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Tao Zhang,1 Zhu-Bin Pan,1 Wen-Jia Tong,2 Yu-Liang Zhou,1 Yuan Cheng,1 Dan-Qun Jin,2 Shi-Qin Qi,1 Zhen-Qiang Zhang1 1Department of General Surgery, Anhui Provincial Children’s Hospital, Children’s Hospital of Fudan University Anhui Hospital, Children’s Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of China; 2Department of Pediatric Intensive Care Unit, Anhui Provincial Children’s Hospital, Children’s Hospital of Fudan University Anhui Hospital, Children’s Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of ChinaCorrespondence: Zhu-Bin Pan, Department of General Surgery, Anhui Provincial Children’s Hospital, Children’s Hospital of Fudan University Anhui Hospital, Children’s Hospital of Anhui Medical University, No. 39 of Wang Jiang Dong Street, Bao He District, Hefei, 230000, People’s Republic of China, Tel +86 13349207050, Fax +86 551 62237461, Email panzhubinpzb5@126.comBackground: Paraneoplastic syndromes often cause endocrine, neurological, cutaneous, and hematologic pathologies, and cases with digestive symptoms as prominent cases are rare.Case Description: A 1-year-old child admitted to the emergency department with severe abdominal distension was later diagnosed with sacrococcygeal yolk cystoma with ulcerative colitis. After symptomatic management, surgical removal of the tumor, and JEB chemotherapy, the symptoms of ulcerative colitis disappeared completely. After 7 years of follow-up, the child grew and developed well, and there was no recurrence of tumor and ulcerative colitis.Conclusion: Yolk sac tumor with ulcerative colitis is a rare paraneoplastic syndrome with complex clinical manifestations.Keywords: children, paraneoplastic syndrome, toxic megacolon, ulcerative colitis, yolk sac tumor

Hao Zhang,1,* Ping Zhou,1,* Yi Jiang,1 Liu Li,1 Fei Ju,2 Quan Cheng,1 You Lang Zhou,2 Yuan Zhou1 1Department of Pain, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, People’s Republic of China; 2Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan Zhou; You Lang Zhou, Tel +86 0513 85052222 ; +86 0513 85052488, Email nina_shine@126.com; zhouyoulang@ntu.edu.cnIntroduction: Esketamine, one of the few non-opioid potent analgesics, has demonstrated efficacy in the treatment of various chronic pain, particularly neuropathic pain. However, its potential clinical applications are confined due to its short half-life and severe side effects including delirium, hallucinations, and other psychiatric symptoms. Here, we reported a nanosized drug delivery system for sustained-release esketamine based on polylactic-co-glycolic acid (PLGA) nanoparticles and hyaluronic acid (HA) hydrogel.Results: In this study, esketamine in the delivery system was continuously released in vitro for at least 21 days, and spinal nerve root administration of the delivery system successfully attenuated (spinal nerve ligation) SNL-induced pain hypersensitivity for at least 14 days. Notably, the excitability of neurons in murine dorsal root ganglion (DRG) was inhibited and the activation of astrocytes in the spinal cord was additionally reduced after administration. Finally, there was no obvious pathophysiological change in the nerves at the administration site after treatment at 14 days.Conclusion: These results indicate that the sustained-release esketamine based on the nanoparticle-hydrogel delivery system can safely produce a lasting analgesic effect on SNL mice, and its mechanism might be related to modulating the activation of astrocytes in the spinal cord and inhibiting the excitability of neurons in DRG.Keywords: esketamine, nanoparticles, hyaluronic acid hydrogel, neuropathic pain

An Wen,1,2 Er-Ling Leng,3 Wen-Feng Cao,1,2 Zheng-bing Xiang,1,2 Wei Rao,1,2 Wen Cai,1,2 Yong-Liang Zhou,1,2 Fan Hu,1,2 Ling-feng Wu,1,2 Ping Zhang,1,2 Shi-Min Liu1,2 1Department of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 2Institution of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 3Department of Pediatrics, Jiangxi provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of ChinaCorrespondence: Shi-Min Liu, Department of Neurology, Jiangxi provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), No. 92 Aiguo Road, Nanchang, 330006, People’s Republic of China, Tel +791-8772-1401, Email aifeng420@163.comObjective: Central nervous system (CNS) infection has a high incidence and mortality worldwide. Tuberculous meningitis (TBM) accounts for approximately 5– 6% of all extrapulmonary tuberculosis (TB), and is considered an extremely lethal form of CNS TB, which has become an important threat to human health. Anemia is a common symptom of TB, and its prevalence is generally higher in patients with TBM than in other meningitis patients and healthy individuals. Anemia can increase a person’s susceptibility to common infectious diseases, including TB, by compromising the immune system. Information regarding anemia during the hospitalization of TBM is still scarce in China. This study aimed to describe in detail the prevalence of anemia in patients with TBM in Southern China and its association with the clinical forms of TB, as well as other characteristics of these patients.Methods: We conducted a retrospective analysis of patients diagnosed with TBM at two tertiary hospitals in southern China. The demographic characteristics, clinical characteristics, and laboratory results of 114 patients with TBM were collected. Multivariate logistic regression analysis was performed to explore the risk factors for anemia in patients with TBM.Results: Electronic medical record data of adult patients diagnosed with TBM from January 2004 to December 2019 were reviewed. Among 134 patients with TBM, 20 were excluded and 114 were analyzed, of whom 33 had anemic, the prevalence rate of anemia was 28.9%. Among patients with anemia, 51.5% had hypochromic microcytic anemia, 33.3% had normochromic normocytic anemia, and 15.2% had macrocytic anemia. Fever duration, TBM grade III and ESR were found to be independent predictors of anemia.Conclusion: Anemia was highly prevalent in patients with TBM, mainly hypochromic microcytic anemia. Besides, Fever duration, TBM grade III and ESR are predictors of anemia in patients with TBM.Keywords: tuberculosis, tuberculous meningitis, anemia, risk factors, prediction

An Wen,1,2 Wen-Feng Cao,1,2 Shi-Min Liu,1,2 Yong-Liang Zhou,1,2 Zheng-Bing Xiang,1,2 Fan Hu,1,2 Ling-Feng Wu,1,2 Wen Cai,1,2 Er-Ling Leng3 1Department of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 2Institution of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 3Department of Pediatrics, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of ChinaCorrespondence: Er-Ling Leng, Department of Pediatrics, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), No.92 Aiguo Road, Nanchang, 330006, People’s Republic of China, Tel +86791-8772-1401, Email wenan666@sina.comObjective: Tuberculous meningitis (TBM) is a common form of central nervous system (CNS) tuberculosis (TB). Cranial nerve palsy is a serious complication of TBM. Literature regarding this subject is still limited in China. This study evaluated the incidence of cranial nerve palsy in patients with TBM in South China, its association with the clinical forms of TB, and other patient characteristics.Methods: A retrospective chart review of patients with a diagnosis of TBM between January 2004 and December 2019 was conducted, and the demographic characteristics, clinical characteristics, and laboratory results of 114 patients were collected and followed up for 3 months. A multivariate logistic regression analysis model was used to explore the risk factors of cranial nerve palsy in patients with TBM.Results: A total of 114 patients were enrolled in this study. Cranial nerve palsy was observed in approximately 38 (33.3%) of TBM patients. Among them, 13 (28.3%) had optic nerve palsy, 24 (52.2%) had oculomotor nerve palsy, 5 (10.9%) had abducens nerve palsy, 2 (4.3%) had auditory nerve palsy, 1 (2.2%) had glossopharyngeal nerve palsy, and 1 (2.2%) had vagus nerve palsy. Using logistic regression analysis, focal neurological deficit, extracranial TB and cerebrospinal fluid (CSF) total white cell count (WCC) were shown to be risk factors for cranial nerve palsy.Conclusion: The prevalence rate of cranial nerve palsy was 33.3% in patients with TBM. Focal neurological deficits, extracranial TB and CSF total WCC are important predictors of cranial nerve palsy in patients with TBM.Keywords: tuberculous meningitis, tuberculosis, cranial nerve palsy, risk factors, prediction

Li F, Wang F, Zhu C, Wei Q, Zhang T, Zhou YL. Int J Nanomedicine. 2018;13:2295–2307. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the integrity of the data and an investigation found overlap in images from Figure 4. Specifically, The image used in Figure 4D, 48 hours, Scramble has regions of overlap with Figure 4D, 48 hours, miR-221 inhibitor. The authors responded to our queries and provided data associated with the reported study. However, despite the authors’ assistance, a satisfactory explanation for how the images came to be duplicated could not be provided, and the validity of the published work could not be verified. The decision was made to retract 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”.

Feng Li,1,* Feiran Wang,2,* Changlai Zhu,3 Qun Wei,1 Tianyi Zhang,1 You Lang Zhou4 1Department of Gastroenterology, 2Department of General Surgery, Affiliated Hospital of Nantong University, 3Key Laboratory of Neuroregeneration, Nantong University, 4The Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China *These authors contributed equally to this work Background: MicroRNA-221(miR-221) is frequently dysregulated in cancer. The purpose of this study was to explore whether miR-221 can be used as a potential diagnostic marker or therapeutic target for hepatocellular carcinoma (HCC). Methods: In this study, we investigated whether miR-221 expression was associated with clinicopathological characteristics and prognosis in HCC patients, and we developed a nanoparticle-based miRNA delivery system and detected its therapeutic efficacy in vitro and in vivo. Results: We found that miR-221 was upregulated in HCC tissues, cell lines and blood of HCC patients. Upregulated miR-221 was associated with clinical TNM stage and tumor capsular infiltration, and showed poor prognosis, suggesting that its suppression could serve as an effective approach for hepatocellular carcinoma therapy. Treatment of HCC cells with nanoparticle/miR-221 inhibitor complexes suppressed their growth, colony formation ability, migration and invasion. In vivo, the growth of the tumors treated by the nanoparticle/miR-221 inhibitor complexes were significantly less than those treated by the nanoparticle/miRNA scramble complexes. In addition, circulating miR-221 may act as a potential tumor biomarker for early diagnosis of HCC, and combined serum miR-221 and AFP detection gave a better performance than individual detection in early diagnosis of HCC. Conclusion: These findings suggest that a nanoparticle-based miRNA delivery system could potentially serve as a safe and effective treatment and miR-221 could also be a potential diagnostic marker for HCC. Keywords: hepatocellular carcinoma, nanoparticle, miR-221, biomarker, therapeutic target

Li F, Wang F, Zhu C, Wei Q, Zhang T, Zhou YL. Int J Nanomedicine. 2018;13:2295–2307. The authors have advised Figure 2B on page 2301 is incorrect. Due to an error at the time of figure assembly B1 and B2 were duplicated. The correct Figure 2 is shown below. The authors apologize for this error and advise it does not affect the results of the paper. Read the original article

Ye Jin,1,4 Jingyuan Wen,2 Sanjay Garg,3 Da Liu,1 Yulin Zhou,1 Lirong Teng,1,* Weiyu Zhang,4,*1College of Life Science, Jilin University, Jilin, People’s Republic of China; 2School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; 3School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia; 4School of Pharmacy, Changchun University of Chinese Medicine, Jilin, People’s Republic of China *These authors contributed equally to this workBackground: The aim of this study was to develop an optimal niosomal system to deliver Ginkgo biloba extract (GbE) with improved oral bioavailability and to replace the conventional GbE tablets.Methods: In this study, the film dispersion-homogenization method was used to prepare GbE niosomes. The resulting GbE niosome suspension was freeze-dried or spray-dried to improve the stability of the niosomes. GbE-loaded niosomes were formulated and characterized in terms of their morphology, particle size, zeta potential, entrapment efficiency, and angle of repose, and differential scanning calorimetry analysis was performed. In vitro release and in vivo distribution studies were also carried out.Results: The particle size of the optimal delivery system prepared with Tween 80, Span 80, and cholesterol was about 141 nm. There was a significant difference (P < 0.05) in drug entrapment efficiency between the spray-drying method (about 77.5%) and the freeze-drying method (about 50.1%). The stability study revealed no significant change in drug entrapment efficiency for the GbE niosomes at 4°C and 25°C after 3 months. The in vitro release study suggested that GbE niosomes can prolong the release of flavonoid glycosides in phosphate-buffered solution (pH 6.8) for up to 48 hours. The in vivo distribution study showed that the flavonoid glycoside content in the heart, lung, kidney, brain, and blood of rats treated with the GbE niosome carrier system was greater than in the rats treated with the oral GbE tablet (P < 0.01). No flavonoid glycosides were detected in the brain tissue of rats given the oral GbE tablets, but they were detected in the brain tissue of rats given the GbE niosomes.Conclusion: Niosomes are a promising oral system for delivery of GbE to the brain.Keywords: Ginkgo biloba extract, flavonoid glycosides, niosomes, oral delivery, in vivo distribution

Background: Among the population without cardiovascular diseases (CVD), it is unclear whether pre-diabetes and/or prehypertension elevated the risk of all-cause and cardiovascular mortality., Methods: All participants without CVD at baseline were recruited from the 1999-2014 National Health and Nutrition Examination Survey (NHANES), with survival status being updated until 31 December 2015. Cox proportional hazards models and subgroup analyses were performed to estimate hazard ratios (HRs) and 95% confidence interval (CI)., Results: There were 23,622 participants (11,233 [47.6%] male) with mean age of 37.2 years. Compared to participants without prehypertension or pre-diabetes, the HRs for all-cause mortality among participants with prehypertension alone, pre-diabetes alone, and combined pre-diabetes and prehypertension were 1.04 (95% CI: 0.88, 1.24), 0.96 (95% CI:0.76, 1.21), and 1.19 (95% CI:0.98, 1.46), respectively. The corresponding HRs for cardiovascular mortality were 1.51 (95% CI: 0.83, 2.77), 1.40 (95% CI: 0.64, 3.06), and 1.70 (95% CI: 0.88, 3.27), respectively. A subgroup analysis showed that participants with combined pre-diabetes and prehypertension had a higher risk of all-cause mortality among younger participants, higher BMI, white population, and people with elevated non-HDLC. Moreover, the association between combined pre-diabetes and prehypertension and cardiovascular death was only significant among people with elevated non-HDLC., Conclusion: Pre-diabetes combined with prehypertension might elevate the risk of all-cause mortality among subjects, particularly for those with elevated body weight, high non-HDLC, younger participants or white population., Competing Interests: The authors declare that they have no conflicts of interest., (© 2020 Huang et al.)