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Xiaohui Zhu,1,2 Dongmei Jiang,1 Hongjie Zhang,3 Ruyuan Cai,3 Yuying Wang,1 Fei Hua2 1Department of Endocrinology, Affiliated Hospital 6 of Nantong University, Yancheng, 224000, People’s Republic of China; 2Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, People’s Republic of China; 3Department of Ophthalmology, Affiliated Hospital 6 of Nantong University, Yancheng, 224000, People’s Republic of ChinaCorrespondence: Fei Hua, Email huafeihf@21cn.comObjective: The study aimed to explore the correlation between retinal nerve fiber layer thickness (RNFLT) with blood biochemical indicators and cognitive dysfunction in patients with type 2 diabetes mellitus (T2DM) and the possible mechanism, thereby providing more theoretical basis for the occurrence and prevention of diabetes related complications.Methods: Eighty T2DM patients treated in our hospital from March 2022 to September 2022 were selected as the study subjects, and the clinical data of the patients were retrospectively analyzed. All patients underwent fundus fluorescein angiography (FFA) to analyze the changes in retinal blood vessels. Patients who met the inclusion criteria were divided as the diabetic retinopathy (DR) group (n=46) and simple diabetes group (n=34). The RNFLT, blood biochemical indexes and changes in cognitive functions of the patients were detected. The correlation between RNFLT with blood biochemical indexes and cognitive dysfunction was analyzed.Results: Compared with the simple diabetes group, patients in the DR group had much lower mean, nasal, inferior and superior thicknesses (P< 0.01). There existed no significant difference in blood pressure, body mass index (BMI), blood lipids (triglycerides, cholesterol, low-density lipoprotein, high-density lipoprotein) between the two groups (P> 0.05). Compared with the simple diabetes group, patients in the DR group had much higher fasting blood glucose (FBG), hemoglobin A1c (HbA1c), fasting insulin (FINS), insulin resistance (HOMA-IR) index, apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1) (P< 0.001). Besides, the DR group had sharply lower scores on the Mini-Mental State Examination (MMSE) scale and higher levels of the Trail Making Test-A (TMT-A) and TMT-B (P< 0.001). Spearman correlation analysis confirmed that the mean RNFLT was negatively correlated with the levels of FBG, HbA1c, HOMA-IR index, TMT-A and TMT-B (P< 0.05), positively correlated with the score of mini-mental state examination (MMSE) (P< 0.05), and was no significant correlation with FINS and ApoB/ApoA1 (P> 0.05).Conclusion: DR patients had significantly reduced RNFLT, elevated levels of blood glucose related indicators, and cognitive dysfunction. There existed a correlation between RNFLT and FBG, HbA1c, HOMA-IR index, TMT-A, TMT-B and MMSE.Keywords: type 2 diabetes mellitus, retinal nerve fiber thickness, blood biochemical indicators, cognitive dysfunction, correlation

Qianyu Bai,1,&ast; Yichi Zhang,1,&ast; Runqiu Cai,1 Haiyan Wu,1 Huiqun Fu,2 Xuemei Zhou,2 Jie Chai,3 Xuepeng Teng,3 Tianlong Liu1 1National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agriculture University, Beijing, People’s Republic of China; 2 101 Institute of the Ministry of Civil Affairs, Beijing, People’s Republic of China; 3Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemei Zhou, 101 Institute of the Ministry of Civil Affairs, South Fourth Ring West Road No.188, Beijing, 100070, Email zxmcaur@126.com; Tianlong Liu, College of Veterinary Medicine, China Agriculture University, Yuanmingyuan West Road No. 2, Beijing, 100193, Email liutianlong@cau.edu.cnBackground: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health. Long-term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed.Methods: ZnO@TiO2@AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization. The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated. For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs.Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%. Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (S. pneumoniae) were 10 μg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus, and S. pneumoniae were 50 μg/mL. In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane. Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs. Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (·OH) compared to ZnO NPs.Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro. This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media.Keywords: nanoparticles, otitis media, zinc oxide, mesoporous titanium dioxide, antimicrobial peptide, antimicrobial, hydroxyl radical

Yue Wang,1,2 Jun Li,3 Jianming Wu,3 Shihong Gu,3 Huishu Hu,3 Rongjuan Cai,2 Man Wang,4 Yue Zou3 1Institute of Shanghai Oriental Beauty Valley, Shanghai Institute of Technology, Shanghai, People’s Republic of China; 2School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, People’s Republic of China; 3R&D Center, JALA (Group) Co., Ltd, Shanghai, People’s Republic of China; 4Department of Nutrition, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Shanghai, People’s Republic of ChinaCorrespondence: Yue Zou, R&D Center, JALA (Group) Co., Ltd, Building 2, No. 333, Guiping Road, Xuhui District, Shanghai, 200233, People’s Republic of China, Email zouyue3@jala.com.cnIntroduction: Sensitive scalp is one of the most frequent complaints related to sensitive skin syndrome, characterized by unpleasant sensory reactions in the absence of visible signs of inflammation. In this study, the effects of topical application of postbiotic Himalaya-derived Saccharomyces and Lactobacillus ferment complex (SLFC) on the bacterial and fungal scalp microbiome at the taxonomic level and alleviation of sensitive skin syndrome were investigated.Methods: Firstly, healthy female participants (aged 30– 45) were classified into a healthy scalp group and a sensitive scalp group based on the questionnaire. Thereafter, topical application of SLFC on sensitive scalp as well as scalp microbiome was evaluated, with the difference in the distribution of microbial taxa between healthy and sensitive scalp communities was assessed using 16S rRNA and ITS1 sequencing analysis. In addition, the effect of SLFC on scalp microbiome at the species level for Cutibacterium acnes, Staphylococcus epidermidis, and Malassezia restricta was evaluated by the qPCR assessment.Results: After treatment with SLFC for 28 days, the abundance of Staphylococcus, Lawsonella, and Fusarium in the sensitive scalp group was highly significantly increased (p < 0.001), while the abundance of Cutibacterium and Malassezia was highly significantly decreased (p < 0.001). Furthermore, the self-assessment questionnaire indicated a syndrome alleviation effect of 100% after 28 days with a twice-daily application of the SLFC.Discussion: The obtained results would help to better understand the microbial community of the sensitive scalp and provide useful information on utilization of SLFC for maintaining a healthy scalp and modulating the scalp microbiome.Keywords: sensitive scalp, scalp microbiome, postbiotics, microbial diversity, questionnaire analysis

Yaling Li,1,&ast; Kaiyang Shao,1,&ast; Ruyi Cai,1 Yi Liu,2 Xiaojing Liu,2,3 Feihua Ni,1 Huiyan Zheng,1 Ruying Hu,1 Ting Sun1 1Department of Health Management Center, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Sun, Department of Health Management Center, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, People’s Republic of China, Email 1195037@zju.edu.cnBackground: The coexistence of blaNDM-1 with other resistance determinants is rarely reported for Providencia rettgeri. Therefore, this study investigates the phenotypic and genetic characteristics of a multidrug-resistant P. rettgeri strain YQ150713.Methods: P. rettgeri YQ150713 was identified as carrying blaNDM-1. S1-pulsed-field gel electrophoresis (S1-PFGE), Southern blotting, and conjugation experiments were used to determine plasmid characteristics. An antimicrobial susceptibility test was conducted. The complete genomic sequence of YQ150713 was obtained using Illumina NovaSeq 6000 and Oxford nanopore platforms. To further characterize the phylogenetic structure of P. rettgeri YQ150713, average nucleotide identity (ANI) and phylogenetic analyses were conducted.Results: The S1-PFGE, Southern blot, and conjugation assays have confirmed that the isolate P. rettgeri YQ150713 contains the blaNDM-1 gene on a conjugative plasmid pYQ150713-NDM-1. Antimicrobial susceptibility testing has indicated that strain YQ150713 was resistant to various common antibiotics, except aztreonam and fosfomycin. Bioinformatics analysis has further shown that pYQ150713-NDM-1 was a novel plasmid with a size of 265,883 bp, and blaNDM-1 and blaOXA-10 were co-located on it. Phylogenetic analysis suggesting P. rettgeri has spread widely throughout the world.Conclusion: In this study, blaNDM-1 and blaOXA-10 were co-localized on a novel plasmid pYQ150713-NDM-1 with a horizontal transfer function. To reduce the risk of the dissemination of such P. rettgeri isolates in clinical settings, more surveillance will be required in the future.Keywords: antimicrobial resistance, blaNDM-1, blaOXA-10, Providencia rettgeri, carbapenemase-producing, average nucleotide identity, phylogenetic

Yongai Xiong,1,2 Tingting Chen,1,2 Lei Chen,1,2 Rongshan Cai1,2 1Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 2Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of ChinaCorrespondence: Yongai Xiong, Email yaxiong@zmu.edu.cnIntroduction: Radiotherapy and chemotherapy are the fundamental causes of myelosuppression in cancer patients, which usually induce a serious hematopoietic system toxicity, causing the hemocytes and immunity decline of patients. Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells, which is related to its promotion of autophagy in hematopoietic stem cells.Methods: In the present study, we formulated the SH-PEG-NH2-coated gold nanoparticles loading ZgI (ZgI-AuNPs) with a enhanced autophagy promotion in hematopoietic stem cells. ZgI-AuNPs were prepared by HAuCl4-sodium citrate reduction method, and the synthesis of ZgI-AuNPs was validated by XRD, FT-IR, DSC, and TEM findings. Furthermore, the drug loading rate and the release of ZgI were evaluated, and the ZgI-AuNPs’ effects on autophagy and immunofluorescence staining for LC3B were tested. Finally, the effect of ZgI-AuNPs on the autophagy and hematopoietic ability of HSCs in vivo was also carried out.Results: The prepared ZgI-AuNPs have an irregular cubic crystal structure by TEM observation, and the average particle size was 340 ± 16.5 nm determined by DLS. The XRD, FT-IR and DSC detection showed that the ZgI had been well loaded in AuNPs, and the AuNPs can load the ZgI at a content of 160.63 ± 1.35 μg·mg− 1. Meanwhile, the AuNPs can reduce the drug release rate of ZgI. Importantly, the ZgI-AuNPs enhanced autophagy of HSCs both in vitro and in vivo. At the same time, the gold nanoparticles enhance the hematopoietic effect of ZgI on mice HSCs.Conclusion: Our research suggests that SH-PEG-NH2-coated gold nanoparticles loading ZgI has potential application in myelosuppression therapy.Graphical Abstract: Keywords: myelosuppression, HSCS, autophagy, gold nanoparticles, Ziyuglycoside I

Rongqin Cai,1,&ast; Ya Tan,1,&ast; Mingming Wang,2 Huijun Yu,1 Jing Wang,1 Zhuo Ren,1 Zhe Dong,1 Yiwen He,1 Zhi Li,1 Li Lin,1 Ying Gu1,3 1Department of Obstetrics and Gynecology, Peking University International Hospital, Beijing, 102206, People’s Republic of China; 2Be Creative Lab (Beijing) Co. Ltd, Beijing, 101111, People’s Republic of China; 3Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu, 222000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Lin; Ying Gu, Department of Obstetrics and Gynecology, Peking University International Hospital, Beijing, People’s Republic of China, Tel +86-13683047582 ; +86-18705130302, Email linli488@aliyun.com; guying@pkuih.edu.cnBackground: Congenital heart disease (CHD) is the most common birth defect with strong genetic heterogeneity. To date, about 400 genes have been linked to CHD, including cell signaling molecules, transcription factors, and structural proteins that are important for heart development. Genetic analysis of CHD cases is crucial for clinical management and etiological analysis.Methods: Whole-exome sequencing (WES) was performed to identify the genetic variants in two independent CHD cases with DNA samples from fetuses and their parents, followed by the exclusion of aneuploidy and large copy number variations (CNVs). The WES results were verified by Sanger sequencing.Results: In family A, a compound heterozygous variation in PLD1 gene consisting of c.1132dupA (p.I378fs) and c.1171C>T (p.R391C) was identified in the fetus. The two variants were inherited from the father (c.1132dupA) and the mother (c.1171C>T), respectively. In family B, a hemizygous variant ZIC3: c.861delG (p.G289Afs&ast;119) was identified in the fetus, which was inherited from the heterozygous mother. We further confirmed that these variants PLD1: c.1132dupA and ZIC3: c.861delG were novel.Conclusion: The findings in our study identified novel variants to the mutation spectrum of CHD and provided reliable evidence for the recurrent risk and reproductive care options to the affected families. Our study also demonstrates that WES has considerable prospects of clinical application in prenatal diagnosis.Keywords: congenital heart disease, whole-exome sequencing, PLD1, ZIC3, prenatal diagnosis

Yangyang Dong,1,2 Ling Bai,1,2 Rongrong Cai,1,2 Jinyu Zhou,1,2 Wenqing Ding1,2 1School of Public Health and Management, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of ChinaCorrespondence: Wenqing DingSchool of Public Health and Management, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, 750004, People’s Republic of ChinaTel +86 13519598269Email dwqdz@163.comPurpose: The predictive capacity between children’s lipid accumulation product (CLAP) combining visceral adiposity index (VAI), CLAP, and VAI with metabolically unhealthy phenotype remained unclear. This study aimed to compare the ability of CLAP combining VAI, CLAP, VAI and traditional adiposity indicators (body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR)) to predict metabolically unhealthy phenotype among Chinese children and adolescents.Patients and Methods: In the cross-sectional study, 1714 children and adolescents aged 12 to 18 were selected by random cluster sampling, underwent a questionnaire survey, physical examination, biochemical tests and body composition was measured by bioelectrical impedance analysis (BIA). Participants were divided into four phenotypes according to BMI and metabolic syndrome components. The logarithmic CLAP (LnCLAP), VAI, BMI, WC, WHtR and WHR were standardized for sex and age using the z-score method (standardized variables: LnCLAP-z, VAI-z, BMI-z, WC-z, WHtR-z and WHR-z).Results: LnCLAP-z ≥ 1, VAI-z ≥ 1, WC-z ≥ 1, and WHR-z ≥ 1 increased the risk of metabolically unhealthy normal-weight phenotype (the OR and 95% CI were 4.18 (1.75– 10.02), 24.05 (12.79– 45.21), 6.17 (1.14– 33.51), 2.69 (1.07– 6.72), respectively), LnCLAP-z ≥ 1, VAI-z ≥ 1 and WC-z ≥ 1 increased the risk of metabolically unhealthy overweight or obese phenotype (the OR and 95% CI were 2.67 (1.40– 5.09), 10.30 (3.03– 35.03), 2.19 (1.18– 4.09), respectively). The area under the ROC curve (AUC) for CLAP combining VAI in the prediction of the metabolically unhealthy phenotype were 0.837 (0.776– 0.899) and 0.876 (0.834– 0.918) for boys and girls with normal-weight, 0.853 (0.803– 0.903) and 0.794 (0.711– 0.878) for boys and girls with overweight and obese (all P < 0.001), which were higher than CLAP, VAI, BMI, WC, WHtR and WHR.Conclusion: Among Chinese children and adolescents, CLAP combining VAI was a more effective indicator than CLAP, VAI and traditional adiposity indicators in predicting unhealthy metabolic phenotype.Keywords: children’s lipid accumulation product, visceral adiposity index, unhealthy metabolic phenotype, traditional adiposity indicators, children and adolescents

Rong Cai,1 Long Xiao,1 Meixiu Liu,1 Fengyi Du,2 Zhirong Wang1 1Central Laboratory, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215600, People’s Republic of China; 2School of Medicine, Zhenjiang, Jiangsu, 212013, People’s Republic of ChinaCorrespondence: Zhirong Wang; Fengyi Du Tel +86 138 6222 4593; +86 159 5290 0513Email zjgfy_spine_wzr@njucm.edu.cn; biodfy@ujs.edu.cnAbstract: Carbon quantum dots (CQDs) are an emerging class of quasi-zero-dimensional photoluminescent nanomaterials with particle sizes less than 10 nm. Owing to their favourable water dispersion, strong chemical inertia, stable optical performance, and good biocompatibility, CQDs have become prominent in biomedical fields. CQDs can be fabricated by “top-down” and “bottom-up” methods, both of which involve oxidation, carbonization, pyrolysis and polymerization. The functions of CQDs include biological imaging, biosensing, drug delivery, gene carrying, antimicrobial performance, photothermal ablation and so on, which enable them to be utilized in antitumour applications. The purpose of this review is to summarize the research progress of CQDs in antitumour applications from preparation and characterization to application prospects. Furthermore, the challenges and opportunities of CQDs are discussed along with future perspectives for precise individual therapy of tumours.Keywords: CQDs, antitumour, drug delivery, phototherapy

Chengxin Li,&ast; Jiejiu Lu,&ast; Siru Zhou, Yinyi Wei, Chunle Lv, Taotao Liu, Yun Wu, Dongni Wu, Jianying Qi, Rongda Cai Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taotao LiuDepartment of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi Province, People’s Republic of ChinaTel +86 7715356789Email liutaotao@gxmu.edu.cnPurpose: To analyze factors influencing tacrolimus (TAC) trough concentration (C0) in β-thalassemia major (β-TM) pediatric patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and to investigate the effects of genotype polymorphism and drug-drug interactions on TAC trough concentration in children with β-TM. Furthermore, to analyze the correlation between TAC C0 and efficacy and adverse reactions.Patients and Methods: Prospectively collection of demographic information and details of combined treatment of patients with β-TM receiving HSCT, and genotypes of CYP3A4, CYP3A5, and ABCB1 (rs1045642, rs1128503, rs2032582) were obtained for each patient. Univariate analysis and multiple linear regression analysis were used to investigate influencing factors on TAC C0. The impact of different genotypes and the co-administration of azole antifungal drugs on β-TM patients receiving TAC were evaluated, together with the correlation between acute graft-versus-host disease (aGVHD), infection, and liver injury of TAC C0.Results: A total of 46 patients with 587 concentration data were included. The multiple linear regression results showed that the patient’s sex, weight, postoperative time, hemoglobin, platelet count, serum cystatin C, and combined voriconazole were independent influencing factors of the infusion trough concentration/daily dose, C0/Div. Age, body surface area, postoperative time, co-administration of voriconazole, and CYP3A4&ast;18B are independent influencing factors of C0/Dpo. Group comparisons showed that voriconazole can affect TAC C0 administered intravenously (IV) and orally in β-TM pediatric patients, while patient genotype can affect TAC C0 during oral administration. TAC C0 does not correlate with aGVHD or liver injury, but infection may be associated with TAC C0.Conclusion: The concentration of TAC should be closely monitored when co-administered with voriconazole. It is worth considering that the influence of genotype on the trough concentration of oral TAC and individualized drug administration warrant investigation. Finally, this study indicated that C0 is not suitable as an indicator of the efficacy of TAC.Keywords: β-thalassemia major, allogeneic hematopoietic stem cell transplantation, tacrolimus, trough concentration

Tingting Song,&ast; Hong Wang,&ast; Yue Liu, Rongshan Cai, Dezhi Yang, Yongai Xiong Department of Pharmacy, Zunyi Medical University, Zunyi City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongai Xiong Email yaxiong@zmu.edu.cnBackground: Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells. However, the poor solubility and a short half-life of ZgI limit its bioavailability and efficacy. The D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) has been widely used to increase the solubility, improve the encapsulation rate, and extend the half-life of drugs.Methods: Here, we formulated the TPGS-modified long-circulating liposomes loading ZgI with a sustained drug release and enhanced therapy for myelosuppression. ZgI-TPGS-liposomes were manufactured using a thin-film hydration technique, followed by characterizations of physicochemical properties, including the particle size, zeta potential, TEM, SEM, FTIR, XRD, stability, drug loading (DL), encapsulation efficiency (EE). The in vitro and in vivo delivery efficiency were further evaluated by cellular uptake, in vitro drug release and in vivo pharmacokinetics. Finally, therapeutic effect on myelosuppression was investigated.Results: The ZgI-TPGS-liposomes had an particle size of 97.89 ± 1.42 nm and ZP of − 28.65 ± 0.16 mV. It exhibited DL of 9.06 ± 0.76% and EE of 92.34 ± 3.83%, along with excellent storage stability, cellular uptake and sustained drug release to free ZgI and liposomes without TPGS. Additionally, the TPGS modified liposomes significantly enhanced the therapeutic effect of ZgI on CTX induced myelosuppression, which can be confirmed in the apoptosis inhibition and cell viability promotion of CTX injured HSPC-1 cells. Also, the mice in vivo pharmacodynamics demonstrated that TPGS liposomes promoted ZgI increasing the numbers of leucocytes and neutrophils in myelosuppression mice induced by CTX.Conclusion: Our research suggest that TPGS-modified long-circulating liposomes loading ziyuglycoside I has potential application in myelosuppression therapy.Keywords: myelosuppression, therapy, TPGS, long-circulating liposomes, ziyuglycoside I

Xiaoqin Zhu,1,2,* Jia Zhu,1,2,* Feifei Sun,1,2,* Zijun Zhen,1,2 Dalei Zhou,1,3 Suying Lu,1,2 Junting Huang,1,2 Yi Que,1,2 Lian Zhang,1,2 Ruiqing Cai,1,2 Juan Wang,1,2 Yizhuo Zhang1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Pediatric Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yizhuo Zhang; Juan Wang Email zhangyzh@sysucc.org.cn; wangjuan@sysucc.org.cnObjective: The association between UGT1A1*6/*28 polymorphisms and treatment outcomes of irinotecan in children remains unknown. This retrospective study investigated the influence of UGT1A1*6/*28 polymorphisms on irinotecan toxicity and survival of pediatric patients with relapsed/refractory solid tumors.Methods: The present study enrolled a total of 44 patients aged younger than 18 years at Sun Yat-sen University Cancer Center between 2014 and 2017.Results: There were 26 boys and 18 girls; the median age at first VIT course was six years (range: 1– 18 years). The tumor types included neuroblastoma (n = 25), rhabdomyosarcoma (n = 11), Wilm’s tumor (n = 4), medulloblastoma (n = 2), and desmoplastic small round cell tumor (n = 2). Overall, 203 courses of VIT regimens were prescribed. Neither UGT1A1*6 nor *28 polymorphisms were associated with the incidence rates of severe (grade III–IV) irinotecan-related toxicities, but tended to reduce the patient overall survival (UGT1A1*6, P = 0.146; UGT1A1*28, P = 0.195). Moreover, patients with mutant UGT1A1*6 genotypes were more likely to develop grade I–IV irinotecan-related diarrhea (P = 0.043) and anemia (P = 0.002). Overall, the UGT1A1*28 polymorphism may play a protective role against irinotecan-related diarrhea and abdominal pain.Conclusion: In relapsed/refractory pediatric solid tumors, the UGT1A1*6 polymorphism was a risk factor of irinotecan-related diarrhea and anemia. The UGT1A1*28 polymorphism may serve a protective role in irinotecan-related abdominal pain and diarrhea. Both mutations had a tendency to be risk factors for survival. Nevertheless, prospective studies are required to verify such conclusions.Keywords: UGT1A1 *6/*28 polymorphism, irinotecan toxicity, pediatric, relapsed/refractory solid tumors

Xian Wu,1,* Chaoran Ye,1,* Xingmeng Wang,2 Ruyu Cai,1 Junzhe Yang,1 Xiafei Yu,1 Yi Zhou,1 Li Shen,1 Yanhui Zhu,1 Xiaoan Liu1 1Department of Breast Surgery, The First Affiliated HospitalofNanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of General Surgery, The First People’s Hospital of Yancheng City, Yancheng, 224006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanhui Zhu; Xiaoan Liu Tel +86-25-68308152Email yanhui1002@hotmail.com; liuxiaoan@126.comPurpose: To retrospectively analyze the efficacy and toxicity of epirubicin plus cyclophosphamide followed by docetaxel (EC-D) and epirubicin plus cyclophosphamide followed by paclitaxel (EC-P) efficacy as neoadjuvant chemotherapy regiments by pathological complete response (pCR) in this study.Methods: In total, 455 patients diagnosed with breast cancer who received NAC from January 2014 to January 2019 were enrolled. Of which, 109 patients received EC-D (E: 90, C: 600, D: 80, all in mg/m2) and 346 were treated with EC-P (E: 90, C: 600, D: 175, all in mg/m2). Efficacy of NAC regimens was evaluated by pCR, and the toxicity was studied. Chi-squared test was used at p=0.05.Results: In EC-D, 11 patients received ypT0/isN0, and 6 of them got ypT0N0. Analogously, 67 patients receiving received EC-P obtained ypT0/isN0, and 43 people of them acquired ypT0N0. The rate of pCR in EC-P was higher than EC-D. Patients with ER (-), PR (-), Her-2 (+) and high Ki-67 index were easier to were more likely to acquire pCR. Two pCRs were described, the pCR of NAC differed according to the definition. In terms of side effects, there was no significant difference in platelet and urea, but the decrease of hemoglobin and creatinine levels after EC-P treatment was more significant than that after EC-D treatment.Conclusion: The efficacy of EC-P is better than EC-D if pCR is to be determined as a surrogate end-point for prognosis. The patients with anemia or renal insufficiency who need to receive NAC should choose EC-D.Keywords: neoadjuvant chemotherapy, pathological complete response, EC-D, EC-P, toxicity of anticancer drugs

Suying Lu,1,2,* Chengtao Sun,3,* Huimou Chen,1,2,* Chao Zhang,1,4,* Wei Li,5 Liuhong Wu,1,2 Jia Zhu,1,2 Feifei Sun,1,2 Junting Huang,1,2 Juan Wang,1,2 Zijun Zhen,1,2 Ruiqing Cai,1,2 Xiaofei Sun,1,2 Yizhuo Zhang,1,2 Xing Zhang1,6 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Pediatric Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 3Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of China; 4Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 5Department of Cardiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 6Department of Medical Melanoma and Sarcoma, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing ZhangDepartment of Medical Melanoma and Sarcoma, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, Guangdong 510060, People’s Republic of ChinaTel/Fax +86-020-87343629Email zhangxing@sysucc.org.cnYizhuo Zhang Department of Pediatric OncologySun Yat-sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, Guangdong 510060, People’s Republic of ChinaTel/Fax +86-020-87342458Email zhangyzh@sysucc.org.cnPurpose: The goal of the current study was to identify potential prognostic biomarkers of rhabdomyosarcoma (RMS).Materials and Methods: We screened chip sequencing datasets of RMS through the gene expression omnibus (GEO) database. A total of 74 RMS patient tissues and 39 normal muscle cell tissues were analyzed. Limma R software was used to identify the differentially expressed genes (DEGs) between RMS tissues and normal controls. The GO plot R package was used to visualize the results of the GO analysis. We screened for pathaffy package enrichment of DEGs by the Kyoto Encyclopedia of Genes and Genomes (KEGG). The cutoff criterion was a P-value < 0.05. Immunohistochemistry (IHC) was applied to validate the expression of CDK1 (cyclin-dependent kinases 1) and MAD2L1 (Mitotic Arrest Deficient 2 Like 1) in RMS.Results: We obtained a total of 498 up- and 480 down-regulated DEGs. The hub genes are mainly involved in the cell cycle and P53 singling pathway. CDK1 expression was associated with tumor size and COG-STS (Children’s Oncology Group-soft tissue sarcoma) staging of RMS. For the low CDK1 expression group and high CDK1 expression group, the 5-year overall survival (OS) rate was 83.0% vs 63.5% (P = 0.004), and the 5-year event-free survival (EFS) rate was 47.5% vs 27.5% (P = 0.049) respectively. When compared low MAD2L1 expression group with high MAD2L1 expression group, the 5-year OS rate was 80.0% vs 43.2% (P = 0.001), and the 5-year EFS rate was 45.1% vs 21.8% (P = 0.038), respectively. If patients were divided into three groups: low CDK1 and low MAD2L1 expression group, high CDK1 or high MAD2L1 expression group, and high CDK1 and high MAD2L1 expression group, the 5-year OS rate was 87.1%, 58.6%, 39.6% (P = 0.001), while the 5-year EFS rate of RMS patients was 54.2%, 23.2%, 21.7% (P = 0.028), respectively.Conclusion: This study has identified that CDK1 and MAD2L1 were adverse prognostic factors of RMS.Keywords: rhabdomyosarcoma, GEO, TCGA, CDK1, MAD2L1, prognosis

Qi Lu,1,* Xian Wu,2,* Yanhui Zhu,2,* Junzhe Yang,2 Xingmeng Wang,2 Chaoran Ye,2 Ruyu Cai,2 Kai Zhang,2 Tingyu Xu,3 Bing Wang,3 Jordee S Veeramootoo,2 Tiansong Xia,2 Xiaoan Liu2 1Department of Thyroid and Breast Surgery, The Second People’s Hospital of Kunshan, Kunshan Jiangsu 215300, People’s Republic of China; 2Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, People’s Republic of China; 3Department of Information, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tiansong Xia; Xiaoan LiuThe First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, People’s Republic of ChinaTel/fax +86-25-68308152Email liuxiaoan@126.comPurpose: Chemotherapy is a comprehensive therapy for breast cancer; nevertheless, its associated adverse effects are drawing increasing attention with the continuous improvement of the efficacy. The changes in serum lipids of breast cancer patients caused by chemotherapy have been reported by previous studies, whereby the former increase the incidence rate of cardiovascular disorders. However, the variations in the changes of serum lipids with different chemotherapy regimens have seldom been reported.Methods: From January 2011 to December 2017, 1740 breast cancer patients treated with chemotherapy were recruited at the First Affiliated Hospital of Nanjing Medical University. The chemotherapy regimens included anthracycline-based, taxane-based, and anthracycline-plus-taxane-based regimens, dose-dense and standard-interval regimens. Lipid profiles that contained TG (triglyceride), TC (total cholesterol), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol) and Lpa (lipoprotein a) levels were collected prior to the first, second and last cycles of chemotherapy. The changes of serum lipids with the same or different chemotherapy regimens were analyzed and compared.Results: It was observed that the levels of TG, TC, LDL-C and Lpa increased significantly while that of HDL-C decreased after adjuvant chemotherapy in breast cancer patients (P< 0.05). Besides, dose-dense regimens had more influence in TG and HDL-C and less influence in TC and LDL-C than standard-interval regimens. HDL-C was more sensitive to anthracycline-based regimens than taxane-based regimens. The level of TG with anthracycline-plus-taxane-based regimens was higher than that with only anthracycline-based or taxane-based regimens, and the level of HDL-C with anthracycline-plus-taxane-based regimen showed lower than that with taxane-based regimen.Conclusion: In summary, this study proposed that dyslipidemia was strongly associated with chemotherapy in Chinese breast cancer patients after operative treatment. Furthermore, the changes in levels of serum lipids varied among patients with different chemotherapy regimens and taxane had less effect on dyslipidemia than anthracycline.Keywords: breast cancer, serum lipids, dyslipidemia, chemotherapy, treatment

Huan Yang,1,* Rui Cai,1,* Yangheng Zhang,2,* Yongyan Chen,1 Bing Gu1,3 1Xuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical University, Xuzhou 221004, People’s Republic of China; 2Department of Periodontology, Nanjing Stomatological Hospital of Nanjing University School of Medicine, Nanjing 210008, People’s Republic of China; 3Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing GuDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of ChinaEmail binggu2015@xzhmu.edu.cnBackground: Clostridium difficile infection (CDI) has become one of the most important factors threatening human health, and about 20– 30% antibiotic-related diarrhea cases and almost all pseudomembranous enteritis cases are related to CDI. The high recurrence of Clostridium difficile (C. difficile) and the emergence of drug resistance make clinical treatment of CDI difficult. Therefore, there is an urgent need to develop a non-antibiotic-alternative therapy against CDI. Gold nanoclusters (AuNCs) can better interact with bacteria due to its ultrasmall size. The aim of the present study was to explore whether AuNCs could be used as an antibacterial agent to kill C. difficile.Methods: AuNCs and C. difficile were co-cultivated in an anaerobic atmosphere to evaluate the bactericidal effect of AuNCs. The bacterial growth rate was estimated by using two concentrations of AuNCs (50 and 100 μM). The damage of AuNCs to C. difficile is detected by SYTOX Green staining methods and SEM image analysis. The mechanism of AuNCs on C. difficile was explored by reactive oxygen species (ROS) detection. The toxic effect of AuNCs on human cells was evaluated by MTT method.Results: AuNCs (100 μM) killed C. difficile drastically. AuNCs increased the release of ROS by about 5 fold and destroyed the membrane integrity of C. difficile cells without causing significant toxic effect on human cells.Conclusion: AuNCs showed great potential as an alternative to traditional antibiotics in killing C. difficile and may prove to be an alternative to treat CDI.Keywords: Clostridium difficile, antibacterial effect, gold nanoclusters, reactive oxygen species

Feifei Sun,1,2,* Suying Lu,1,2,* Zijun Zhen,1,2 Jia Zhu,1,2 Juan Wang,1,2 Junting Huang,1,2 Yu Zhang,1,3 Hui Li,1,4 Ruiqing Cai,1,2 Meiling Liu,1,2 Liuhong Wu,1,2 Xiaofei Sun,1,2 Yizhuo Zhang1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Pediatric Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 4Department of Imaging, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaofei Sun; Yizhuo Zhang Email sunxf@sysucc.org.cn; zhangyzh@sysucc.org.cnBackground: The prognosis of recurrent or refractory advanced childhood solid tumor patients is very poor and new therapeutic strategies are in urgent need. This study aimed to determine the efficacy and safety of apatinib in pediatric refractory/relapse advanced solid tumor patients.Patients and Methods: The study retrospectively reviewed recurrent or refractory advanced pediatric solid tumor patients who were treated with apatinib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets vascular endothelial growth factor receptor-2 (VEGFR2), at the Sun Yat-sen University Cancer Center (China) from January 2016 to March 2019.Results: Fifty-six patients were included in the safety evaluation and 49 patients were included in the efficacy evaluation. The objective responses rate (ORR) was 26.5% (95% CI 15– 41): 0 CR (complete response) and 13 PR (partial response). Disease control rate (DCR) (CR+PR+SD) was 79.6% (95% CI 65– 90). The median progression-free survival (PFS) was 4.0 months (95% CI 2.6– 5.4). There was no significant difference for ORR or PFS between the A (apatinib monotherapy), A+MT (apatinib combined with oral metronomic therapy) and A+SC (apatinib combined with salvage combination chemotherapy) group (p> 0.05). The most common grade 3 or 4 adverse events were neutropenia (9[16.1%]), thrombocytopenia (8[14.3%]), hand-foot syndrome (3[5.4%]), hypertension (3[5.4%]), anaemia (3[5.4%]) and mucositis (2[3.6%]). Hypertension was the most serious adverse event and one death that occurred was considered as drug-related.Conclusion: Apatinib showed promising clinical activity in heavily treated recurrent or refractory advanced childhood solid tumor patients. However, it is necessary to pay special attention to monitoring blood pressure when using apatinib in children. Prospective randomized controlled clinical trial is warranted.Keywords: apatinib, angiogenesis, cancer, pediatric, vascular endothelial growth factor receptor

Jialyu Huang,* Qin Xie,* Jiaying Lin, Xuefeng Lu, Jing Zhu, Hongyuan Gao, Renfei Cai, Yanping Kuang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Renfei Cai; Yanping KuangDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People’s Republic of ChinaTel +86-21-2327 1699 Ext 5539Fax +86-21-6313 6856Email cairenfei070@sina.com; kuangyp9hospital@126.comPurpose: Dydrogesterone (DYG) is an alternative progestin in progestin-primed ovarian stimulation (PPOS) protocol with weaker pituitary suppression than medroxyprogesterone acetate (MPA) in normal ovulatory women. However, the endocrinological characteristics, oocyte retrieval and pregnancy outcomes of DYG application in polycystic ovarian syndrome (PCOS) patients undergoing in vitro fertilization (IVF) remain unclear.Patients and methods: This retrospective cohort study included 420 PCOS patients who underwent controlled ovarian stimulation with human menopausal gonadotropin (hMG) and DYG (n=105) or MPA (n=315) from January 2014 to December 2017. Baseline characteristics of the two groups were balanced with propensity score matching using the nearest-neighbor random matching algorithm in a ratio of 1:3. The primary outcome measure was the number of oocytes retrieved. Other main outcome measures included the number of viable embryos, incidence of premature luteinizing hormone (LH) surge and live birth rate per frozen-thawed embryo transfer (FET) cycle.Results: A similar number of oocytes was retrieved in the two protocols (16.1±6.5 vs 15.1±10.0, P=0.342). Patients in both groups achieved consistent LH suppression with no premature LH surge detected. In the DYG + hMG group, the mean LH levels were significantly higher than the MPA + hMG group on cycle day 9–11 and trigger day (all P

Ziyan Kong,1,* Rui Cai,1,* Chen Cheng,1 Chuanling Zhang,2 Haiquan Kang,3 Ping Ma,3 Bing Gu1,3 1Medical Technology School, Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China; 2Department of Laboratory Medicine, XuZhou Children’s Hospital, Xuzhou, Jiangsu Province, People’s Republic of China; 3Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing GuDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of ChinaTel +8615862163560Email gb20031129@163.comPurpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) have emerged worldwide and also being a major threat to children and neonate. In this study, we describe a nosocomial outbreak of NDM-5-producing Klebsiella pneumoniae in neonatal unit of a teaching hospital in China from September 2015 to September 2016.Patients and methods: We collected 12 carbapenem-resistant K. pneumoniae outbreak strains from 12 newborns and characterized these isolates for their antimicrobial susceptibility, clone relationships, and multi-locus sequence types using vitek-2 compact system, pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Resistant genes were detected by using PCR and sequencing. Plasmid conjugation experiment was carried out to determine the transferability of carbapenem resistance. PCR-based replicon typing (PBRT), S1 nuclease-PFGE, and southern blotting were conducted for plasmid profiling.Results: All 12 K. pneumoniae isolates were resistant to carbapenems and carried blaNDM-5, blaTEM-1 and blaSHV-11. Furthermore, PFGE analysis showed that NDM-5-producing K. pneumoniae were clonally related and MLST assigned them to sequence type 337. Conjugative assays showed that plasmids harboring blaNDM-5 gene were self-transmissible. Plasmid analysis suggested that all blaNDM-5 gene located on a ∼45 kb IncX3 type plasmid.Conclusion: To the best of our knowledge, this is the first report of a clone outbreak of blaNDM-5-carrying K. pneumoniae isolates from neonates. There is an urgent need for effective infection control measures to prevent blaNDM-5 variants from becoming epidemic in the neonates in the future.Keywords: Klebsiella pneumoniae, carbapenemases, blaNDM-5, ST337, neonate, IncX3

Jiaying Lin,* Ningling Wang,* Jialv Huang, Renfei Cai, Yong Fan, Yanping Kuang, Yun Wang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanping Kuang; Yun WangDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People’s Republic of ChinaEmail kuangyp1506@sh9hospital.com; Helen_982@126.comObjective: Frozen–thawed embryo transfer enables surplus embryos derived from IVF or IVF-ICSI treatment to be stored and transferred in subsequent cycles into a more “physiologic environment”. This study aimed to investigate the clinical effect of letrozole use or hMG stimulation on pregnancy and neonatal outcomes in ovulatory patients undergoing FET.Methods: This study includes a total of 5901 FET cycles with letrozole use (n = 1569), HMG (n =1827) or letrozole + HMG (n = 2505). In the letrozole group, 2.5 mg of letrozole was administered on menstrual cycle day 3 to 5 for 3 days for patients, and then follicle growth was monitored beginning on day 10. If the follicular diameter was ≥14 mm on the 10th day, no other ovarian stimulation drugs were needed. If the follicular diameter was Results: Compared with the patients undergoing hMG stimulation, the group receiving letrozole or letrozole+HMG stimulation exhibits significantly higher clinical pregnancy rates per transfer (hMG: 47.02% vs letrozole: 52.07% vs letrozole+HMG: 52.26%) and implantation rates (hMG: 31.76% vs letrozole: 34.36% vs letrozole+HMG: 34.24%). In addition, the letrozole group was associated with a statistically significantly lower incidence of miscarriage (hMG: 14.78% vs letrozole: 10.53% vs letrozole+HMG: 14.13%) and ectopic pregnancies (hMG: 1.83% vs letrozole: 0.97% vs letrozole+HMG: 1.58%) than the letrozole + HMG and HMG groups. Neonatal outcomes are similar among the three groups.Conclusion: Our data demonstrate that the letrozole use may improve clinical pregnancy outcomes and decrease the risk of ectopic pregnancies and miscarriage in ovulatory patients who receive FET cycles.Keywords: frozen–thawed embryo transfer, Letrozole, ovulation induction, hMG, clinical efficacy

Jian Chen,*,1,2 Gang Ren,1 Rong Cai,3 Xiangru Wu,*,4 Ting Gui,1 Jianxi Zhao,1 Huali Li,1 Chen Guo11Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, People’s Republic of China; 2Department of Radiology, Children’s Hospital of Fudan University, Shanghai 201102, People’s Republic of China; 3Department of Radiotherapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China; 4Department of Pathology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, People’s Republic of China*These authors contributed equally to this workBackground: Monitoring the fate of implanted cells over time in an experimental animal may provide a new way to track the metastatic process. Lymph node metastase is of extremely importance for the prognostic prediction of gastric carcinoma. The aim of this study was to assess the feasibility of magnetic resonance imaging (MRI), using micron-sized superparamagnetic iron oxide particles (MPIO), for monitoring of the fate of gastric cancer cells and detecting the migration of gastric cancer cells through the lymphatic system in a mouse model.Methods: SGC-7901 gastric cancer cells were labeled with green fluorescent MPIO. The cells were monitored in vitro at multiple time points by staining for iron-labeled cells and by flow cytometric detection of the fluorescent MPIO. MPIO-labeled cells were implanted subcutaneously into nude mice, and cellular MRI was performed at different time points until 35 days postinjection.Results: The potential for retention of the iron particles in vitro was evaluated. Our results showed that the labeling and uptake efficiency of MPIO reached 90.0% after 24 hrs of incubation, and a small percentage of cells that retained MPIO could be examined until 16 days after labeling. In vivo MRI-based tracking over several weeks in mice revealed regions of signal loss in the primary tumors for up to 5 weeks. Furthermore, small regions of signal void were detected in images of the inguinal lymph nodes in three mice at day 28 postinjection or later, and histological assays confirmed the presence of iron-labeled cancer cells.Conclusion: This study supports MPIO-based cell tracking is a useful tool for monitoring the fate of gastric cancer cells in mice over time, which may facilitate progress in understanding the mechanisms of early regional lymph node micrometastases.Keywords: magnetic resonance imaging, magnetic iron oxide particles, lymph node metastasis, gastric cancer

Fengyi Du,*,1,2 Yunchao Wu,*,2 Fengting Du,*,3 Lirong Zhang,3 Weiwei Feng,4 Lulu Zhao,2 Rong Cai,3 Lixia Xu,2 Gaorui Bian,5 Jiangang Li,5 Shengqiang Zou,1 Aihua Gong,2 Miaomiao Zhang21Department of Hepatosis, The Affiliated Third Hospital of Zhenjiang, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 2School of Medicine, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 3Department of Physiotherapy, Huangnihe Town Hospital, Huangnihe 133704, People’s Republic of China; 4School of Environmental and Safety Engineering, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 5Tianyi Health Sciences Institute (Zhenjiang) Co. Ltd, Zhenjiang 212013, People’s Republic of China*These authors contributed equally to this workBackground: The gastroretentive drug delivery system is an effective administration route, which can improve the bioavailability of the drug and the therapeutic effect by prolonging the release time of the drug and controlling the release rate in the stomach.Methods: Inspired by the excellent adhesion properties of mussel protein, we prepared novel catechol-grafted chitosan alginate/barium sulfate microcapsules (Cat-CA/BS MCs) with mucoadhesive properties and computed tomography (CT) imaging function for gastric drug delivery. First, barium sulfate nanoclusters used as CT contrast agent were synthesized in situ in the Cat-CA/BS MCs through a one-step electronic spinning method. Next, catechol-grafted chitosan as the mucoadhesive moiety was coated on the surface of Cat-CA/BS MCs by polyelectrolyte molecule self-assembly.Results: The prepared Cat-CA/BS MCs could effectively retained in the stomach for 48 hours and successively released ranitidine hydrochloride, which could be used for the treatment of gastric ulcer. Cat-CA/BS MCs exhibited superior CT contrast imaging properties for real-time tracking in vivo after oral administration.Conclusion: These findings demonstrate that Cat-CA/BS MCs serving as multifunctional oral drug carriers possess huge potential in gastroretentive drug delivery and non-invasive visualization.Keywords: catechol, mucoadhesive, microcapsules, CT imaging, gastroretentive drug delivery

Jialyu Huang,* Qin Xie,* Jiaying Lin, Xuefeng Lu, Ningling Wang, Hongyuan Gao, Renfei Cai, Yanping KuangDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China*These authors contributed equally to this workPurpose: Dydrogesterone (DYG) has been demonstrated to be an alternative progestin in the progestin-primed ovarian stimulation (PPOS) protocol with comparable oocyte retrieval and pregnancy outcomes. However, its safety regarding neonatal outcomes and congenital malformations is still unclear.Patients and methods: This retrospective cohort study included 3556 live-born infants after in vitro fertilization and vitrified embryo transfer cycles using the DYG + human menopausal gonadotropin (hMG) protocol (n=1429) or gonadotropin-releasing hormone (GnRH)-agonist short protocol (n=2127) from January 2014 to December 2017. Newborn information was gathered from standardized follow-up questionnaires and/or access to medical records within 7 days after birth. Associations between ovarian stimulation protocols and outcome measures were analyzed by binary logistic regression after adjusting for confounding factors.Results: In both singletons and twins, birth characteristics regarding mode of delivery, newborn gender, gestational age, birthweight, length at birth and Z-scores were comparable between the two protocols. For adverse neonatal outcomes, the two protocols showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, very preterm birth, small-for-gestational age, large-for-gestational age and early neonatal death after adjustment. Furthermore, the incidence of major congenital malformations in the DYG + hMG protocol (1.12%) was similar to that in the GnRH-agonist short protocol (1.08%), with the adjusted odds ratio of 0.98 (95% confidence interval [CI]: 0.40–2.39) and 0.90 (95% CI: 0.33–2.41) in singletons and twins, respectively.Conclusion: Our data suggested that compared with the conventional GnRH-agonist short protocol, application of DYG in the PPOS protocol was a safe option for the newborn population without compromising neonatal outcomes or increasing congenital malformation risks.Keywords: neonatal outcomes, congenital malformations, dydrogesterone, progestin-primed ovarian stimulation, in vitro fertilization

Yiqun Han,1 Jiayu Wang,1 Weiming Liu,2 Peng Yuan,1 Qing Li,1 Pin Zhang,1 Fei Ma,1 Yang Luo,1 Ying Fan,1 Shanshan Chen,1 Ruigang Cai,1 Qiao Li,1 Binghe Xu11National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, China Rehabilitation Research Center, Beijing, People’s Republic of ChinaBackground: This meta-analysis assessed the safety and effectiveness of retreatment with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (HER2+MBC).Materials and methods: Randomized controlled trials (RCTs) and cohort studies that compared the clinical outcomes of continuation and termination of trastuzumab treatment in HER2+MBC after failure of trastuzumab-based regimens were analyzed. Pooled estimates of time to progression (TTP) survival, overall survival (OS), the incidence of adverse events and central nervous system (CNS) perturbations were determined.Results: Four RCTs and six cohort studies with 2,409 patients were identified. The continuation of trastuzumab presented a statistical significance in prolonging TTP (HR 0.88; 95% CI: 0.82–0.94; P

Ruiming Cai,1 Meng Wu,2 Yanfang Xing3 1Department of Organ Transplantation, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong, China; 2Department of Nephrology, Longyan First Hospital, Longyan 364000, Fujian, China; 3Department of Nephrology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong, China Background: Post-transplantation diabetes mellitus (PTDM) remains a major clinical challenge following renal transplant. Identification of pretransplant modifiable risk factors may allow timely interventions to prevent PTDM. This study aims to determine whether pretransplant metabolic syndrome and its components are able to predict PTDM in Chinese patients receiving their first renal transplant.Patients and methods: We conducted a single-center retrospective study of 633 non-diabetic patients receiving a first kidney transplant. PTDM was diagnosed between 1 month and 1 year post-transplant. Multivariable logistic regression and Cox proportional hazards model were applied to detect potential pretransplant risk factors for PTDM.Results: One year post-transplant, 26.2% of recipients had developed PTDM. PTDM patients had significantly higher fasting plasma glucose (FPG) (P=0.026) and body mass index (BMI) (P=0.006) than non-PRDM patients, and lower levels of high-density lipoprotein cholesterol (P=0.015). The presence of metabolic syndrome was an independent risk factor for PTDM, as assessed by multivariable logistic regression analysis (OR 1.28, 95% CI 1.04–1.51, P=0.038) and Cox proportional hazards model (OR 2.75, 95% CI 1.45–6.05, P=0.021). Moreover, both FPG >5.6 mmol/L and BMI >28 kg/m2 (obesity) were able to predict PTDM.Conclusion: Our results suggest that the presence of metabolic syndrome and its components, impaired fasting glycemia and obesity, are independent risk factors for PTDM in Chinese non-diabetic patients receiving a first renal transplant. Interventions aimed at improving pretransplant metabolic syndrome may reduce the incidence of PTDM. Keywords: post-transplantation diabetes mellitus, renal transplant, metabolic syndrome, body mass index, fasting plasma glucose