1 is a member of Sirtuins, a group of highly conserved histone deacetylases regulated by NAD+, and plays a vital role in regulating cholesterol and lipid metabolism, improving oxidative stress, inflammation, and insulin resistance through deacetylating some downstream transcription factors and thus improving NAFLD. Although there are no currently approved drugs for treating NAFLD and some unresolved limitations in developing SIRT1 activators, SIRT1 holds promise as a proper therapeutic target for NAFLD and other metabolic diseases. In recent years, natural products have played an increasingly important role in drug development due to their safety and efficacy. It has been discovered that some natural products may be able to prevent and treat NAFLD by targeting SIRT1 and its related pathways. This paper reviews the mechanism of SIRT1 in the improvement of NALFD and the natural products that regulate NAFLD through SIRT1 and its associated pathways, and discusses the potential of SIRT1 as a therapeutic target for treating NAFLD and the effectiveness of these related natural products as clinical drugs or dietary supplements. These works may provide some new ideas and directions for finding new therapeutic targets for NAFLD and the development of anti-NAFLD drugs with good pharmacodynamic properties. Keywords: NAFLD, SIRT1, natural products, FFA, TG

Yijin Wu,1 Gaohui Yin,1 Linzi Li2 1School of Translation Studies, Qufu Normal University, Rizhao, People’s Republic of China; 2Department of Obstetrics, Rizhao Maternal and Child Health Hospital, Rizhao, People’s Republic of ChinaCorrespondence: Yijin Wu, School of Translation Studies, Qufu Normal University, No. 5, Yantai Road, Donggang District, Rizhao, Shandong, 250100, People’s Republic of China, Tel/Fax +86 531 88377118, Email wuyijin9972@126.comBackground: University students who possess an open-minded attitude and are receptive to new concepts represent a significant potential donor group. Their knowledge and attitudes toward organ donation have a considerable impact on the advancement of organ transplantation.Methods: Using the method of content analysis, this qualitative study examine the knowledge and attitude of Chinese university students concerning cadaveric organ donation.Results: The research identified five themes, including cadaveric organ donation as a commendable act, disincentives to cadaveric organ donation, ways to understand cadaveric organ donation, strategies to increase donation rates, and cultural influences regarding cadaveric organ donation.Conclusion: The findings revealed that some participants lacked adequate knowledge of cadaveric organ donation and were unwilling to donate organs after their death due to traditional Chinese family values and culture. Therefore, it is necessary to implement effective measures to enhance death education among Chinese university students and encourage their understanding and acceptance of cadaveric organ donation.Keywords: cadaveric organ donation, university students, content analysis

Xinhua Zou, Qingyu Xu, Ran You, Guowen Yin Department of Tumor Interventional Therapy, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing City, People’s Republic of ChinaCorrespondence: Guowen Yin, Tel +86-19868589105, Email jsnjgwy@163.comPurpose: To evaluate the efficacy and safety of TACE combined with regorafenib plus PD-1 inhibitor as a second-line therapy for hepatocellular carcinoma after sorafenib resistance.Materials and Methods: The clinical data of 76 patients with hepatocellular carcinoma who were drug-resistant to sorafenib from September 2018 to May 2022 in the tumor intervention department were collected. Among them, 35 patients used TACE combined with regorafenib plus PD-1 inhibitor (TACE-R-P) as second-line treatment, and the remaining 41 patients used TACE combined with regorafenib (TACE-R) as second-line treatment. The mRECIST (modified Response Evaluation Criteria in Solid Tumors) standard was used to evaluate the therapeutic effect. The progression-free survival (PFS) and overall survival (OS) of the two groups were compared. Blood samples were collected before and after treatment to detect the changes in biochemical indicators, and the adverse events (AEs) related to treatment were recorded.Results: A total of 76 patients were included in the study, including 35 patients receiving TACE-R-P treatment and 41 patients receiving TACE-R treatment. Patients in the TACE-R-P group had longer median OS (19.7months vs 15.2months, HR:0.7716, 95% CI:0.4767– 1.2490, P=0.03), longer median PFS (6.3months vs 3.8months, HR:0.6032, 95% CI:0.3727– 0.9763, P=0.0029), higher objective response rate (37.14% vs 19.51%, P=0.001) and higher disease control rate (71.43% vs 48.78%, P=0.001) than those in the TACE-R group. Multivariate analysis showed that Child–Pugh grade (B/A; HR=1.283, 95% CI: 0.623– 1.707, P=0.014), PVTT (Yes/No, HR=1.455, 95% CI: 0.977– 2.038, P=0.018), extrahepatic metastasis (Yes/No, HR=1.766, 95% CI: 1.135– 2.302, P=0.022) and treatment option (TACE-R/TACE-R-P, HR=1.930, 95% CI: 1.461– 2.850, P=0.017) were independent prognostic factors for OS. There was no significant difference in the incidence and severity of AEs between the two groups.Conclusion: TACE-R-P treatment can be more effective than TACE-R treatment for HCC after sorafenib resistance and can be given priority as a second-line treatment for HCC.Keywords: hepatocellular carcinoma, transarterial chemoembolization, regorafenib, sorafenib, PD-1 inhibitor

Yitong Zheng,1,&ast; Guoshu Yin,1,&ast; Fu Chen,2 Ling Lin,3,4 Yongsong Chen1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 2Department of Nutrition, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 3Department of Rheumatology and Immunology, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 4Department of Rheumatology, Shantou University Medical College, Shantou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Lin, Department of Rheumatology and Immunology, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China, Tel +86-0754-88258290, Fax +86-0754-88259850, Email llinc@163.net Yongsong Chen, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China, Tel +86-0754-88258290, Fax +86-0754-88259850, Email yongsongchen@126.comPurpose: To use the triglyceride glucose (TyG) index to evaluate insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS) and to explore alternative indicators for early identification of IR.Patients and Methods: This study included 114 patients with PCOS and 61 healthy volunteers. Pearson or Spearman correlations were calculated to compare the association between the TyG index and triglyceride glucose body mass index (TyG-BMI) with homeostatic model assessment for IR (HOMA-IR), homeostasis model assessment for β-cell function (HOMA-β), quantitative insulin sensitivity check index (QUICKI), and fasting glucose-to-insulin ratio (FG-IR). The receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the TyG index and TyG-BMI in identifying IR (defined as HOMA-IR ≥ 2.5) in patients with PCOS.Results: Correlation analyses revealed that the TyG index of the PCOS group was positively correlated with HOMA-IR (r=0.515, P< 0.01) and HOMA-β (r=0.348, P< 0.01), but negatively correlated with QUICKI (r=− 0.532, P< 0.01) and FG-IR (r=− 0.394, P< 0.01). The ROC curve of IR defined by HOMA-IR showed that the AUC value of TyG-BMI was the highest, at 0.796 (95% confidence interval (CI): 0.710– 0.866, P< 0.001) when the cut-off point was 191.53, with 85.3% sensitivity and 73.9% specificity values. For the TyG index, the AUC was 0.781 (95% CI: 0.693– 0.853, P< 0.001) when 8.51 was the cut-off point, with a sensitivity of 63.2% and specificity of 87.0%.Conclusion: This study found that the TyG index and TyG-BMI performed better than traditional lipid ratios, such as triglycerides/high density lipoprotein cholesterol (TG/HDL-C), in predicting IR and may be used as markers of IR in Chinese patients with PCOS.Keywords: triglyceride glucose body mass index, triglycerides/high density lipoprotein cholesterol, quantitative insulin sensitivity check index, fasting glucose-to-insulin ratio

Hui Hou, Jiao Li, Juanjuan Wang, Ling Zhou, Junqin Li, Jiannan Liang, Guohua Yin, Xinhua Li, Yueai Cheng, Kaiming Zhang Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Kaiming Zhang, Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, No. 5 Dong San Dao Xiang, Jiefang Road, Taiyuan, Shanxi Province, People’s Republic of China, Tel +86-351-5656080, Email zhangkaiming@sina.comBackground: Cell proliferation, migration, and angiogenesis are aberrant in psoriatic human dermal microvascular endothelial cells (HDMECs), resulting in abnormal endothelial function and microvascular dilation in psoriasis.Objective: To explore the role of Integrin subunit alpha 9 (ITGA9) in proliferation and migration of dermal microvascular endothelial cells.Methods: HDMECs were isolated from the skin of 6 psoriatic patients and 6 healthy controls. Expression levels of ITGA9 mRNA and protein were assessed with qRT-PCR and Western blot, respectively, while miqRT-PCR was used to determine expression levels of miR-146a-3p. Cell proliferation and migration were assessed in human microvascular endothelial cell line (HMEC-1), following overexpression of either ITGA9 or miR-146a-3p, or co-transfection with miR-146a-3p-mimic and pLVX - ITGA9. Cell viability was detected by Cell Counting Kit-8 assay and 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation assay. Cell apoptosis was assessed, using annexin V-FITC/PI apoptosis detection kit, while cell migration was detected by wound healing and transwell assay.Results: Expression levels of ITGA9 were significantly decreased in psoriatic HDMECs compared to normal controls. Moreover, expression levels of miR-146a-3p were higher in psoriatic HDMECs than in normal controls. Overexpression of miR-146a-3p lowered expression levels of ITGA9, accompanied by increased proliferation and migration of HMEC-1 in vitro. In contrast, overexpression of ITGA9 inhibited proliferation and migration of HMEC-1, while increasing expression levels of cdc42, ki67, focal adhesion kinase (FAK), c-Src tyrosine kinase (Src), RAC1 and RhoA.Conclusion: ITGA9 can repress the proliferation and migration of HMEC-1, suggesting utility of ITGA9 as a potential therapeutic intervention for psoriasis.Keywords: ITGA9, miR-146a-3p, human dermal microvascular endothelial cells, psoriasis, proliferation, migration

Yanan Feng,1,&ast; Wenxiu Sun,2,&ast; Fengcui Sun,1 Guoliang Yin,1 Pengpeng Liang,1 Suwen Chen,1 Xiangyi Liu,1 Tongfei Jiang,3 Fengxia Zhang4 1Shandong University of Traditional Chinese Medicine, Jinan, 250000, People’s Republic of China; 2Department of Nursing, Taishan Vocational College of Nursing, Taian, People’s Republic of China; 3Capital Medical University, Beijing, 100069, People’s Republic of China; 4Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengxia Zhang, Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China, Tel +86-131-5317-5246, Email fxzhang0987@163.comAbstract: Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disorders from non-alcoholic fatty liver (NAFL) to the more severe non-alcoholic steatohepatitis (NASH), is the leading etiology of chronic liver disease and its global prevalence is increasing. Hepatic steatosis, a condition marked by an abnormal buildup of triglycerides in the liver, is the precursor to NAFLD. Differentiated cluster 36 (CD36), a scavenger receptor class B protein, is a membrane receptor that recognizes multiple lipid and non-lipid ligands. It is generally agreed that CD36 contributes significantly to hepatic steatosis by taking part in fatty acid uptake as well as triglyceride storage and secretion. While there has not been any conclusive research on how CD36 inhibitors prevent NAFLD from progressing and no clinically approved CD36 inhibitors are currently available for use in NAFLD, CD36 remains a target worthy of further investigation in NAFLD. In recent years, the potential role of natural products acting through CD36 in treating non-alcoholic fatty liver disease has attracted much attention. This paper offers an overview of the pathogenesis of CD36 in NAFLD and summarizes some of the natural compounds or extracts that are currently being investigated for modulating NAFLD via CD36 or the CD36 pathway, providing an alternative approach to the development of CD36-related drugs in NAFLD.Keywords: NAFLD, CD36, natural inhibitors, FFA, TG

Aihong Peng,1 Funa Lu,1 Jianxiao Xing,1 Yu Dou,1 Yuanjun Yao,1 Juan Li,1 Junqin Li,1 Ruixia Hou,1 Kaiming Zhang,2 Guohua Yin1 1Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, People’s Republic of ChinaCorrespondence: Guohua Yin, Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, No. 5, Dong San Dao Xiang, Jiefang Road, Taiyuan, People’s Republic of China, Tel +86-0351-5656080, Email yinguohua1999@sina.comPurpose: Our recent studies found a splice region mutation in C3 accompanied by a significantly increased C3 in psoriatic peripheral blood. Mesenchymal stem cells (MSCs) are a key immunological suppression cell. We further investigate the regulation of MSCs on C3 in psoriasis.Patients and Methods: We analyzed the C3 and its upstream S100A9, S100A8 and downstream MCP1 in psoriatic and control skin, and in normal human epidermal keratinocytes (NHEKs) co-cultured with psoriatic versus control dermal-derived mesenchymal stem cells (DMSCs) by mRNA, iTRAQ (isobaric tags for relative and absolute quantitative) and simple Western analysis.Results: The mRNA and Simple Western analysis showed that the expression of C3, S100A8 and S100A9 are upregulated in psoriatic lesion (C3: mRNA, 9.23-fold, p = 0.0092; protein, 3.56-fold, p = 0.0244. S100A8: mRNA, 28.35-fold, p = 0.0015; protein, 4.68-fold, p = 0.0215. S100A9: mRNA, 79.45-fold, p = 0.0066; protein, 12.42-fold, p > 0.05). Moreover, the iTRAQ showed that C3 and S100A9 were significantly increased in NHEKs after co-cultured with psoriatic DMSCs compared to that of control DMSCs (C3: 3.40-fold, p = 0, FDR = 0; S100A9: 2.30-fold, p = 9.86E-241, FDR = 6.50E-239), verified by Simple Western. However, the expression of S100A8 and MCP1 was slightly different between the two groups.Conclusion: Our results suggest that psoriatic DMSCs contribute to the increased C3 expression in psoriatic lesion via upregulating S100A9, providing the theoretical basis for the role of C3 and DMSCs in the pathogenesis of psoriasis.Keywords: psoriasis, dermal mesenchymal stem cells, keratinocytes, C3, S100A9

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

Jianxiao Xing,1 Ying Wang,1 Xincheng Zhao,1 Junqin Li,1 Ruixia Hou,1 Xuping Niu,1 Guohua Yin,1 Xinhua Li,1 Kaiming Zhang2 1Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, 030009, Shanxi Province, People’s Republic of China; 2Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Taiyuan Central Hospital, Taiyuan, 030009, Shanxi Province, People’s Republic of ChinaCorrespondence: Kaiming Zhang, Taiyuan Central Hospital, No, 5 Dong San Dao Xiang, Jiefang Road, Taiyuan, Shanxi Province, People’s Republic of China, Tel +86-0351-5656080, Email zhangkaiming@sina.comPurpose: Psoriasis is a multifactorial disease with a complex genetic predisposition. The pathophysiology of psoriasis is associated with genetic variants. To better characterize gene variants in psoriasis and identify the relationship between clinical characteristics and variant genes in its pathogenesis.Patients and Methods: DNA was extracted and purified from eight pairs of monozygotic twins with psoriasis discordance and 282 type I psoriasis patients. Thirteen variable genes were amplified and sequenced using the Sanger method after whole genome sequencing.Results: Thirteen genes were found to be variable in eight pairs of monozygotic twins with psoriasis discordance. Among the 13 genes, the variant frequencies of protein kinase C epsilon (PRKCE) (c.240T>C, 35.9% vs 47.7%, P < 0.05) and kinesin light chain 1 (KLC1) (c.216A>G, 2.9% vs 98.1%, P< 0.01) were significantly lower in psoriasis than in normal Asian individuals. Additionally, we found considerable differences in the relationship between variants in genes CADM2, JPH2, SPTLC3 and clinical characteristics stratified by medical history and family history. Moreover, the variants in MEGF6 (39.52% vs 22.50%, χ2=3.83, p < 0.05) showed a stronger association with the mild group (PASI ≤ 10) than the heavy group.Conclusion: Our results provide a comprehensive correlation analysis of regulatory genes that are regulated in psoriasis. This integrated analysis offers novel insight into the pathogenic mechanisms involved in psoriasis.Graphical Abstract: Keywords: psoriasis, gene variants, PRKCE, KLC1

Jingchao Wei,1 Xiaohang Wu,2 Yuxiang Li,2 Xiaowu Tao,2 Bo Wang,2 Guangming Yin2 1Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of ChinaCorrespondence: Guangming Yin, Email yingm75@126.comBackground: Prostate cancer is a common malignancy in men. Radical prostatectomy is one of the primary treatment modalities for patients with prostate cancer. However, early identification of biochemical recurrence is a major challenge for post-radical prostatectomy surveillance. There is a lack of reliable predictors of biochemical recurrence. The purpose of this study was to explore potential biochemical recurrence indicators for prostate cancer.Materials and Methods: We analyzed transcriptomic data of cases with biochemical recurrence in The Cancer Genome Atlas (TCGA). Then, we performed integrative bioinformatics analyses to establish a biochemical recurrence predictor model of prostate cancer.Results: There were 146 differentially expressed genes (DEGs) between prostate cancer and normal prostate, including 12 upregulated and 134 downregulated genes. Comprehensive pathway enrichment analyses revealed that these DEGs were associated with multiple cellular metabolic pathways. Subsequently, according to the random assignment principle, 208 patients were assigned to the training cohort and 205 patients to the validation cohort. Univariate Cox regression analysis showed that 7 genes were significantly associated with the biochemical recurrence of prostate cancer. A model consisting of 5 genes was constructed using LASSO regression and multivariate Cox regression to predict biochemical recurrence of prostate cancer. Expression of PAH and AOC1 decreased with an increasing incidence of prostate cancer, whereas expression of DDC, LINC01436 and ORM1 increased with increasing incidence of prostate cancer. Kaplan–Meier curves and receiver operator characteristic (ROC) curves indicated that the 5-gene model had reliable utility in identifying the risk of biochemical recurrence of prostate cancer.Conclusion: This study provides a model for predicting prostate cancer recurrence after surgery, which may be an optional indicator for postoperative follow-up.Keywords: prostate cancer, biochemical recurrence, predictor, signature, follow-up

Jingjing Li,1 Jingyuan You,2 Guoping Yin,1 Jinkun Xu,1 Yuhuan Zhang,1 Xuemei Yuan,1 Qiang Chen,1 Jingying Ye1,3 1Department of Otorhinopharyngology–Head and Neck Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 2Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, People’s Republic of China; 3Institute of Precision Medicine, Tsinghua University, Beijing, People’s Republic of ChinaCorrespondence: Jingying Ye, Department of Otorhinopharyngology–Head and Neck Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Litang Road 168, Beijing, 102218, People’s Republic of China, Tel +86-13701396970, Email yejingying@mail.tsinghua.edu.cnPurpose: Accumulating evidence suggests that theta/beta ratio (TBR), an electroencephalographic (EEG) frequency band parameter, might serve as an objective marker of executive cognitive control in healthy adults. Obstructive sleep apnea (OSA) has a detrimental impact on patients’ behavior and cognitive performance while whether TBR is different in OSA population has not been reported. This study aimed to explore the difference in relative EEG spectral power and TBR during sleep between patients with severe OSA and non-OSA groups.Patients and Methods: 142 participants with in-laboratory nocturnal PSG recording were included, among which 100 participants suffered severe OSA (apnea hypopnea index, AHI > 30 events/hour; OSA group) and 42 participants had no OSA (AHI ≤ 5 events/h; control group). The fast Fourier transformation was used to compute the EEG power spectrum for total sleep duration within contiguous 30-second epochs of sleep. The demographic and polysomnographic characteristics, relative EEG spectral power and TBR of the two groups were compared.Results: It was found that the beta band power during NREM sleep and total sleep was significantly higher in the OSA group than controls (p < 0.001, p = 0.012, respectively), and the theta band power during NREM sleep and total sleep was significantly lower in the OSA group than controls (p = 0.019, p = 0.014, respectively). TBR during NREM sleep, REM sleep and total sleep was significantly lower in the OSA group compared to the control group (p < 0.001 for NREM sleep and total sleep, p = 0.015 for REM sleep). TBR was negatively correlated with AHI during NREM sleep (r=− 0.324, p < 0.001) and total sleep (r=− 0. 312, p < 0.001).Conclusion: TBR was significantly decreased in severe OSA patients compared to the controls, which was attributed to both increased beta power and decreased theta power. TBR may be a stable EEG-biomarker of OSA patients, which may accurately and reliably identify phenotype of patients.Keywords: sleep electroencephalography, spectral power, frequency band ratio, theta/beta ratio, OSA

Yizhou Huang,1,&ast; Yu Min,2,&ast; Gangyi Yang,1 Hanghang Wang,3 Guobing Yin,2 Lili Zhang1 1Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Zhang, Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong Dist, Chongqing, 404100, People’s Republic of China, Email 302424@hospital.cqmu.edu.cn; zhanglili.jl@foxmail.com Guobing Yin, Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong Dist, Chongqing, 404100, People’s Republic of China, Email yinguobing@cqmu.edu.cnPurpose: Medullary thyroid carcinoma (MTC) is a rare but highly invasive malignancy, especially in terms of cervical lymph node metastasis. However, the role of prophylactic lateral lymph node dissection (LLND) is still controversial. We hereby aim to explore the risk factors of lateral lymph node metastasis (LLNM) in patients with MTC to guide clinical practice.Patients and Methods: The clinicopathological characteristics of patients with MTC from the Surveillance, Epidemiology, and End Results (SEER) Program and the Second Affiliated Hospital of Chongqing Medical University were reviewed and analyzed. Univariate and multivariate logistics regression analyses were used to screen the risk factors of LLNM in patients with MTC.Results: Four variables, including male gender, multifocality, extrathyroidal invasion (EI), and large tumor size (all p < 0.05), were identified as potential independent factors of LLNM in patients with MTC. Based on these results, an individualized prediction model was subsequently developed with a satisfied C-index of 0.798, supported by both internal and external validation with a C-index of 0.816 and 0.896, respectively. We also performed the decision curve analysis (DCA) and calibration curve, which indicated a remarkable agreement in our model for predicting the risk of LLNM.Conclusion: We determined that various clinical characteristics, male gender, multifocality, EI, and large tumor size, were significantly associated with LLNM in patients with MTC. Thus, a validated prediction model utilizing readily available variables was successfully established to help clinicians make individualized clinical decisions on MTC management, especially regarding whether the LLND is necessary for patients with clinical negative lateral lymph node involvement and the frequency of follow-up without LLND.Keywords: medullary thyroid carcinoma, lateral lymph node metastasis, risk factors, SEER, predicting model

Jiajie Li, Yanmin Liu, Yue Cao, Juanjuan Wang, Xingcheng Zhao, Juanjuan Jiao, Junqin Li, Kaiming Zhang, Guohua Yin Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, 030009, Shanxi Province, People’s Republic of ChinaCorrespondence: Guohua Yin, Tel +86 0351-5656079, Email yinguohua1999@sina.comPurpose: Previous studies showed the link of CD14+ monocytes to inflammation and oxidation in psoriasis. In the present study, we investigated the regulatory role of miR-155 in CD14+ monocyte function in psoriasis.Materials and Methods: CD14+ monocytes were isolated from peripheral blood by magnetic bead separation method and its function was assessed following silence of miR-155 by lentivirus transfection with or without inhibition of TLR4 pathway. CCK8 and EdU were used to assess the proliferation of CD14+ monocytes. Expression levels of SOCS1, TLR4 and MyD88 proteins were determined by Western blotting, while expression levels of IL-6, TNF-α, ROS, MDA and T-AOC were measured by ELISA kit. The expression levels of mRNA for miR-155, NF-κB and its subunit NF-κB-p65 were assessed by q-PCR.Results: The results showed that compared with normal control CD14+ monocytes, the expression levels of miR-155, NF-κB and NF-κB-p65, TLR4, MyD88 and IL-6, TNF-α were increased, while expression levels of SOCS1 were decreased in CD14+ monocytes from psoriatic patients. Enhanced cell proliferation and oxidation were also observed in CD14+ monocytes from psoriatic patients. Inhibition of miR-155 partially corrected the abnormalities of cell proliferation and expression levels of biomarkers mentioned above in CD14+ monocytes from psoriatic patients. Inhibitions of both TLR4 pathway and miR-155 further corrected abnormalities of proliferation and the above biomarkers in CD14+ monocytes from psoriatic patients.Conclusion: These results suggest that increased expression levels of miR-155 contribute to CD14+ monocyte-mediated inflammation and oxidation in psoriasis via TLR4 pathway.Keywords: psoriasis CD14+ monocytes, miR-155, TLR4 pathway, inflammatory, oxidation

Siling Xu,1 Lu Liu,1 Guoqing Yin,1 Abdul-Quddus Mohammed,1 Xian Lv,1 Cailing Feng,1 Tingting Shi,1 Fuad A Abdu,1 Wenliang Che1,2 1Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Cardiology, Shanghai Tenth People’s Hospital Chongming Branch, Shanghai, People’s Republic of ChinaCorrespondence: Wenliang Che; Fuad A AbduDepartment of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Jingan District, Shanghai, 200072, People’s Republic of ChinaTel +86-21-66307259Fax +86-21-66301051Email chewenliang@tongji.edu.cn; 1691026@tongji.edu.cnPurpose: The association of serum uric acid (SUA) levels with cardiovascular outcomes in patients with coronary artery disease (CAD) has been extensively studied and yielded conflicting results. We aimed to investigate whether the severity of coronary stenosis and ischemia influences the prognostic impact of SUA levels in patients with CAD undergoing D-SPECT.Patients and Methods: This study consecutively included patients who were admitted for CAD in Shanghai Tenth People’s Hospital between June 2014 and August 2018, had complete SUA data and underwent both coronary angiography and D-SPECT within 3 months. Hyperuricemia was defined as an SUA level of > 7 mg/dL in men and > 6 mg/dL in women. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, unplanned coronary revascularization, nonfatal myocardial infarction, ischemic stroke, heart failure, and angina-related hospitalization.Results: A total of 695 patients were included, of whom 432 (62.2%) presented with obstructive CAD and 117 (16.8%) had hyperuricemia. During a median follow-up of 26 months, the incidence rates of MACE in patients with hyperuricemia and normouricemia were 15.2% and 21.1%, respectively. After a multivariable adjustment, hyperuricemia was significantly associated with an increased risk of MACE (HR: 1.39, 95% CI: 1.03– 1.87, p = 0.033) when compared with normouricemia. When repeating the primary analysis in patients with and without obstructive CAD, we showed that hyperuricemia was independently associated with an 80% increased risk of MACE among patients with nonobstructive CAD (HR: 1.80, 95% CI: 1.04– 3.11, p = 0.035), while such a significant association was not found among those with obstructive CAD (HR: 1.18, 95% CI: 0.82– 1.72, p = 0.373). Moreover, we uncovered a U-shaped and linear trajectory of SUA levels with MACE in the obstructive and nonobstructive CAD, respectively. The sex-specific analysis showed that the adverse impact of hyperuricemia was only pronounced in males (HR: 1.73, 95% CI: 1.18– 2.53, p = 0.005) but not in females (HR: 0.98, 95% CI: 0.57– 1.66, p = 0.933).Conclusion: Hyperuricemia is significantly associated with increased risk of MACE in the nonobstructive CAD rather than in the obstructive CAD.Keywords: coronary artery disease, serum uric acid, D-SPECT, nonobstructive, outcomes

Fengcui Sun,1 Xiufen Yang,1 Chaoqun Ma,1 Shizhao Zhang,1 Lu Yu,2 Haifei Lu,3 Guoliang Yin,1 Pengpeng Liang,1 Yanan Feng,1 Fengxia Zhang4 1Shandong University of Traditional Chinese Medicine, Jinan, 250000, People’s Republic of China; 2Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China; 3Hubei University of Traditional Chinese Medicine, Wuhan, 430065, People’s Republic of China; 4Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of ChinaCorrespondence: Fengxia ZhangDepartment of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of ChinaTel +8653168616011Email fxzhang0987@163.comAbstract: Hyperlipidemia is a disorder of lipid metabolism, which is a major cause of coronary heart disease. Although there has been considerable progress in hyperlipidemia treatment, morbidity and risk associated with the condition continue to rise. The first-line treatment for hyperlipidemia, statins, has multiple side effects; therefore, development of safe and effective drugs from natural products to prevent and treat hyperlipidemia is necessary. Diosgenin is primarily derived from fenugreek (Trigonella foenum graecum) seeds, and is also abundant in medicinal herbs such as Dioscorea rhizome, Dioscorea septemloba, and Rhizoma polygonati, is a well-known steroidal sapogenin and the active ingredient in many drugs to treat cardiovascular conditions. There is abundant evidence that diosgenin has potential for application in correcting lipid metabolism disorders. In this review, we evaluated the latest evidence related to diosgenin and hyperlipidemia from clinical and animal studies. Additionally, we elaborate the pharmacological mechanism underlying the activity of diosgenin in treating hyperlipidemia in detail, including its role in inhibition of intestinal absorption of lipids, regulation of cholesterol transport, promotion of cholesterol conversion into bile acid and its excretion, inhibition of endogenous lipid biosynthesis, antioxidation and lipoprotein lipase activity, and regulation of transcription factors related to lipid metabolism. This review provides a deep exploration of the pharmacological mechanisms involved in diosgenin-hyperlipidemia interactions and suggests potential routes for the development of novel drug therapies for hyperlipidemia.Keywords: diosgenin, hyperlipidemia, serum cholesterol, lipoprotein cholesterol, mechanism

Surface degradation on cycled lithium-ion battery cathode particles is governed not only by intrinsic thermodynamic properties of the material but also, oftentimes more predominantly, by the side reactions with the electrolytic solution. A superior electrolyte inhibits these undesired side reactions on the cathode and at the electrolyte interface, which consequently minimizes the deterioration of the cathode surface. The present study investigates a new boron-based anion receptor, tris(2,2,2-trifluoroethyl)borate (TTFEB), as an electrolyte additive in cells containing a lithium- and manganese-rich layered oxide cathode, Li1.16Ni0.2Co0.1Mn0.54O2. Our electrochemical studies demonstrate that the cycling performance and Coulombic efficiency are significantly improved because of the additive, in particular, under elevated temperature conditions. Spectroscopic analyses revealed that the addition of 0.5 wt % TTFEB is capable of reducing the content of lithium-containing inorganic species within the cathode-electrolyte interphase layer and minimizing the reduction of tetravalent Mn4+ at the cathode surface. Our work introduces a novel additive highly effective in improving lithium-ion battery performance, highlights the importance in preserving the surface properties of cathode materials, and provides new insights on the working mechanism of electrolyte additives.

OBJECTIVE: This study aimed to assess the risks and benefits of reinitiating antiplatelet therapy after spontaneous intracerebral hemorrhage (ICH) through a systematic review and meta-analysis. The reinitiation of antiplatelet therapy is commonly used to reduce major vascular events in patients with occlusive vascular diseases, but its use in ICH patients may increase the risk of bleeding. MATERIALS AND METHODS: A comprehensive search was conducted on databases including MEDLINE, Embase, Cochrane Library, clinicaltrials. gov, and the International Standard Randomized Controlled Trial Number Register (ISRCTN). Randomized controlled trials and cohort studies that investigated the use of reinitiation of antiplatelet therapy after hemorrhagic stroke were included. Data on ICH recurrence, major bleeding events, major occlusive cerebrovascular events, ischemic stroke, and all-cause mortality were extracted and analyzed using R software. RESULTS: The study included a total of 10 studies with 6,340 participants. The control group consisted of 2,964 patients who did not receive antiplatelet therapy, while the study group included 1,285 patients who received antiplatelet therapy without restrictions on the specific drug type. The meta-analysis showed that antiplatelet therapy significantly reduced the risk of ICH recurrence (RR=0.72, 95% CI: 0.59, 0.87), had no significant impact on the risk of severe bleeding events (RR=0.93, 95% CI: 0.80, 1.08), significantly lowered the risk of major occlusive cerebrovascular events (RR=0.59, 95% CI: 0.46, 0.77), had no significant effect on the risk of ischemic stroke (RR=0.77, 95% CI: 0.53, 1.12), and did not significantly influence the risk of all-cause mortality (RR=0.75, 95% CI: 0.45, 1.15). CONCLUSIONS: Based on the findings, reinitiating antiplatelet therapy after spontaneous ICH appears to be generally safe. However, the benefits in terms of reducing the risk of allcause mortality are not evident and require confirmation through large-scale, long-term, prospective, randomized controlled trials. [ABSTRACT FROM AUTHOR]

Xin Xin, Chuandong Cheng, Churong Li, Jie Li, Pei Wang, Gang Yin, Jinyi Lang Department of Radiation Therapy, Sichuan Cancer Hospital, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, People’s Republic of ChinaCorrespondence: Gang Yin; Jinyi LangDepartment of Radiation Therapy, Sichuan Cancer Hospital, Radiation Oncology Key Laboratory of Sichuan Province, No. 55, The 4th Section of Renmin South Road, Chengdu, People’s Republic of ChinaEmail cxqyguestc@163.com; langjy610@163.comPurpose and Objective: Auto planning might reduce the manual time required for the optimization and could also potentially improve the overall plan quality. The aim of this study is to demonstrate the statistical comparison of automatic (AU) and manually (MA) generated nasopharyngeal carcinoma (NPC) intensity-modulated radiation therapy (IMRT) plans.Materials and Methods: The study included 105 nasopharyngeal carcinoma patients, admitted to our hospital. The patients underwent IMRT treatments. The clinically delivered plans were performed with Eclipse (Version 11.0) using manual optimization. The same plans were optimized successively in PinnacleTM3 (version 9.10) treatment planning system using the auto plan software package module. D95 (dose of 95% volume) and D98 (dose of 98% volume) were calculated for the targets and maximum dose (Dmax) and mean dose (Dmean) for the organ at risks (OARs); moreover, the average doses of each target and OARs for 105 patients were evaluated.Results: There is no significant difference in the homogeneity of the target between AU and MA treatment plans, while a significant difference is observed for what is concerning the OARs or most of OARs in 105 patients, OAR doses were significantly reduced in AU plan. For OARs which have no significant difference between AU and MA plans are highlighted, the mean dose of OARs in AU plans was at least not higher than MA plans.Conclusion: Nasopharyngeal carcinoma IMRT plans made by an automatic planning tool met the clinical requirements for target prescription dose; moreover, the dose of normal tissues was lower than in MA plans. Clinical physicists’ time can be saved and the influence of factors such as the lack of experience in treatment planning can be avoided.Keywords: auto planning, manual planning, nasopharyngeal carcinoma

Yu Min, Xing Wang, Hang Chen, Jialin Chen, Ke Xiang, Guobing Yin Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 404100, People’s Republic of ChinaCorrespondence: Guobing YinDepartment of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong Dist, Chongqing 404100, People’s Republic of ChinaTel +86 15823267119Email yinguobing@cqmu.edu.cnPurpose: Thermal ablation (TA), as one of the most currently remarkable technologies, has achieved great success in many malignant diseases including but not limited to hepatic and renal carcinoma. In recent years, this technology was gradually introduced to the treatment of papillary thyroid microcarcinoma (PTMC) and even papillary thyroid carcinoma (PTC). Thereby, we summarized the current progress of TA development in the treatment of PTMC.Methods: The latest relevant literature from the PubMed database with keywords “thermal ablation”, “papillary thyroid microcarcinoma”, “microwave ablation”, “radio-frequency ablation”, and “laser ablation”, among others, were comprehensively reviewed in this article. The follow-up outcomes of patients in these articles were analyzed.Results: The efficacy and safety of TA including microwave ablation (MWA), laser ablation (LA), and radiofrequency ablation (RFA) in the treatment of PTC and PTC have been intensively studied. Based on existing clinical trials, the relatively long-term follow-up (range, from 6 to 64.2 months) results in MWA, LA, and RFA were satisfactory that tumor volume reduction rate (VRR) reached and even surpass 99%. Compared with routine surgery methods (total thyroidectomy and lobectomy), the incidence rate of complications was relatively lower and the recurrence rate of TA techniques was not statistically significant, whereas the operative time, blood loss, length of hospital stay, and hospital cost were significantly decreased.Conclusion: TA presents the same satisfactory therapeutic effects but minimal postoperative trauma can significantly improve the patients’ quality of life. However, future larger sample, multicenter, and prospective randomized controlled trials are urgently needed to validate the feasibility of TA in dealing with PTMC.Keywords: thermal ablation, microwave ablation, laser ablation, radiofrequency ablation, papillary thyroid microcarcinoma

Fengsheng Yu,1 Pingping Qiao,2 Guangjie Yin,1 Yewu Sun,1 Xiao Yu,1 Xin Sun,1 Yijing Chu,1 Yankui Wang1 1Department of Gynaecology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Neurology, The Third People’s Hospital of Qingdao, Qingdao, People’s Republic of ChinaCorrespondence: Yankui Wang; Yijing ChuDepartment of Gynaecology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266061, People’s Republic of ChinaTel +86-18661808529; +86-17853297008Email ykwqd@hotmail.com; chuyijing@163.comBackground: Ovarian cancer is the fifth most common cause of cancer-related deaths and accounts for 3% of cancer cases occurring in women. Therefore, determining the underlying genes that can promote ovarian cancer progression is of great urgency. It has been reported that RHPN2 promotes tumour progression in various types of cancer, but its role in ovarian cancer pathogenesis remains unknown.Materials and Methods: In this study, bioinformatic datasets were used to predict the expression of RHPN2 in clinical samples and determine the relationship between RHPN2 and the prognosis of ovarian cancer patients. Clinical samples were used to verify the prediction. RHPN2-targeting shRNA was used to investigate the effect of RHPN2 on ovarian cancer cells, and following RHPN2 knockdown, the proliferative and migratory capacities of ovarian cancer cells were tested. To determine the downstream signalling target of RHPN2, a luciferase reporter assay was conducted, and an animal experiment was carried out to confirm the effect of RHPN2 in vivo.Results: The public datasets indicated that ovarian cancer tissues showed significantly higher RHPN2 expression than para-cancer normal tissues, and poor prognosis was observed in patients with higher RHPN2 expression, which was further confirmed in clinical samples. After RHPN2 was knocked down, the proliferation and migration of ovarian cancer cells were significantly impaired; a luciferase reporter assay indicated that the STAT3 signalling pathway was the most highly affected, and RHPN2 downregulation inhibited STAT3 nuclear translocation. STAT3 inhibitors partially rescued the tumour-promoting effect induced by RHPN2 overexpression, which was further confirmed by animal experiments.Conclusion: Collectively, our results indicate that RHPN2 promotes malignant behaviours in ovarian cancer by activating STAT3 signalling.Keywords: ovarian cancer, STAT3, RHPN2

Xiaofeng Li,1– 3,* Guotao Yin,1– 3,* Wei Ji,2– 4,* Jianjing Liu,1– 3 Yufan Zhang,1– 3 Jian Wang,1– 3 Xiang Zhu,1– 3 Lei Zhu,1– 3 Dong Dai,1– 3 Wenchao Ma,1– 3 Wengui Xu1– 3 1Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of China; 3Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of China; 4Public Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wengui XuDepartment of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, Tianjin 300060, People’s Republic of ChinaTel +86 22 23340123Fax +86-22-23359337Email wenguixy@yeah.netBackground: To further improve the efficiency of adoptively transferred cytokine-induced killer (CIK) cell immunotherapy in breast cancer (BC), a reliable imaging method is required to visualize and monitor these transferred cells in vivo.Methods: Herpes simplex virus 1-thymidine kinase (HSV1-TK) and 9-(4-[18F]fluoro-3-(hydroxymethyl)butyl)guanine (18F-FHBG) were used as a pair of reporter gene/reporter probe for positron emission tomography (PET) imaging in this study. Following the establishment of subcutaneous BC xenograft-bearing nude mice models, induced human CIK cells expressing reporter gene HSV1-TK through lentiviral transduction were intravenously injected to nude mice. γ-radioimmunoassay was used to determine the specific uptake of 18F-FHBG by these genetically engineered CIK cells expressing HSV1-TK in vitro, and 18F-FHBG micro positron emission tomography-computed tomography (PET-CT) imaging was performed to visualize these adoptively transferred CIK cells in tumor-bearing nude mice.Results: Specific uptake of 18F-FHBG by CIK cells expressing HSV1-TK was clearly observed in vitro. Consistently, the localization of adoptively transferred CIK cells in tumor target could be effectively visualized by 18F-FHBG micro PET-CT reporter gene imaging.Conclusion: PET-CT reporter gene imaging using 18F-FHBG as a reporter probe enables the visualization and monitoring of adoptively transferred CIK cells in vivo.Keywords: breast cancer, CIK immunotherapy, HSV1-TK, reporter gene, 18F-FHBG PET-CT

Gang Yin, PeiRong Tian, Amin BuHe, Wei Yan, TianXiong Li, ZhiPeng Sun Oncology Surgery Department, Beijing Shijitan Hospital, Capital Medical University (Peking University Ninth School of Clinical Medicine), Beijing 100038, People’s Republic of ChinaCorrespondence: ZhiPeng SunOncology Surgery Department, Beijing Shijitan Hospital, Capital Medical University (Peking University Ninth School of Clinical Medicine), Beijing 100038, People’s Republic of ChinaEmail zhipeng9733@163.comIntroduction: Increasing studies have demonstrated that noncoding RNAs, including miRNAs and lncRNAs, have vital roles in mediating cancer progression. However, the expression features and biological functions of LINC00689 in gastric cancer (GC) remain largely unknown. This study was designed to investigate the functions of LINC00689, miR-526b-3p and ADAM9 as well as their interactions in GC.Methods: Real time PCR(RT-PCR) was used to detect the expression of LINC0068, miR-526b-3p and ADAM9 in both GC tissues or cell lines. Gain- and loss- of functions of assays were conducted to verify the role of LINC0068, miR-526b-3p and ADAM9 in GC development. Cell proliferation were determined by CCK8 assay and transwell assay and scratch wound-healing assay were used to test cell invasion and migration. Further, the relationships between LINC00689 and miR-526b-3p, miR-526b-3p and ADAM9 were predicted by bioinformatics analysis and then proved by Luciferase reporter assay and RNA Immunoprecipitation(RIP) assay.Results: We found that LINC00689 was upregulated in GC tissues and positively correlated with advanced tumor stage and tumor size, while miR-526b-3p was downregulated. Furthermore, gain- and loss-of-function experiments revealed that LINC00689 promoted the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of GC cells, while miR-526b-3p had the opposite effects. The underlying mechanisms indicated that LINC00689 functioned as a competing endogenous RNA (ceRNA) by sponging miR-526b-3p in GC cells. Further investigations confirmed that ADAM9 was a direct target of miR-526b-3p and positively modulated the progression of GC.Conclusion: Our study suggests that LINC00689 functions as a novel oncogenic lncRNA in the development of GC by promoting ADAM9 expression through suppression of miR-526b-3p.Keywords: gastric cancer, LINC00689, miR-526b-3p, ADAM9, competing endogenous RNA