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Qizhi Diao,1 Yongpei Long,2 Fangyu Yang,3 Cuihui Nong,1 Huamiao Tang,1 Xiangmin Zhou,1 Guoqiang Zhu,4 Qiang Ding5 1Hainan Branch, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Sanya, People’s Republic of China; 2Department of Laboratory Medicine, The People’s Hospital of Jianyang City, Sichuan, People’s Republic of China; 3Department of Clinical Laboratory Medicine, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Chong Qing King Med Center for Clinical Laboratory Co., Ltd, Chongqing, People’s Republic of China; 5The Sixth People’s Hospital of Chongqing, Chongqing, People’s Republic of ChinaCorrespondence: Guoqiang Zhu; Qiang Ding, Email Guoqiangzhu01@163.com; yung10167086@126.comBackground and Objective: Inadequate risk assessment and a lack of risk monitoring are common deficiencies in clinical laboratory, and are also the main causes of biosafety incidents. Therefore, we summarized the experience of implementing adequate risk assessment and maintaining risk monitoring, and established a procedure for continuously improving biosafety management.Methods: Learning from our laboratory’s experience in implementing risk assessment, risk response, and risk monitoring before and during the COVID-19 epidemic, we summarized the procedures for fully identifying risks, accurately evaluating risks, maintaining risk monitoring, establishing and regular reviewing safety indicators. On this basis, we established a system for continuously improving biosafety management through risk monitoring and reviewing safety indicator.Results: We identified a total of 30 unacceptable risks prior to the COVID-19 pandemic, and developed and implemented appropriate risk control measures. After risk control, residual risks were acceptable, and no biosafety incidents have occurred. During the COVID-19 pandemic, after multiple risk monitoring, we identified ten new risks, three ineffective risk control measures, and multiple control measures for excessive protection. Then, we timely adjusted risk control measures to avoid laboratory personnel infection and excessive protection. Meanwhile, We established eight safety indicators and identified two improvement opportunities through regular reviews.Conclusion: Adequate risk identification and accurate risk assessment are particularly important for effectively controlling biosafety risks. Biosafety management should be continuously improved to deal with ineffective and excessive protection caused by various changes in experimental activities. Continuous improvement of biosafety management can be achieved through risk monitoring, regular review of safety indicators, and management reviews. This study will help laboratory managers to fully and accurately assess risks, as well as update risks and their control measures through risk monitoring, and the continuous improvement procedure established in the study has certain reference value for laboratories to effectively respond to emerging infectious diseases and avoid excessive protection.Keywords: risk assessment, risk monitoring, management review, continuous improvement, biosafety management

Ne Yan,1,2 Ying Long,2 Huiling Yuan,3 Xiaofei Zhou,3,4 Bin Xie,2 Ying Wang1,3 1Department of Psychiatry, Xi’an Honghui Hospital, Xi’an, Shaanxi, 710054, People’s Republic of China; 2Department of Psychology, Xi’an Physical Education University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Psychiatry, Xi’an International Medical Center Hospital, the Affiliated Hospital of Northwest University, Xi’an, Shaanxi, People’s Republic of China; 4The College of Life Sciences and Medicine, Northwest University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Ying Wang, Xi’an Honghui Hospital, 666 Jianyuan 2nd Road, Economic and Technological Development Zone, Xi’an City, Shaanxi Province, 710000, People’s Republic of China, Email fgx995@163.comBackground: The 18– 24 age group has a much higher rate of depression risk than other age groups, and this age group has the highest proportion among users of mobile social media. The relationship between the use of mobile social media and depressive mood is inconsistent and the mechanism of action is controversial.Purpose: This study explored the relationship among the intensity of social media use, upward social comparison, cognitive overload and depressive mood.Methods: In this research, we used the Brief Self-rating Depression Scale (PHQ-9), the Social Media Usage Intensity Questionnaire, the Social Comparison Scale on Social Networking Sites and the Social Networking Site Cognitive Overload Scale to investigate the depressive mood and mobile social media use of 568 college students.Results: The intensity of mobile social media use, social networking site upward social comparison, and social networking site cognitive overload are all positively correlated with depressive mood. The intensity of mobile social media use has a positive predictive effect on depressive mood, with upward social comparison and cognitive overload acting as independent mediators in the relationship between mobile social media use intensity and depressive symptoms, as well as exhibiting a chained mediating effect of upward social comparison-cognitive overload.Conclusion: The upward social comparison and cognitive load that occur during the use of mobile social media are important predictive factors for the occurrence of depressive mood. This study is a supplement to the mechanism of the relationship between mobile social media use and depression, providing more evidence-based evidence and intervention directions for university teachers, mobile social media developers, and psychologists.Keywords: mobile social media, upward social comparison, cognitive overload, depressive mood, chain mediation

Chunxia Jiang,1– 4,&ast; Xiumei Ma,1– 4,&ast; Jiao Chen,2– 5,&ast; Yan Zeng,1– 4 Man Guo,2– 4 Xiaozhen Tan,2– 4 Yuping Wang,1,6 Peng Wang,1 Pijun Yan,2– 4 Yi Lei,1– 4 Yang Long,2– 4 Betty Yuen Kwan Law,1 Yong Xu1– 4 1Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Endocrinology, The Third’s Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, People’s Republic of China; 6Department of Breast, Thyroid and Vascular Surgery, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Betty Yuen Kwan Law, Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, 999078, People’s Republic of China, Email yklaw@must.edu.mo Yong Xu, Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Email xywyll@swmu.edu.cnPurpose: To establish nomograms integrating serum lactate levels and traditional risk factors for predicting diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients.Patients and methods: A total of 570 T2DM patients and 100 healthy subjects were enrolled. T2DM patients were categorized into normal and high lactate groups. Univariate and multivariate logistic regression analyses were employed to identify independent predictors for DKD. Then, nomograms for predicting DKD were established, and the model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA).Results: T2DM patients exhibited higher lactate levels compared to those in healthy subjects. Glucose, platelet, uric acid, creatinine, and hypertension were independent factors for DKD in T2DM patients with normal lactate levels, while diabetes duration, creatinine, total cholesterol, and hypertension were indicators in high lactate levels group (P< 0.05). The AUC values were 0.834 (95% CI, 0.776 to 0.891) and 0.741 (95% CI, 0.688 to 0.795) for nomograms in both normal lactate and high lactate groups, respectively. The calibration curve demonstrated excellent agreement of fit. Furthermore, the DCA revealed that the threshold probability and highest Net Yield were 17– 99% and 0.36, and 24– 99% and 0.24 for the models in normal lactate and high lactate groups, respectively.Conclusion: The serum lactate level-based nomogram models, combined with traditional risk factors, offer an effective tool for predicting DKD probability in T2DM patients. This approach holds promise for early risk assessment and tailored intervention strategies.Keywords: serum lactate, diabetic kidney disease, nomograms, prediction model, risk factors

Maolu Tian,1– 3 Zuping Qian,4 Yanjun Long,1,2 Fangfang Yu,1 Jing Yuan,1 Yan Zha1,2 1Department of Nephrology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 2NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 3Medical College, Guizhou University, Guiyang, Guizhou, People’s Republic of China; 4Clinical Medical College, Zunyi Medical University, Zunyi, Guizhou, People’s Republic of ChinaCorrespondence: Yan Zha, Department of Nephrology, Guizhou Provincial People’s Hospital, 83 Zhongshan Road, Nanming District, Guiyang, Guizhou, 550002, People’s Republic of China, Email zhayansy@163.comObjective: Depression is a common psychiatric disorder and related to poor outcomes in patients undergoing maintenance hemodialysis (MHD). Previous studies have reported some associations between sarcopenia and depressive symptoms. Recently, intracellular water (ICW) and total body water (TBW) have been found to reflect muscle function and muscle mass. ICW/TBW ratio is a marker of sarcopenia that is simple to assess. However, the relationship between ICW/TBW ratio and depression has not been explored in MHD patients.Methods: In our cross-sectional and multi-center study, 3300 adult MHD patients were included from June 1, 2021, to August 30, 2021. Depressive symptoms were evaluated using the Beck Depression Inventory-II (BDI-II). TBW and ICW were measured by Body Composition Monitor (BCM). Multivariable logistic regression, stratified analyses, and interactive analyses were conducted to assess the relationship between ICW/TBW ratio and depression.Results: About 16.5% of the 3300 MHD patients were found to have depressive symptoms. The prevalence of depression increased with decreasing quartiles of ICW/TBW ratios, and decreased ICW/TBW ratio was independently associated with depression after adjusting for potential confounders. Patients in Quartile 1 of ICW/TBW ratios were more likely to have depressive symptoms (odds ratio 1.55, 95% confidence interval 1.07– 2.22; p=0.002) than those in Quartile 4. History of diabetes and education status had interactive roles in the relationship between depression and ICW/TBW ratios (p < 0.05). The association of ICW/TBW ratios and depression existed in patients of both genders and different education levels, but only in non-diabetic patients.Conclusion: In MHD patients, the decreased ratio of ICW/TBW was independently related to high depression rates.Keywords: depression, hemodialysis, intracellular water, total body water

Yan Long, Chang-Sheng Xia, Xingyue Zeng, Jinghong Feng, Yinting Ma, Chen Liu Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yan Long; Chen Liu, Department of Clinical Laboratory, Peking University People’s Hospital, 11 Xizhimen South Street, Beijing, 100044, People’s Republic of China, Email longyan_good@bjmu.edu.cn; liuchen-best@pku.edu.cnBackground: Follicular helper T (Tfh), follicular regulatory T (Tfr), and follicular cytotoxic T (Tfc) cells play important roles in autoimmune diseases. Nevertheless, their changes of functional phenotypes in ulcerative colitis (UC), most importantly, their changes in colon tissue as the target-organ, have not been explored.Methods: DSS-colitis was induced in Balb/c mice and lymphocytes were collected from spleen, mesenteric lymph nodes, peripheral blood and colon. Tfh, Tfr, and Tfc cells were analyzed using flow cytometry based on their CD4+CXCR5+FOXP3-Tfh, CD4+CXCR5+FOXP3+Tfr and CD8+CXCR5+Tfc expressions. Various functional characterization markers including CD44, CD62L, TIGIT, CD226, PD-1, ICOS, Helios, CTLA-4 and Bcl6 were analyzed in the T cell subsets of the organs.Results: Tfh and Tfr cells in the colon were significantly increased in DSS-colitis mice. Additionally, the proportions of Tfr and Tfc cells in the peripheral blood were also increased, while Tfc cell proportions in the colon were decreased. The proportion of naïve cells in the Tfh, Tfr and Tfc cells in the colon and peripheral blood decreased, while the proportion of effector memory T cells increased. The TIGIT+CD226-Tfh and Tfc cells were upregulated in the colon of DSS-colitis mice. The PD-1+, ICOS+ and PD-1+ICOS+ Tfh cells were increased in both the colonic and peripheral blood Tfh and Tfc of DSS-colitis mice. The Bcl6+ proportions in the Tfh and Tfr were increased in the colon of DSS-colitis mice.Conclusion: The colonic and peripheral blood Tfh and Tfc cells of DSS-colitis mice have a significantly activated T cell phenotype, which may play a significant role in the pathogenesis of UC.Keywords: DSS-induced colitis, follicular helper T cells, follicular regulatory T cells, follicular cytotoxic T cells, PD-1, ICOS

Yunhao Zheng,1 Rui Zhu,2 Chuqiao Xiao,3 Qiaoyu Cheng,3 Yifei Long,3 Xueman Zhou,3 Shilong Zhang,4 Jun Wang,3 Xin Xiong1,3 1Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 4Department of Orthodontics, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Shijiazhuang, People’s Republic of ChinaCorrespondence: Xin Xiong, National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China, Tel/Fax +86-28-85503898, Email drxiongxin@scu.edu.cnPurpose: This study aims to explore the association of pressure pain thresholds (PPTs) with age, gender, and pain in patients with temporomandibular disorders (TMD).Patients and Methods: A total of 301 TMD patients (248 female and 53 male) were recruited and classified into the high and low age groups according to their median age of 26 years. Patients’ demographics, pain-related variables, TMD-related variables, and PPTs of both left and right temporomandibular joints (TMJs), masseter, and temporalis were collected.Results: Pain duration and visual analog scale of pain (VAS) showed no significant correlations with PPTs (P> 0.05). Multiple linear regression analysis revealed a significant positive association of PPTs of all six sites with males (β=0.41– 0.72 kg·cm− 2, 95% CI (0.19– 0.38, 0.74– 0.99), P< 0.001), as well as with the high age group [β=0.28– 0.36 kg·cm− 2, 95% CI (0.07– 0.20, 0.47– 0.53), P< 0.020]. Furthermore, PPTs of the left TMJ showed a significant negative association with left pain-related TMD (PT) [β=− 0.21 kg·cm− 2, 95% CI (− 0.38, − 0.04), P=0.026], but PPTs of the remaining sites did not show a significant association with PT (P> 0.05). Stratified analysis showed that PPTs in females were associated with the high age group [β=0.25– 0.37 kg·cm− 2, 95% CI (0.04– 0.20, 0.45– 0.56), P< 0.020] and that PPT of the left TMJ was associated with left PT [β=− 0.21 kg·cm− 2, 95% CI (− 0.39, − 0.03), P=0.043]. The remaining PPTs did not show a significant association with PT (P> 0.05). In males, PPTs did not show significant correlations with age, PT and VAS (P> 0.05).Conclusion: PPTs in the orofacial region are associated with gender and age in TMD patients. Pain duration and intensity show no significant correlations with PPTs in TMD patients. Researchers and dentists should take age and gender into account when using PPTs as auxiliary diagnostic indicators for PT.Keywords: pain sensitivity, temporomandibular disorders, pressure pain threshold, age, gender

Liping Luo,1,2,&ast; Ronghua Yan,3,4,&ast; Qingjing Zeng,2 Yinglin Long,2 Xuqi He,2 Kai Li,2 Erjiao Xu1 1Department of Medical Ultrasonics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of China; 2Department of Medical Ultrasonics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Radiology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 4Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Erjiao Xu, Department of Medical Ultrasonics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025, Shennanzhong Road, Shenzhen, 518033, People’s Republic of China, Email xuerjiao@mail.sysu.edu.cn Kai Li, Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People’s Republic of China, Email likai@mail.sysu.edu.cnObjective: This study intends to compare the efficacy and safety between patients undergoing invasive isolation or monitoring measures and patients undergoing intra-operative contrast-enhanced ultrasound (CEUS) monitoring who underwent radiofrequency ablation (RFA) of hepatocellular carcinomas (HCC) adjacent to the gallbladder (GB).Methods: We retrospectively assessed patients with HCC adjacent to the GB who underwent ultrasound-guided RFA. They were divided into two groups: group A was monitored under intra-operative CEUS, while group B was assisted by invasive auxiliary means. The efficacy, complications and survival were followed up and compared.Results: Thirty-eight patients with 39 HCCs were enrolled into group A and 31 patients with 35 HCCs were enrolled into group B. The technique efficacy rates were both 100% in the two groups. There were no significant differences of the cumulative 1-, 3-, and 5-year local tumor progression, tumor-free survival and overall survival between the two groups (P = 0.851, 0.081 and 0.700, respectively). There were no significant differences of major and minor complications rates between the two groups (P = 1.000, 0.994, respectively). More importantly, no GB related complications occurred in group A.Conclusion: Intra-operative CEUS monitoring without protective isolation of the GB might be also a potentially safe and effective method for the RFA of HCC adjacent to the GB, when compared with those assisted with invasive auxiliary means.Keywords: hepatocellular carcinoma, gallbladder, contrast-enhanced ultrasound, thermal ablation, monitoring

Zheng Y, Zhu R, Xiao C, et al. J Pain Res. 2023;16:2205–2216. The authors have advised that they neglected to include a funding statement on page 2215 of the published paper. The funding statement should read as follows. Funding This work was supported by the Technology Innovation Project of Science and Technology Bureau of Chengdu (2022-YF05-01691-SN) and Clinical Research Project of West China Hospital of Stomatology, Sichuan University (LCYJ-2023-YY-2). The authors apologize for this error.

Peiyi Luo,1,2,&ast; Yanqiong Long,1,&ast; Liang Ma,2 Ye Tao,1 Shenju Gou1 1Department of Nephrology, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Tao; Shenju Gou, Department of Nephrology, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China, Tel/Fax +86-28-85423341, Email yehtao11@qq.com; goushenju@163.comBackground: The elevation of serum procalcitonin (PCT) has been considered as a marker of systemic bacterial infection and sepsis. However, the marked elevation of PCT in non-sepsis conditions was rare. Here, we report a rare case of sustained markedly elevation of serum PCT in a dialysis patient with tuberculosis, but without the evidence of sepsis.Case Presentation: A 25-year-old man on maintenance hemodialysis was admitted to the hospital for kidney transplantation. On admission, physical examination revealed multiple lymph nodes were palpable on both sides of the neck which was later confirmed as tuberculosis with biopsy pathology. On the 3rd day after admission, the patient suffered from fever with a temperature of 38.8°C. The white blood cells 12.35 × 109/L and the PCT level was 5.73 ng/mL. Lately the PCT increased to 63.10 ng/mL, and the level of C-reactive protein was 186.00 mg/L. After the antibiotics upgraded from cefmetazole to meropenem, and vancomycin was added, the body temperature dropped to the normal range on the 17th day and remained normal thereafter. The PCT level declined gradually to 4.18 ng/mL on the 21st day and an antituberculosis regimen was started. After that, the PCT levels fluctuated between 2.9 ng/mL and 94.9 ng/mL without any manifestation of sepsis. The markedly elevation of serum PCT level persisted despite normal C-reactive protein level and leukocyte counts.Conclusion: Persistently elevated serum PCT level might occur in conditions without evidence of sepsis. Taking consideration of multiple inflammatory factors to determine infection when the markedly elevated PCT level was not correlated with the clinical manifestations.Keywords: procalcitonin, bacterial infection, dialysis, tuberculosis

Liang Wang,1,&ast; Longjiao Hu,2,&ast; Zhilian Peng,3 Honghong Cao,1 Danfeng Cao,4 Yiqin Long,4 Zhengyu Zou4 1Pharmacy Department, Traditional Chinese Medicine Hospital of Jiulongpo Distriction Chongqing, Chongqing, People’s Republic of China; 2Pharmacy Department, Chongqing Jiulongpo People’s Hospital, Chongqing, People’s Republic of China; 3Administrative Department, Traditional Chinese Medicine Hospital of Jiulongpo Distriction Chongqing, Chongqing, People’s Republic of China; 4Clinical Laboratory, Chongqing Jiulongpo People’s Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengyu Zou, Clinical Laboratory, Chongqing Jiulongpo People’s Hospital, Chongqing, People’s Republic of China, Email hulongjiao494@126.com Liang Wang, Pharmacy Department, Traditional Chinese Medicine Hospital of Jiulongpo Distriction Chongqing, Chongqing, People’s Republic of China, Email askliang621129@126.comBackground: Platycodon grandiflorus could significantly improve the pathological results of cutaneous scald injury, reduce the release of inflammatory factors and promote angiogenesis. This study investigated the wound healing effect of luteolin, an active component of P. grandiflorus, on induced cutaneous scald injury in Sprague-Dawley (SD) rats.Methods: The protein expression levels of TNF-α and IL-6 were detected by ELISA. QRT-PCR was adopted to detect the expression of TGF-β 1 and VEGF. Histopathological changes of scald wounds were analyzed by hematoxylin-eosin staining. Cell viability and migration ability were detected by CCK-8 assay and scratch assay.Results: Both in vivo and in vitro experiments showed that luteolin promoted wound healing of cutaneous scald injury. Gene Oncology (GO) functional analysis and rescue experiments showed that endothelial nitric oxide synthase 3 (NOS3) was the critical target of luteolin in treating cutaneous scald.Conclusion: This study demonstrated that luteolin is an effective component of P. grandiflorus and is effective in the treatment of cutaneous scald injury.Keywords: Platycodon grandiflorus, luteolin, scald injury, nitric oxide synthase, network pharmacology

Jie Yang,1,2 Lihong Jiang,1,2 Haiyan Yao,1,2 Li Huang,1,2 Youming Long1,2 1Department of Neurology, The Second Affiliated Hospital of GuangZhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and The Ministry of Education of China, Institute of Neuroscience and the Second Affiliated Hospital of GuangZhou Medical University, Guangzhou, Guangdong Province, People’s Republic of ChinaCorrespondence: Youming Long, Tel/Fax +86-20-34153147, Email youminglong@126.comPurpose: Currently, no uniform diagnostic criteria or treatment consensus is available for patients with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). The aim of this registry is to develop diagnostic and therapeutic recommendations for GFAP-A based on clinical features, neuroimaging, neuroelectrophysiological examinations, laboratory tests, specific antibody tests, immunotherapy, and prognosis.Patients and methods: This multicenter, nationwide ambispective registry includes twenty-seven hospitals in China. From January 2020 to December 2022, consecutive hospitalized patients with symptoms of meningoencephalitis, as well as GFAP-IgG positive cerebrospinal fluid (CSF) or serum will be invited to join this study. It is conservatively estimated that over 300 patients will join the study. Data on demographics, medical history, treatment details and imaging features will be collected after discharge. Outcome events of interest will include modified Rankin Scale (mRS) and Expanded Disability Status Scale (EDSS), readmission with relapsed meningoencephalomyelitis, all-cause mortality, and mortality resulting from complications of GFAP-A. The follow-up will be conducted at six months and twelve months after discharge. Univariate and multivariate regression models will be used to calculate identify independent predictors of outcomes. Stratification analysis will be used to test whether results are similar between key subgroups.Discussion: This study will describe the risk factors, disease course, response to immunotherapy, and long-term prognosis of a large cohort of GFAP-A patients. By using these data, a relatively rational recommendation process for the diagnosis and treatment of GFAP-A will be developed.Trial Registration Number: ChiCTR2000041291.Keywords: glial fibrillary acidic protein, astrocytopathy, antibody, diagnosis, prognosis

Tao Wang,1,2,* Junfei Guo,1,2,* Yubin Long,1,2 Zhiyong Hou1– 3 1Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Orthopaedic Research Institute of Hebei Province, Shijiazhuang, Hebei, People’s Republic of China; 3NHC Key Laboratory of Intelligent Orthopaedic Equipment (Third Hospital of Hebei Medical University), Shijiazhuang, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiyong Hou, Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Email drzyhou@gmail.comPurpose: The purpose of this study was to explore risk factors for mortality after intertrochanteric fracture (IF) surgery in nonagenarians and centenarians based on subgroups of follow-up time.Patients and Methods: A total of 144 nonagenarians and centenarians who underwent IF surgery between Jan. 2014 and Dec. 2018 were included. Data were compared between the mortality and the survival groups based on the subgroups of follow-up time in univariate, logistic regression, and Cox regression analyses.Results: In our study, the rates of mortality were 7.6%, 13.9%, and 28.5% at 6-month, 1-year, and 2-year follow-up, respectively. Univariate analysis showed that prolonged time from injury to surgery, more transfusion volume, lower hemoglobin (minimum), and complications (respiratory failure and anemia) were associated with mortality at 6-month follow-up. However, three factors were found to be related to mortality at 1-year and 2-year follow-up, respectively. Our results showed that postoperative respiratory failure and anemia were independent risk factors for mortality after IF surgery at 6-month in logistic regression analysis. However, postoperative respiratory failure was found as an independent risk factor for mortality at 1-year and 2-year follow-up. Moreover, Cox regression analysis showed that postoperative respiratory failure was an independent risk factor for mortality after IF surgery, which was consistent with results in logistic regression analysis.Conclusion: Postoperative respiratory failure was an independent risk factor for mortality in nonagenarians and centenarians at any follow-up. Additionally, postoperative anemia was closely related to mortality. Preoperative measures should be taken to lower mortality.Keywords: nonagenarians and centenarians, mortality, intertrochanteric fracture, risk factors

Tingyu Ou,1,2 Yousheng Wei,1 Ying Long,1 Xinbin Pan,3 Desheng Yao1 1Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China; 2Department of Gynecology, The Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Desheng Yao, Email yaodesheng@gxmu.edu.cnPurpose: Pyroptosis has vital roles in tumorigenesis and cancer development; however, its relationship with cervical squamous cell cancer (CSCC) remains unexplored. In this study, we aimed to develop a CSCC prediction signature related to pyroptosis.Patients and Methods: Consensus clustering analysis was conducted to detect pyroptosis-related subclusters for CSCC. Next, differentially expressed genes (DEGs) between subclusters were identified. Univariate, least absolute shrinkage and selection operator, and stepwise multivariate Cox regression analyses were applied to establish a prognostic model and a nomogram drawn. Additionally, functional enrichment analysis, tumor mutation burden, and immune characteristics associated with this signature were investigated.Results: We constructed a seven-gene signature that functions as an independent predictor of prognosis in CSCC using data from The Cancer Genome Atlas. Patients with CSCC were divided into two groups based on median risk score, and patients in the low-risk group had significantly longer survival time than those in the high-risk group. Our findings were validated using Gene Expression Omnibus cohort data. We also established a nomogram, to expand the clinical applicability of our findings. The seven gene signature was associated with various molecular pathways, tumor mutation status, and immune microenvironment.Conclusion: The pyroptosis-related risk signature consisting of seven genes developed here represents a potential robust biomarker for predicting prognosis and immunotherapy response in patients with CSCC.Keywords: pyroptosis, cervical squamous cell carcinoma, prognosis, immune microenvironment, nomogram

Yiming Ma, Xue He, Xiangming Liu, Yingjiao Long, Yan Chen Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of ChinaCorrespondence: Yan Chen; Yingjiao Long, Email chenyan99727@csu.edu.cn; longyingjiao@csu.edu.cnBackground: Extracellular vesicles (EVs) are considered to new types of intercellular communication media, and microRNA is one of the most common transferring components of EVs. This study aimed to explore the potential role of endothelial microparticles (EMPs) derived from primary pulmonary microvascular endothelial cells in regulating lung inflammation of chronic obstructive pulmonary disease (COPD) through transferring microRNA-126 (miR-126).Methods: EMPs generated from primary pulmonary microvascular endothelial cells were isolated by gradient centrifugation and characterized by transmission electron microscopy, flow cytometry and Western blotting. EMPs were treated to in vitro and in vivo COPD models induced by cigarette smoke extract (CSE). miR-126 mimics or inhibitors were transfected into EMPs by calcium chloride. Pathological changes of lung tissue, mRNA and protein levels of inflammation-related factors were measured to explore the effect of EMPs transferring miR-126 on CSE-induced inflammation.Results: Both in vitro and in vivo studies demonstrated that mRNA and protein levels of inflammation-related factors were significantly increased in COPD group, while EMPs could dramatically reverse these increases. In vitro, overexpression of miR-126 in EMPs decreased HMGB1 expression and magnified the decreasing effect of EMPs on inflammation-related factors.Conclusion: The present study reveals that EMPs are capable of alleviating lung inflammation and transferring miR-126 can magnify the anti-inflammatory effect of EMPs, which may provide a novel therapeutic alternative for COPD.Keywords: chronic obstructive pulmonary disease, endothelial microparticles, primary pulmonary microvascular endothelial cell, inflammation, microRNA-126

Yu-qin Long,1,2 Xi-sheng Shan,1,2 Xiao-mei Feng,3 Hong Liu,4 Fu-hai Ji,1,2 Ke Peng1,2 1Departments of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, University of Utah Health, Salt Lake City, UT, USA; 4Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USACorrespondence: Ke PengDepartment of Anesthesiology, First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu, 215006, People’s Republic of ChinaTel +86-159-6215-5989Email pengke0422@163.comPurpose: Patients undergoing major laparoscopic surgery often experience significant pain and postoperative nausea and vomiting (PONV). Deep neuromuscular block (NMB) improves surgical conditions and facilitates the application of low intra-abdominal pressure (IAP), which may be beneficial for these patients. This study is designed to determine the effects of deep NMB combined with low IAP, as compared to moderate NMB combined with standard IAP, on patients’ nociceptive recovery after major laparoscopic gastrointestinal surgery.Study Design and Methods: This single-center randomized controlled trial will include 220 patients scheduled for major laparoscopic gastrointestinal surgery (lasts for ≥ 90 minutes). Patients will be randomly assigned, with a 1:1 ratio, into a deep NMB + low IAP group (train of four = 0, post-tetanic count = 1– 3, IAP = 8 mmHg) and a moderate NMB + standard IAP group (train of four = 1– 3, IAP = 12 mmHg). If the surgical workspace is inadequate, the surgeons can request a step increase of 1 mmHg in IAP during 3-min intervals. The upper limit of IAP will be set at 15 mmHg. Postoperative recovery will be assessed using the postoperative quality recovery scale (PQRS). The primary outcome of this trial is the PQRS nociceptive recovery (including pain and PONV) at postoperative day (POD) 1. The secondary outcomes include recovery in other PQRS domains at POD 1, and recovery in all PQRS domains in a post-anesthesia care unit, at POD 3 in the surgical wards, at hospital discharge, and at postoperative 30 days. For the sample size estimation, 110 patients in each group (220 in total) would be needed to detect an absolute increase rate of 20% in the PQRS nociceptive domain in the deep NMB + low IAP group at POD 1.Discussion: This study investigates the effects of deep NMB combined with low IAP on postoperative PQRS nociceptive recovery in patients undergoing major laparoscopic gastrointestinal surgery. We expect that this deep NMB + low IAP strategy would improve postoperative pain and PONV following major laparoscopic gastrointestinal surgery.Keywords: major laparoscopic surgery, pneumoperitoneum pressure, neuromuscular block, postoperative quality recovery scale, randomized controlled trial

Honglian Huang,1,&ast; Renjie Wei,1,&ast; Ying Long,2 Yu Mo,1 Yu Xie,3 Desheng Yao2 1Hechi People’s Hospital, Hechi City, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Gynecologic Oncology Department, Guangxi Medical University Affiliated Cancer Hospital, Nanning City, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Desheng Yao; Yu Xie Tel/Fax +86-771-5330700; Tel +86-21-33189900Fax +86-21-63450900Email yaodesheng@gxmu.edu.cn; yuxie18@fudan.edu.cnObjective: This review aims to clarify the necessity of hepatic hilar lymph node resection on advanced ovarian cancer patients.Background: PARP inhibitors and surgery have significantly improved the survival of patients with ovarian cancer. However, for patients with advanced ovarian cancer, there are often extensive epigastric disseminated metastatic lesions, especially the lymph nodes in the hepatic hilar area. Because of the complicated anatomical relationship and lack of experience in this area, this is easily ignored by gynecological oncologists.Methods: Through the retrieval and analysis of the current database, namely PubMed, Medline, Web of Science, EMBASE, Cochrane Library, and Wangfang, etc., the literature regarding this topic published before March 2021 were thoroughly investigated.Conclusion: For the hepatic hilar regional lymph node surgery, through careful preoperative evaluation, surgical-indication clarification, appropriate case selection, standardized surgical operations and multidisciplinary cooperation with general surgeons, the prognosis of patients is significantly improved. Postoperative complications are also safe and controllable and convincing. To conclude, the application of hilar region lymph node cytoreductive surgery for patients with advanced ovarian cancer is a feasible and preferred choice.Keywords: advanced ovarian cancer, hilar lymph node, cytoreductive surgery

Zhibiao Xiang1 12 23 3, Zhening Liu1 12 23 3, Hengyi Cao4 45 5, Zhipeng Wu1 12 23 3, Yicheng Long1 12 23 3 1Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Mental Health Institute of Central South University, Changsha, Hunan, People’s Republic of China; 3China National Clinical Research Center on Mental Disorders, Changsha, Hunan, People’s Republic of China; 4Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Hempstead, NY, USA; 5Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USACorrespondence: Yicheng Long Email yichenglong@csu.edu.cnBackground: Many studies have reported an association between childhood trauma exposure and schizophrenia. Among these studies, the Short-form Childhood Trauma Questionnaire (CTQ-SF) is one of the most widely used measures of childhood trauma. However, little is known regarding the long-term reliability of the CTQ-SF, especially in patients with psychopathology.Methods: The CTQ-SF was administered to 50 patients diagnosed with schizophrenia from a hospital in Changsha, Hunan, China. These patients were asked to re-complete the CTQ-SF when they were re-hospitalized or received outpatient treatments in the same hospital within 4 years of follow-up. Intraclass correlation coefficient (ICC) was used to assess test–retest reliability of the CTQ-SF over the intervals. Associations of the CTQ-SF with the Positive and Negative Syndrome Scale (PANSS) and Wechsler Adult Intelligence Scale (WAIS) were tested using Spearman correlation coefficients.Results: Among the participants, 35 (70.0%) patients re-completed the CTQ-SF after an interval averaging 11.26 months. Excellent test–retest reliabilities (with ICC > 0.75) were found for the total CTQ-SF score (ICC = 0.772) as well as scores of the emotional abuse (ICC = 0.808), physical abuse (ICC = 0.756), sexual abuse (ICC = 0.877) and physical neglect (ICC = 0.751) subscales. Meanwhile, a moderate test–retest reliability was found for the emotional neglect subscale (ICC = 0.538). At both baseline and follow-up, no significant correlations (p > 0.05) were found between CTQ-SF scores and any other clinical assessments.Conclusion: Our results suggest that CTQ-SF is reliable to assess childhood trauma exposures in schizophrenia over relatively long intervals, regardless of patients’ current symptoms and states of cognition.Keywords: childhood trauma questionnaire, childhood adversity, childhood trauma, schizophrenia, test–retest reliability

Wencui Wan,1,&ast; Wei Zhu,2,&ast; Yan Wu,3,4,&ast; Yang Long,1 Hongzhuo Liu,1 Weiwei Wan,1 Guangming Wan,1 Jing Yu3 1Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Ophthalmology, Changshu No. 2 People’s Hospital, Changshu, People’s Republic of China; 3Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, People’s Republic of China; 4Mois Biotech Company, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangming WanDepartment of Ophthalmology, First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou, Henan, 450052, People’s Republic of ChinaEmail wgm6608@163.comJing Yu No. 301, Yanchang Road, Shanghai, 200072, People’s Republic of ChinaEmail dryujing@aliyun.comBackground: Retinal pigment epithelium (RPE) cellular senescence is an important process in degenerative retinal disorders. Grape seed proanthocyanidin extract (GSPE) alleviates senescence-related degenerative disorders; however, the potential effects of GSPE intake on RPE cellular senescence through regulating NAMPT/SIRT1/NLRP3 pathway remain unclear.Methods: The effects of GSPE on NAMPT expression and NAD+ contents were detected with Western blot and assay kit in both in-vivo and in-vitro AMD models. Senescence-related biomarkers, including p16, p21 expressions and β-gal staining, were conducted in different groups. The protective effects of GSPE treatment on the mitochondrial homeostasis and barrier function of RPE cells were detected using mtDNA lesions analyses, JC-1 staining, ZO1 staining and trans-epithelial cell resistance (TEER) detection. The expression of senescence-associated secretory phenotype (SASP) in different groups would be conducted with qPCR. To demonstrate the potential effects of NAMPT/SIRT1/NLRP3 pathway after GSPE treatment, the protein levels of relevant key regulators after applications of NAMPT inhibitor, Fk866, and SIRT1 inhibitor, EX-527.Results: GSPE significantly improves the NAMPT expression and NAD+ content in aging mice, and thus alleviates the RPE cellular senescence. In advanced in-vitro studies, GSPE significantly up-regulated NAMPT content and thus relieved H2O2 induced NAD+ depression through analyzing the NAD+ contents in different groups. In advanced analyses, it was reported that GSPE could alleviate mitochondrial permeability, mtDNA damage, ZO1 expression and SASP levels in aging RPE cells. Thus, GSPE treatment significantly decreased senescence-related protein p16 and p21, as well as SASP levels in in-vitro aging model, and it was demonstrated that GSPE could illustrate a significant anti-aging effect. The Western blot data in GSPE treatment of aging RPE cells demonstrated that GSPE could significantly improve NAMPT and SIRT1 levels, and thus depressed NLRP3 expression.Conclusion: This study indicated that GSPE alleviated RPE cellular senescence through NAMPT/SIRT1/NLRP3 pathway. This study highlighted the potential effects of GSPE on degenerative retinopathy through the crosstalk of NAD+ metabolism, SIRT1 function and NLRP3 activation.Keywords: cellular senescence, retinal pigment epithelium, nicotinamide phosphoribosyltransferase, sirtuin 1, inflammasome, NLRP3

Cheng Zhou,1 Chunlin Song,1 Xiang Huang,1 Shufen Chen,1 Yan Long,2 Shanshui Zeng,2 Hongling Yang,2 Min Jiang2 1Laboratory of Molecular Diagnostics, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, 528000, People’s Republic of China; 2Department of Laboratory, Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University, Guangzhou, 510623, People’s Republic of ChinaCorrespondence: Hongling Yang; Min JiangDepartment of Laboratory, Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University, No. 9, Jinsui Road, Guangzhou, 510623, People’s Republic of ChinaTel +86-20-38857723; +86-20-38076256Email hlyang62@163.com; jiangmin2011@126.comBackground: Gestational hypertension (GH), a hypertensive disorder of pregnancy (HDP), is a leading cause of maternal and fetal mortality due to the lack of clarity on its exact etiology and clinically feasible prediction models. This study was performed to discover novel biomarkers before 20 weeks gestation and thereby construct an early GH prediction model.Methods: This study was designed based on differentially expressed protein screening followed by clinical validation. In the screening phase, a nested case-controlled study was conducted by plasma proteomic analyses using label-free LC-MS/MS and plasma samples from seven pre-GH cases before 20-week gestation and seven age- and gestational week-matched controls. In the validation phase, 10 proteins with differential expression in the screening phase were validated by ELISA or electrochemiluminescence in an independent study consisting of 29 pre-GH cases before 20-week gestation and 29 matched controls.Results: In the screening phase, 149 proteins were found to be differentially expressed between the two groups and were predominantly involved in complement and coagulation cascades, platelet degranulation and positive regulation of cell motility. Further validation showed that serpin family C member 1 (SERPINC1), serpin family A member 5 (SERPINA5), complement factor H-related protein 5 (CFHR5), clusterin, cytokeratin 18 (CK18) and histidine-rich glycoprotein (HRG) levels were significantly higher in women who later developed GH compared to women with uncomplicated pregnancies (P< 0.05). Binary logistic regression analysis was used to determine the combination efficacy of models for early prediction of GH. The model with a combination of SERPINC1, CK18 and HRG had a significantly better discriminatory power (AUC = 0.91, 95% CI 0.83– 0.98) compared to the models with those proteins alone as independent predictors of GH.Conclusion: Plasma levels of SERPINC1, SERPINA5, CFHR5, clusterin, CK18 and HRG are potential novel predictive biomarkers of GH, and a prediction model using a combination of SERPINC1, CK18 and HRG has good discriminatory performance for GH before 20 weeks gestation.Keywords: label-free LC-MS/MS, gestational hypertension, biomarkers

Yinbo Long, Heyang Li, Zhibin Jin, Xiang Zhang Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou City, Hebei Province, 061000, People’s Republic of ChinaCorrespondence: Xiang ZhangDepartment of Neurosurgery, Cangzhou Central Hospital, Cangzhou City, Hebei Province, 061000, People’s Republic of ChinaEmail yb5052@163.comIntroduction: LncRNA SLC16A1-AS1 has been characterized as a critical player in lung cancer, while its role in glioblastoma (GBM) is unknown. By analyzing the TCGA dataset, we observed the upregulation of SLC16A1-AS1 expression in GBM. Therefore, we aimed to investigate the role of SLC16A1-AS1 in this cancer.Methods: GBM tissues and paired non-tumor tissues were collected from 62 GBM patients through biopsy. RT-qPCR was performed to determine the expression of SLC16A1-AS1 and miR-149. Linear regression was used to analyze their correlations. The relationship between SLC16A1-AS1 and miR-149 was assessed by gain and loss of function experiments. Methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) were performed to analyze the methylation status of miR-149. Cell proliferation was evaluated by CCK-8 assay and colony formation experiments in GBM cells.Results: We found that SLC16A1-AS1 expression was upregulated in GBM tissues, and the upregulated expression of SLC16A1-AS1 predicted poor survival of GBM patients. MiR-149 was downregulated in GBM tissues and inversely correlated with the expression of SLC16A1-AS1. In GBM cells, overexpression of SLC16A1-AS1 downregulated the expression of miR-149 and increased the methylation of miR-149 gene. In cell proliferation and colony formation assay, overexpression of SLC16A1-AS1 reduced the inhibitory effects of miR-149 on GBM cell proliferation.Conclusion: SLC16A1-AS1 may promote GBM cell proliferation by regulating miR-149 methylation. SLC16A1-AS1 can be considered as a potential diagnostic marker in GBM.Keywords: GBM, SLC16A1-AS1, miR-149, methylation, proliferation

Yan Long,1,2 Fangying Quan,3 Yong Zheng4 1Center for Studies of Education and Psychology of Ethnic Minorities in Southwest China, Southwest University, Chongqing, People’s Republic of China; 2Department of Student Affairs, Guilin Tourism University, Guilin, People’s Republic of China; 3Faculty of Education, Guangxi Normal University, Guilin, People’s Republic of China; 4Faculty of Psychology, Southwest University, Chongqing, People’s Republic of ChinaCorrespondence: Yong ZhengFaculty of Psychology, Southwest University, Chongqing, 400715, People’s Republic of ChinaTel +86 136 6763 6167Email zhengy@swu.edu.cnPurpose: The current study investigated the association between bicultural identity integration (BII, incorporating BII-harmony and BII-blendedness), national identity, and anxiety related to Coronavirus disease 2019 (COVID-19) among ethnic minority college students. In addition, this research examined the mediation role of power values in the relationship between BII, national identity, and COVID-19-related anxiety.Methods: This cross-sectional research design made use of online surveys. Using convenience sampling, participants comprised 235 Chinese ethnic minority college students drawn from four colleges in the ethnic minority autonomous regions of China. Data were collected during June 2020. Participants mainly lived in ethnic minority communities or villages in southwest China before receiving higher education at urban campuses.Results: Correlation analysis revealed that BII-harmony, BII-blendedness, and national identity were significantly negatively correlated with COVID-19-related anxiety. Mediation model analysis showed that power values were significantly positively correlated with COVID-19-related anxiety. Power values play a mediating role in the relationship between BII-harmony, national identity, and COVID-19-related anxiety, and have an inhibitory effect on this relationship.Conclusion: Our findings indicate that BII-harmony and national identity could have the function of protecting ethnic minority college students from COVID-19-related anxiety. Emphasizing individualistic personal power values could increase COVID-19-related anxiety, whereas a collectivist identity reduces anxiety. These findings could provide another perspective on psychological interventions to reduce anxiety during the COVID-19 pandemic.Keywords: bicultural identity integration, national identity, power values, COVID-19-related anxiety, ethnic minority college students

Liuyue Xu,1 Qian Dong,2 Yaoying Long,1 Xiaoqiong Tang,1 Nan Zhang,2 Kai Lu2 1Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaCorrespondence: Kai LuDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, People’s Republic of ChinaTel/Fax +86 23 89011562Email lukai2013@foxmail.com; zncqmu@126.comBackground: Previous studies indicated that the (neo)adjuvant chemotherapy for breast cancer can cause significant dyslipidemia in patients, but how long this abnormality can persist is unclear so far. The purpose of this study is to investigate whether (neo)adjuvant chemotherapy has a long-term effect on blood lipids in breast cancer patients.Methods: A total of 159 newly diagnosed female breast cancer patients receiving the (neo)adjuvant chemotherapy subsequently and 159 female healthy controls were enrolled into the observational study. All participants’ blood lipid profiles which included TC, TG, HDL-C, and LDL-C before and at the end of the 1st and 12th month after chemotherapy were retrieved from the electronic medical record system. The blood lipid profiles and the percentage of dyslipidemia before and after chemotherapy in breast cancer patients and controls were compared.Results: Compared with the baseline before chemotherapy, TC, LDL-C, and TG increased significantly at the end of the 1st month after chemotherapy, but only the abnormal increase in TG (2.98± 0.71 mmol/L vs 2.82± 0.63 mmol/L, P< 0.05) and LDL-C (1.82± 0.42 mmol/L vs 1.59± 0.42 mmol/L, P< 0.05) continued until the 12th month after chemotherapy. Levels of HDL-C in breast cancer patients and all the blood lipid parameters in controls remained stable during the observation period. The percentage of dyslipidemia in breast cancer patients rose from 41.5% at baseline to 54.1% at the 12th month after chemotherapy. Subgroup analysis demonstrated that the increase in dyslipidemia percentage was more pronounced in patients with low body mass index and aged over 50 years.Conclusion: The (neo)adjuvant chemotherapy used for treating breast cancers can cause significant abnormalities in blood lipid profiles, and the abnormal increase in LDL-C and TG can last at least 12 months after chemotherapy, which indicates long-term management of blood lipid is necessary for those patients.Keywords: breast cancer, dyslipidemia, adjuvant chemotherapy

Yulu Zhang,1,* Songyu Liu,1,* Jinyan Wan,1,* Qiyue Yang,2 Yan Xiang,1 Li Ni,1 Yu Long,1 Mingquan Cui,1 Zhimin Ci,1 Donglei Tang,1 Nan Li1 1College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, People’s Republic of China; 2Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nan LiCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, People’s Republic of ChinaTel +86-28-61801001Email 55743198@qq.comPurpose: Baicalin (BA) has a good neuroprotective effect, but it is eliminated quickly in the body and does not easily reach the brain. In this experiment, borneol (BO) was used as an auxiliary drug to prepare borneol-baicalin-liposomes (BO-BA-LP) to prolong the efficacy time of BA, synergistically synergize, introduce drugs into the brain, and better exert the therapeutic effect on cerebral ischemia-reperfusion (I/R) injury.Methods: Through single-factor inspection and response surface optimization analysis, obtained the best preparation process of BO-BA-LP and characterized by various analytical techniques. Validated the long-term effectiveness of BA-BO-LP through pharmacokinetic studies and conducted pharmacodynamic studies on the middle cerebral artery occlusion (MCAO) rat model to verify the therapeutic effect of BO-BA-LP on cerebral I/R injury.Results: The optimum preparation conditions of BO-BA-LP were as follows: the dosage of BO was 9.55 mg, the ratio of phospholipid to drug was 4.02:1, the ratio of phospholipid to cholesterol was 7.25:1, the entrapment efficiency (EE) was 41.49%, and the drug loading (DL) was 4.29%. The particle size range of the liposomes was 167.1 nm, and the polydispersity index (PDI) range was 0.113. The results of pharmacokinetic experiments showed that the combination of BA and BO liposomes effectively improved the pharmacokinetic parameters of BA and prolonged the half-life of BA. Pharmacodynamic studies have found that, compared with BA-LP, BO-BA-LP can significantly improve neurological deficits, cerebral infarction volume, and brain pathological states on MCAO rats.Conclusion: These results demonstrated that BO-BA-LP can improve the circulation of drugs in the blood, and the addition of BO can enhance the therapeutic effect of BA and effectively improve cerebral I/R.Keywords: borneol-baicalin-liposome, pharmacokinetics, pharmacodynamics, MCAO

Peixian Zhang,* Lan Shi,* Linjing Song, Yi Long, Kehua Yuan, Wanbao Ding, Lei Deng Department of Oncology, Yan’an Hospital of Kunming City & Yan’an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, People’s Republic of China *These authors contributed equally to this workCorrespondence: Lei Deng; Wanbao DingDepartment of Oncology, Yan’an Affiliated Hospital of Kunming Medical University. No. 245 East of Renmin Road, Kunming, Yunnan 650051, People’s Republic of ChinaEmail leidengkm@163.com; wabading@163.comPurpose: Synchronous colorectal liver metastasis (SCLM) had limited availability of tools to predict survival and tumor recurrence. LncRNA CRNDE and lncRNA SNHG7 have been proven to be closely related to cancer progression. However, the predictive value of lncRNA CRNDE and lncRNA SNHG7 in cancer prognosis is still unclear. The purpose of this study was to investigate whether lncRNA CRNDE and lncRNA SNHG7 could be used as promising biomarkers for prognosis prediction of SCLM patients who underwent hepatectomy.Methods: The expression profile of lncRNA CRNDE and lncRNA SNHG7 in serum of SCLM patients was examined by qRT-PCR. The relationship between lncRNA expression and clinicopathological characteristics was analyzed. The Cox proportional-hazards regression model and Kaplan-Meier analysis were performed to analyze the association between lncRNA expression and overall survival (OS) and tumor recurrence of SCLM patients.Results: Levels of lncRNA CRNDE and lncRNA SNHG7 in patients who underwent recurrence or death were significantly higher than that of patients with recurrence-free or survival (P< 0.01). Both lncRNA CRNDE high level and lncRNA SNHG7 high level showed a significant correlation with differentiation of primary tumor, invasion depth of primary focus, lymph node metastases, number of liver metastases, and liver metastasis grade. High levels of lncRNA CRNDE or lncRNA SNHG7 predicted shorter recurrence time, shorter OS time, higher recurrence rate and lower OS rate. Furthermore, lncRNA CRNDE and lncRNA SNHG7 were independent risk factors for high recurrence and poor OS in SCLM underwent hepatectomy.Conclusion: Taken together, lncRNA CRNDE and lncRNA SNHG7 could be promising biomarkers for prediction of OS and tumor recurrence in SCLM underwent hepatectomy.Keywords: lncRNA CRNDE, lncRNA SNHG7, prognosis, recurrence, synchronous colorectal liver metastasis, SCLM

Xiaoqiong Tang, Yaoying Long, Liuyue Xu, Xinyu Yan Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing City 400016, People’s Republic of ChinaCorrespondence: Xiaoqiong TangDepartment of Hematology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, YuZhong District, Chongqing City 400016, People’s Republic of ChinaTel +86 23-89011508Email cebzpn3@163.comIntroduction: LncRNA mortal obligate RNA transcript (MORT) is downregulated in different types of cancer, indicating its involvement in cancer biology.Methods: In this study, MORT and miRNA-16 were both downregulated in plasma of mantle cell lymphoma (MCL) patients than that in the controls. The low levels of MORT and miRNA-16 were correlated with poor survival of MCL patients. The expression of MORT and miRNA-16 was positively correlated only in MCL patients.Results: Overexpression of MORT and miRNA-16 suppressed cell proliferation but promoted cancer cell apoptosis, while miRNA-16 inhibitor reduced the effects of MORT overexpression. Overexpression of MORT led to upregulated expression of miRNA-16, while overexpression of miRNA-16 had no effect on the expression of MORT.Conclusion: Therefore, MORT may inhibit cancer cell proliferation and promote apoptosis in mantle cell lymphoma by upregulating miRNA-16.Keywords: mantle cell lymphoma, MORT, miRNA-16, prognosis, cancer cell

Wei Yu,1,* Dulei Xiang,1,* Houjun Jia,2,* Xin He,1 Jie Sheng,1 Yuxiang Long,1 Shujuan Zhu,1 Kejian Wang,1 Qian Liu1 1Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Liu Tel +86 186 2355 1357Email qianliu@cqmu.edu.cnIntroduction: Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) are deregulated in many cancers and exert their functions through multiple cancer-related biological processes. Glioma is the most common primary malignant central nervous system tumor and has a high fatality rate in adults. In current study, we aimed to determine the role and functional mechanism of the lncRNA BCYRN1 in glioma.Methods: Gain-of-function and loss-of function approaches were used to investigate the function of BCYRN1. The effects of BCYRN1 on glioma cell proliferation, migration and invasion were evaluated using MTS, Transwell and wound-healing assays. The correlation between the expression of BCYRN1 and miR-125a-5p was verified by quantitative real-time PCR.Results: The upregulation of BCYRN1 promoted the proliferation, migration and invasion of glioma cells. Meanwhile, the knockdown of BCYRN1 had the opposite effects. BCYRN1 was negatively correlated with miR-125a-5p. Additionally, TAZ, the endogenous target of miR-125a-5p, could be regulated by BCYRN1 in RNA and protein levels. A miR-125a-5p inhibitor restored BCYRN1 siRNA function in glioma.Conclusion: The present study indicates that BCYRN1 promotes glioma cell proliferation, invasion and migration in vitro. Mechanistically, upregulated expression of BCYRN1 in glioma acts as a sponge to sequester the endogenous tumor suppressor miR-125a-5p and to further increase the expression TAZ. Our findings suggest that BCYRN1 is a novel oncogene and a new therapeutic target for glioma.Keywords: BCYRN1, glioma, miR-125a-5p, ceRNA, TAZ

Ying Long,1,* De-Sheng Yao,1 You-Sheng Wei,1,* Chang-Hong Wei,2 Xiao-Yu Chen21Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guang Xi Medical University, Nanning, People’s Republic of China; 2Department of Pathology, Affiliated Tumor Hospital of Guang Xi Medical University, Nanning, People’s Republic of China *These authors contributed equally to this workBackground: Perineural invasion (PNI) is closely associated with poor survival in several types of malignant tumours, but whether this is true in vulvar squamous cell carcinoma (VSCC) is unclear. The aims of this study were to determine the prognostic significance of PNI in patients with VSCC.Patients and methods: We retrospectively analysed clinico-pathological data on 105 patients with VSCC (stages IB-IV) treated surgically at our medical center between 2005 and 2015.Results: PNI was detected in 30 (28.6%) patients, and it was significantly associated with well-known clinical risk factors: large tumour size, depth of invasion, lymphatic vascular space invasion (LVSI), and intra- or extra-nodal spread. Significantly greater proportions of patients with PNI received adjuvant therapy after surgery (P=0.001) or showed local recurrence (P=0.002). Multivariable analysis indicated that risk factors for disease-free survival were tumour size (HR 3.02, 95%CI 1.75–7.75), LVSI (HR 4.82, 95%CI 1.36–17.07), depth of invasion (HR 3.11, 95%CI 1.50–6.44), lymph node metastasis (HR 3.15, 95%CI 1.14–8.96) and positive or close surgical margins (HR 4.86, 95%CI 1.67–14.19). The latter three variables were also risk factors for overall survival. PNI was associated with significantly shorter disease-free survival (DFS) (P=0.020) and overall survival (OS) (P=0.017) based on the log-rank test. Among patients who received adjuvant treatment, Kaplan-Meier curves indicated no significant differences between PNI-positive or -negative subgroups in disease-free survival (P=0.085) or overall survival (P=0.061). Based on multivariable analysis of all patients, PNI was not a significant risk factor for either type of survival .Conclusion: PNI in VSCC is associated with significantly shorter disease-free and overall survival, though it appears to be a weak independent predictor of worse prognosis. Combining PNI with other risk factors may be useful for predicting whether postoperative adjuvant therapy will be needed.Keywords: Perineural invasion, vulvar squamous cell carcinoma, adjuvant therapy, prognostic significance

Kankan Gao,1 Xiaoshan Guan,1 Lanlan Zeng,1 Jiabi Qian,2 Sufei Zhu,1 Qiulian Deng,1 Huamin Zhong,1 Shuying Pang,1 Fei Gao,1 Jielin Wang,1 Yan Long,1 Chien-Yi Chang,3 Haiying Liu1 1Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China; 2Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China; 3School of Chemistry and Biosciences, University of Bradford, Bradford, BD7 1DP, UK Background: A multidrug-resistant (MDR) RR2 gene cluster was identified by whole-genome sequencing in several highly virulent (ST-17) Group B streptococcus (GBS) isolates, which caused neonatal invasive infections in southern China in 2016. Tracing the transmission and distribution of MDR isolates in this area is important for the effective management of future infections. The aim of this study was to obtain longitudinal data of MDR isolates to monitor epidemiological trends of general common isolates in southern China, and provide evidence for future characterization of antimicrobial resistance mechanisms.Methods: Clinical information and antimicrobial susceptibility of GBS isolates were acquired from electronic information management system databases of the hospital under study between January 2011 and December 2017. To confirm the presence of intact RR2, the tetO, ant6, lnuB, and ant9 genes located upstream, midstream, and downstream of RR2 were detected by PCR and DNA sequencing.Results: A total of 149 cases of neonatal invasive GBS infection were identified during the period 2011–2017. Among them, 119 cases (79.9%) were caused by MDR isolates, with a general increasing trend over the past 7 years. Further characterization of 11 isolates showed that six isolates causing late-onset disease (LOD) carry the tetO, ant6, and lnuB genes, which are located on RR2. Moreover, lnuB and ant9 consistently co-occurred in GBS isolates, which suggests their close proximity to one another in the RR2 gene cluster.Conclusion: The MDR GBS is responsible for a large number of neonatal invasive infections and occurs with increasing frequency over time. Particularly, the MDR GBS isolates that cause LOD are more likely to carry the RR2 gene cluster, compared with those that cause early-onset disease. The rise in number of MDR GBS isolates emphasizes the pressing need for continuous surveillance to monitor their antibiotic susceptibility and epidemiology. Keywords: invasive infection, gene cluster, neonates, multidrug-resistance

Yan-Min Long,1,2 Li-Gang Hu,1,3 Xue-Ting Yan,1,3 Xing-Chen Zhao,1,3 Qun-Fang Zhou,1,3 Yong Cai,2,4 Gui-Bin Jiang1,3 1State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Beijing, China; 2Institute of Environment and Health, Jianghan University, Wuhan, Hubei, China; 3College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, China; 4Department of Chemistry and Biochemistry, Southeast Environmental Research Center, Florida International University, Miami, FL, USA Abstract: Understanding the mechanism of nanosilver-dependent antibacterial activity against microorganisms helps optimize the design and usage of the related nanomaterials. In this study, we prepared four kinds of 10 nm-sized silver nanoparticles (AgNPs) with dictated surface chemistry by capping different ligands, including citrate, mercaptopropionic acid, mercaptohexanoic acid, and mercaptopropionic sulfonic acid. Their surface-dependent chemistry and antibacterial activities were investigated. Owing to the weak bond to surface Ag, short carbon chain, and low silver ion attraction, citrate-coated AgNPs caused the highest silver ion release and the strongest antibacterial activity against Escherichia coli, when compared to the other tested AgNPs. The study on the underlying antibacterial mechanisms indicated that cellular membrane uptake of Ag, NAD+/NADH ratio increase, and intracellular reactive oxygen species (ROS) generation were significantly induced in both AgNP and silver ion exposure groups. The released silver ions from AgNPs inside cells through a Trojan-horse-type mechanism were suggested to interact with respiratory chain proteins on the membrane, interrupt intracellular O2 reduction, and induce ROS production. The further oxidative damages of lipid peroxidation and membrane breakdown caused the lethal effect on E. coli. Altogether, this study demonstrated that AgNPs exerted antibacterial activity through the release of silver ions and the subsequent induction of intracellular ROS generation by interacting with the cell membrane. The findings are helpful in guiding the controllable synthesis through the regulation of surface coating for medical care purpose. Keywords: silver nanoparticles, surface chemistry, silver ion release, Trojan-horse-type mechanism, respiratory chain, oxidative stress

Tao Wan,* Wenhui Pan,* Yueming Long, Kaiyue Yu, Sibo Liu, Wenyi Ruan, Jingtong Pan, Mengyao Qin, Chuanbin Wu, Yuehong Xu Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The hybrid system based on nanoparticles (NPs) self-assembled by the conjugations of hyaluronic acid with cholesterol (HA–Chol NPs) combined with nicotinamide (NIC) for tacrolimus (FK506), ie, FK506 NPs–NIC, has been confirmed to exhibit a significant synergistic effect on FK506 permeation through and into intact skin; thus, it may be a promising approach for FK506 to effectively treat skin diseases. The aim of this study was to evaluate its potential for the treatment of psoriasis. In vitro permeation through the psoriatic skin was carried out, and the results revealed that the combination of NPs with NIC exhibited a significant synergistic effect on FK506 deposition within the psoriatic skin (3.40±0.67 µg/cm2) and penetration through the psoriatic skin (30.86±9.66 µg/cm2). The antipsoriatic activity of FK506 NPs–NIC was evaluated through the treatment for imiquimod (IMQ)-induced psoriasis. The psoriasis area and severity index (PASI) score demonstrated that FK506 HA–Chol NPs–NIC exerted the effect on ameliorating the skin lesions comparable to clobetasol propionate (a positive drug for psoriasis) and superior to commercial FK506 ointment (Protopic®), and the histological study showed that it presented a synergistic effect on antipsoriasis after FK506 incorporation into NPs combined with NIC hydrotropic system, which might ultimately increase the therapeutic effect and minimize the systemic side effects by reducing the overall dose of FK506. RAW 264.7 cell uptake presented the enhancement of drugs delivered into cells by HA–Chol NPs–NIC. The antiproliferative activity on HaCaT cells identified that FK506 HA–Chol NPs–NIC exhibited significant inhibiting effects on HaCaT proliferation. The results support that the combination of HA–Chol NPs with NIC is a promising approach for FK506 for the treatment of psoriasis. Keywords: tacrolimus, nanoparticles, nicotinamide, percutaneous delivery, psoriasis, antiproliferation

Wenhui Pan, Mengyao Qin, Guoguang Zhang, Yueming Long, Wenyi Ruan, Jingtong Pan, Zushuai Wu, Tao Wan, Chuanbin Wu, Yuehong Xu Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Tacrolimus (FK506), an effective immunosuppressant for treating inflammatory skin diseases, hardly penetrates into and through the skin owing to its high hydrophobicity and molecular weight. The aim of this study was to develop a hybrid system based on nicotinamide (NIC) and nanoparticles (NPs) encapsulating FK506, such as FK506–NPs–NIC, for facilitating percutaneous delivery, which exploited virtues of both NIC and NPs to obtain the synergetic effect. Solubility and percutaneous permeation studies were carried out. The results showed that NIC could increase the solubility and permeability of FK506 and that 20% (w/v) NIC presented higher FK506 permeability and was thus chosen as the hydrotropic solution to solubilize FK506 and prepare FK506–NPs–NIC. Hyaluronic acid (HA) was chemically conjugated with cholesterol (Chol) to obtain amphiphilic conjugate of HA–Chol, which self-assembled NPs in 20% NIC solution containing FK506. The particle size, zeta potential, and morphology of NPs were characterized. The encapsulation efficiency and in vitro percutaneous permeation of NPs were evaluated in the presence and absence of NIC. The results demonstrated that hydrotropic solubilizing FK506 was readily encapsulated into NPs with a higher encapsulation efficiency of 79.2%±4.2%, and the combination of NPs with NIC exhibited a significantly synergistic effect on FK506 deposition within the skin (2.39±0.53 µg/cm2) and penetration through the skin (13.38±2.26 µg/cm2). The effect of the combination of NPs with NIC on drug permeation was further visualized by confocal laser scanning microscope through in vivo permeation studies, and the results confirmed that NPs–NIC synergistically enhanced the permeation of the drug into the skin. The cellular uptake performed in HaCaT cells presented a promoting effect of NPs on cellular uptake. These overall results demonstrated that HA–Chol–NPs–NIC can synergistically improve the percutaneous delivery of FK506, and it is a novel potential strategy based on a nano-sized carrier for FK506 to treat skin diseases. Keywords: tacrolimus, nicotinamide, hyaluronic acid, nanoparticles, percutaneous delivery

Gao K, Guan X, Zeng L, et al. Infect Drug Resist. 2018;11:2561–2569.In this article both Wenjing Ji and David J McIver were erroneously listed in the acknowledgements but should have been included as coauthors. A communication error at the manuscript submission stage led to both authors being left off the original authorship list. Both Wenjing Ji and David J McIver were originally acknowledged for their assistance with formatting and proofreading and language editing, respectively. However, it was shown both authors also assisted with the interpretation of data and analysis, as well as assisting in drafting the manuscript, extensive editing, recommendations for analysis and the interpretation of findings. The authors wish to apologize for this error. The correct author list and affiliations are shown below.Read the original article

We designed and synthesized several nanomaterials 3 of three-layered core-shell (γ-FeOx@AuNP)@[C60(>DPAF-C9)1or2]n nanoparticles (NPs). These NPs having e−-polarizable fullerosome structures located at the outer layer were fabricated from highly magnetic core-shell γ-FeOx@AuNPs. Fullerosomic polarization of 3 was found to be capable of causing a large amplification of material permittivity that is also associated with the photoswitching effect in the frequency range of 0.5‒4.0 GHz. Multilayered synthetic construction allows Förster resonance energy transfer (FRET) of photoinduced accumulative surface plasmon resonance (SPR) energy in the gold layer to the partially bilayered C60(>DPAF-C9)1or2-derived fullerosome membrane shell layer in a near-field of direct contact without producing radiation heat, which is commonly associated with SPR.

A novel highly luminescent tris-fluorenyl ring-interconnected chromophore tris(DPAF-C9) was synthesized using a C3 symmetrical triaminobenzene core as the synthon. This structure bears three light-harvesting 2-diphenylamino-9,9-dialkylfluorenyl (DPAF) ring moieties with each attached by two branched 3',5',5'-trimethylhexyl (C9) arms. A major stereoisomer was chromatographically isolated and characterized to possess a 3D structural configuration of cis-conformer in a cup-form. Molecular calculation at B3LYP/6-31G* level revealed the unexpected stability of this cis-cup-conformer of tris(DPAF-C9) better than that of the stereoisomer in a propeller-form and the trans-conformer. The structural geometry is proposed to be capable of minimizing the aggregation related self-quenching effect in the condensed phase. Fluorescence emission wavelength of tris(DPAF-C9) was found to be in a close range to that of PVK that led to its potential uses as the secondary blue hole-transporting material for enhancing the device property toward the modulation of PLED performance.

New 3D conformers were synthesized to show a nanomolecular configuration with geometrically branched 2-diphenylaminofluorene (DPAF-C2M) chromophores using a symmetrical 1,3,5-triaminobenzene ring as the center core for the connection of three fused DPAF-C2M moieties. The design led to a class of cis-cup-tris[(DPAF-C2M)-C60(>DPAF-C9)] 3D conformers with three bisadduct-analogous 60> cages per nanomolecule facing at the same side of the geometrical molecular cis-cup-shape structure. A sequential synthetic route was described to afford this 3D configurated conformer in a high yield with various spectroscopic characterizations. In principle, a nanostructure with a non-coplanar 3D configuration in design should minimize the direct contact or π-stacking of fluorene rings with each other during molecular packing to the formation of fullerosome array. It may also prevent the self-quenching effect of its photoexcited states in solids. Photophysical properties of this cis-cup-conformer were also investigated.

Broadband nonlinear optical (NLO) organic nanostructures exhibiting both ultrafast photoresponse and a large cross-section of two-photon absorption throughout a wide NIR spectrum may make them suitable for use as nonlinear biophotonic materials. We report here the synthesis and characterization of two C60-(antenna)x analogous compounds as branched triad C60(>DPAF-C18)(>CPAF-C2M) and tetrad C60(>DPAF-C18)(>CPAF-C2M)2 nanostructures. These compounds showed approximately equal extinction coefficients of optical absorption over 400–550 nm that corresponds to near-IR two-photon based excitation wavelengths at 780–1,100 nm. Accordingly, they may be utilized as potential precursor candidates to the active-core structures of photosensitizing nanodrugs for 2γ-PDT in the biological optical window of 800–1,050 nm.

Chong Li, Yan Zhang, Tingting Su, Lianlian Feng, Yingying Long, Zhangbao ChenKey Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, ChinaAbstract: We investigated flexible liposomes as a potential oral drug delivery system. However, enhanced membrane fluidity and structural deformability may necessitate liposomal surface modification when facing the harsh environment of the gastrointestinal tract. In the present study, silica-coated flexible liposomes loaded with curcumin (CUR-SLs) having poor water solubility as a model drug were prepared by a thin-film method with homogenization, followed by the formation of a silica shell by the sol-gel process. We systematically investigated the physical properties, drug release behavior, pharmacodynamics, and bioavailability of CUR-SLs. CUR-SLs had a mean diameter of 157 nm and a polydispersity index of 0.14, while the apparent entrapment efficiency was 90.62%. Compared with curcumin-loaded flexible liposomes (CUR-FLs) without silica-coatings, CUR-SLs had significantly higher stability against artificial gastric fluid and showed more sustained drug release in artificial intestinal fluid as determined by in vitro release assays. The bioavailability of CUR-SLs and CUR-FLs was 7.76- and 2.35-fold higher, respectively, than that of curcumin suspensions. Silica coating markedly improved the stability of flexible liposomes, and CUR-SLs exhibited a 3.31-fold increase in bioavailability compared with CUR-FLs, indicating that silica-coated flexible liposomes may be employed as a potential carrier to deliver drugs with poor water solubility via the oral route with improved bioavailability.Keywords: silica, flexible liposome, oral bioavailability, curcumin

We designed and synthesized two analogous pentacationic [60]fullerenyl monoadducts, C60(>ME1N6+C3) (1) and C60(>ME3N6+C3) (2), with variation of the methoxyethyleneglycol length. Each of these derivatives bears a well-defined number of cationic charges aimed to enhance and control their ability to target pathogenic Gram-positive and Gram-negative bacterial cells for allowing photodynamic inactivation. The synthesis was achieved by the use of a common synthon of pentacationic N,N′,N,N,N,N-hexapropyl-hexa(aminoethyl)amine arm (C3N6+) having six attached propyl groups, instead of methyl or ethyl groups, to provide a well-balanced hydrophobicity–hydrophilicity character to pentacationic precursor intermediates and better compatibility with the highly hydrophobic C60 cage moiety. We demonstrated two plausible synthetic routes for the preparation of 1 and 2 with the product characterization via various spectroscopic methods.

Novel 3D-configurated stereoisomers cis-cup-tris[C60>(DPAF-C9)] and trans-chair-tris[C60>(DPAF-C9)] were designed and synthesized in good yields. The former, with three C60> cages per molecule facing at the same side of the geometrical molecular cup-shape, was proposed to provide excellent binding interaction forces at the gold surface of core-shell γ-FeOx@AuNP nanoparticles and to direct the subsequent formation of a fullerene cage array (defined as fullerosome). Upon photoactivation of the Au-layer and cis-cup-tris[C60>(DPAF-C9)] itself, the degree of photoinduced intramolecular e−-transfer from DPAF to a C60> moiety was found to be largely enhanced by the accumulated plasmonic resonance energy at the near-field surface. Distribution of resulting negative charges along the outer (C60>)-derived fullerosome shell layer of the trilayered NPs was correlated with the detected photoswitchable dielectric amplification phenomena using white LED light at 1.0 GHz.

C48H40BCuF4N4OP2, triclinic, P1 (no. 2), a = 11.909(2) Å, b = 13.046(2) Å, c = 15.144(3) Å, α = 99.617(4)°, β = 96.925(4)°, γ = 96.039(3)°, V = 2283.9 Å3, Z = 2, Rgt(F) = 0.048, wRref(F2) = 0.123, T = 293 K.

We synthesized four C60-(light-harvesting antenna) dyads C60 (>CPAF-Cn) (n = 4, 9, 12, or 18) 1-Cn for the investigation of their broadband nonlinear absorption effect. Since we have previously demonstrated their high function as two-photon absorption (2PA) materials at 1000 nm, a different 2PA wavelength of 780 nm was applied in the study. The combined data taken at two different wavelength ranges substantiated the broadband characteristics of 1-Cn. We proposed that the observed broadband absorptions may be attributed by a partial π-conjugation between the C60 > cage and CPAF-Cn moieties, via endinitrile tautomeric resonance, giving a resonance state with enhanced molecular conjugation. This transient state could increase its 2PA and excited-state absorption at 800 nm. In addition, a trend of concentration-dependent 2PA cross-section (σ2 ) and excited-state absorption magnitude was detected showing a higher σ value at a lower concentration that was correlated to increasing molecular separation with less aggregation for dyads C60(>CPAF-C18) and C60(>CPAF-C9), as better 2PA and excited-state absorbers.