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Di Zhang,1,2 Yichong She,1,2 Jinbo Sun,1,2 Yapeng Cui,1,2 Xuejuan Yang,1,2 Xiao Zeng,1,2 Wei Qin1,2 1Engineering Research Center of Molecular and Neuro Imaging of the Ministry of Education, School of Life Science and Technology, Xidian University, Xi’an, Shaanxi, 710126, People’s Republic of China; 2Intelligent Non-Invasive Neuromodulation Technology and Transformation Joint Laboratory, Xidian University, Xi’an, People’s Republic of ChinaCorrespondence: Xiao Zeng, Xidian University, 266 Xifeng Road, Xinglong, Xi’an, Shaanxi, People’s Republic of China, 710126, Email xiaozeng1024@gmail.comPurpose: This study aims to improve brain age estimation by developing a novel deep learning model utilizing overnight electroencephalography (EEG) data.Methods: We address limitations in current brain age prediction methods by proposing a model trained and evaluated on multiple cohort data, covering a broad age range. The model employs a one-dimensional Swin Transformer to efficiently extract complex patterns from sleep EEG signals and a convolutional neural network with attentional mechanisms to summarize sleep structural features. A multi-flow learning-based framework attentively merges these two features, employing sleep structural information to direct and augment the EEG features. A post-prediction model is designed to integrate the age-related features throughout the night. Furthermore, we propose a DecadeCE loss function to address the problem of an uneven age distribution.Results: We utilized 18,767 polysomnograms (PSGs) from 13,616 subjects to develop and evaluate the proposed model. The model achieves a mean absolute error (MAE) of 4.19 and a correlation of 0.97 on the mixed-cohort test set, and an MAE of 6.18 years and a correlation of 0.78 on an independent test set. Our brain age estimation work reduced the error by more than 1 year compared to other studies that also used EEG, achieving the level of neuroimaging. The estimated brain age index demonstrated longitudinal sensitivity and exhibited a significant increase of 1.27 years in individuals with psychiatric or neurological disorders relative to healthy individuals.Conclusion: The multi-flow deep learning model proposed in this study, based on overnight EEG, represents a more accurate approach for estimating brain age. The utilization of overnight sleep EEG for the prediction of brain age is both cost-effective and adept at capturing dynamic changes. These findings demonstrate the potential of EEG in predicting brain age, presenting a noninvasive and accessible method for assessing brain aging.Keywords: brain age, sleep polysomnography, electroencephalography, deep learning, swin transformer

Shiyu Wang,1– 4 Wei Qin,1– 4 Tingting Cheng,1– 4 Cong Zeng,1– 4 Xu Chen,1– 4 Yajing Xu1– 4 1Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Changsha, Hunan, People’s Republic of China; 3Hunan Hematologic Neoplasms Clinical Medical Research Center, Changsha, Hunan, People’s Republic of China; 4National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Soochow, Jiangsu, People’s Republic of ChinaCorrespondence: Yajing Xu, Department of Hematology, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha, Hunan, People’s Republic of China, Email xyyajingxu@csu.edu.cnPurpose: Acute graft-versus-host disease (aGVHD) poses a significant impediment to achieving a more favourable therapeutic outcome in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The tumour suppressor p53 plays a pivotal role in preventing aGVHD development. However, whether P53 pathway which contains p53 family members and other related genes participates in aGVHD development remains an unsolved question.Patients and Methods: Transcriptomic data was obtained from Gene Expression Omnibus (GEO) database. Gene set enrichment analysis was applied to determine the enrichment degree of signaling pathways. CIBERSORT and ssGSVA were used to evaluate immune cell compositions. Univariate and multivariate logistic regression analysis were performed to examine the independent diagnostic variables. qRT-PCR was utilized to validate the genes expression levels in our cohort.Results: A total number of 102 patients (42 aGVHD patients vs 60 non-aGVHD patients) were obtained after integrating two datasets in GEO database (GSE73809 and GSE4624). P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways. A risk model for aGVHD built by four genes (DDIT3, FBXW7, TPRKB and TOB1) in P53 pathway, exhibiting high differentiate and predictive value. DDIT3 and FBXW7 mRNA expression levels significantly decreased in peripheral blood mononuclear cells (PBMCs) from aGVHD patients compared with non-aGVHD group in our patient cohort, consisting with bioinformatics analysis.Conclusion: P53 pathway plays a potential role in impeding T cell activation through suppressing its related signaling pathways, thereby preventing aGVHD development. P53 pathway may emerge as a promising therapeutic target in aGVHD treatment.Keywords: allogeneic hematopoietic stem cell transplantation, aGVHD, P53 pathway, T cells, activation

Yiyue Xu,1,* Haoqian Li,1,* Xiaoqing Wang,2 Butuo Li,1 Aiqin Gao,1 Qian Zhao,1 Linlin Yang,1 Wenru Qin,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 2Department of Portal Hypertension, Shandong Public Health Clinical Center, Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 JiYan Road, Jinan, 250117, People’s Republic of China, Tel +86-13793187739, Email wanglinlinatjn@163.comBackground: COVID-19 has spread worldwide, becoming a global threat to public health and can lead to complications, especially pneumonia, which can be life-threatening. However, in lung cancer patients, the prediction of pneumonia and severe pneumonia has not been studied. We aimed to develop effective models to assess pneumonia after SARS-CoV-2 infection in lung cancer patients to guide COVID-19 management.Methods: We retrospectively recruited 621 lung cancer patients diagnosed with COVID-19 via SARS-CoV-2 RT-PCR analysis in two medical centers and divided into training and validation group, respectively. Univariate and multivariate logistic regression analysis were used to identify independent risk factors of all-grade pneumonia and ≥ grade 2 pneumonia in the training group. Nomograms were established based on independent predictors and verified in the validation group. C-index, ROC curves, calibration curve, and DCA were used to evaluate the nomograms. Subgroup analyses in immunotherapy or thoracic radiotherapy patients were then conducted.Results: Among 621 lung cancer patients infected with SARS-CoV-2, 203 (32.7%) developed pneumonia, and 66 (10.6%) were ≥ grade 2. Multivariate logistic regression analysis showed that diabetes, thoracic radiotherapy, low platelet and low albumin at diagnosis of COVID-19 were significantly associated with all-grade pneumonia. The C-indices of the prediction nomograms in the training group and validation group were 0.702 and 0.673, respectively. Independent predictors of ≥ grade 2 pneumonia were age, KPS, thoracic radiotherapy, platelet and albumin at COVID 19 diagnosis, with C-indices of 0.811 and 0.799 in the training and validation groups. In the thoracic radiotherapy subgroup, 40.8% and 11% patients developed all-grade and ≥grade 2 pneumonia, respectively. The rates in the immunotherapy subgroup were 31.3% and 6.6%, respectively.Conclusion: We developed nomograms predicting the probability of pneumonia in lung cancer patients infected with SARS-CoV-2. The models showed good performance and can be used in the clinical management of COVID-19 in lung cancer patients. Higher-risk patients should be managed with enhanced protective measures and appropriate intervention.Keywords: COVID-19, pneumonia, lung cancer, risk factor, nomogram

Lini Chen,&ast; Weiyong Qin,&ast; Jiangdong Wu, Guilin Zhao, Xiaoqing Jiang, Minghui Li, Zijin Huang,&ast; Xueke Du&ast; Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zijin Huang; Xueke Du, Department of Anesthesiology, the Second Affiliated Hospital of Guangxi Medical University, No. 166 of Daxue East Road, Nanning, Guangxi, 530007, People’s Republic of China, Tel +86-13768114848 ; Tel +86-17307711159, Email batistuta921@163.com; duxueke@gxmu.edu.cnPurpose: This study aims to evaluate the effect of remimazolam on induction and maintenance of general anesthesia in kidney transplant patients.Methods: 120 patients undergoing kidney transplant were divided into two groups: Propofol group (Group P) and Remimazolam group (Group R). Anesthesia induction: remimazolam had injected IV at a dose of 0.15– 0.35 mg/kg in Group R, while propofol had injected IV at a dose of 2.0– 2.5 mg/kg in Group P. Anesthesia maintenance: remimazolam was injected IV at a dose of 0.3– 1.0 mg·kg− 1·h− 1 and propofol was injected IV at a dose of 1– 12 mg·kg− 1·h− 1 in Group R, propofol was injected IV at a dose of 3– 12 mg·kg− 1·h− 1 in Group P. All patients have the same remaining anesthesia durgs.Results: Compared with Group P, in Group R the time of disappearance of the eyelash reflex and the time to drop to 60 in BIS was longer (P < 0.05), the time of awakening was shorted (P < 0.05), the MAP of T6 was fluctuated less (P < 0.05), the incidence of hypotension and injection pain during induction was reduced (P < 0.001), the incidence of intraoperative bradycardia during operation was reduced (P < 0.05), the dosages of sedatives drug during maintenance was reduced (P < 0.05). There was no statistically significant difference in postoperative renal function between the two groups of patients (P > 0.05).Conclusion: Remimazolam can be safely and effectively used for the induction and maintenance of general anesthesia in kidney transplant patients.Keywords: remimazolam, propofol, general anesthesia, kidney transplant

Jie Liu,1,&ast; Xiajie Huang,1,&ast; Hongjie Su,1 Jie Yu,1 Xinyu Nie,1 Kaibing Liu,1 Wencong Qin,1 Yongxin Zhao,1 Yongfeng Su,1 Xiaocong Kuang,2 Di Chen,3 William W Lu,4 Yan Chen,1 Qikai Hua1 1Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Yulin Campus of Guangxi Medical University, Yulin, Guangxi, People’s Republic of China; 3Research Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 4Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong&ast;These authors contributed equally to this workCorrespondence: Yan Chen; Qikai Hua, Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email cy003@connect.hku.hk; hqk100@yeah.netPurpose: Management of severe diabetic foot ulcers (DFUs) remains challenging. Tibial cortex transverse transport (TTT) facilitates healing and limb salvage in patients with recalcitrant DFUs. However, the underlying mechanism is largely unknown, necessitating the establishment of an animal model and mechanism exploration.Methods: Severe DFUs were induced in rats, then assigned to TTT, sham, or control groups (n=16/group). The TTT group underwent a tibial corticotomy, with 6 days each of medial and lateral transport; the sham group had a corticotomy without transport. Ulcer healing was assessed through Laser Doppler, CT angiography, histology, and immunohistochemistry. Serum HIF-1α, PDGF-BB, SDF-1, and VEGF levels were measured by ELISA.Results: The TTT group showed lower percentages of wound area, higher dermis thickness (all p < 0.001 expect for p = 0.001 for TTT vs Sham at day 6) and percentage of collagen content (all p < 0.001) than the other two groups. The TTT group had higher perfusion and vessel volume in the hindlimb (all p < 0.001). The number of CD31+ cells (all p < 0.001) and VEGFR2+ cells (at day 6, TTT vs Control, p = 0.001, TTT vs Sham, p = 0.006; at day 12, TTT vs Control, p = 0.003, TTT vs Sham, p = 0.01) were higher in the TTT group. The activity of HIF-1α, PDGF-BB, and SDF-1 was increased in the TTT group (all p < 0.001 except for SDF-1 at day 12, TTT vs Sham, p = 0.005). The TTT group had higher levels of HIF-1α, PDGF-BB, SDF-1, and VEGF in serum than the other groups (all p < 0.001).Conclusion: TTT enhanced neovascularization and perfusion at the hindlimb and accelerated healing of the severe DFUs. The underlying mechanism is related to HIF-1α-induced angiogenesis.Keywords: distraction osteogenesis, tibial cortex transverse transport, diabetic foot, HIF-1α, angiogenesis

Qi Wang,1– 3,&ast; Jiaxin Dong,4,&ast; Mengxian Du,1,3,&ast; Xinna Liu,1– 3 Shiqi Zhang,1 Di Zhang,1,3 Wanyun Qin,1,3 Xikun Xu,1,2 Xianghui Li,1,3 Ruidong Su,1,2 Leyi Qiu,1,2 Baoqiang Li,4,5 Huiping Yuan1 1Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry Education, Harbin, People’s Republic of China; 3Future Medical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, People’s Republic of China; 5Laboratory of Dynamics and Extreme Characteristics of Promising Nanostructured Materials, Saint Petersburg State University, St. Petersburg, Russia&ast;These authors contributed equally to this workCorrespondence: Huiping Yuan, Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China, Email yuanhp2013@126.com Baoqiang Li, Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150081, People’s Republic of China, Email libq@hit.edu.cnIntroduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications.Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined.Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1β and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-β. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function.Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy. Keywords: retina, ischemia/reperfusion injury, rapamycin, carbon dots, microglial polarization, autophagy

Longbin Zheng,1,&ast; Tao Fang,2,&ast; Wei Zhang,1 Xiaojing Zhang,1 Zhiqiang Ren,1 Weimin Qin,1 Wenbo Liang,1 Qing Ma,1 Ning Yin1 1Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Anesthesiology, Xinchang County People’s Hospital, Xinchang, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yin, Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Avenue, Nanjing, Jiangsu Province, 211112, People’s Republic of China, Email yinning882000@126.comPurpose: Dexmedetomidine (Dex) is a potent and highly selective α 2-adrenergic receptor agonist. Within an appropriate dose range, Dex can effectively attenuate the surgical stress response, provide intraoperative hemodynamic stability, and improve the patient recovery quality. High-dose Dex can delay patient awakening from anesthesia and increase the incidence of bradycardia. This randomized controlled trial aimed to investigate the effects of low-dose intravenous Dex premedication in patients undergoing laparoscopic cholecystectomy (LC).Material and Methods: In total, 100 patients undergoing LC were equally randomized into Group C (premedication with saline) and Group D (premedication with 0.5 μg/kg Dex). The patients were premedicated with saline or Dex, depending on the group, before anesthesia induction. Following this, anesthesia induction and endotracheal intubation was performed, and anesthesia was maintained during surgery. Following the completion of the surgery, the patients were transferred the post-anesthesia care unit (PACU) and stayed there until they met the PACU discharge criteria. The hemodynamic parameters, consumption of anesthetics, surgical duration, postoperative awakening time, extubation time, postoperative pain, and complications were recorded.Results: No significant differences were observed in the heart rate (HR) and mean arterial pressure (MAP) between the two groups before premedication (P> 0.05). The MAP and HR immediately after endotracheal intubation and immediately after extubation were significantly lower in Group D than in Group C (P< 0.05 for both). The incidence of bradycardia was significantly higher in Group D than in Group C (P< 0.05), while atropine was used in neither group. Propofol and remifentanil consumption was significantly lower in Group D than in Group C (P< 0.05). The postoperative awakening and extubation times were significantly shorter in Group D than in Group C (P< 0.05). The postoperative visual analog scale scores for pain and incidence of nausea, vomiting, and cough were significantly lower in Group D than in Group C (P< 0.05 for all).Conclusion: Our data suggest that premedication with dexmedetomidine (0.5 μg/kg) before general anesthesia induction can effectively attenuate intraoperative stress response and postoperative pain, maintain perioperative hemodynamic stability, and decrease the incidence of adverse events, which might be an effective and safe anesthetic protocol during LC worthy of further clinical application.Keywords: dexmedetomidine, laparoscopic cholecystectomy, general anesthesia, premedication

Jiemei Ye,1,2,&ast; Xiaoying Huang,3,4,&ast; Weiling Qin,1,2,&ast; Pan Liang,3,4 Jun Zhao,4 Yinxin Ye,1,2 Huojin Ji,1,2 Xinyun Peng,1,2 Yushan Liang,3,4 Yonglin Cai1,5 1Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, People’s Republic of China; 2Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, People’s Republic of China; 3Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 5Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonglin Cai, Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, 543002, People’s Republic of China, Email cylzen@163.com Yushan Liang, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email yushanliang33@outlook.comPurpose: Paired Box 5 (PAX5) is a transcription factor that is widely associated with carcinogenesis. PAX5 can maintain Epstein-Barr virus (EBV) latency in B cells, while a close association exists between EBV infection and nasopharyngeal carcinoma (NPC). However, there are very few reports on the correlation between PAX5 and NPC development. The aim of this study was to investigate the role of PAX5 in NPC.Patients and Methods: The clinical value and prognostic significance of PAX5 in NPC and the association with PAX5 expression and immune cell infiltration were analyzed by multiple GEO datasets. In vivo and in vitro experiments including real-time PCR, Western blot, CCK-8 assay, and methylation sequencing were used to validate the results of bioinformatics analysis.Results: The expression of PAX5 was significantly reduced in NPC tissues, with the low expression being correlated with advanced clinical stage, low tumor mutation burden and immune activation, high relative expression of EBV, poor survival for NPC patients. PAX5 exhibited excellent diagnostic performance and had potential as a predictive factor for response to the immune checkpoint inhibitors therapy. Enrichment analysis suggested that the low expression of PAX5 was associated with the dysregulation of Hippo and Wnt signaling pathways. The promoter of PAX5 gene was hypermethylated in NPC tissues. Furthermore, the in vitro and in vivo experiments revealed that NPC tissue and cell lines had low mRNA expression levels of PAX5, the PAX5 promoter was hypermethylated in NPC cell lines, and PAX5 overexpression inhibited NPC cell proliferation and tumor growth in nude mice.Conclusion: PAX5 may be a tumor suppressor and serve as a novel potential diagnostic and prognostic marker for NPC.Keywords: nasopharyngeal carcinoma, transcription factor, PAX5, prognosis, immunity, Epstein-Barr virus

Junjie Chen,1,&ast; Xiwen Liao,1,2 Yining Wu,1,&ast; Shenjian Ou,1 Wei Qin,1 Chengkun Yang,1,2 Yufeng Tan,1 Quan Lao,1 Minhao Peng,1 Tao Peng,1,2 Xinping Ye1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinping Ye; Tao Peng, Tel +86-771-5356528, Fax +86-771-5350031, Email yexinping@gxmu.edu.cn; pengtaogmu@163.comAbstract: Hepatocellular carcinoma (HCC) recurrence, which encompasses both true recurrence resulting from cancer spread and de novo tumors developing within the same cancer-prone liver, presents a complication in approximately 70% of cases within a 5-year timeframe. The efficacy of neoadjuvant therapy for recurrence after hepatectomy for hepatocellular carcinoma is still unclear. We report a case of recurrent massive advanced hepatocellular carcinoma with pathological complete remission was treated by continuous hepatic arterial infusion chemotherapy (HAIC) and sequential transcatheter arterial embolization (TAE) combined with secondary operation. One month after resection, the patient recurred (massive type 141mm× 76mm). After 4 times of HAIC sequential TAE conversion therapy, the tumor shrank significantly (70mm× 29mm), alpha-fetoprotein(AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels decreased significantly, residual liver volume[left half liver accounted for 39.85% of standard liver volume(left half liver + right anterior lobe) accounted for 80.17% of standard liver volume] and Indocyanine green 15-minute retention(ICG R15 8.0%) complies with surgical requirement.The second operation was performed, and the tumor was completely resected after hepatic blood flow occlusion Requirement. The postoperative pathological results showed complete remission (PCR) of the tumor, and no recurrence was found during the follow-up of 16 months. In this case, HAIC sequential TAE conversion therapy has good short-term effect on patients with postoperative recurrence of hepatocellular carcinoma, tumor burden is significantly reduced, the second surgery pathology achieves complete remission, safety and tolerance, it is worthy of study and promotion.Keywords: hepatocellular carcinoma, recurrence after resection, two-stage hepatectomy, complete remission, sequential therapy

Lini Chen,&ast; Yongguo Xie,&ast; Xueke Du, Weiyong Qin, Lifu Huang, Junmin Dai, Ke Qin,&ast; Jianfeng Huang&ast; Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Qin; Jianfeng Huang, Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China, Tel/Fax +8613878103578 ; +8613978896039, Email qinke303@163.com; 295812612@qq.comBackground: Ciprofol is currently used for painless gastrointestinal endoscopy and anesthesia induction. However, whether it is superior to propofol and its optimal dose remains unknown.Methods: A total of 149 patients, 63 males and 86 females, aged 18– 80 years, BMI 18– 28 kg/m2, ASA I–III, were divided randomly into four groups: propofol group (group P, n = 44), ciprofol 0.2mg/kg group (group C2, n = 38), ciprofol 0.3mg/kg group (group C3, n = 36) and ciprofol 0.4 mg/kg group (group C4, n = 31). Groups C2, C3 and C4 had injected IV with ciprofol 0.2, 0.3 and 0.4 mg/kg, respectively. Group P had injected IV with propofol 1.5mg/kg. The time for disappearance of the eyelash reflex, gastrointestinal endoscopy time, recovery time, and the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score at awakening (T1), 15 minutes after awakening (T2) and 30 minutes after awakening (T3) were recorded.Results: Compared with group P, the time to fall asleep was significantly shortened, and the incidence of nausea and vomiting and injection pain was significantly lower in groups C2, C3 and C4 (P < 0.05). There was no significant difference in recovery time and recovery quality between each group (P > 0.05). Compared with group P and C4, the incidence of hypotension and respiratory depression was significantly lower in groups C2 and C3 (P < 0.05).Conclusion: The appropriate dose of ciprofol for painless gastrointestinal endoscopy is more advantageous than propofol in hemodynamics and respiratory stability, with less injection pain and nausea and vomiting, which is worthy of clinical promotion.Keywords: ciprofol, propofol, painless gastrointestinal endoscopy

Longbin Zheng,1,&ast; Yiteng Wang,2,&ast; Qing Ma,1,&ast; Wenbo Liang,1 Xiaojing Zhang,1 Zhiqiang Ren,1 Weimin Qin,1 Fan Meng,1 Yuhong Li,1 Guoxiang Fan,1 Ning Yin1 1Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Anesthesiology, Xinchang County People’s Hospital, Xinchang, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yin, Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Avenue, Nanjing, Jiangsu Province, 211112, People’s Republic of China, Email yinning882000@126.comPurpose: Patients with obesity are more susceptible to hypoxemia. Anesthetic management for patients with obesity undergoing painless gastroscopy presents a severe challenge for anesthesiologists. Esketamine is a NMDA antagonist that has been proven to be beneficial for ameliorating respiratory depression owing to its sympathomimetic effect; however, there are no relevant reports on its use in patients with obesity. We designed a randomized controlled trial to evaluate whether esketamine can be the ideal adjuvant to propofol sedation in patients with obesity undergoing painless gastroscopy.Patients and Methods: A total of 104 patients with obesity undergoing painless gastroscopy were randomly divided into group C (propofol+saline) and group S (propofol+esketamine 0.25 mg/kg). Anesthesia was induced by 2 mg/kg propofol with saline or esketamine. The consumption of propofol, hemodynamic parameters, duration of procedure, induction time, postoperative awakening time, and orientation recovery time were recorded. Adverse events and satisfaction scores were also recorded.Results: Propofol consumption was 274.4± 22.6 mg and 201.3± 16.6 mg in groups C and S, respectively. The induction time of groups C and S were 25.4± 2.3 s and 17.8± 1.9 s, respectively. The postoperative awakening times of groups C and S were 6.2± 1.1 min and 4.8± 1.3 min, respectively. Hemodynamic parameters were more stable in group S than in group C. The incidence of adverse events such as injection pain, hypoxemia, hypotension, bradycardia, choking, and body movement were significantly lower in group S. The satisfaction scores of the endoscopist and anesthesiologist were (4.58± 0.49 vs 3.71± 0.83) and (4.75± 0.44 vs 3.33± 0.92), respectively.Conclusion: The combination of propofol and esketamine (0.25 mg/kg) improves the safety and reduces the incidence of adverse events in patients with obesity during painless gastroscopy. Thus, this method is worthy of clinical application.Clinical Trials Registration: ChiCTR 2200062547.Keywords: esketamine, propofol, patients with obesity, painless gastroscopy

Fengchun Mu,1,2,&ast; Bingjie Fan,1,&ast; Butuo Li,1 Wenru Qin,1 Haoqian Li,1,2 Chunni Wang,1 Bing Zou,1 Shijiang Wang,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 2Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 271016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Tel +86-531-67626142, Fax +86-531-67626141, Email wanglinlinatjn@163.comPurpose: The present study aimed to evaluate the incidence rate of radiation pneumonitis (RP) in patients with advanced lung adenocarcinoma treated with first-generation (1G), second-generation (2G), or third-generation (3G) epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with thoracic radiotherapy (TRT).Patients and Methods: Patients with advanced lung adenocarcinoma simultaneously treated with 1G/2G/3G EGFR-TKIs and TRT between 2015– 2021 at Shandong Cancer Hospital and Institute were screened. The incidence rate of clinical and imaging RP was compared between the three groups.Results: A total of 200 patients treated with EGFR-TKIs were enrolled in this study, including 100 patients who were treated with 1G EGFR-TKIs, 50 patients who were treated with 2G EGFR-TKIs, and 50 patients who were treated with 3G EGFR-TKIs (patients matched in a 2:1:1 ratio for tumor characteristics). The overall incidence of clinical RP in the 1G, 2G, and 3G EGFR-TKI groups were 29%, 48%, and 28% (p=0.043), respectively, and that of imaging RP were 33%, 58%, and 36% (p=0.010), respectively. The incidence of RP with a clinical grade ≥ 3 in the three groups were 14%, 28%, and 12% (p=0.055), respectively, and that with an imaging grade ≥ 3 in the three groups were 11%, 32%, and 10% (p=0.002), respectively. The incidence of clinical RP was higher in the CFRT group than in the SBRT group, with an overall clinical grade of 38% vs 10% (p< 0.001) and imaging grade of 46% vs 10% (p< 0.001), respectively. In the multivariate analysis, only GTV volume was an independent predictive factor for all risks of clinical and imaging RP. V20 and grouping of 1G/2G/3G EGFR-TKIs were other independent predictive factors for the risk factors of RP for imaging grades.Conclusion: Compared with 2G EGFR-TKIs combined with TRT, 1G or 3G EGFR-TKIs combined with TRT achieved a lower incidence of RP.Keywords: EGFR-TKI, molecular targeted therapy, radiation pneumonitis, thoracic radiotherapy, lung adenocarcinoma

Yue-yang Yu,1,2 Mei Yuan,1 Wei-jie Qin,3 Hai-hong Bai,4 Hong-zhuo Liu,2 Jin-jing Che1 1Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, People’s Republic of China; 2Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 3State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing, People’s Republic of China; 4Phase I Clinical Trial Center, Beijing Shijitan Hospital of Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Hong-zhuo Liu, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, People’s Republic of China, Tel/Fax +86 13236637187, Email liuhongzhuo@syphu.edu.cn Jin-jing Che, Beijing Institute of Pharmacology and Toxicology, No. 27 Taiping Road, Beijing, People’s Republic of China, Tel/Fax +86 01066930633, Email chejinjing80@126.comPurpose: Liposomes are nano-scale materials with a biofilm-like structure. They have excellent biocompatibility and are increasingly useful in drug delivery systems. However, the in vivo fate of liposomal drugs is still unclear because existing bioanalytical methods for quantitation of total and liposomal-encapsulated drugs have limits. A novel strategy for liposomal-encapsulated drug separation from plasma was developed via the specific coordinate binding interaction of TiO2 microspheres with the phosphate groups of liposomes.Methods: Liposomal-encapsulated docetaxel was separated from plasma by TiO2 microspheres and analyzed by the UPLC-MS/MS method. The amount of TiO2, pH of the dilutions, plasma dilution factors and incubation time were optimized to improve extraction recovery. The characterization of the adsorption of liposome-encapsulated drugs by TiO2 microspheres was observed by electron microscopy. For understanding the mechanism, pseudo-first and the pseudo-second order equations were proposed for the adsorption process. The study fully validated the method for quantitation of liposomal-encapsulated in plasma and the method was applied to the pharmacokinetic study of docetaxel liposomes.Results: The encapsulated docetaxel had a concentration range of 15– 4000 ng/mL from the plasma sample using a TiO2 extraction method. Successful method validation proved the method was sensitive, selective and stable, and was suitable for quantitation of docetaxel liposomes in plasma samples. Extraction recovery of this method was higher than that of SPE method. As shown in electron microscopy, the liposomes adsorbed on TiO2 microspheres were intact and there was no drug leakage. The study proposed pseudo-first and the pseudo-second order equations to facilitate the adsorption of liposomal drugs with TiO2 microspheres. The proposed strategy supports the pharmacokinetic study of docetaxel liposomes in rats.Conclusion: TiO2 extraction method was stable, reproducible, and reliable for quantitation of encapsulated docetaxel. Because of versatility of lipids, it is expected to a universal bioanalysis method for the pharmacokinetic study of liposomes.Graphical Abstract: Keywords: liposomal-encapsulated drug, docetaxel liposomes, TiO2 microspheres, coordinate binding, bioanalysis

Yining Wu,1,&ast; Shenjian Ou,1,&ast; Xiwen Liao,1,2 Chuangye Han,1,2 Chengkun Yang,1,2 Wei Qin,1 Yufeng Tan,1 Quan Lao,1 Tao Peng,1,2 Xinping Ye1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinping Ye; Tao Peng, Tel +86-771-5356528, Fax +86-771-5350031, Email yexinping@gxmu.edu.cn; pengtaogmu@163.comAbstract: Situs inversus totalis (SIT) is a rare congenital condition in which abdominal and thoracic organs are transposed from normal positions. Two-stage hepatectomy (TSH) combined with translational therapy for hepatocellular carcinoma (HCC) with SIT has been rarely reported. We report a 41-year-old man with giant hepatocellular carcinoma (71 mm × 55 mm × 51 mm) whose future residual liver (FLR) and standard liver volume (SLV) ratio at first diagnosis was 37.4%. Preoperative volume assessment of portal vein ligation (PVL) revealed inadequate hypertrophy of FLR. After a multidisciplinary group discussion (MDT), the patient decided to follow conversion therapy. Three months later, ratio of the FLR/SLV increased from 37.4% to 71% after operation, which met the surgical requirements. Second hepatectomy, right lobectomy was successful. There was no recurrence after six months of follow-up. In our case, conversion therapy appears to be effective in maintaining residual liver hyperplasia, reducing tumor load, and preventing tumor progression in patients with large HCC during TSH.Keywords: situs inversus totalis, two-stage hepatectomy, hepatocellular carcinoma, future residual liver, multidisciplinary group discussion

Yanan Duan,1,2 Wenru Qin,1,3 Linlin Yang,1,4 Bing Zou,1 Wenting Qie,1,3 Ruiting Song,1,2 Lu Xue,1,2 Linlin Wang1 1Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Weifang Medical University, Weifang, People’s Republic of China; 4Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Linlin Wang, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, Shandong, People’s Republic of China, Email wanglinlinatjn@163.comPurpose: We assess real-world outcomes, including safety and efficacy, of concurrent or sequential treatment with radiotherapy plus programmed cell death protein 1 (PD-1) inhibitors in patients with oligometastatic esophageal cancer (OMEC).Methods: This cohort study retrospectively collected clinical data of patients with synchronous or metachronous OMEC. All patients underwent concurrent or sequential treatment with radiotherapy plus PD-1 inhibitors. Each patient had up to five measurable metastatic lesions and up to three organs involved. Study endpoints were progression-free survival (PFS), treatment-related toxicities, locoregional progression-free survival (LRPFS), objective response rate (ORR), and disease control rate (DCR). Description statistics and Kaplan–Meier models were used for statistical analysis.Results: A total of 86 patients were included, most of whom were diagnosed with squamous cell carcinoma histology (98%) and presented with synchronous OMEC (64%). The median follow-up period was 17 months (range: 6– 32 months), the median PFS was 15.2 months (95% confidence interval: 12.1– 18.2 months); and the 1- and 2-year PFS rates were 61.4% and 26.7%, respectively. The 1- and 2-year LRPFS were 91.3% and 57.3%, respectively. The ORR and DCR were 46.5% and 91.8%, respectively. Forty-two patients (48.8%) experienced grade 3 or higher treatment-related adverse events (TRAEs); a grade 5 treatment-related adverse event was observed in one patient (1.2%) who died of immune-related pneumonitis.Conclusion: Combining radiotherapy with PD-1 inhibitors is a safe and effective treatment option for patients with OMEC. No new safety concerns were identified in this study. However, due to the potential risk of cumulative toxicity, an individual risk-benefit assessment for each patient is required prior to treatment initiation.Keywords: oligometastatic disease, esophageal cancer, PD-1 inhibitors, radiotherapy

Wangjun Qin,1 Siyu Yuan,2 Li Zhao,1 Ying Liu,1 Liyuan Xu,3 Yi Zhang,3 Lihong Liu,1 Bifa Fan3 1Department of Pharmacy, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Department of Pharmacy, Siping Central Hospital, Siping, Jilin Province, People’s Republic of China; 3Department of Pain Management, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Lihong Liu; Bifa Fan, China-Japan Friendship Hospital, 2 Yinghua Road, Heping District, Beijing, 100029, People’s Republic of China, Tel +860184205959, Fax +860184205559, Email hongllh@126.com; fyinsuo@yeah.netPurpose: Pharmacists are key members of the pain management interdisciplinary team in many developed countries. However, the implementation of clinical pharmacy services in pain management is impeded by the imbalance between the pain physicians and clinical pharmacists specializing in pain management in China. The purpose of this study was to elucidate the perceptions, expectations and current experience of Chinese pain physicians regarding clinical pharmacy services.Patients and Methods: An anonymous, self-administered questionnaire was designed according to previously published studies with minor modifications and distributed online to 1100 pain physicians selected randomly in hospitals across all 31 provinces of mainland China in 2021. Data were analyzed using descriptive and inferential statistics.Results: A total of 1071 valid questionnaires were included for analysis. The pain physicians were from all 31 provinces of mainland China and most of them were from tertiary hospitals holding an undergraduate degree. Among listed kinds of clinical pharmacy services, pain physicians were less comfortable with pharmacists treating minor illnesses (p < 0.001). Pain physicians’ experiences with clinical pharmacy services were far less than their expectations (p < 0.001), which is in line with the results that most of pain physicians (65.9%) interacted with pharmacists at a frequency of less than once a week. Significant differences in the experiences were found among ages (p < 0.01) and among years of work experience (p < 0.05) of pain physicians. Pain physicians’ expectations of pharmacists were positively correlated with their experiences with clinical pharmacy services (p < 0.001).Conclusion: Pain physicians in China had positive perceptions and high expectations, but relatively low experiences regarding clinical pharmacy services. Expanding clinical pharmacist pain management credentialing and increasing pain physicians’ exposure to clinical pharmacy services are favourable to support the interdisciplinary collaboration in pain management in China.Keywords: clinical pharmacy services, pain management, interdisciplinary collaboration, professional competence, primary health care

Wenqi Qin,1 Yan Wu,1 Jieting Liu,1 Xiaohuan Yuan,1 Jie Gao2 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of ChinaCorrespondence: Xiaohuan Yuan, College of Life Science, Mudanjiang Medical University, Mudanjiang, Heilongjiang, 157001, People’s Republic of China, Tel/Fax +86 453 6984647, Email yuanxiaohuan@mdjmu.edu.cn Jie Gao, Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China, Tel/Fax +86 021 31166666, Email gaojiehighclea@163.comAbstract: Diabetic wounds are one of the most challenging public health issues of the 21st century due to their inadequate vascular supply, bacterial infections, high levels of oxidative stress, and abnormalities in antioxidant defenses, whereas there is no effective treatment for diabetic wounds. Due to the distinct properties of nanoparticles, such as their small particle size, elevated cellular uptake, low cytotoxicity, antibacterial activity, good biocompatibility, and biodegradability. The application of nanoparticles has been widely used in the treatment of diabetic wound healing due to their superior anti-inflammatory, antibacterial, and antioxidant activities. These nanoparticles can also be loaded with various agents, such as organic molecules (eg, exosomes, small molecule compounds, etc.), inorganic molecules (metals, nonmetals, etc.), or complexed with various biomaterials, such as smart hydrogels (HG), chitosan (CS), and hyaluronic acid (HA), to augment their therapeutic potential in diabetic wounds. This paper reviews the therapeutic potential and future perspective of nanoparticles in the treatment of diabetic wounds. Together, nanoparticles represent a promising strategy in the treatment of diabetic wound healing. The future direction may be to develop novel nanoparticles with multiple effects that not only act in wound healing at all stages of diabetes but also provide a stable physiological environment throughout the wound-healing process.Keywords: nanoparticles, biomaterials, wound healing, diabetic wound, diabetic complications

Xiao Chen,1,&ast; Wenjuan Zhao,2,&ast; Jie Yuan,3 Wei Qin,1 Yuhong Zhang,1 Yuxia Zhang1 1Department of Nursing, Zhongshan Hospital of Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Nursing, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 3Department of Nursing, Shanghai Fengxian District Hospital of Traditional Chinese Medicine, Shanghai, 201499, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuxia Zhang; Yuhong Zhang, Department of Nursing, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China, Tel +86 13816881925, Fax +86 64041990, Email zhang.yx@aliyun.com; zhang.yuhong@zs-hospital.sh.cnPurpose: When creating and managing patient loyalty, medical institutes always focus on medical technicians, overall healthcare quality, and hospital brands, and the role of nursing seems to be underappreciated. Empirical evidence about the relationship between patient experience with nursing care and patient loyalty is limited, especially in the Chinese healthcare system. This study aimed to explore to what extent patient experience with nursing care influences patient loyalty to the hospital and the impact routes.Patients and Methods: This study is a multicenter cross-sectional survey. The STROBE was selected as the checklist in this study. Patient experience with nursing care, patient satisfaction and patient loyalty were collected from 1469 inpatients in three hospitals in China through a paper-based survey. Data were analyzed using SPSS and AMOS software; a structural equation model was established to explore the effect of patient experience with nursing care and satisfaction on patient loyalty using the PROCESS macro.Results: There were significant direct and indirect effects between patient experience with nursing care and patient loyalty, explaining 32.0% of patient loyalty variance. Patient experience with nursing care had a direct and positive impact on patient loyalty (β=0.298, P< 0.01), and better patient experience with nursing care was directly associated with better patient loyalty. In addition, the results also revealed the effect of patient experience with nursing care on patient loyalty was partially mediated by patient satisfaction with nursing care and overall hospital services (β=0.162, P< 0.01).Conclusion: This study confirmed the importance of nursing care in creating patient loyalty; improving the patient experience with nursing care would be beneficial to patient loyalty. When creating patient loyalty, hospital administrators and nursing managers should make efforts to develop positive patient experience of nursing care in daily clinical practice through organizational changes, culture shaping and staff education.Keywords: patient experience, nursing care, patient satisfaction, patient loyalty

Liu D, Zhao J, Wang H, Li H, Li Y, Qin W. Onco Targets Ther. 2020;13:11975–11990. We, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors did not respond to our queries, nor did they provide original data for their study. As verifying the validity of the published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Shuna Yang, Xuanting Li, Wei Qin, Lei Yang, Wenli Hu Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wenli Hu, Email wenlihu3366@126.comBackground and Objective: Motor dysfunction is common in the elderly, and is associated with adverse consequences. Enlarged perivascular spaces in basal ganglia (BG-EPVSs) are considered an MRI marker of cerebral small-vessel diseases. However, the consequences of BG-EPVSs are largely unknown. In the present study, we aimed to explore the association between large numbers of BG-EPVSs and motor performance.Methods: We prospectively recruited elderly individuals in the Neurology Department of our hospital from December 1, 2020 to January 31, 2022. Participants with > 20 BG-EPVSs on the unilateral side of the slice containing the most EPVSs were classified as the BG-EPVS group (n=99) and the rest as controls (n=193). Motor performance was assessed by quantitative gait analysis, Tinetti test, timed up-and-go (TUG) test, and the Short Physical Performance Battery (SPPB). Spearman correlation analysis and multivariate linear regression analysis were performed to investigate the association between BG-EPVSs and motor performance.Results: Compared with the control group, the BG-EPVS group had lower gait speed and cadence, shorter stride length, longer TUG duration, and lower Tinetti gait test, Tinetti balance test, and SPPB scores (P< 0.01). Spearman correlation analysis showed that BG-EPVSs were negatively related to gait speed, gait cadence, stride length, and Tinetti gait test, Tinetti balance test, and SPPB scores (ρ= – 0.539 to – 0.223, P< 0.001) and positively related to TUG duration (ρ=0.397, P< 0.001). Regression analysis indicated that BG-EPVSs were an independent risk factor of lower gait speed, shorter stride length, poor balance, and poor general physical performance after adjusting for confounders (β= – 0.313 to – 0.206, P< 0.01).Conclusion: Large numbers of BG-EPVSs were independently related to poor gait, balance, and general physical performance in elderly individuals, which provides information about the consequences of BG-EPVSs and risk factors for motor dysfunction.Keywords: cerebral small-vessel diseases, enlarged perivascular spaces, motor, gait, balance, physical performance

Wenru Qin,1,2,&ast; Bing Zou,2,&ast; Xinyu Fan,2,3 Bingjie Fan,2 Shijiang Wang,2 Linlin Wang2 1Department of Oncology, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Oncology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, 250117, People’s Republic of China, Tel +86-531-67626142, Email wanglinlinatjn@163.comAbstract: The most common pathologic type of thymic carcinoma (TC) is squamous cell carcinoma (SCC). Small cell carcinoma is relatively rare, accounting for approximately 2% to 5% of all thymic tumors. Histologic transformation of TC has not yet been reported. Available treatments for TC patients who progress after first-line therapy are limited, which contributes to their poor prognosis. We reported an extraordinary case of a 66-year-old man who was diagnosed with thymic small cell carcinoma that transformed into SCC after third-line treatment. Surprisingly, the patient had a progression-free survival (PFS) of 25 months and an overall survival (OS) of 10 years on anlotinib as fourth-line therapy. The tolerance was well. Thus, anlotinib may be a safe and promising treatment for TC patients, especially those who undergo histologic transformation.Keywords: thymic carcinoma, squamous cell carcinoma, small cell carcinoma, histologic transformation, anlotinib

Han Cen,1– 3 Qin-Wen Wen,4 Han-Qing Zhang,4 Hang Yu,4 Zhen Zeng,2 Ting Jin,2 Ting-Hui Wang,4 Wen Qin,4 Hua Huang,4 Xiu-Di Wu4 1Institute of Geriatrics, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 2Department of Preventive Medicine, Medical School of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 4Department of Rheumatology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Xiu-Di Wu, Department of Rheumatology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, 59 Liuting Road, Ningbo, Zhejiang, 315010, People’s Republic of China, Tel +86 574 87085588, Fax +86 574 87291583, Email awu1100@aliyun.comPurpose: To investigate the associations between genetic polymorphisms within transporter genes and clinical response to methotrexate (MTX) in Chinese rheumatoid arthritis (RA) patients.Patients and Methods: A total of 100 RA patients receiving MTX were prospectively followed up for approximately 3 months to determine the clinical response based on several criteria, including European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts – erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR > 0.6. Fifty-four single nucleotide polymorphisms (SNPs) within seven transporter genes, including SLC19A1, ABCB1, ABCC1∼ 4 and ABCG2, were genotyped.Results: Multivariable analysis revealed that SLC19A1 rs12659 and rs3788200, ABCC2 rs3740066, rs4148396 and rs717620 were significantly associated with EULAR good and moderate response, and ABCC2 rs3740066 and rs717620 were significantly associated with DAS28-ESR LDA, and ABCB1 rs1128503, rs4148737 and ABCC3 rs2277624, rs4148416 were significantly associated with ΔDAS28-ESR. Moreover, 12 genetic polymorphisms were found to be significantly associated with ΔDAS28-ESR > 0.6. With adjustment for corresponding confounders, SLC19A1 TGAA haplotype consisting of rs1051266, rs1131596, rs12659 and rs3788200 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR > 0.6 compared with the most common haplotype CAGG. The ABCC2 haplotype TTT composed of rs717620, rs4148396 and rs3740066 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR > 0.6 compared with the most common haplotype CCC.Conclusion: Our results highlight the potential of genetic polymorphisms within transporter genes, particularly SLC19A1 and ABCC2, as predictors of clinical response to MTX in Chinese RA patients.Keywords: rheumatoid arthritis, methotrexate, transporter, single-nucleotide polymorphism, clinical response

Chun Liu,1 Wen Qin,1 Yan Wang,2 Jiayi Ma,1 Jun Liu,1 Siyu Wu,1 Hongbin Zhao1 1Medical Research Centre, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, Changzhou, 213164, People’s Republic of China; 2Department of Clinical Laboratory, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, Changzhou, 213164, People’s Republic of ChinaCorrespondence: Hongbin ZhaoMedical Research Centre, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, No. 68, Gehu Road, Changzhou, Jiangsu, 213164, People’s Republic of ChinaTel/Fax +86 13919761032Email zhao761032@163.comIntroduction: Bone tissue engineering (BTE) is a new strategy for bone defect repair, but the difficulties in the fabrication of scaffolds with personalized structures still limited their clinical applications. The rapid development in three-dimensional (3D) printing endows it capable of controlling the porous structures of scaffolds with high structural complexity and provides flexibility to meet specific needs of bone repair.Methods: In this study, sodium alginate (SA)/gelatin (Gel) hydrogel scaffolds doped with different contents of nano-attapulgite were fabricated via 3D printing. The surface microstructure, hydrophilicity and mechanical properties were fully evaluated. Furthermore, mouse bone marrow-derived mesenchymal stem cells (BMSCs) were cultured with the composite hydrogels in vitro, and proliferation and osteoblastic differentiation were assessed. A rabbit tibia plateau defect model was used to evaluate the osteogenic potential of the composite hydrogel in vivo.Results: When increasing nano-ATP content, the Gel/SA/nano-ATP composite hydrogels showed better mechanical property and printability. Moreover, Gel/SA/nano-ATP composite hydrogels showed excellent bioactivity, and a significant mineralization effect was observed on the surface after being incubated in simulated body fluid (SBF) for 14 days. The Gel/SA/nano-ATP composite hydrogel also showed good biocompatibility and promoted the osteogenesis of BMSCs. Finally, histological analysis demonstrates that the Gel/SA/nano-ATP composite hydrogels could effectively enhance bone regeneration in vivo.Conclusion: These properties render the Gel/SA/nano-ATP composite hydrogel scaffolds an ideal bone tissue engineering material for the repair of bone defects.Keywords: 3D printing, attapulgite, composite hydrogel, osteogenesis, bone repair

Weiwei Qin,1,2 Ting Wang,2 Guangwei Liu,3 Lixin Sun,1 Wei Han,4 Youhe Gao2 1Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing Normal University, Beijing, 100875, People’s Republic of China; 3Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing, 100875, People’s Republic of China; 4Department of Respiratory Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, People’s Republic of ChinaCorrespondence: Youhe Gao; Wei Han Tel +86 10 58804382; +86 532 85937809Email gaoyouhe@bnu.edu.cn; sallyhan1@163.comBackground: In this work, we aim to investigate dynamic urinary proteome changes during asthma development and to identify potential urinary protein biomarkers for the diagnosis of asthma.Methods: An ovalbumin (OVA)-induced mouse model was used to mimic asthma. The urinary proteome from asthma and control mice was determined using data-independent acquisition combined with high-resolution tandem mass spectrometry.Results: Overall, 331 proteins were identified, among which 53 were differentially expressed (26, 24, 14 and 20 on days 2, 8, 15 and 18, respectively; 1.5-fold change, adjust P< 0.05). Gene Ontology annotation of the differential proteins showed that the acute-phase response, innate immune response, B cell receptor signaling pathway, and complement activation were significantly enriched. Protein–protein interaction network revealed that these differential proteins were partially biologically connected in OVA-induced asthma, as a group. On days 2 and 8, after two episodes of OVA sensitization, six differential proteins (CRAMP, ECP, HP, F2, AGP1, and CFB) were also reported to be closely associated with asthma. These proteins may hold the potential for the early screening of asthma. On days 15 and 18, after challenged with 1% OVA by inhalation, seven differential proteins (VDBP, HP, CTSE, PIGR, AAT, TRFE, and HPX) were also reported to be closely associated with asthma. Thus, these proteins hold the potential to be biomarkers for the diagnosis of asthma attack.Conclusion: Our results indicate that the urinary proteome could reflect dynamic pathophysiological changes in asthma progression.Keywords: OVA-induced asthma, mice, urine, proteome, data-independent acquisition

Hui Han,1,&ast; Weidong Qin,1,&ast; Yue Zheng,2– 5 Dongming Cao,6 Haining Lu,7 Lu Zhang,8 Yi Cui,1 Yuanyuan Hu,1 Wei Li,9 Haipeng Guo,1 Dawei Wu,7 Chen Li,1 Hao Wang,1,2,10 Yuguo Chen2– 5 1Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 3Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 4Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 5The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 6Department of Critical Care Medicine, Liaocheng People’s Hospital Affiliated with Shandong First Medical University, Liaocheng, People’s Republic of China; 7Department of Critical Care Medicine, Qilu Hospital of Shandong University (Qingdao), Qingdao, People’s Republic of China; 8Department of Critical Care Medicine, The Second Hospital of Shandong University, Jinan, People’s Republic of China; 9Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 10Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao WangDepartment of Critical Care Medicine, Qilu Hospital of Shandong University, 107 Wenhua-xi Road, Jinan, 250012, People’s Republic of ChinaTel +86 18560081013Email wanghao34@126.comYuguo ChenDepartment of Emergency Medicine, Qilu Hospital of Shandong University, 107 Wenhua-xi Road, Jinan, 250012, People’s Republic of ChinaTel +86 0531-8216 6843Email chen919085@sdu.edu.cnBackground: Extensively drug-resistant Acinetobacter baumannii (XDR-AB) infections have become difficult to treat and are associated with a high mortality rate. Tigecycline is one of the most effective agents used to treat XDR-AB infections, but data from treating bloodstream infection (BSI) in standard dose do not look promising, because of its low plasma concentration. Secondary BSI with primary infection source may indicate tigecycline treatment with a higher dose. Currently, little is known about the application of high-dose tigecycline among patients with secondary BSI caused by XDR-AB. We aimed to investigate the outcomes for high-dose (HD) tigecycline treatment versus standard-dose (SD) treatment of these patients.Methods: An observational cohort study was conducted at four university affiliated hospitals in mainland China. Adult inpatients who were confirmed as having secondary BSI caused by XDR-AB and received definitive tigecycline treatment were consecutively included. Patients who were treated with 50 mg every 12 h were defined as the SD group, and a twice dose was defined as the HD group.Results: Of the enrolled patients, 63 received SD and 88 received HD tigecycline treatment. Patients in the two groups had similar with regard to baseline clinical conditions. The 30-day survival was affected by the source of the primary infection. Survival was significantly better in patients with non-pulmonary-infection-related BSI than in patients with pulmonary-infection-related BSI. Multivariate Cox regression confirmed that HD had a protective effect only observed in patients with non-pneumonia-related BSI.Conclusion: A tigecycline dose that is twice its standard dose is better for the treatment of XDR-AB infection only in BSI associated with non-pulmonary infection.Keywords: Acinetobacter baumannii, bloodstream infection, extensively drug-resistant, tigecycline, high-dose

Wantong Han,1– 3 Lingzhong Xu,1– 3 Aimin Niu,4 Yurong Jing,1– 3 Wenzhe Qin,1– 3 Jiao Zhang,1– 3 Xiang Jing,5 Yali Wang6 1Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2NHC Key Laboratory of Health Economics and Policy Research, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 3Center for Health Economics Experiment and Public Policy Research, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 4Department of Public Health, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 5Yuncheng Central Hospital, Yuncheng, Shanxi, People’s Republic of China; 6Henan Provincial Center for Disease Control and Prevention, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Lingzhong XuSchool of Public Health, Cheeloo College of Medicine, Shandong University, Mailbox No. 110, 44 Wenhuaxi Road, Jinan, 250012, Shandong, People’s Republic of ChinaTel +86-0531-8838-2648Fax +86-0531-88382533Email lzxu@sdu.edu.cnAimin NiuDepartment of Public Health, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Huaiyin District, Jinan, 250021, People’s Republic of ChinaTel +86-1866-370-2722Fax +86-0531-87921022Email nam1106@163.comPurpose: Studies have suggested that public health emergencies can have many psychological effects on college students, therefore, the aim of this study is to investigate current situation of college students’ anxiety and its determinants in the time of an unexpected pandemic.Patients and Methods: We conducted convenience sampling to collect the data through network-based online questionnaires in February 2020, a total of 17,876 college students were included in the analysis. Chi-square test and multivariate logistic were used to identify the associations between the outbreak experiences and anxiety detection.Results: This study found that detection rate of anxiety among college students was 18.2%. The differences in male students, students whose self-perceived risk of infection were high, who were greatly affected by the outbreak, eager to go back to school, reluctant to leave home and stay at home enough were of statistical significance among different anxiety level (OR> 1, P< 0.05). And the severe anxiety rate of students who living in cities was significantly higher (2.337[1.468, 3.721]).Conclusion: Although our results show that anxiety among college students was at a low level, various universities should focus on the online activities and develop appropriate epidemic management plans to prevent their feelings of worry, tension and panic.Keywords: anxiety, college students, network-based, COVID-19

Zepeng Yu,1,* Xingwei Sun,1,* Xuming Bai,1 Wei Ding,2 WeiDong Wang,2 Liang Xu,3 Wenming Qin,4 Ling Wen,5 Yong Jin1 1Department of Intervention, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People’s Republic of China; 2Department of Intervention, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, Jiangsu Province, People’s Republic of China; 3Department of General Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, 215500, Jiangsu, People’s Republic of China; 4Department of Anesthesiology, Bazhong Central Hospital, Bazhong, Sichuan, 636000, People’s Republic of China; 5Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong JinDepartment of Intervention, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People’s Republic of ChinaTel +86 13776097707Email 578898234@qq.comLing WenDepartment of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People’s Republic of ChinaEmail wenling@suda.edu.cnPurpose: The totally implantable venous access port (TIVAP) provides patients with safe, effective and long-term convenient venous access for the administration of medications such as chemotherapy drugs. The implantation and long-term use of TIVAP are related to thrombosis, infection and other complications. In this study, the medical records of multicentre patients were collected, and the perioperative and postoperative complications were retrospectively analysed to objectively evaluate the safety of the implantation of supraclavicular, ultrasound-guided TIVAP via the brachiocephalic vein (BCV).Patients and Methods: We retrospectively analysed the clinical data of 433 adult patients who had undergone ultrasound-guided TIVAP implantation via the BCV at four hospitals in China from March 2018 to May 2019. The success rates of the first puncture, operation time, and perioperative and postoperative complications were analysed.Results: All the TIVAPs were implanted successfully (100%). The average TIVAP carrying time was 318.15 ± 44.22 days (range: 38– 502 days) for a total of 197,694 catheter days. The success rate of the first puncture was 94.92% (411/433), and the average operation time was 29.66 ± 7.45 min (range: 18– 60 min). The perioperative complications included arterial puncture in 4 patients and pneumothorax in 1 patient. The incidence of postoperative complications was 5.08% (22/433), including poor incision healing (n = 2), catheter-related infection (n = 3), port infection (n = 6), thrombosis (n = 2) and fibrin sheath formation (n = 8). Another patient had infusion disturbance 2 days after the operation, and chest X-ray showed bending at the connection between the catheter and port. No other serious complications occurred, such as catheter rupture and drug leakage. The total incidence of complications was 6.24% (27/433).Conclusion: This study showed excellent tolerance of supraclavicular, ultrasound-guided BCV puncture to implant TIVAP and a low incidence of complications. As a safe and effective method of TIVAP implantation, it can provide a new choice for clinicians.Keywords: complications, totally implantable venous access ports, ultrasound-guided, brachiocephalic vein

Dejun Liu, Jing Zhao, Huiling Wang, Hui Li, Yanjie Li, Wangsen Qin Department of Clinical Laboratory, Henan Provincial People’s Hospital, Zhengzhou, Henan 450003, People’s Republic of ChinaCorrespondence: Wangsen QinDepartment of Clinical Laboratory, Henan Provincial People’s Hospital, 7 Weiwu Road, Zhengzhou, Henan 450003, People’s Republic of ChinaEmail jianyan_qinwangsen@163.comPurpose: Long intergenic non-protein coding RNA 519 (LINC00519) promotes the development of lung squamous cell carcinoma. In this study, we detected the expression of LINC00519 in tongue squamous cell carcinoma (TSCC) and examined its clinical significance. Additionally, the regulatory effects of LINC00519 on behaviors of TSCC tumor cells were explored through functional experiments. Finally, mechanistic studies were performed to elucidate the molecular events underlying the tumor-promoting actions of LINC00519 in TSCC.Materials and Methods: The expression of LINC00519 in TSCC tissues and cell lines was determined using quantitative reverse transcription-polymerase chain reaction. Cell counting kit-8 assay, flow cytometric analysis, cell migration and invasion assays and xenograft tumor model analyses were used to detect TSCC cell proliferation, apoptosis, migration and invasion and in vivo tumor growth, respectively. Mechanistic studies were performed using bioinformatics analysis, RNA immunoprecipitation assay, luciferase reporter assay and rescue experiments.Results: LINC00519 was overexpressed in both TSCC tissues and cell lines. A high LINC00519 level was associated with poor overall survival in patients with TSCC. In vitro, LINC00519 played cancer-promoting roles in TSCC progression by facilitating cell proliferation, migration and invasion and restraining cell apoptosis. In vivo, LINC00519 downregulation resulted in decreased TSCC tumor growth. Mechanistically, LINC00519 acted as a competing endogenous RNA for microRNA-876-3p (miR-876-3p), which directly targets metastasis associated with colon cancer-1 (MACC1), in TSCC cells. LINC00519 upregulated the expression of MACC1 in TSCC cells by sequestering miR-876-3p. Rescue experiments further affirmed that miR-876-3p inhibition or MACC1 overexpression mitigated the inhibitory influences of LINC00519 depletion on cell proliferation, migration and invasion and neutralized the promoting actions of LINC00519 knockdown on cell apoptosis in TSCC.Conclusion: LINC00519 aggravated the oncogenicity of TSCC by regulating the miR-876-3p/MACC1 axis. Our findings suggest that the LINC00519/miR-876-3p/MACC1 pathway may be an underlying therapeutic target in TSCC.Keywords: competing endogenous RNA pathway, metastasis associated in colon cancer-1, tongue squamous cell carcinoma, miRNAs

Tongxin Liu,1– 4,* Quanquan Sun,1– 3,* Weifeng Qin,1– 4 Xiaozhong Chen,1– 4 Qiaoying Hu1– 4 1Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, People’s Republic of China; 2Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of China; 3Key Laboratory of Radiation Oncology in Zhejiang Province, Hangzhou, Zhejiang 310022, People’s Republic of China; 4Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Hangzhou, Zhejiang 310022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiaoying HuDepartment of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, People’s Republic of ChinaEmail huqy316@hotmail.comPurpose: Esthesioneuroblastoma (ENB) is a type of rare malignant neoplasm of the sinonasal cavity. Optimal treatment for ENB is still controversial. A retrospective study was conducted to identify the clinical outcome and optimal treatment for ENB in the era of intensity-modulated radiation therapy (IMRT).Patients and Methods: Between December 2006 and August 2018, 37 patients with ENB without distant metastasis who underwent neoadjuvant chemotherapy followed by chemoradiotherapy (C+RC) or surgery followed by radiotherapy or chemoradiotherapy (S+R/RC) were retrospectively reviewed at our center.Results: The median follow-up period was 63.7 months (range, 13.2– 111.5 months). Five-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were similar between treatment arms (P values > 0.05). With a multivariate analysis, a Karnofsky Performance Status (KPS) of ≤ 80 was a prognostic factor for poor five-year OS. A KPS of ≤ 80 and Kadish class C–D tumors were prognostic factors for poor PFS. A KPS of ≤ 80 was a prognostic factor for poor LRFS. When KPS was ≤ 80 and tumors were Kadish class C–D, T3– 4 and N1 were prognostic factors for poor DMFS. Subgroup analyses also demonstrated that the two treatment arms exhibited similar trends for OS, PFS, LRFS, and DMFS, excluding patients with N1 or Kadish class A–B tumors (P values > 0.05).Conclusion: In the era of IMRT, S+R/RC failed to improve the outcomes of patients with ENB. C+RC may be a feasible treatment option for patients with ENB.Keywords: olfactory neuroblastoma, neoadjuvant chemotherapy, precise radiotherapy

Fuqiang Liu,1– 4 Lei Gong,1– 4 Weidong Qin,5 Chen Cui,1– 4 Li Chen,1– 4 Mingxiang Zhang5 1Department of Endocrinology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases, Shandong University, Jinan 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine and Health, Jinan, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, People’s Republic of China; 5Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan Shandong 250012, People’s Republic of ChinaCorrespondence: Li ChenDepartment of Endocrinology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Road, Jinan, Shandong 250012, People’s Republic of China, Tel +86-531-8216-9255Fax +86-531-86169356Email chenli191125@126.comMingxiang ZhangKey Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, 107 Wen Hua Xi Road, Jinan, Shandong 250012, People’s Republic of China, Tel +86-531-8216-9255Fax +86-531-86169356Email zhangmingxiang2019@126.comAim: Glucagon-like peptide-1 (GLP1) is known to decrease glucagon release and may be beneficial for the reduction of elevated blood glucose. However, its role and mechanism of action in diabetes remain elusive. This study aimed to examine the function of GLP1 and analyze the mechanism of effect that GLP1exerts on inducible nitric oxide synthase (iNOS) in diabetic mice.Methods: A diabetes model was established in ApoE–/– mice fed a high-fat diet and treated with GLP1 and/or lentivirus-expressing PARP1. PARP1, iNOS, and inflammatory factors in islets were detected by Western blot and ELISA. Islet α cells and β cells and CD8+ T lymphocytes were detected by immunostaining. Islet-cell apoptosis was detected by TUNEL.Results: GLP1 inhibited the expression of PARP1 and iNOS in islets, alleviated decrease in β cells, and suppressed cell apoptosis induced by the high-fat diet. Moreover, GLP1 recovered the decline in insulin sensitivity and glucose tolerance in ApoE–/– mice fed the high-fat diet, and the effects of GLP1 were related to the inhibition of COX2 and NFκB expression.Conclusion: GLP1 significantly alleviated the decrease in β-cell numbers, suppressed β-cell apoptosis induced by the high-fat diet, inhibited the expression of iNOS, and alleviated inflammatory islet injury via inhibiting the COX2–NFκB pathway.Keywords: GLP1, islet function, PARP1

Hongbin Zhao,1 Junjie Tang,1 Dong Zhou,1 Yiping Weng,1 Wen Qin,1 Chun Liu,1 Songwei Lv,2 Wei Wang,3 Xiubo Zhao2,4 1Medical Research Centre, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, Changzhou 213164, People’s Republic of China; 2School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, People’s Republic of China; 3Medical School, Hexi University, Zhangye 730041, People’s Republic of China; 4Department of Chemical and Biological Engineering, University of Sheffield, Sheffield S1 3JD, UKCorrespondence: Hongbin Zhao; Xiubo Zhao Email zhao761032@163.com; xiubo.zhao@sheffield.ac.ukBackground: Electrospinning is a widely used technology that can produce scaffolds with high porosity and surface area for bone regeneration. However, the small pore sizes in electrospun scaffolds constrain cell growth and tissue-ingrowth. In this study, novel drug-loading core-shell scaffolds were fabricated via electrospinning and freeze drying to facilitate the repair of tibia bone defects in rabbit models.Materials and Methods: The collagen core scaffolds were freeze-dried containing icariin (ICA)-loaded chitosan microspheres. The shell scaffolds were electrospun using collagen, polycaprolactone and hydroxyapatite materials to form CPH composite scaffolds with the ones containing ICA microspheres named CPHI. The core-shell scaffolds were then cross-linked by genipin. The morphology, microstructure, physical and mechanical properties of the scaffolds were assessed. Rat marrow mesenchymal stem cells from the wistar rat were cultured with the scaffolds. The cell adhesion and proliferation were analysed. Adult rabbit models with tibial plateau defects were used to evaluate the performance of these scaffolds in repairing the bone defects over 4 to 12 weeks.Results: The results reveal that the novel drug-loading core-shell scaffolds were successfully fabricated, which showed good physical and chemical properties and appropriate mechanical properties. Furthermore, excellent cells attachment was observed on the CPHI scaffolds. The results from radiography, micro-computed tomography, histological and immunohistochemical analysis demonstrated that abundant new bones were formed on the CPHI scaffolds.Conclusion: These new core-shell composite scaffolds have great potential for bone tissue engineering applications and may lead to effective bone regeneration and repair.Keywords: icariin (ICA), electrospinning, polycaprolactone, collagen 1, hydroxyapatite, bone regeneration

Wei Qin, 1,* Xiao Wang, 1,* Jing Yang, 2 Wenli Hu 1 1Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 2Department of Hyperbaric Oxygen, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing YangDepartment of Hyperbaric Oxygen, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, People’s Republic of ChinaTel +86 1085232005Email jyangu@hotmail.comWenli HuDepartment of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, People’s Republic of ChinaTel +86 1085231376Email stroke2019@126.comAbstract: Anti-γ-aminobutyric acid B receptor (anti-GABABR) encephalitis is a rare type of autoimmune encephalitis (AE). Although it responds well to immunomodulating therapy and has favorable prognosis, anti-GABABR AE has often been misdiagnosed as infectious encephalitis. Herein, we present a case of a 59-year-old female with anti-GABABR AE associated with small cell lung cancer (SCLC) that was once misdiagnosed as infectious encephalitis. Our findings increase the awareness that patients presenting with a clinical trial of cognitive impairment, seizures and SCLC may harbor AE. Our case also highlights the importance of anti-SOX1 antibody in the detection of SCLC.Keywords: autoimmune encephalitis, anti-GABAB receptor, small cell lung cancer

Yicheng Li,1,2,* Wentao Xu,1,* Pu Chen,1,* Minjun Liao,1,3 Wanying Qin,1 Weijia Liao,1 Zhaoquan Huang1,4 1Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, People’s Republic of China; 2Second Clinical Medical College, Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China; 3Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China; 4Department of Pathology, Guilin Medical University, Guilin 541001, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weijia LiaoLaboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, People’s Republic of ChinaEmail liaoweijia288@163.comZhaoquan HuangDepartment of Pathology, Guilin Medical University, Guilin 541001, Guangxi, People’s Republic of ChinaEmail 191990449@qq.comBackground: The purpose of this retrospective study was to investigate the relationship between serum iron levels and the prognosis and risk of recurrence in patients with hepatocellular carcinoma (HCC).Methods: A total of 253 HCC patients who underwent radical resection were involved in this study.Results: According to the receiver operating characteristic (ROC) curve, the optimal cut-off value for preoperative serum iron in the assessment of HCC postoperative prognosis was 94 ug/dL. The overall survival (OS) of patients in the high iron group was significantly better than that in the low iron group (p < 0.001). The recurrence rate of patients in the low iron group was higher than that in the high iron group (p = 0.011). Correlation analysis showed that preoperative serum iron level was correlated with tumor size >5 cm (χ2 = 11.590, p < 0.001), recurrence (χ2 = 5.714, p = 0.017) and microvascular invasion (χ2 = 5.087, p = 0.024). In addition, univariate analysis showed that OS and disease-free survival (DFS) of HCC patients with high iron level were better than those with low iron level. Furthermore, multivariate COX proportional hazards regression analysis showed that serum iron ≤94 μg/dL, tumor size >5 cm, and microvascular invasion were independent predictors for shorter OS and DFS in HCC patients after operation, while recurrence was for shorter OS.Conclusion: Patients with low preoperative serum iron level had worse postoperative survival and higher recurrence rate in HCC. Preoperative serum iron is an independent predictor of HCC patients. For HCC patients with low iron levels, prognosis of patients may be improved if appropriate iron is supplemented.Keywords: HCC, serum iron, prognosis, recurrence, survival rate

Wangjun Qin, 1 Yifan Li, 2 Botao Liu, 2 Ying Liu, 1 Yi Zhang, 2 Xianglin Zhang, 1 Pengmei Li, 1 Bifa Fan 2 1Department of Pharmacy, China–Japan Friendship Hospital, Beijing, People’s Republic of China; 2Department of Pain Management, China–Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Pengmei Li; Bifa Fan 2 Yinghua Dongjie, Hepingli, Beijing 100029, People’s Republic of ChinaTel/Fax +86 10 8420 5330; +86 10 84205959Email article2019@163.com; fyinsuo@yeah.netPurpose: Intrathecal morphine infusion therapy via a percutaneous port (IMITPP) has been used widely for its relatively low initial cost. However, there is scarce knowledge about IMITPP. In this study, we sought to evaluate efficacy, complications, and the interval required to achieve the cost equivalence of IMITPP in patients with refractory cancer pain in China.Patients and Methods: A retrospective chart review was conducted on cancer patients who had received IMITPP at our hospital between April 2017 and April 2019. Data from the numeric pain rating scale and Karnofsky performance scores, and complications and costs related to IMITPP were collected from medical records. Daily analgesic costs before and after IMITPP were calculated based on the doses of opioids on admission and at discharge, respectively. The doses of systemic opioids before IMITPP were stratified into very high doses [VHD, oral morphine equivalent dose (OMED) > 599 mg/day], high doses (HD, 300 mg/day ≤ OMED ≤ 599 mg/day), and regular doses (RD, OMED < 300 mg/day).Results: Intrathecal morphine infusion therapy via a percutaneous port provided significant pain relief, but impaired activities of daily living in patients with refractory cancer pain. The commonly reported complications included nausea/vomiting and urinary retention, most of which were managed with symptomatic therapies. The median interval required to achieve cost equivalence was 11.44 months. The median intervals of VHD group and HD group were significantly shorter than that of RD group.Conclusion: Intrathecal morphine infusion therapy via a percutaneous port provided effective cancer pain management without causing serious complications. Patients with higher doses of systemic opioids would economically benefit from IMITPP in a shorter time.Keywords: intrathecal, morphine, port catheter, cost-benefit analysis, cancer pain

Danyang Zhao,1,* Wenban Qin,2,* Chuanxiang Zhao,3 Jianxiong Long,4 Mujun Li1 1Department of Reproductive Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 2Department of Oncology, Chongzuo People’s Hospital, Nanning 530021, Guangxi Province, People’s Republic of China; 3Department of General Surgery, The Second People’s Hospital of Shenzhen, Nanning 530021, Guangxi Province, People’s Republic of China; 4School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianxiong LongSchool of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530021, Guangxi Province, People’s Republic of ChinaEmail longjx12345@163.comMujun LiDepartment of Reproductive Center, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi 530021, People’s Republic of ChinaEmail sciencecid@126.comPurpose: Recent studies indicate that CXC chemokine receptor type 7 (CXCR7) is associated with tumorigenesis, progression, and metastasis of various cancers, but its roles and molecular mechanisms of action in cervical squamous cell carcinoma (CSCC) remain unclear. Our purpose was to explore the expression patterns of CXCR7 and epidermal growth factor receptor (EGFR) in CSCC and to identify possible correlations with clinical characteristics. We also tested whether CXCR7 can be a screening index for treatment options for CSCC stages IB1 and IIA1.Methods: Expression of CXCR7 and EGFR in tumors from 165 patients with CSCC was evaluated by immunohistochemistry and compared with the clinical data including survival.Results: Patients at CSCC stages IB1 and IIA1 received different treatment options, including radical hysterectomy, pelvic lymph node dissection, and para-aortic lymph node sampling (RH group, 67 patients) or pelvic external-beam radiation therapy with brachytherapy (EBRT group, 34 patients). Disease-free survival (DFS) and overall survival (OS) were compared between two groups at different CXCR7 expression levels. Immunohistochemical staining showed that CXCR7, EGFR, phospho-ERK, and phospho-AKT amounts increased from normal cervical epithelia and cervical intraepithelial neoplasia to CSCC, and CXCR7 was associated with the disease stage, lymph node metastasis, tumor size ≥40 mm, and EGFR expression. Kaplan–Meier analysis revealed that CXCR7 and EGFR expression was associated with shorter DFS and OS. Multivariate analysis suggested that CXCR7 was independently associated with DFS and OS. Prevalence of recurrence and distant metastasis was significantly lower in the EBRT group than in the RH group during CXCR7 expression. Besides, CXCR7 knockdown significantly decreased the proliferation and invasion of CSCC cells.Conclusion: CXCR7 is coexpressed with EGFR, which may be involved in ERK or AKT pathway activation. CXCR7 may be a screening index for treatment options at CSCC stages IB1 and IIA1.Keywords: CXC chemokine receptor type 7, cervical cancer, cancer treatment protocol

Shanshan Ma,* Tingting Zhang,* Li Jiang,* Wen Qin, Keyu Lu, Yong Zhang, Rensheng WangDepartment of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China*These authors contributed equally to this workObjective: This study aimed to investigate the impact of bladder volume on treatment planning and clinical outcomes of radiotherapy for patients with cervical cancer.Materials and methods: One hundred and sixty-six patients with locally advanced cervical cancer were selected in this retrospective study. The patients were divided into four groups according to their average bladder volume during radiotherapy (external beam radiation therapy and intracavitary brachytherapy): group A: V200 mL. The bladder volume and the cumulative dose to planning target (D90), bladder (D2cc), rectum (D2cc), and sigmoid (D2cc) were calculated using the treatment planning system. Treatment outcomes including late adverse events (the maximum grade of radiation-induced proctitis and cystitis), the objective response rate of tumor and lymph node, overall survival (OS), and progression-free survival (PFS) were collected. Additionally, the correlation between bladder volume and the irradiated dose of organs at risk and treatment outcomes was analyzed.Results: The median follow-up time was 28 months. The D90 and D2cc of the rectum in group A were the highest (P

Junliang Yuan, Zejin Jia, Wei Qin, Wenli HuDepartment of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, People’s Republic of ChinaAbstract: Neuromyelitis optica spectrum disorder (NMOSD) is a group of inflammatory disease involving the central nervous system. Although most commonly an idiopathic autoimmune condition, NMOSD may also occur as a paraneoplastic syndrome in rare instances. Herein, we report a rare case of a 60-year-old woman with paraneoplastic NMOSD associated with breast cancer. Our findings increase the recognition that NMOSD may present as a paraneoplastic neurological syndrome associated with breast cancer. Our case also raises awareness of an important complication of neurological complications of breast cancer. Early diagnosis of paraneoplastic NMOSD may be imperative for a better prognosis.Keywords: neuromyelitis optica spectrum disorder, paraneoplastic syndrome, breast cancer

Yue Li,1 Man Li,2 Lei Yang,1 Wei Qin,1 Shuna Yang,1 Junliang Yuan,1 Tao Jiang,2 Wenli Hu11Department of Neurology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaPurpose: Enlarged perivascular spaces (EPVS) have been widely considered as a feature of cerebral small vessel disease (cSVD) but the pathogenesis of EPVS remains unclear. Compromised blood–brain barrier (BBB) integrity may play a role since previous studies have shown that BBB breakdown is a critical contributor to the pathogenesis of other cSVD markers. This study aimed to investigate the association of EPVS in the centrum semiovale (CSO) and basal ganglia (BG) with BBB permeability.Patients and methods: Consecutive participants free of symptomatic stroke history presented for physical examination were enrolled in this cross-sectional study. CSO- and BG-EPVS on T2-weighted (T2-W) magnetic resonance imaging (MRI) were rated using a five-point validated scale. Dynamic contrast-enhanced (DCE)-MRI and Patlak pharmacokinetic model were applied to quantify BBB permeability in the CSO and BG.Results: A total of 109 participants aged 49–90 years (mean age of 69.85 years) were enrolled. The proportions of participants presenting high-grade (>10) EPVS in the CSO and BG were 50.5% and 44.0%, respectively. After adjustments for potential confounders by logistic regression, leakage rate and fractional blood plasma volume were correlated with the severity of BG-EPVS (OR: 5.33; 95%CI: 1.95–14.60 and OR: 0.93; 95%CI: 0.87–0.99).Conclusion: Our study demonstrates that BG-EPVS are associated with compromised BBB integrity, supporting the hypothesis that the BBB dysfunction may be involved in the pathogenesis of BG-EPVS. EPVS in the CSO and BG may have distinct pathophysiology.Keywords: enlarged perivascular spaces, cerebral small vessel disease, blood–brain barrier, dynamic contrast-enhanced, DCE, magnetic resonance imaging, MRI

Liu D, Zhao J, Wang H, Li H, Li Y, Qin W. Onco Targets Ther. 2020;13:11975–11990. The Editor and Publisher of OncoTargets and Therapy wish to publish an Expression of Concern for the published article. Following publication, concerns were raised about the scientific integrity of the articles content. We reached out to the authors requesting they supply information that would confirm the integrity of the data. However, the authors did not provide the requested files and could not satisfy our requirements to confirm the authenticity of some types of data. In addition, there were unexplained similarities between some of the figures presented in this article, and figures presented in articles by different authors groups. As yet, the authors have not provided a satisfactory explanation for this. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern. Read the original article

Xiaoyun Hu,1 Wenyan Qin,1 Shanqiong Li,1 Miao He,1 Yilin Wang,1 Shu Guan,2 Haishan Zhao,1 Weifan Yao,1 Minjie Wei,1 Mingyan Liu,1 Huizhe Wu1 1Department of Pharmacology, School of Pharmacy, Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang 110122, China; 2Department of Breast Surgery, First Hospital of China Medical University, Shenyang 110001, China Objective: Multiple factors are involved in oxaliplatin-resistant process in colorectal cancer (CRC) patients including decreased drug accumulation and enhanced capacity to repair and tolerate DNA damage. In the present study, we aimed to assess the impact of six single-nucleotide polymorphisms (SNPs) in DNA repair genes and ABCG2 gene on prognosis in advanced CRC patients treated with oxaliplatin-based chemotherapy. Methods: In this study, 580 advanced CRC patients were recruited. Six SNPs of DNA repair genes (XPA rs10817938, XPA rs2808668, XPC rs2607775, and WRN rs1346044) and ABCG2 gene (rs2231142 and rs2622621) were genotyped by using the TaqMan assay. Results: Regarding interaction with environmental factors, ABCG2 rs2231142 and the first-degree family history of cancer and XPC rs2607775 or ABCG2 rs2622621 and lymph node metastases status demonstrated significant interactions. Of these six SNPs, XPA rs10817938 CT/TT genotypes retained its significant association with longer overall survival (OS) (P=0.008) in CRC patients receiving oxaliplatin-based chemotherapy (n=580). Furthermore, a significantly better impact on the disease-free survival (DFS) (P=0.001) and OS (P

Tongxin Liu,1–3,* Quanquan Sun,1,2,* Jing Chen,1–3 Fangzheng Wang,1–3 Bin Li,1–3 Weifeng Qin,1–3 Zhimin Ye,1–3 Fujun Hu1–3 1Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China; 2Key Laboratory of Radiation Oncology in Zhejiang Province, Hangzhou, China; 3Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Hangzhou, China *These authors contributed equally to this work Purpose: To compare the efficacy and safety of neoadjuvant chemotherapy (NACT) with gemcitabine (GEM) vs docetaxel plus cisplatin (CDDP) in locoregionally advanced nasopharyngeal carcinoma (NPC).Methods: A total of 222 patients with locoregionally advanced NPC between February 2012 and May 2014 in our hospital who received NACT with GEM or docetaxel plus CDDP combined with concurrent chemoradiotherapy (CCRT) were retrospectively analyzed. Fifty-two patients treated with GEM plus CDDP (GP) combined with CCRT were matched with 52 patients who received docetaxel plus CDDP (TP) combined with CCRT.Results: With a median follow-up time of 60 months (range, 14–72 months), the 5-year overall survival, progression-free survival (PFS), local relapse-free survival and distant metastasis-free survival (DMFS) rates were 78.8%, 66.0%, 81.0% and 75.9%, respectively, in the GP group and 79.4%, 60.5%, 79.6% and 73.6%, respectively, in the TP group. No statistically significant survival differences were found between the two groups. In multivariate analysis, T3–4 and N2–3 were prognostic factors for poor 5-year PFS and DMFS (all P-values 0.05).Conclusion: NACT with GP or TP regimen achieved comparable clinical outcome with acceptable toxicities. Both regimens might be a treatment option for patients with locoregionally advanced NPC. Keywords: nasopharyngeal carcinoma, IMRT, neoadjuvant chemotherapy, concurrent chemoradiotherapy

Shuna Yang,* Junliang Yuan,* Wei Qin, Lei Yang, Huimin Fan, Yue Li, Wenli Hu Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China *These authors contributed equally to this work Background: Lacunae, brain atrophy, white matter hyperintensity, enlarged perivascular space and microbleed are magnetic resonance imaging (MRI) markers of cerebral small-vessel disease (cSVD). Studies have reported that higher blood pressure variability (BPV) predicted cardiovascular risk in hypertensive patients; however, the association between BPV and the total MRI burden of cSVD has not been investigated. In this study, we aimed to explore this relationship between BPV and cSVD MRI burden. Methods: We prospectively recruited patients who attended our hospital for annual physical examination. Twenty-four-hour ambulatory BP monitoring was performed using an automated system. BPV was quantified by SD, weighted SD, and coefficient of variation. One point was awarded for the presence of each marker, producing a score between 0 and 5. Spearman correlation and ordinal logistic regression analyses were used to test the relationship between BPV and total cSVD MRI burden. Results: A total of 251 subjects with an average age of 68 years were enrolled in this study, and 52.6% were male; 163 (64.94%) had one or more markers of cSVD. Correlation analysis indicated that higher systolic BP (SBP) levels and BPV metrics of SBP were positively related to higher cSVD burden. Ordinal logistic regression analyses demonstrated that higher SBP levels and SBP variability were independent risk factors for cSVD. There were no significant differences in 24-hour, day and night diastolic BP levels or BPV metrics of diastolic BP among the five subgroups. Conclusion: Twenty-four-hour, day and night SBP levels and SBP variability were positively related to cSVD burden. Higher SBP levels and SBP variability were independent risk factors for cSVD. Keywords: cerebral small-vessel diseases, blood pressure variability, ambulatory blood pressure monitoring, magnetic resonance-imaging burden

Tingdong Yu, Xiangkun Wang, Guangzhi Zhu, Chuangye Han, Hao Su, Xiwen Liao, Chengkun Yang, Wei Qin, Ketuan Huang, Tao Peng Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China Objective: The activities of four cytochrome P3A (CYP3A) subfamily members (CYP3A4, CYP3A5, CYP3A7, and CYP3A43) are well documented in drug metabolism. However, the association between CYP3A subfamily members and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic value of CYP3A subfamily mRNA expression levels with HCC prognosis. Materials and methods: Data from a total of 360 HCC patients were retrieved from The Cancer Genome Atlas database, and data from 231 HCC patients were retrieved from the Gene Expression Omnibus database. Kaplan–Meier analysis and Cox regression models were utilized to determine median survival, overall survival, and recurrence-free survival. Hazard ratios and 95% CI were calculated. Results: Low expression of CYP3A4, CYP3A5, and CYP3A43 in the tumor tissue was associated with short median survival (crude p=0.004, 0.001, and 0.001; adjusted p=0.022, 0.005, and 0.013, respectively). Joint-effects combination analysis of CYP3A4, CYP3A5/CYP3A4, CYP3A43/CYP3A5, and CYP3A43 revealed that high expression groups of two genes (group C, group c, group 3) were associated with a reduced risk of death, as compared to low expression of two genes (group A, group a, group 1), and the adjusted p values were 0.001, 0.004, and 0.001, respectively. Joint-effects analysis of CYP3A4, CYP3A5, and CYP3A43 showed that groups III and IV had a reduced risk of death, as compared to group I (adjusted p=0.024 and 0.002, respectively). Conclusion: CYP3A4, CYP3A5, and CYP3A43 mRNA expression levels are potential prognostic markers of HCC. Keywords: mRNA expression, CYP3A subfamily, hepatocellular carcinoma, prognosis, biomarker

Xiwen Liao,1,* Long Yu,1,* Xiaoguang Liu,1,2 Chuangye Han,1 Tingdong Yu,1 Wei Qin,1 Chengkun Yang,1 Guangzhi Zhu,1 Hao Su,1 Tao Peng1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Background: The aim of this investigation was to identify candidate single nucleotide polymorphisms (SNPs) and molecular pathways associated with tumor protein p53 (TP53) expression status in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), clarify their potential mechanisms, and generate SNP-to-gene to pathway hypothesis. Materials and methods: Identify candidate Causal SNPs and Pathways (ICSNPathway) was used to perform pathway analysis based on the results of our previous genome-wide association study of TP53 expression status in 387 HBV-related HCC patients. Results: Through the ICSNPathway analysis, we identified 18 candidate SNPs and 10 candidate pathways that are associated with TP53 expression status in HBV-related HCC. The strongest mechanism involved the modulation of major histocompatibility complex, class II, DP beta 1 (human leukocyte antigen [HLA]-DPB1-rs1042153), major histocompatibility complex, class II, DQ beta 1 (HLA-DQB1-rs1130399, HLA-DQB1-rs1049056, HLA-DQB1-rs1049059, and HLA-DQB1-rs1049060), and major histocompatibility complex, class II, DR beta 1 (HLA-DRB1-rs35445101). SNPs consequently affected regulatory roles in all the candidate pathways except hematopoietic cell lineage pathways. Association analysis using the GSE14520 data set, Gene Multiple Association Network Integration Algorithm, and Search Tool for the Retrieval of Interacting Genes/Proteins suggests that all genes of the candidate SNPs were associated with TP53. Survival analysis showed that the collagen type VI alpha 3 chain (COL6A3) rs111231885 and COL6A3-rs113155945 and COL6A3 block 4 CC haplotypes with TP53 negative status may have protective effects in HBV-related HCC patients after hepatectomy. Conclusion: Our pathway analysis identified 18 candidate SNPs and 10 candidate pathways that were associated with TP53 expression status in HBV-related HCC. Among these candidate SNPs, the genetic variation of COL6A3 may be a potential prognostic biomarker of HBV-related HCC. Keywords: TP53, hepatocellular carcinoma, hepatitis B virus, genome-wide association study, pathway analysis

Xinping Ye,* Xiangkun Wang,* Liming Shang, Guangzhi Zhu, Hao Su, Chuangye Han, Wei Qin, Guanghui Li, Tao Peng Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China *These authors contributed equally to this work Objective: Acetaldehyde dehydrogenase 2 (ALDH2) and cytochrome P450 2E1 (CYP2E1) have been associated with hepatocellular carcinoma (HCC) susceptibility and prognosis. The polymorphisms ALDH2 rs671 and CYP2E1 rs2031920 are reportedly correlated with the prevalence of HCC in other countries. The aim of this study was to investigate associations between ALDH2 and CYP2E1, and HCC susceptibility in a population of Guangxi, southern China, an area with a high incidence of HCC.Patients and methods: The study cohort included 300 HCC cases, 292 healthy controls for HCC susceptibility analysis, and another 20 HCC cases and 10 healthy controls for ascertainment. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method.Results: The study results demonstrated that mutant genotypes of ALDH2 (G/A and A/A) led to significant differences in HCC susceptibility, as compared with the wild genotype (G/G) with the same C1/C1 genotype in non-drinking individuals (adjusted P=0.010, OR=0.20, 95% CI=0.06–0.68). The mutant genotypes of CYP2E1 (C1/C2 and C2/C2) brought about significant differences in HCC susceptibility, as compared with the wild genotype (C1/C1) and the same G/G genotype (adjusted P=0.025, OR=0.42, 95% CI=0.20–0.90). Drinking plays a role in HCC susceptibility in the same G/G genotype individuals (adjusted P=0.004, OR=0.32, 95% CI=0.15–0.69), but had no impact when combined with CYP2E1 for analysis (all P>0.05).Conclusion: These results suggest that the mutant genotypes of ALDH2 and CYP2E1 may be protective factors for HCC susceptibility in Guangxi province, China. Keywords: hepatocellular carcinoma susceptibility, genetic polymorphism, ALDH2, CYP2E1, Chinese population

Xiaoguang Liu,* Chuangye Han,* Xiwen Liao, Long Yu, Guangzhi Zhu, Hao Su, Wei Qin, Sicong Lu, Xinping Ye, Tao Peng Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China *These authors contributed equally to this work Background: The upregulated expression of versican (VCAN) promotes the proliferation, invasion, and metastasis of various types of human cancer cells, including hepatocellular carcinoma (HCC) cells. Patients and methods: In this study, genetic variants in the exon region of VCAN were genotyped by DNA sequencing. Prognostic values of VCAN exon single nucleotide polymorphisms (SNPs) were assessed by Kaplan–Meier with the log-rank test, and uni- and multivariate Cox proportional hazard regression model. Results: A total of 111 patients with resected hepatitis B virus-associated early-stage HCC were collected for genotyping VCAN exon SNPs using Sanger DNA sequencing. Haplotype analysis was performed using Haploview 4.2. Survival data were analyzed using Kaplan–Meier curves and Cox proportional hazards regression analyses. The rs2652098, rs309559, rs188703, rs160278, and rs160277 SNPs were significantly associated with overall patient survival (p

Lingmin Jin,1 Xuejuan Yang,1 Peng Liu,1 Jinbo Sun,1 Fei Chen,1 Ziliang Xu,1 Wei Qin,1 Jie Tian2 1Sleep and Neuroimage Group, School of Life Science and Technology, Xidian University, Xi’an, Shaanxi, 2Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China Purpose: This study aimed to investigate the regional spontaneous brain activity changes in primary dysmenorrhea (PD) patients in different phases of the menstrual cycle by regional homogeneity (ReHo) analysis. Patients and methods: Thirty-three PD patients and 32 healthy controls (HCs) separately received resting-state functional magnetic resonance imaging during menstrual phase and follicular phase (non-menstrual phase). Cox retrospective symptom scale (RSS), Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were applied to assess related symptoms and emotions. Results: There was no significant difference between the two groups in demographic data. The PD patients obtained higher RSS score, SAS score and SDS score than HCs. Compared with HCs, the ReHo values of the PD patients were increased in left midbrain and hippocampus, right posterior cingulate cortex (PCC), insula and middle temporal cortex (MTC) and decreased in left dorsolateral prefrontal cortex and right medial prefrontal cortex (mPFC) in menstrual phase. In non-menstrual phase, enhanced ReHo values were found in bilateral S1 and precuneus, left S2 and MTC, and reduced ReHo values were observed in left mPFC and orbital frontal cortex. RSS score positively correlated with ReHo values of midbrain and negatively correlated with mPFC and PCC. Conclusion: Our results suggested that PD is accompanied by dynamic regional spontaneous activity changes across the menstrual cycle, and the altered regions were involved in descending pain modulation, default mode network and sensory modulation. These abnormal activations might contribute to maintain the menstrual pain. Keywords: primary dysmenorrhea, resting-state functional magnetic resonance imaging, regional homogeneity, spontaneous brain activity, descending pain modulation

Shuping Zhao,1 Jihong Deng,2 Yan Wang,3 Shiliang Bi,4 Xiaoye Wang,5 Wen Qin,6 Zirong Huang,7 Li Li,8 Xin Mi,9 Liping Han,10 Qing Chang,11 Jian Li12 1The Affiliated Hospital of the Medical College Qingdao University, Qingdao, 2Kunming Maternal and Child Health Hospital, Kunming, 3Hubei Maternity and Child Health Hospital, Wuhan, 4West China Second University Hospital, Sichuan University, Chengdu, 5Peking University Third Hospital, Beijing, 6Changzhou Maternity and Child Health Hospital, Affiliated to Nanjing Medical University, Jiangsu, 7The Affiliated Women’s Hospital of Fudan University, Shanghai, 8Guangzhou Women and Children’s Medical Center, Guangzhou, 9Maternity and Child Health Care Hospital, Shunyi District, Beijing, 10The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan, 11Southwest Hospital, Chongqing City, Chongqing, 12Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, People’s Republic of China Background: Although surveys conducted in Western countries have shown that the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena®) is well accepted by European women, its acceptance by Chinese women is not yet clearly known. The purpose of this study was to analyze the experiences and levels of satisfaction with Mirena among Chinese women living in 12 different cities. Methods: In total, 1,021 women who attended 21 medical centers for insertion of Mirena were invited to complete a questionnaire regarding their contraceptive decision at baseline (preinsertion), and two further questionnaires on their experience and satisfaction with Mirena at 3–6 months and 1 year after insertion. Results: At baseline, 36% of women self-reported heavy or very heavy menstrual bleeding, while 41% reported normal bleeding. The majority of women (98%) were satisfied with the preinsertion counseling, during which contraceptive reliability was identified as the most important reason for considering Mirena. Continuation rates for Mirena were 99% at 3–6 months and 93% at 12 months after insertion, and most women (92% and 93%, respectively) had less bleeding at these times. The percentage of women who rated Mirena as better than their previous contraceptive method was 63%. Overall, around 90% of respondents were very satisfied or rather satisfied with Mirena, and 64% stated that they would recommend it to their friends. Conclusion: These data suggest that continuation and satisfaction rates with Mirena were very high, and that the device is well accepted by Chinese women. Keywords: levonorgestrel-releasing intrauterine system, intrauterine device, contraception, user satisfaction

Bin Yang,1 Haolei Cai,1 Wenjie Qin,1 Bo Zhang,1 Chuanxin Zhai,2 Biao Jiang,3 Yulian Wu1 1Department of Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2State Key Lab of Silicon Materials and Department of Materials Science and Engineering, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Radiology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Abstract: Based on their versatile, biocompatible properties, superparamagnetic iron oxide (SPIO) or ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are utilized for detecting and tracing cells or tumors in vivo. Here, we developed an innoxious and concise synthesis approach for a novel B-cell lymphoma (Bcl)-2 monoclonal antibody-functionalized USPIO nanoparticle coated with an amphiphilic polymer (carboxylated polyethylene glycol monooleyl ether [OE-PEG-COOH]). These nanoparticles can be effectively internalized by beta cells and label primary islet cells, at relatively low iron concentration. The biocompatibility and cytotoxicity of these products were investigated by comparison with the commercial USPIO product, FeraSpin™ S. We also assessed the safe dosage range of the product. Although some cases showed a hypointensity change at the site of transplant, a strong magnetic resonance imaging (MRI) was detectable by a clinical MRI scanner, at field strength of 3.0 Tesla, in vivo, and the iron deposition/attached in islets was confirmed by Prussian blue and immunohistochemistry staining. It is noteworthy that based on our synthesis approach, in future, we could exchange the Bcl-2 with other probes that would be more specific for the targeted cells and that would have better labeling specificity in vivo. The combined results point to the promising potential of the novel Bcl-2-functionalized PEG-USPIO as a molecular imaging agent for in vivo monitoring of islet cells or other cells. Keywords: USPIO, MRI, beta cells, nanoparticle functionalization, islet transplantation, cell tracing