Search

Li-Ping Ou,* Yong-Jian Liu,* Shi-Tong Qiu,* Chen Yang, Ji-Xin Tang, Xiao-Yu Li, Hua-Feng Liu, Zhen-Nan Ye Institute of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, and Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen-Nan Ye; Hua-Feng Liu, Email yezhennan12@mails.ucas.ac.cn; liuhf@gdmu.edu.cnAbstract: Metabolic reprogramming contributes to the progression and prognosis of various kidney diseases. Glutamine is the most abundant free amino acid in the body and participates in more metabolic processes than other amino acids. Altered glutamine metabolism is a prominent feature in different kidney diseases. Glutaminolysis converts glutamine into the TCA cycle metabolite, alpha-ketoglutarate, via a cascade of enzymatic reactions. This metabolic pathway plays pivotal roles in inflammation, maladaptive repair, cell survival and proliferation, redox homeostasis, and immune regulation. Given the crucial role of glutaminolysis in bioenergetics and anaplerotic fluxes in kidney pathogenesis, studies on this cascade could provide a better understanding of kidney diseases, thus inspiring the development of potential methods for targeted therapy. Emerging evidence has shown that targeting glutaminolysis is a promising therapeutic strategy for ameliorating kidney disease. In this narrative review, equation including keywords related to glutamine, glutaminolysis and kidney are subjected to an exhaustive search on Pubmed database, we identified all relevant articles published before 1 April, 2024. Afterwards, we summarize the regulation of glutaminolysis in major kidney diseases and its underlying molecular mechanisms. Furthermore, we highlight therapeutic strategies targeting glutaminolysis and their potential clinical applications.Keywords: glutamine, glutaminolysis, kidney diseases, therapeutic target

Cheng-Yi Hu,1 Wen-Shuai Cui,1 Yi Lei,1 Yu-Wen Tang,1 Yan-Yan Zhang,1 Qi-Min Su,1 Fang Peng,2 Yun-Fei Zeng,1 Jia-Lin Song,1 Cheng-Na Luo,1 Yan Zhou,1 Xin-Yan Li,1 Zhu-Xiang Zhao1 1Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 2Department of Critical Care Medicine, the Third Affiliated Hospital of Guang Zhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Zhu-Xiang Zhao, Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510515, People’s Republic of China, Email zhaozhuxiang@126.comPurpose: To compare the effectiveness of azvudine and nirmatrelvir/ritonavir for the treatment of coronavirus disease (COVID-19).Patients and Methods: We conducted a retrospective analysis of data from 576 patients with COVID-19, comprising 195 patients without antiviral therapy, 226 patients treated with azvudine, 114 patients treated with nirmatrelvir/ritonavir, and 41 patients were treated with azvudine and nirmatrelvir/ritonavir concurrently. We compared their symptoms, mortality rates, and the length and cost of hospitalization.Results: The incidence of symptoms was similar in patients treated with azvudine and in those treated with nirmatrelvir/ritonavir. However, among patients experiencing weakness, the duration of weakness was significantly shorter in the azvudine group than in the nirmatrelvir/ritonavir group (P=0.029). Mortality did not differ significantly between the azvudine group and the nirmatrelvir/ritonavir group (18.14% vs.10.53%, P=0.068). Among “severe patients”, the mortality rate was markedly lower in patients treated with nirmatrelvir/ritonavir than in patients treated with azvudine (16.92% vs.32.17%, P=0.026). In patients with hepatic insufficiency, those treated with nirmatrelvir/ritonavir had substantially lower mortality than those treated with azvudine (15.09% vs.34.25%, P=0.016). In addition, patients treated with nirmatrelvir/ritonavir had longer hospital stays (P=0.002) and higher hospital costs (P< 0.001) than those receiving azvudine. Compared with patients treated with nirmatrelvir/ritonavir or azvudine alone, patients taking nirmatrelvir/ritonavir and azvudine concurrently had no significant improvement in survival (P> 0.05), length of stay (P> 0.05), or hospital costs (P> 0.05).Conclusion: Azvudine is recommended for patients with non-severe COVID-19 with weakness. Nirmatrelvir/ritonavir is recommended for patients with severe COVID-19, to reduce mortality, and it could be the best choice for patients with hepatic insufficiency. The concurrent use of nirmatrelvir/ritonavir and azvudine in patients with COVID-19 could be not recommended.Keywords: azvudine, nirmatrelvir/ritonavir, COVID-19, SARS-CoV-2

Xiu-Jie Zhao,1 Chun-Yu Bai,2 Xiao-Yan Li,1 Lei Wang,2 Ren-Ping Wang,2 Yue Xia,1,2 Gang Liu,1 Hong-Liang Zhao,1,&ast; Hong-Zun Xu2,&ast; 1Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People’s Republic of China; 2Department of Cardiology, Shijiazhuang Great Wall Cardiovascular Hospital, Shijiazhuang, 050035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-Liang Zhao; Hong-Zun Xu, Email Doc_zhl@163.com; 116281970@qq.comAbstract: Carvajal syndrome is a rare hereditary cardiocutaneous syndrome caused by the variants of the desmoplakin (DSP) gene. In this study, we report a patient of Carvajal syndrome with a novel homozygous missense variant of DSP gene. We diagnosed a 7-year-old female patient with Carvajal syndrome characterized by dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia, who disclosed a novel homozygous missense variant c.4597C > T (p.Q1533X) in exon 6 of the DSP gene found for the first time. Both her parents were heterozygous for the identified nonsense variant c.4597C > T (p.Q1533X) in DSP gene but neither showed evidence of Carvajal syndrome, indicating that this novel variant causes the disease in an autosomal recessive manner. Genotypes of Carvajal syndrome are even broader than so far anticipated. When patients with dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia are found in clinical practice, Carvajal syndrome should be highly suspected, and family gene sequencing should be actively carried out.Keywords: Carvajal syndrome, desmoplakin, genotype, variant, novel

Xiao-Yan Li,1 Xin-Guang Liu,2 Zhi-Ling Dong,1 Liang-Ting Chai,3 Yan-Jun Liu,4 Jie Qi,3 Jie Zhao1 1Department of Clinical Laboratory, Handan Central Hospital, Handan, Hebei, People’s Republic of China; 2Department of Clinical Laboratory, Children’s Hospital of Hebei, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Clinical Laboratory, Handan First Hospital, Handan, Hebei, People’s Republic of China; 4Department of General Surgery, Handan Central Hospital, Handan, Hebei, People’s Republic of ChinaCorrespondence: Jie Zhao, No. 59 Congtai North Road, Congtai District, Handan City, Hebei Province, 057150, People’s Republic of China, Tel +86-18003205055, Email zjlxy8160@163.comBackground: Drug-resistant Pseudomonas aeruginosa infections rapidly increased and contributed to life-threatening nosocomial infections; however, the distribution, species, drug susceptibility and dynamic trends of P. aeruginosa infection in China remained unclear. This study was conducted to better understand the epidemiological data of increased P. aeruginosa infections from 2016 to 2022 in a hospital in China.Methods: This study involved 3301 patients infected with P. aeruginosa, diagnosed using a nosocomial infection surveillance system in a tertiary hospital between 2016 and 2022. The P. aeruginosa infections from 2016 to 2022 were assessed according to the hospital department and species, and the drug susceptibility was evaluated using 16 antimicrobial agents.Results: The P. aeruginosa infection prevalence in the hospital department was: Neurosurgery (14.30%), Emergency (13.30%), and Critical Care Medicine (11.69%). Samples for P. aeruginosa infection identification were from sputum (72.52%) and other secreta (9.91%). The P. aeruginosa infections demonstrated a greater sensitivity to amikacin (AMK, 91.82%), tobramycin (TOB, 82.79%), and gentamycin (GEN, 82.01%); however, P. aeruginosa infection demonstrated greater resistance to ticarcillin (22.57%), levofloxacin (21.63%), and ciprofloxacin (18.00%).Conclusion: The P. aeruginosa infections were commonly observed in the Neurosurgery, Emergency, and Critical Care Medicine departments and demonstrated greater sensitivity to AMK, TOB, and GEN than the other drugs.Keywords: Pseudomonas aeruginosa, distribution, drug susceptibility, dynamic trend

David Callanan,1 Rahul N Khurana,2 Raj K Maturi,3,4 Sunil Patel,5 Charles C Wykoff,6 David Eichenbaum,7,8 Arshad M Khanani,9,10 Tarek Hassan,11 Hanh Badger,12 Shraddha Mehta,12 Grace Le,12 Mayssa Attar,13 Jennifer Seal,13 Xiao-Yan Li12,14 1Texas Retina Associates, Arlington, TX, USA; 2Northern California Retina Vitreous Associates, Mountain View, CA, USA; 3Midwest Eye Institute, Indianapolis, IN, USA; 4Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA; 5West Texas Retina, Abilene, TX, USA; 6Retina Consultants of Houston, Retina Consultants of America, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA; 7Retina Vitreous Associates of Florida, St. Petersburg, FL, USA; 8Morsani College of Medicine, University of South Florida, Tampa, FL, USA; 9Sierra Eye Associates, Reno, NV, USA; 10University of Nevada, Reno School of Medicine, Reno, NV, USA; 11Associated Retinal Consultants, Royal Oak, MI, USA; 12Allergan plc, Irvine, CA, USA, at the time of this work; 13Allergan, an AbbVie company, Irvine, CA, USA; 14VivaVision Biotech, Inc, Shanghai, People’s Republic of ChinaCorrespondence: David Callanan, Texas Retina Associates, 801 West Randol Mill Road, Suite 101, Arlington, TX, USA, 76012, Tel +1 817-261-9625, Fax +1 817-261-9586, Email dcallanan@gmail.comPurpose: To evaluate the impact of modifying the abicipar pegol (abicipar) manufacturing process on the safety and treatment effect of abicipar in patients with neovascular age-related macular degeneration (nAMD).Methods: A new process for manufacturing abicipar was developed to reduce host cell impurities. In a prospective, Phase 2, multicenter, open-label, 28-week clinical trial, patients (n=123) with active nAMD received intravitreal injections of abicipar 2 mg at baseline (day 1) and weeks 4, 8, 16, and 24. Outcome measures included proportion of patients with stable vision (< 15-letter loss from baseline; primary endpoint), change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and adverse events.Results: Overall, 8.9% (11/123) of patients experienced intraocular inflammation (IOI) and discontinued treatment. IOI cases were assessed as mild (2.4% [3/123]), moderate (4.9% [6/123]), or severe (1.6% [2/123]) and resolved with steroid treatment. Visual acuity in most patients with IOI (8 of 11) recovered to baseline BCVA or better by study end. No cases of endophthalmitis or retinal vasculitis were reported. Stable vision was maintained for ≥ 95.9% (≥ 118/123) of patients at all study visits. At week 28, treatment-naïve patients showed a greater mean improvement from baseline in BCVA compared with previously treated patients (4.4 vs 1.8 letters) and a larger mean CRT reduction from baseline (98.5 vs 45.5 μm).Conclusion: Abicipar produced using a modified manufacturing process showed a moderately lower incidence and severity of IOI compared with Phase 3 abicipar studies. Beneficial effects of treatment were demonstrated.Keywords: abicipar, age-related macular degeneration, inflammation

Xin-Qi He,1,&ast; Hui-Qing Qiu,2,&ast; Meng Wang,3,&ast; Ya-Fei Mao,4 Xin-Yuan Li,4 Xian-Yun Wang,5 Yu-Lan Geng,4 Le Wang6 1Department of Vascular Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Radiology and Nuclear Medicine, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Department of Laboratory Medicine, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 5Scientific Research Data Center, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 6Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu-Lan Geng, Department of Laboratory Medicine, The First Hospital of Hebei Medical University, No. 89 of Donggang Road, Yuhua District, Shijiazhuang, 050031, People’s Republic of China, Tel +86 311 87156567, Fax +86 311 85917029, Email ylgeng123@163.com Le Wang, Department of Cardiology, The First Hospital of Hebei Medical University, No. 89 of Donggang Road, Yuhua District, Shijiazhuang, 050031, People’s Republic of China, Tel +86 311 87155263, Fax +86 311 85917029, Email coronary2012@163.comBackground: A thoracic aortic aneurysm (TAA) is a known condition seen in cardiovascular practice. A TAA rupture and postoperative infection may result in death. Preoperative infections leading to death are extremely rare.Case Study: A 62-year-old Chinese female was admitted to The First Hospital of Hebei Medical University with a two-day history of abdominal pain. She was diagnosed with a TAA rupture and underwent immediate surgery. The preoperative urine analysis indicated that the positive bacteria and white blood cell count suggested a urinary tract bacterial infection. The patient was administered the empiric antibiotics, cefazolin; however, her blood pressure continued to drop during the perioperative period and she died of uncorrectable acidosis 8 h after the operation. On the second day after death, both the blood and urine cultures were positive for Pseudomonas aeruginosa.Conclusion: Given that this patient with a TAA rupture died of uncorrected acidosis caused by preoperative infection, it is important to evoke the diagnosis in the context of TAA. Routine laboratory indicators are valuable factors for surgeons and physicians in assessing a patient’s condition and improving their prognosis.Keywords: thoracic aortic aneurysm, infection, sepsis, acidosis, urine routine, emergency surgery, empirical medication, Pseudomonas aeruginosa

Xiao-Yan Li,1,&ast; Shu-Min Zhu,2,&ast; Xin-Yuan Li,2,&ast; Rui-Sheng Dong,3 Ai-Ai Zhang,1 Shu-Jing Li,4 Yu-Lan Geng2 1Department of Laboratory Medicine, Shanxi Province Fenyang Hospital, Fenyang, 032200, People’s Republic of China; 2Department of Laboratory Medicine, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People’s Republic of China; 3Department of Imaging Medicine, Shanxi Province Fenyang Hospital, Fenyang, 032200, People’s Republic of China; 4Department of Radiology, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Yan Li, Department of Laboratory Medicine, Shanxi Province Fenyang Hospital, No. 186 of Shengli Road, Fenyang, Shanxi, 032200, People’s Republic of China, Tel +86 358 7222225, Fax +86 358 7222615, Email lixiaoyanlxy8@126.com Yu-Lan Geng, Department of Laboratory Medicine, The First Hospital of Hebei Medical University, No. 89 of Donggang Road, Shijiazhuang, Hebei, 050031, People’s Republic of China, Tel +86 311 87156567, Fax +86 311 85917029, Email gengyulangyl9@126.comBackground: Hemophagocytic lymphohistiocytosis (HLH), a syndrome of immune hyperactivation and abnormal regulation that causes life-threatening inflammation, is mainly characterized by fever, hepatosplenomegaly, cytopenia, and other symptoms. Reactive HLH (rHLH) is typically secondary to immune deregulation caused by underlying rheumatologic, infectious, or malignant conditions. Malignancy-associated HLH (M-HLH) continues to be a critical health problem worldwide. Most malignancies associated with HLH are hematologic tumors, and M-HLH in non-hematologic tumors very rarely occurs.Case Report: A 34-year-old Chinese woman had a history of persistent fever, acute dizziness, and bicytopenia. She was found to have developed bilateral ovarian cancer. Additional tests showed splenomegaly, hemophagocytes in the bone marrow, low natural killer activity, and hyperferritinemia, which met the diagnostic criteria put forth in the Histiocyte Society HLH-2004. The patient was treated with correcting anemia, increased platelets, and glucocorticoid therapy but showed no response. She progressively deteriorated and died 55 days later.Conclusion: Hemophagocytic lymphohistiocytosis related to a solid tumor is extremely rare. To the best of the authors’ knowledge, the present case was the first to report rHLH secondary to ovarian adenocarcinoma. It is very significant for a better understanding of the disease mechanisms of HLH and should attract the attention of hematologists and other clinicians as the condition progresses and the cost of treating it increases.Keywords: ovarian adenocarcinoma, reactive hemophagocytic lymphohistiocytosis, hyperferritinemia, cytopenia, high reticulocyte, natural killer activity

Xin-Yu Li,1,2 Xi-Tao Yang1 1Department of Interventional Therapy, Multidisciplinary Team of Vascular Anomalies, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Xi-Tao Yang, Department of Interventional Therapy, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Huangpu District, Shanghai, 200011, People’s Republic of China, Email xitao123456@126.comBackground: RNA methylation is one of the most common RNA modifications and is dynamic and reversible. The enzymes and downstream effectors associated with RNA methylation modifications can be targeted to regulate RNA methylation levels. This mechanism can affect RNA processing, metabolism, cell proliferation and migration, and regulation of physiological or pathological processes. The aim of this study was to investigate the role of RNA methylation-related genes in hepatocellular carcinoma (HCC).Methods: Baseline RNA methylation data were extracted from The Cancer Genome Atlas database. The expression pattern, predictive value, mutational profile, and interaction network of RNA methylation genes in pancancer were examined. Then, the association between the expression of RNA methylation genes and immune infiltration was investigated. In addition, a risk score model for HCC was developed and analyzed.Results: Cancer cells had a higher expression of RNA methylation genes than normal cells in some cancer cells, and a higher expression of RNA methylation genes could negatively affect patient prognosis. Enrichment analysis revealed that RNA methylation genes are involved in the mRNA surveillance pathway and RNA degradation and transport. A 4-gene (ALYREF, NSUN4, TRMT6, YTHDF1) prognostic signature was established to predict HCC prognosis based on RNA methylation-related genes. Finally, the role of prognostic models in HCC was validated.Conclusion: RNA methylation genes can be an indicator of oncogenicity in relation to HCC prognosis and are associated with immune infiltration in the tumour microenvironment. This finding could provide clinicians with the opportunity to explore new strategic approaches.Keywords: RNA methylation, pan-cancer, genes

Xiao-Yuan Li,1,&ast; Yang Rao,2,&ast; Bing Sun,3 Xue-Mei Mao4 1Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2Department of Gynecological Oncology, Tianjin Central Obstetrics and Gynecology Hospital, Tianjin, 300199, People’s Republic of China; 3Department of Radiation Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, 100071, People’s Republic of China; 4Department of Obstetrics and Gynecology, Tianjin Integrated Traditional Chinese and Western Medicine Hospital (Nankai Hospital), Tianjin, 300102, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue-Mei Mao; Bing Sun, Tel +86 13820312420 ; +86 13810193881, Email mxm0206@163.com; sunice116@163.comPurpose: This study was to investigate the efficacy and safety of anlotinib combined with programmed cell death protein 1 (PD-1) blockades for patients with previously treated advanced epithelial ovarian cancer (EOC).Patients and Methods: Present study was designed as a retrospective study, a total of 32 patients with advanced EOC who progressed after at least two lines previously available standard therapy were included in this study. All the patients were administered with anlotinib combined with PD-1 blockades administration. Clinical activity was implemented and analyzed, which was assessed according to the change of target lesion by imaging evidence and all the subjects were followed up regularly. Safety profile were collected and documented during the treatment. Univariate analysis was carried out using log rank test and multivariate analysis were adjusted by Cox regression analysis.Results: The best overall response suggested that partial response was noted in 12 patients, stable disease was observed in 14 patients, progressive disease was found in 6 patients. Therefore, the objective response rate (ORR) of the 32 patients was 37.5% (95% CI: 21.1– 56.3%), disease control rate (DCR) of the patients was 81.3% (95% CI: 63.6– 92.8%). The median follow-up duration of this study was 17.5 months (follow-up range: 0.9– 33.5 months). And the median PFS and OS of the 32-patient cohort was 6.8 months (95% CI: 2.64– 10.96) and 18.5 months (95% CI: 14.08– 22.92), respectively. The most common treatment-related adverse reactions were fatigue (68.8%), nausea and vomiting (56.3%), hypertension (50.0%) and diarrhea (40.6%). Multivariate Cox regression analysis for PFS indicated that ECOG performance status and FIGO stage were independent factors to predict PFS of patients with previously treated EOC.Conclusion: Anlotinib combined with PD-1 blockades demonstrated promising efficacy and tolerable safety profile for patients with previously treated advanced EOC preliminarily. The conclusion should be confirmed in more patients with advanced EOC subsequently.Keywords: epithelial ovarian cancer, anlotinib, PD-1 blockade, efficacy, safety

Peng Cui,1– 3 Peng Wang,1– 3 Chao Kong,1– 3 Xiang Yu Li,1– 3 Shuai Kang Wang,1– 3 Jia Lin Wang,1– 3 Xu Liu,1– 3 Shi Bao Lu1– 3 1Department of Orthopedics, Xuanwu Hospital Capital Medical University, Beijing, People’s Republic of China; 2National Clinical Research Center for Geriatric Diseases, Beijing, People’s Republic of China; 3Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Shi Bao Lu, Email spinelu@163.comPurpose: To compare pain scores (visual analog scale) on postoperative days 1– 3 and length of stay after implementing enhanced recovery after surgery (ERAS) in elderly patients undergoing multi-segments lumbar fusion surgery.Methods: We performed a retrospective analysis of prospectively collected data, patients older than 75 years were enrolled in the study. We selected two periods, before (Pre-ERAS, n =54 patients) and after (ERAS, n =46 patients) implementation of ERAS. Data were collected on patient demographics, operative and perioperative details, 30-day readmission. The primary outcome was the length of stay (LOS), and the secondary outcomes were postoperative mean pain scores on postoperative days (POD) 1– 3 and 30-day readmission rates.Results: A total of 100 patients (46 in ERAS and 54 in pre-ERAS) were enrolled in this study. There were no significant differences in age, sex, body mass index (BMI), smoking and comorbidities between the groups. However, there was a significant difference in pain on postoperative day (POD) 1 (5.31 ± 1.98 vs 4.37 ± 0.85, p = 0.002), while there was no difference in postoperative complications. The mean LOS was significantly shorter in the ERAS than in the pre-ERAS group, it reduced from 12.29 ± 3.93 to 9.45 ± 2.72 days (p < 0.001).Conclusion: To our knowledge, this is the first ERAS protocol used in patients (older than 75 years) undergoing polysegmental lumbar fusion surgery. Pain scores on POD 1 and LOS were significantly lower without increased adverse events after implementation of ERAS. This finding suggests that elderly people (> 75 years of age) undergoing polysegmental lumbar fusion surgery could also benefit from ERAS.Keywords: enhanced recovery after surgery, elderly, multi-segment, lumbar fusion surgery

Xue-Jun Wang,1,&ast; Xiao-Ying Li,1,&ast; Xiao-Cong Guo,1,&ast; Li Liu,1 You-You Jin,1 Yun-Qiong Lu,1 Yao-Jia-Ni Cao,1 Jun-Yi Long,1 Huan-Gan Wu,2 Dan Zhang,2 Guang Yang,2 Jue Hong,2 Yan-Ting Yang,2 Xiao-Peng Ma1,2 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Key Laboratory of Acupuncture-Moxibustion and Immunology, Shanghai Research Institute of Acupuncture and Meridian, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Peng Ma; Yan-Ting Yang, Key Laboratory of Acupuncture-Moxibustion and Immunology, Shanghai Research Institute of Acupuncture and Meridian, Shanghai, People’s Republic of China, Email pengpengma@163.com; tcmyyt@126.comBackground: Long noncoding RNA (lncRNA) is receiving growing attention in Crohn’s disease (CD). However, the mechanism by which herb-partitioned moxibustion (HPM) regulates the expression and functions of lncRNAs in CD rats is still unclear. The aim of our study is to identify lncRNA-miRNA-mRNA network potential biological functions in CD.Methods: RNA sequencing and microRNA (miRNA) sequencing were carried out to analyze lncRNA, miRNA and mRNA expression profiles among the CD rats, normal control rats, and CD rats after HPM treatment and constructed the potential related lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein–protein interaction (PPI) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to explore potentially important genes in ceRNA networks.Results: A total of 189 lncRNAs, 32 miRNAs and 463 mRNAs were determined as differentially expressed (DE) genes in CD rats compared to normal control rats, and 161 lncRNAs, 12 miRNAs and 130 mRNAs were identified as remarkably DE genes in CD rats after HPM treatment compared to CD rats. GO analysis indicated that the target genes were most enriched in cAMP and in KEGG pathway analysis the main pathways included adipocytokine, PPAR, AMPK, FoxO and PI3K-Akt signaling pathway. Finally, qRT-PCR results confirmed that lncRNA LOC102550026 sponged miRNA-34c-5p to regulate the intestinal immune inflammatory response by targeting Pck1.Conclusion: By constructing a ceRNA network with lncRNA-miRNA-mRNA, PCR verification, and KEGG analysis, we revealed that LOC102550026/miRNA-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways might regulate the intestinal immune-inflammatory response, and HPM may regulate the lncRNA LOC102550026/miR-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways, thus improving intestinal inflammation in CD. These findings may be novel potential targets in CD.Keywords: herb-partitioned moxibustion, Crohn’s disease, lncRNA, ceRNA, lncRNA LOC102550026/miR-34c-5p/Pck1 axis

Wenbin Wei,1 Youxin Chen,2 Bojie Hu,3 Mingwei Zhao,4 Mei Han,5 Hong Dai,6 Harvey S Uy,7 Michelle Y Chen,8 Kate Wang,8 Jenny Jiao,8 Jean Lou,8 Xiao-Yan Li8 1Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China; 4Peking University People’s Hospital, Beijing, People’s Republic of China; 5Tianjin Eye Hospital, Tianjin, People’s Republic of China; 6Beijing Hospital, Beijing, People’s Republic of China; 7Peregrine Eye and Laser Institute, Makati City, Philippines; 8Allergan, an AbbVie company, Irvine, CA, USACorrespondence: Wenbin WeiBeijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang, Dongcheng District, Beijing, 100730, People’s Republic of ChinaEmail tr_weiwenbin@163.comPurpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant 0.7 mg (DEX) compared with laser photocoagulation in patients with diabetic macular edema (DME).Patients and Methods: This Phase 3, multicenter, randomized, efficacy evaluator–masked, parallel-group, 12-month clinical study enrolled adults in China and the Philippines with reduced visual acuity secondary to fovea-involved DME in the study eye. Participants were randomized 1:1 to study eye treatment with laser photocoagulation every 3 months as needed (n = 139) or DEX every 5 months (n = 145). The main efficacy measures were best-corrected visual acuity (BCVA), central retinal thickness (CRT), and leakage area. The primary endpoint was the average change in BCVA from baseline over 12 months (area-under-the-curve method). Preplanned subgroup analyses evaluated outcomes in Chinese patients.Results: Mean average change in BCVA from baseline during the study (letters) was 4.3 with DEX (n = 145) versus 1.4 with laser (n = 127) overall (P = 0.001) and 4.6 with DEX (n = 129) versus 0.6 with laser (n = 113) in Chinese patients (P < 0.001). At Month 12, mean change in CRT from baseline was − 209.5 μm with DEX versus − 120.3 μm with laser (P < 0.001) and mean change in total leakage area from baseline was − 8.367 mm2 with DEX versus − 0.637 mm2 with laser (P < 0.001). The most common treatment-emergent adverse events in the DEX group were increased intraocular pressure and cataract.Conclusion: DEX administered every 5 months provided significantly greater improvement in BCVA, CRT, and total leakage area compared with laser treatment. DEX demonstrated an acceptable safety profile, consistent with an intraocular corticosteroid, and similar to that reported in completed global registration studies.Keywords: central retinal thickness, corticosteroid, dexamethasone, diabetic retinopathy, drug delivery device, laser photocoagulation, randomized controlled trial, macular edema, visual acuity

Xin-Ying Li,1 Shuang Yao,1 Yang-Ting He,1 Song-Qing Ke,1 Yi-Fei Ma,2 Ping Lu,3 Shao-Fa Nie,1 Shao-Zhong Wei,2 Xin-Jun Liang,3 Li Liu1 1Department of Epidemiology and Biostatistics, The Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Gastrointestinal Oncology Surgery, Hubei Cancer Hospital, The Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Abdominal Oncology, Hubei Cancer Hospital, The Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Li LiuDepartment of Epidemiology and Biostatistics, the Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaTel/Fax +86-27-83693763Email liul2012@hust.edu.cnXin-Jun LiangDepartment of Abdominal Oncology, Hubei Cancer Hospital, The Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaTel/Fax +86-27-87671663Email doctorlxj@163.comPurpose: This study was designed to investigate the prognostic value of the combination of high-sensitivity C-reactive protein, lymphocyte, and albumin in patients with resectable colorectal cancer.Patients and Methods: Seven-hundred-and-nineteen patients who underwent colorectal cancer resection in Hubei Cancer Hospital were included. Inflammation-Immunity-Nutrition score (0– 6) was constructed based on preoperative high-sensitivity C-reactive protein, lymphocyte, and albumin. Time-dependent receiver operating characteristic curve, decision curve, Kaplan-Meier survival curve, Cox regression, and C-index were conducted to detect the prognostic values of inflammation-immunity-nutrition score. The prognostic values of inflammation-immunity-nutrition score in different subgroups by sex, location of tumor, pathologic stage, and KRAS mutation were also explored. The prognostic performance of inflammation-immunity-nutrition score was further compared with that of other traditional prognostic indicators.Results: The median follow-up time was 40 months. High inflammation-immunity-nutrition score (> 2 scores) presented worse survival, with the adjusted hazard ratios (95% confidence intervals) of 3.106 (2.202– 4.380) for overall survival and 2.105 (1.604– 2.764) for disease-free survival. Besides, the associations of high inflammation-immunity-nutrition score with overall survival were even stronger in cases with wild type KRAS, with the adjusted hazard ratios (95% confidence intervals) of 4.018 (2.355– 6.854). Considering the AUCs, C-indices, and hazard ratios estimates, inflammation-immunity-nutrition score presented better prognostic performance than high-sensitivity modified Glasgow prognostic score, high-sensitivity C-reactive protein to albumin ratio, prognostic nutrition index, carcinoembryonic antigen, and carbohydrate antigen 19-9 for overall survival.Conclusion: Inflammation-immunity-nutrition score might serve as a powerful prognostic score in patients with colorectal cancer for overall survival, particularly in patients with wild type KRAS.Keywords: high-sensitivity C-reactive protein, survival, colorectal cancer, inflammation

Yi-Fang Meng,1,2,* Qi Pu,1,* Qian Ma,1 Wei Zhu,2 Xin-Yu Li1 1Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Ophthalmology, Changshu No. 2 People’s Hospital, Changshu, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin-Yu LiDepartment of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People’s Republic of ChinaTel/Fax +86-027-83663456Email xinyu@tjh.tjmu.edu.cnWei ZhuDepartment of Ophthalmology, Changshu No. 2 People’s Hospital, Changshu, Jiangsu, People’s Republic of ChinaEmail shzhuwei0722@163.comBackground: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been used as indicators of inflammation, however, their roles in dry eye disease (DED) patients require advanced studyMaterials and Methods: A total of 104 DED cases and 97 healthy controls from January 2020 to May 2020 were enrolled in this study. The dry eye related clinical variables, including Schirmer I test, tear break-up time (TBUT), corneal fluorescein staining (CFS) and Ocular Surface Disease Index (OSDI), were detected in all the participants. Besides, the NLR and PLR pattern in DED cases were detected and their potential value as inflammatory predictors of DED were evaluated. In advanced analyses, the correlation between NLR and DED severity was examined.Results: The NLR and PLR were 2.59 ± 1.25 and 117.48 ± 54.68 in the DED group, respectively, while they were 2.20 ± 1.24 and 115.48 ± 54.33 in the control group, respectively. The NLR was higher in the DED group (p = 0.027), however, PLR was not significantly different compared with the control group (p = 0.951). In advanced analyses, it was found that more severe TBUT, CFS, and OSDI scores were detected in the high NLR group (NLR ≥ 2.145, p = 0.003, 0.013, and 0.017, respectively) compared with the low NLR group (NLR < 2.145).Conclusion: The NLR value, but not PLR, of DED patients was higher than that of healthy controls. The NLR could be used as an inflammatory predictor to estimate the severity of DED.Keywords: dry eye disease, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, case-control study, risk factor

Yun-Xiao Zhang,1,2 Dong-Liang Mu,1 Ke-Min Jin,3 Xue-Ying Li,4 Dong-Xin Wang1,5 1Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), The Department of Anesthesiology, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 3Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), The First Department of Hepatic, Biliary & Pancreatic Surgery, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 4Department of Biostatistics, Peking University First Hospital, Beijing, People’s Republic of China; 5Outcomes Research Consortium, Cleveland, Ohio, United States of AmericaCorrespondence: Dong-Xin WangDepartment of Anesthesiology and Critical Care Medicine, Peking University First Hospital, No. 8 Xishiku Street, Beijing 100034, People’s Republic of ChinaTel +8610 83572784Fax +86 10 66551057Email dxwang65@bjmu.edu.cnPurpose: Perioperative anesthetic management may affect long-term outcome after cancer surgery. This study investigated the effect of perioperative glucocorticoids on long-term survival in patients after radical resection for pancreatic cancer.Methods: In this retrospective cohort study with propensity score-matching, patients who underwent radical resection for pancreatic cancer from January 2005 to December 2016 were recruited. Baseline and perioperative data including use of glucocorticoids for prevention of postoperative nausea and vomiting were collected. Patients were followed up by qualified personnel for cancer recurrence and survival. The primary outcome was the recurrence-free survival. Outcomes were compared before and after propensity matching. The association between perioperative glucocorticoid use and recurrence-free survival was analyzed with multivariable regression models.Results: A total of 215 patients were included in the study; of these, 112 received perioperative glucocorticoids and 103 did not. Patients were followed up for a median of 74.0 months (95% confidence interval [CI] 68.3– 79.7). After propensity score-matching, 64 patients remained in each group. The recurrence-free survivals were significantly longer in patients with glucocorticoids than in those without (full cohort: median 12.0 months [95% CI 6.0– 28.0] vs 6.9 months [4.2– 17.0], P< 0.001; matched cohort: median 12.0 months [95% CI 5.8– 26.3] vs 8.3 months [4.3– 18.2], P=0.015). After correction for confounding factors, perioperative glucocorticoids were significantly associated with prolonged recurrence-free survivals (full cohort: HR 0.66, 95% CI 0.48– 0.92, P=0.015; matched cohort: HR 0.54, 95% CI 0.35– 0.84, P=0.007).Conclusion: Perioperative use of low-dose glucocorticoids is associated with improved recurrence-free survival in patients following radical surgery for pancreatic cancer.Keywords: pancreatic cancer, surgery, perioperative management, glucocorticoids, survival

Li-Hong Han,1,2,* Yan-Yan Xue,1,* Yi-Cen Zheng,3 Xiao-Yan Li,1 Rong-Rong Lin,1 Zhi-Ying Wu,1 Qing-Qing Tao1 1Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Neurology, Second People’s Hospital of Luqiao District, Taizhou, People’s Republic of China; 3Department of Psychology, Tulane University School of Science and Engineering, New Orleans, LA, USA*These authors contributed equally to this workCorrespondence: Zhi-Ying Wu; Qing-Qing Tao Email zhiyingwu@zju.edu.cn; qingqingtao@zju.edu.cnObjective: Early-onset dementia (EOD) is a relatively uncommon form of dementia that afflicts people before age 65. Only a few studies analyzing the genetics of EOD have been performed in the Chinese Han population. Diagnosing EOD remains a challenge due to the diverse genetic and clinical heterogeneity of these diseases. The aim of this study was to investigate the genetic spectrum and clinical features of Chinese patients with EOD.Materials and Methods: A total of 49 EOD patients were recruited. Targeted next-generation (NGS) analyses were performed to screen for all of the known genes associated with dementia. Possible pathogenic variants were confirmed by performing Sanger sequencing. The genetic spectrum and clinical features of the EOD patients were analyzed.Results: Seven previously reported pathogenic variants (p.I213T and p.W165C in PSEN1; p.D678N in APP; c.1349_1352del in TBK1; p.P301L and p.R406W in MAPT; p.R110C in NOTCH3) and two novel variants of uncertain significance (p.P436L in PSEN2; c.239-11G>A in TARDBP) were identified.Conclusion: Our study demonstrated the genetic spectrum and clinical features of EOD patients, and it reveals that genetic testing of known causal genes in EOD patients can help to make a precise diagnosis.Keywords: Chinese, genetic analysis, early-onset dementia, next-generation sequencing

Ping Zhang,1,* Ying-Xue Li,1,* Zhe-Zhe Zhang,2 Ye Yang,1 Ji-Xian Rao,1 Lan Xia,3 Xue-Yan Li,1 Gui-Hai Chen,1 Fang Wang2 1Department of Sleep Disorders, The Affiliated Chaohu Hospital of Anhui Medical University, Hefei 238000, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fang WangDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, People’s Republic of ChinaTel/Fax +86-551-62922426Email doctorwangfang2006@163.comGui-Hai ChenDepartment of Sleep Disorders, The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, (Chaohu) 238000, People’s Republic of ChinaTel/Fax +86-551-82324252Email doctorcgh@163.comPurpose: The objective of this study was to investigate whether the serum biomarkers S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) change in patients with chronic insomnia disorder (CID), and if this is the case, whether the altered levels of these serum biomarkers are associated with poor sleep quality and cognitive decline in CID.Patients and Methods: Fifty-seven CID outpatients constituted the CID group; thirty healthy controls (HC) were also enrolled. Questionnaires, polysomnography, Chinese-Beijing Version of Montreal Cognitive Assessment (MoCA-C) and Nine Box Maze Test (NBMT) were used to assess their sleep and neuropsychological function. Serum S100B, GFAP, BDNF, and GDNF were evaluated using enzyme-linked immunosorbent assay.Results: The CID group had higher levels of S100B and GFAP and lower levels of BDNF and GDNF than the HC group. Spearman correlation analysis revealed that poor sleep quality, assessed by subjective and objective measures, was positively correlated with S100B level and negatively correlated with BDNF level. GFAP level correlated positively with poor subjective sleep quality. Moreover, S100B and GFAP levels correlated negatively with general cognitive function assessed using MoCA-C. GFAP level correlated positively with poor spatial working memory (SWM) in the NBMT; BDNF level was linked to poor SWM and object recognition memory (ORcM) in the NBMT. However, principal component analysis revealed that serum S100B level was positively linked to the errors in object working memories, BDNF and GDNF concentrations were negatively linked with errors in ORcM, and GFAP concentration was positively correlated with the errors in the SWM and spatial reference memories.Conclusion: Serum S100B, GFAP, BDNF, and GDNF levels were altered in patients with CID, indicating astrocyte damage, and were associated with insomnia severity or/and cognitive dysfunction.Keywords: cognition, S100 calcium binding protein B, glial fibrillary acidic protein, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor

Zhen Su,1,* Guo-rong Zou,1,* Jie Tang,1 Xiu Yue Li,1 Fang-Yun Xie2 1Panyu Central Hospital, Cancer Institute of Panyu, Guangzhou, People’s Republic of China; 2Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fang-Yun XieDepartment of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of ChinaTel +86 20 87343484Email xiefy0758@sina.comBackground: The aim of this study was to evaluate the efficacy of induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients with moderate-risk treated with intensity-modulated radiotherapy (IMRT).Methods: We retrospectively assessed 506 patients with T1-2N1M0 or T3-4N0-1M0 NPC (according to the 2010 UICC/AJCC staging system) who received concurrent chemoradiotherapy (CCRT) with or without IC at a single center in China between 2005 and 2010. Survival outcomes were compared between the IC + CCRT and CCRT groups using the Kaplan–Meier method, Log-rank test and a Cox regression model.Results: Among the 506 patients, CCRT alone resulted in equivalent overall survival (86.8% vs 88.5%, p=0.661), progression-free survival (79.6% vs 79.6%, p=0.756), locoregional relapse-free survival (90.2% vs 87.0%, p=0.364) and distant metastasis-free survival (88.0% vs 89.8%, p= 0.407) to IC plus CCRT. In multivariate analysis, IC did not lower the risk of death (HR 0.76, 95% CI 0.46– 1.25, p= 0.278), progression (HR 0.78, 95% CI 0.51– 1.19, p= 0.244), locoregional relapse (HR 1.06, 95% CI 0.81– 1.42, p= 0.651) or distant metastasis (HR 0.66, 95% CI 0.38– 1.15, p= 0.140) in the entire cohort; similar results were obtained in stratified analysis based on N category (N0 vs N1) and EBV DNA (< vs ≥ 4000 copies/mL).Conclusion: Addition of IC to CCRT does not improve survival outcomes in moderate-risk NPC; the use of IC should be carefully considered in these patients, though additional prospective trials are warranted to confirm the conclusions of this study.Keywords: nasopharyngeal carcinoma, induction chemotherapy, prognosis, survival

Xiao-Yu Li,1,* Hui-Ling Meng,2,* Kai-Guo Li,1 Xiao-Hui Yang,1 Xiao-Dong Zhu,1,3 Ling Li,1 Zhong-Guo Liang,1 Xin-Bin Pan,1 Fan-Yan Zeng,1 Song Qu1,3 1Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, People’s Republic of China; 2Department of Radiation Oncology, Liuzhou People’s Hospital, Liuzhou, Guangxi 545000, People’s Republic of China; 3Key Laboratory of High-Incidence-Tumor Prevention & Treatment, Guangxi Medical University, Ministry of Education, Nanning, Guangxi 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Song QuDepartment of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, People’s Republic of ChinaEmail 13607887386@163.comBackground and Aim: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Southern China, Southeast Asia. Radiotherapy is the main treatment for NPC. Still, about 20% of patients with NPC have a recurrence. No effective serum biomarkers are available for recurrent nasopharyngeal carcinoma (rNPC) to date. This study aimed to explore whether amyloid beta (A4) precursor protein (APP) might serve as a valuable diagnostic and prognostic biomarker for patients with rNPC.Methods: In a previous study, a tandem mass tag–based proteomic test was performed, which screened 59 differentially expressed proteins (DEPs) between nonrecurrent nasopharyngeal carcinoma (nrNPC) and rNPC. In this study, a protein–protein interaction was conducted to screen the key proteins among the 59 DEPs. APP was validated and evaluated by enzyme-linked immunosorbent assay in 70 serum samples [recurrence (n = 35) and no-recurrence (n = 35)]. Also, the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of APP.Results: The area under the ROC curve was 0.666 (95% CI: 0.514–0.818, P = 0.044). The best cutoff point of the relative expression levels for APP was 1.23 (concentration = 16.95 ng/mL), at which the sensitivity was 55.2% and the specificity was 90.9%.Conclusion: The findings indicated that APP might be a valuable diagnostic and prognostic biomarker for patients with rNPC.Keywords: amyloid beta precursor protein, biomarker, enzyme-linked immunosorbent assay, protein–protein interaction, recurrent nasopharyngeal carcinoma

Yan Huang,1,2,* Dan Zhang,1,3,* Zhi-Yuan Li,4,* Yan-Ting Yang,3 Li-Jie Wu,1 Ji Zhang,1 Fang-Yuan Zhi,1 Xi-Ying Li,1 Zheng Shi,3 Jue Hong,3 Xiao-Peng Ma1,3 1Yueyang Clinical Medical School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China; 2Acupuncture and Moxibustion Department, Huangpu District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200010, People’s Republic of China; 3Laboratory of Acupuncture, Moxibustion, and Immunology, Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, People’s Republic of China; 4Acupuncture and Moxibustion Department, Zhejiang Provincial Hospital of TCM, Hangzhou, Zhejiang 310006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Peng MaShanghai Research Institute of Acupuncture and Meridian, No. 650 South Wanping Road, Xuhui District, Shanghai, People’s Republic of ChinaTel +86 021 64690257Fax +86 021 64382181Email pengpengma@163.comPurpose: The purpose of this study was to explore the central analgesia mechanism of moxibustion for chronic inflammatory visceral pain (CIVP).Methods: A CIVP rat model was established by 2,4,6-trinitrobenzene sulfonic acid (TNBS) plus 50% ethanol via enema. The analgesic effect of moxibustion was evaluated using the abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL). The expression profile of phosphorylated proteins of the mitogen-activated protein kinase (MAPK) signaling pathway in the spinal cord was assayed by protein microarray. The differentially expressed proteins were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional clusters and corresponding signaling pathways.Results: Moxibustion exerted a significant analgesic effect for CIVP rats, mainly presenting as a decrease in the AWR score (all P1.3 or

Xue-Song Sun,1–3,* Yu-Jing Liang,1–3,* Xiao-Yun Li,1–3,* Sai-Lan Liu,1–3 Qiu-Yan Chen,1–3 Lin-Quan Tang,1–3 Hai-Qiang Mai1–3 1Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Centre, Guangzhou, People’s Republic of China; 2Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangzhou, People’s Republic of China; 3Department of Nasopharyngeal Carcinoma, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin-Quan Tang;Hai-Qiang MaiDepartment of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, People’s Republic of ChinaTel +86 208 734 3643Fax +86 208 734 3392Email maihq@mail.sysu.edu.cn; tanglq@sysucc.org.cnObjective: We aimed to investigate the efficacy and safety of cetuximab (CTX) or nimotuzumab (NTZ) on the addition of palliative chemotherapy (PCT) in patients with de novo metastatic nasopharyngeal carcinoma (NPC).Materials and methods: From 2007 to 2016, 451 eligible patients with de novo metastatic NPC were enrolled in the study. With propensity score matching technique, we created a well-balanced cohort by matching patients who received CTX/NTZ plus PCT (62 patients) with those receiving PCT alone (248 patients) in a ratio of 1:4. The primary endpoint was overall survival (OS). All potential prognostic factors were involved in the multivariate analysis with the Cox regression hazards model. Kaplan–Meier curves were used to compare the survival status, and log-rank test to measure the significance.Results: The median follow-up time was 27.7 months (range, 1–126 months). No significant difference in survival was observed between the CTX/NTZ plus PCT group and PCT group. (3-year OS: 63.0% vs 58.1%; P=0.485). The administration of CTX/NTZ was not found to be an independent prognostic factor in multivariate analysis. With regard to toxicity, the development of a G3-4 skin reaction and mucositis was more common in patients receiving CTX plus PCT. Interaction effects analysis did not show any significant interaction effects on OS between the treatment regimen and prognostic factors (P>0.05).Conclusion: The efficacy of CTX/NTZ and PCT is comparable to single PCT treatment in terms of survival outcomes among de novo metastatic NPC patients. Moreover, the application of CTX exacerbated skin reactions and mucositis.Keywords: targeted drug, chemotherapy, treatment, nasopharyngeal carcinoma and overall survival

Tao-Yan Lin,1,* Yan Chen,1,* Jun-Shuang Jia,1,* Chen Zhou,2 Mei Lian,3 Yue-Ting Wen,1 Xiao-Yan Li,3 Heng-Wei Chen,3 Xiao-Lin Lin,1 Xiao-Ling Zhang,4 Sheng-Jun Xiao,2 Yan Sun,5 Dong Xiao1,31Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin 541199, People’s Republic of China; 3Institute of Comparative Medicine and Laboratory Animal Center, Southern Medical University, Guangzhou 510515, People’s Republic of China; 4Department of Physiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin 541004, People’s Republic of China; 5Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China*These authors contributed equally to this workPurpose: The correlation of cold-inducible RNA-binding protein (Cirbp) expression with clinicopathological features including patient prognosis in nasopharyngeal carcinoma (NPC) was investigated.Methods: The expression of Cirbp in NPC cell lines and tissue specimens was examined by qRT-PCR or immunohistochemistry (IHC).Results: Immunohistochemistry (IHC) results showed that high Cirbp expression was detected in 61 of 61 non-cancerous nasopharyngeal squamous epithelial biopsies, whereas the significantly reduced expression of Cirbp was observed in NPC specimens. In addition, IHC assay for Cirbp protein illustrated that the cells of 177 NPC samples and nasopharyngeal squamous epithlial cells displayed strong signals in nuclei and faint signals in cytoplasm, whereas Cirbp protein is mainly detected in the cell’s cytoplasm in many other cancers. More importantly, TNM classification displayed that the low expression of Cirbp was more frequently observed in T3-T4, N2-N3, M1 and III-IV NPC biopsies, and undifferentiated carcinoma (UDC) than T1-T2, N0-N1, M0 and I-II tumors, and differentiated nonkeratinizing carcinoma (DNKC), suggesting that Cirbp loss is a key molecular event in advanced cases of NPC. Kaplan–Meier survival analysis indicated that NPC patients showing lower Cirbp expression had a significantly shorter overall survival time than those with high Cirbp expression. Multivariate analysis suggested that the level of Cirbp expression was an independent prognostic indicator for NPC survival. Finally, we revealed a significant positive association between Cirbp expression and E-cadherin, and a notable negative correlation between Cirbp expression and Ki67 labeling index in NPC biopsies.Conclusion: Collectively, these findings demonstrate that loss of Cirbp expression is correlated with malignant progression and poor prognosis in NPC.Keywords: cirbp, nasopharyngeal carcinoma; NPC, TNM stage, prognosis, E-cadherin, Ki67

Xiao-Yun Li,1,2,* Xue-Song Sun,1,2,* Sai-Lan Liu,1,2,* Qiu-Yan Chen,1,2 Shan-Shan Guo,1,2 Li-Ting Liu,1,2 Jin-Jie Yan,1,2 Hao-Jun Xie,1,2 Qing-Nan Tang,1,2 Yu-Jing Liang,1,2 Ling Guo,1,2 Lin-Quan Tang,1,2,* Hai-Qiang Mai1,2,*1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 2Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China*These authors contributed equally to this workObjective: This study aimed to establish a nomogram to predict the risk of post-radiation necrosis in nasopharyngeal carcinoma (NPC) patients.Background: This study was performed to identify influencing factors for developing post-radiation necrosis, and to establish an effective nomogram model to predict individual risks in NPC patients.Methods: 7144 NPC patients receiving radical radiotherapy from 2007 to 2012 were involved in the study, and 207 of them developed nasopharyngeal necrosis (NPN). The clinical characteristics and baseline laboratory results were collected and analyzed. Independent predictive factors were selected using the Cox proportional model and incorporated into the nomogram. The receiver operating characteristic curve and the calibration curve were used to verify discrimination and calibration.Results: The experience of re-irradiation contributed most to the occurrence of NPN (HR, 15.56, 95% CI 10.84–22.35, p

Ren Gong,1 Xi-Yong Li,1 Huai-Jing Chen,2 Cong-Cong Xu,1 Hai-Yang Fang,1 Jian Xiang,1 Yan-Qing Wu11Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Cardiology, Baoan Central Hospital of Shenzhen, Shenzhen, People’s Republic of ChinaObjective: The aim was to investigate the role and potential mechanism of geranylgeranylacetone (GGA) in the development of atherosclerosis, and to explore the role of heat shock protein 22 (HSP22) in mediating GGA effect.Methods: Human coronary artery endothelial cell (HCAEC) was used for in vitro study. RNA interference was applied to suppress HSP22 in the cells. Cellular apoptosis and intracellular level of reactive oxygen species (ROS) were detected by flow cytometer, and proteins of HSP22, NF-κB, eNOS, and ICAM-1 were assessed by immunoblotting. HSP22-/-//ApoE,-/- and HSP22+/+//ApoE-/- mice were used to investigate the effect of GGA in the animal model of atherosclerosis. Atherosclerotic lesion of the mice aortas was evaluated by Oil Red O staining and H&E staining.Results: GGA significantly inhibited HCAEC apoptosis in response to oxidized-LDL (ox-LDL), but stimulated HSP22 synthesis in the cells. Transfection of HSP22-siRNA in the cells resulted in complete blockage of the GGA effect on apoptosis. GGA also significantly inhibited ROS, NF-κB, and ICAM-1 in the cells transfected control siRNA, but not in the cells transfected with HSP22-siRNA. Atherosclerotic plaque in the aorta was significantly less in the wild type (WT) animals treated with GGA as stained either by Oil Red O or by H&E staining, but not in the HSP22-KO mice. GGA significantly inhibited expression of NF-κB and ICAM-1 in the WT mice, but not in the HSP22-KO mice.Conclusion: GGA-induced HSP22, and inhibited ox-LDL-induced apoptosis as well as expression of NF-κB and ICAM-1 in the HCAECs. GGA also attenuated formation of atherosclerotic plaques in mice aorta. Suppression of HSP22 by siRNA resulted in blockage of the GGA inhibition on apoptosis or stimulation on NF-κB and ICAM-1. These findings suggested that GGA protects endothelial cells from injury in response to ox-LDL and block atherosclerotic development in mice aorta through induction of HSP22.Keywords: geranylgeranylacetone (GGA), heat shock protein 22 (HSP22), endothelial cells, inflammatory response, atherosclerosis

Shang-Bin Qin,1 Xian-Shu Gao,1 Hong-Zhen Li,1 Chao-Xing Liu,2 Dong-Liang Hou,3 Wei-Dong Nian,4 Xue-Ying Li,5 Dian Wang61Department of Radiation Oncology, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Radiation Oncology, Shijiazhuang City First Hospital, Shijiazhuang, People’s Republic of China; 3Department of Radiation Oncology, Beijing Shijitan Hospital, Beijing, People’s Republic of China; 4Department of General Surgery, Peking University First Hospital, Beijing, People’s Republic of China; 5Department of Medical Statistics, Peking University First Hospital, Beijing, People’s Republic of China; 6Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, USAPurpose: The aim of the study was to evaluate the feasibility and toxicity of intra-rectal epinephrine during prostatic radiotherapy.Materials and methods: A total of 34 patients with prostate cancer were randomized to receive daily intra-rectal epinephrine (4 mg in 40 mL, n=16) or placebo (40 mL normal saline, n=18) 5 min before daily radiotherapy. Physical examination including systolic blood pressure (SBP) and heart rate (HR) was performed before, 5 min after, and 20 min after intra-rectal use. Toxicities were graded using the Radiation Therapy Oncology Group standard. A two-sided Fisher’s exact test was used to compare proportions between groups. A mixed-effects model was used to analyze multiple measurements of SBP and HR. Survival curves were calculated using the Kaplan–Meier method and compared between groups using the log-rank test.Results: All patients completed the protocol treatment and reported no cardiovascular symptoms after intra-rectal administration. There were no differences in SBP and HR between these two groups at any time point (before, 5 min after, and 20 min after epinephrine). At 5 weeks after the start of radiotherapy, the incidence of rectal toxicity≥grade 2 was 27.8% (5/18) for the control group versus 12.5% (2/16) for the epinephrine group, but was not statistically significant (p=0.4). There was no rectal toxicity≥grade 2 in these two groups beyond 2-year follow-up. The 5-year biochemical relapse-free survival was 75.0% and 72.2% for the epinephrine and control group, respectively.Conclusion: Results of this pilot randomized trial have demonstrated that intra-rectal administration of epinephrine is feasible and safe in prostatic radiotherapy. Its radio-protective effect warrants further investigation.Keywords: radiation proctitis, epinephrine, radiotherapy

Hang Xue, Ying Xu, Shuo Wang, Zi-Yi Wu, Xing-Yue Li, Ya-Han Zhang, Jia-Yuan Niu, Qiu-Shi Gao, Ping ZhaoDepartment of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, People’s Republic of ChinaBackground: When neonatal rats suffer hypoxic-ischemic brain injury (HIBI), autophagy is over-activated in the hippocampus, and inhibition of autophagy provides neuroprotection. The aim of this study was to investigate the possible roles of autophagy and Ezh2-regulated Pten/Akt/mTOR pathway in sevoflurane post-conditioning (SPC)-mediated neuroprotection against HIBI in neonatal rats.Methods: Seven-day-old Sprague–Dawley rats underwent left common artery ligation followed by 2 h hypoxia as described in the Rice–Vannucci model. The roles of autophagy and the Ezh2-regulated Pten/Akt/mTOR signaling pathway in the neuroprotection conferred by SPC were examined by left-side intracerebroventricular injection with the autophagy activator rapamycin and the Ezh2 inhibitor GSK126.Results: SPC was neuroprotective against HIBI through the inhibition of over-activated autophagy in the hippocampus as characterized by the rapamycin-induced reversal of neuronal density, neuronal morphology, cerebral morphology, and the expression of the autophagy markers, LC3B-II and Beclin1. SPC significantly increased the expression of Ezh2, H3K27me3, pAkt, and mTOR and decreased the expression of Pten induced by HI. The Ezh2 inhibitor, GSK126, significantly reversed the SPC-induced changes in expression of H3K27me3, Pten, pAkt, mTOR, LC3B-II, and Beclin1. Ezh2 inhibition also reversed SPC-mediated attenuation of neuronal loss and behavioral improvement in the Morris water maze.Conclusion: These results indicate that SPC inhibits excessive autophagy via the regulation of Pten/Akt/mTOR signaling by Ezh2 to confer neuroprotection against HIBI in neonatal rats.Keywords: sevoflurane post-conditioning, hypoxic-ischemic brain injury, neonatal rat, autophagy, Ezh2, Pten/Akt/mTOR

Xin-Yu Li,1,2 Liang Shen,1,2 Hong-Fang Ji1,21Institute of Biomedical Research, Shandong University of Technology, Zibo, Shandong, People’s Republic of China; 2Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Zibo Key Laboratory of New Drug Development of Neurodegenerative Diseases, School of Life Sciences, Shandong University of Technology, Zibo, Shandong, People’s Republic of ChinaBackground: Astragalus possesses therapeutic effects for type 2 diabetes (T2D), while its action mechanisms remain to be elucidated. In view of the pathogenic associations between gut microbiota and T2D, we explored the effect of astragalus on gut-microbiota composition of T2D mice.Materials and methods: Modulation effects of astragalus on gut microbiota of T2D-model mice were assessed by 16S rRNA gene sequencing.Results: Inhibited blood-glucose and body-weight levels of T2D mice by astragalus were accompanied by gut microbiota–composition alteration. Astragalus administration significantly increased gut-microbiota richness and diversity in T2D mice and significantly altered the abundance of several bacterial taxa, inducing increased abundance of Lactobacillus and Bifidobacterium. PICRUSt software revealed the relationship between astragalus and T2D.Conclusion: Due to previously reported decreased gut-microbiota richness and diversity and reduced abundance of key species of Lactobacillus and Bifidobacterium, more studies are encouraged to explore the contribution of gut-microbiota alteration by astragalus to its anti-T2D effect.Keywords: astragalus, type 2 diabetes, gut microbiota, alteration, 16S rRNA gene sequencing

Adnan Tufail,1 Sue Lightman,1 Ahmed Kamal,2 Uwe Pleyer,3 Nuria María Gajate Paniagua,4 Corrine Dot,5,6 Xiao-Yan Li,7 Jenny Jiao,7 Jean Lou,7 Yehia Hashad7 For the CONSTANCE Study Group 1Moorfields Eye Hospital, London, UK; 2Aintree University Hospital, Liverpool, UK; 3University Eye Hospital, Uveitis Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt University Berlin, and Berlin Institute of Health, Berlin, Germany; 4University Hospital of Burgos, Burgos, Spain; 5Department of Ophthalmology, Desgenettes Military Hospital, Lyon, France; 6French Military Health Service Academy, Val de Grâce, Paris, France; 7Allergan Plc, Irvine, CA, USA Purpose: To evaluate the long-term safety of dexamethasone intravitreal implant (DEX) in patients treated for macular edema associated with retinal vein occlusion (RVO) or noninfectious posterior segment uveitis (NIPSU) in clinical practice.Patients and methods: Multicenter (102 sites in France, Germany, Spain, UK), prospective, observational, post-authorization safety study in adult patients treated with DEX. Data collected up to 2 years after enrollment included serious adverse events (SAEs) and adverse events of special interest (AESIs; adverse drug reactions that are considered important risks associated with DEX and listed in the European Union Ozurdex Risk Management Plan).Results: Overall, 803 patients (652 RVO, 151 NIPSU) received on-study DEX treatment, and 73.1% completed 24 months of follow-up; 72.6% were DEX-naïve. Median number of on-study injections per treated eye was 2 (range, 1–7); median reinjection interval was 27.1 weeks. Nonocular SAEs affected 9.5% of patients; none were considered DEX-related. Ocular SAEs (most common: cataract progression) occurred in 3.2% of treated eyes. SAEs were similar in eyes stratified by previous DEX use and number of on-study DEX injections (≤2 or >2), in both RVO and NIPSU. The most common AESIs were cataract formation and progression (20.0% and 19.2% of treated phakic eyes, n=551), increased intraocular pressure (19.0% of treated eyes), and vitreous hemorrhage (3.3% of treated eyes). Cataract progression was more frequent in baseline phakic eyes that were previously treated with DEX or received >2 on-study DEX injections.Conclusion: The long-term safety profile of DEX was acceptable. No new safety concerns were identified. Keywords: corticosteroid, dexamethasone, drug delivery device, retinal vein occlusion, safety profile, uveitis

Xiaoying Li,1,* Xin Hong,2,* Xianshu Gao,1 Xiaobin Gu,1 Wei Xiong,3 Jing Zhao,4 Hongliang Yu,5 Ming Cui,1 Mu Xie,1 Yun Bai,1 Shaoqian Sun6 1Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, China; 2Department of Urology, Peking University International Hospital, Peking University, Beijing, China; 3Department of Oncology, Tangshan People’s Hospital, Hebei, China; 4Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China; 5Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China; 6College of Biochemical Engineering, Beijing Union University, Beijing, China *These authors contributed equally to this work Purpose: In our previous study, we found that AKR1C3 was a radioresistance gene in KY170R cells. Downregulating the expression of AKR1C3 could enhance the radiosensitivity of esophageal carcinoma cells. In this study, we investigated whether methyl jasmonate (MeJ), an inhibitor of Aldo-keto reductase family1 member C3 (AKR1C3), could overcome radiation resistance in AKR1C3 highly expressed cells.Patients and methods: We used clone formation assays to detect radiosensitivity effects. Flow cytometry assays were used to detect reactive oxygen species (ROS) accumulation and apoptosis. Enzyme linked immunosorbent assays (ELISAs) were used to detect the concentrations of prostaglandin F2 (PGF2) and prostaglandin D2 (PGD2) in the cells after incubation with MeJ. Western blotting was used to detect AKR1C3 and peroxisome proliferator-activated receptor gamma (PPARγ) expression.Results: We found that AKR1C3 was highly expressed in radioresistant esophageal carcinoma cells. MeJ inhibited the expression of AKR1C3 and enhanced the radiation sensitivity of esophageal carcinoma cells expressing high levels of AKR1C3 (P0.05).The radiation sensitivity effect of MeJ also depended upon the generation of ROS in KY170R cells; 48 h after irradiation, ROS levels in the MeJ group was twofold higher than in the untreated KY170R cells (P0.05).Conclusion: Our results indicate that MeJ can increase the radiation sensitivity of AKR1C3-overexpressing KY170R cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3 and increasing cellular ROS levels. Keywords: radiosensitivity, esophageal carcinoma, methyl jasmonate, AKR1C3

Lili Guan,1,* Jiawen Xu,1,* Weiliang Wu,1,* Jianhua Chen,1,* Xiaoying Li,2,* Bingpeng Guo,1 Yuqiong Yang,1 Yating Huo,1 Luqian Zhou,1 Rongchang Chen1 1State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; 2The First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China *These authors contributed equally to this work Purpose: Patients with advanced-stage COPD often experience severe hypoxemia. Treatment with long-term oxygen therapy (LTOT) may relieve patients’ symptoms and increase survival. As COPD is incurable, improving patients’ health-related quality of life is important. The Chinese version of the Severe Respiratory Insufficiency Questionnaire (SRI) is valid for patients with hypercapnic COPD undergoing noninvasive positive airway pressure ventilation at home. However, the reliability and validity of the Chinese SRI for patients with COPD undergoing LTOT have not been investigated. Patients and methods: We analyzed reliability using Cronbach’s α coefficient. Construct validity was assessed with principal, exploratory, and confirmatory factor analysis. Concurrent validity was evaluated through the correlation between SRI domains and Chronic Respiratory Disease Questionnaire (CRQ) domains. Content validity was assessed by calculating the correlation between each SRI item score and the total score for the relevant domain. Results: In total, 161 patients participated in this study. The Cronbach’s α coefficient for all SRI domains was >0.7, except for the attendant symptoms and sleep domain. Exploratory and confirmatory factor analysis showed a good model fit for each domain, but the factors extracted from each domain were correlated. SRI and CRQ domains correlated well with respect to similar aspects of health-related quality of life, indicating good concurrent validity. Content validity was indirectly shown by a good correlation between each item score and the total score of the relevant domain. Conclusion: The Chinese version of the SRI has a good reliability and validity for patients with COPD undergoing LTOT in China. Keywords: severe respiratory insufficiency questionnaire, long-term oxygen therapy, health-related quality of life, chronic obstructive pulmonary disease

Weiliang Wu,1,* Lili Guan,1,* Xiaoying Li,2,* Lin Lin,1 Bingpeng Guo,1 Yuqiong Yang,1 Zhenyu Liang,1 Fengyan Wang,1 Luqian Zhou,1 Rongchang Chen1 1Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, 2Department of Respiratory Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China *These authors contributed equally to this work Purpose: To evaluate the compatibility and correlation between noninvasive surface respiratory electromyography and invasive transesophageal diaphragmatic electromyography measurements as facilitating indicators of neural respiratory drive (NRD) evaluation during treadmill exercise.Patients and methods: Transesophageal diaphragmatic electromyogram activity (EMGdi,es) and surface inspiratory electromyogram (EMG) activity, including surface diaphragmatic EMG activity (EMGdi,sur), surface parasternal intercostal muscle EMG activity (EMGpara), and surface sternocleidomastoid EMG activity (EMGsc), were detected simultaneously during increasing exercise capacity in 20 stable patients with COPD. EMGdi,es, EMGdi,sur, EMGpara, and EMGsc were quantified using the root mean square (RMS) and were represented as RMSdi,es, RMSdi,sur, RMSpara, and RMSsc, respectively.Results: There was a significant association between EMGdi,es and EMGdi,sur (r=0.966, p

M Bajc,1 Y Chen,2 J Wang,3 XY Li,4 WM Shen,4 CZ Wang,3 H Huang,2 A Lindqvist,5 XY He6 1Department of Clinical Science Physiology and Nuclear Medicine, Skåne University Hospital, Lund, Sweden; 2Respiratory Department, Changzheng Hospital, Shanghai, 3Respiratory Department, Xinqiao Hospital, Chongqing, 4Respiratory Department, Huadong Hospital, Shanghai, China; 5Department of Pulmonary Medicine, Heart and Lung Center, Helsinki University Hospital and Helsinki University, Helsinki, Finland; 6Suzhou University Affiliated Tumor Hospital, Wuxi, China Introduction: Airway obstruction and possible concomitant pulmonary diseases in COPD cannot be identified conventionally with any single diagnostic tool. We aimed to diagnose and grade COPD severity and identify pulmonary comorbidities associated with COPD with ventilation/perfusion single-photon emission computed tomography (V/P SPECT) using Technegas as the functional ventilation imaging agent.Methods: 94 COPD patients (aged 43–86 years, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I–IV) were examined with V/P SPECT and spirometry. Ventilation and perfusion defects were analyzed blindly according to the European guidelines. Penetration grade of Technegas in V SPECT measured the degree of obstructive small airways disease. Total preserved lung function and penetration grade of Technegas in V SPECT were assessed by V/P SPECT and compared to GOLD stages and spirometry.Results: Signs of small airway obstruction in the ventilation SPECT images were found in 92 patients. Emphysema was identified in 81 patients. Two patients had no signs of COPD, but both of them had a pulmonary embolism, and in one of them we also suspected a lung tumor. The penetration grade of Technegas in V SPECT and total preserved lung function correlated significantly to GOLD stages (r=0.63 and −0.60, respectively, P

Yingpeng Li,1 Xiuyan Li,2 Qingxia Guan,2 Chunjing Zhang,2 Ting Xu,2 Yujing Dong,2 Xinyu Bai,2 Weiping Zhang3 1College of Pharmacy, Tianjin University of Traditional Chinese Medicine, Tianjin, 2College of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People’s Republic of China; 3Pope John XXIII High School, Everett, MA, USA Background: Enhancing drug delivery is an ongoing endeavor in pharmaceutics, especially when the efficacy of chemotherapy for cancer is concerned. In this study, we prepared and evaluated nanosized HKUST-1 (nanoHKUST-1), nanosized metal-organic drug delivery framework, loaded with 5-fluorouracil (5-FU) for potential use in cancer treatment.Materials and methods: NanoHKUST-1 was prepared by reacting copper (II) acetate [Cu(OAc)2] and benzene-1,3,5-tricarboxylic acid (H3BTC) with benzoic acid (C6H5COOH) at room temperature (23.7°C±2.4°C). A central composite design was used to optimize 5-FU-loaded nanoHKUST-1. Contact time, ethanol concentration, and 5-FU:material ratios were the independent variables, and the entrapment efficiency of 5-FU was the response parameter measured. Powder X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen adsorption were used to determine the morphology of nanoHKUST-1. In addition, 5-FU release studies were conducted, and the in vitro cytotoxicity was evaluated.Results: Entrapment efficiency and drug loading were 9.96% and 40.22%, respectively, while the small-angle X-ray diffraction patterns confirmed a regular porous structure. The SEM and TEM images of the nanoHKUST-1 confirmed the presence of round particles (diameter: approximately 100 nm) and regular polygon arrays of mesoporous channels of approximately 2–5 nm. The half-maximal lethal concentration (LC50) of the 5-FU-loaded nanoHKUST-1 was approximately 10 µg/mL.Conclusion: The results indicated that nanoHKUST-1 is a potential vector worth developing as a cancer chemotherapeutic drug delivery system. Keywords: 5-fluorouracil, drug delivery, nanoparticles, nano-MOFs

Xu Xu,* Zhaokang Xu,* Junyi Liu, Zhaoliang Zhang, Hao Chen, Xingyi Li, Shuai Shi Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China *These authors contributed equally to this work Abstract: To visually trace the diffusion and biodistribution of amphiphilic cation micelles after vitreous injection, various triblock copolymers of monomethoxy poly(ethylene glycol)–poly(ε-caprolactone)–polyethylenimine were synthesized with different structures of hydrophilic and hydrophobic segments, followed by labeling with near-infrared fluorescent dye Cyanine5 or Cyanine7. The micellar size, polydispersity index, and surface charge were measured by dynamic light scattering. The diffusion was monitored using photoacoustic imaging in real time after intravitreal injections. Moreover, the labeled nanoparticle distribution in the posterior segment of the eye was imaged histologically by confocal microscopy. The results showed that the hydrophilic segment increased vitreous diffusion, while a positive charge on the particle surface hindered diffusion. In addition, the particles diffused through the retinal layers and were enriched in the retinal pigment epithelial layer. This work tried to study the diffusion rate via a simple method by using visible images, and then provided basic data for the development of intraocular drug carriers. Keywords: visible tracing, cavum vitreum, biodistribution, diffusion rate

Ying Liu,1,* Xin Wu,1,* Yuan Gao,2,* Jigang Zhang,1 Dandan Zhang,1 Shengying Gu,1 Guanhua Zhu,1 Gaolin Liu,1 Xiaoyu Li1 1Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 2Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Liver cancer is the fifth most commonly diagnosed malignancy, of which hepatocellular carcinoma (HCC) represents the dominating histological subtype. Antiangiogenic therapy aimed at vascular endothelial growth factor (VEGF) has shown promising but deficient clinical prospects on account of vasculogenic mimicry, a highly patterned vascular channel distinguished from the endothelium-dependent blood vessel, which may function as blood supply networks occurring in aggressive tumors including HCC. In this study, we used a new cationic peptide, disulfide cross-linked stearylated polyarginine peptide modified with histidine (H3R5), as a reducible vector, cell penetrating peptide-modified aptamer (ST21) with specific binding to HCC cells to conjugate to peptide H3R5 as the targeting probe, miRNA-195 (miR195)as a powerful gene drug to inhibit VEGF, and fasudil to suppress vasculogenic mimicry by blocking ROCK2, all of which were simultaneously encapsulated in the same nanoparticles. Fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient and miR195 was condensed through electrostatic interaction. ST21-H3R5-polyethylene glycol (PEG) exhibited excellent loading capacities for both fasudil and miR195 with adjustable dosing ratios. Western blot analysis showed that FasudilST21-H3R5-PEGmiR195 had strong silencing activity of ROCK2 and VEGF, as compared with FasudilH3R5-PEGmiR195. In vitro and in vivo experiments confirmed that ST21-modified nanoparticles showed significantly higher cellular uptake and therapeutic efficacy in tumor cells or tumor tissues than the unmodified counterparts. These findings suggest that aptamer-conjugated peptide holds great promise for delivering chemical drugs and gene drugs simultaneously to overcome HCC. Keywords: aptamer, fasudil, miR195, combined therapy, hepatocellular carcinoma

Li X-Y, Sun X-S, Liu S-L, et al. Cancer Manag Res. 2019;11:6253–6263.In Table 2, the authors identified the risk factors of nasopharyngeal necrosis using a logistic regression model, andthe final nomogram model was constructed based on these results. However, the outcome of the univariable analysisand multivariable analysis reported in Table 2 was mistakenly listed as overall survival (HR) and should have been reported as the likelihood of necrosis (OR).Table 2, column 2 heading reads "Univariable analyses HR (95% CI)" should read "Univariable analyses OR (95% CI)". Table 2, column 4 heading reads "Univariable analyses HR (95% CI)" should read "Multivariable analyses OR (95% CI)". The authors wish to apologize for this error.Read the original article

Qingyuan Lv,1 Xianyi Li,2 Baode Shen,1 He Xu,1 Chengying Shen,1 Ling Dai,1 Jinxia Bai,1 Hailong Yuan,1 Jin Han11Department of Pharmacy, 302 Military Hospital, 2Institute for Drug and Instrument Control, Health Department, General Logistics Department of People's Liberation Army, Beijing, People's Republic of ChinaAbstract: The aim of this study was to investigate the feasibility of using spray granulation as a drying method to convert phospholipid (PL)-sodium deoxycholate (SDC)-mixed micelles (MMs) containing a water-insoluble drug to a solid dosage form and to evaluate how drugs with significantly different physicochemical properties affect the spray granulation process and subsequent in vitro and in vivo processes. Cucurbitacin B (Cu B) and glycyrrhizin (GL) were used as the model drugs. After spray granulation, the dried Cu B-PL/SDC-MM powder was completely redispersible within 15 minutes in vitro. Meanwhile, the area under the curve during 24 hours (AUC0–24) and peak serum concentration from the dried powder were significantly (P

Kunchi Zhang, Shaowa Lv, Xiuyan Li, Yufei Feng, Xin Li, Lu Liu, Shuang Li, Yongji Li School of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang Province, People’s Republic of China Background: The purpose of this work was to develop nanostructured lipid carriers (NLCs) loaded simultaneously with oleanolic acid and gentiopicrin. Methods: An aqueous dispersion of NLCs was prepared successfully using a film-ultrasonic method, with glycerin monostearate as the solid lipid and oleic acid as the liquid lipid. Poloxamer 188 was used as the surfactant. A central composite design was used to optimize the technologic parameters. The characteristics of the NLCs were then investigated. Results: The encapsulation efficiency was 48.34% ± 2.76%, drug loading was 8.06% ± 0.42%, particle size was 111.0 ± 1.56 nm, polydispersity index was 0.287 ± 0.01, and zeta potential was –23.8 ± 0.36 mV for the optimized NLCs. The other physicochemical properties were characterized by transmission electron microscopy and differential scanning calorimetry. Drug release followed first-order kinetics and release studies confirmed that oleanolic acid and gentiopicrin fitted a sustained-release model. Compared with NLCs loaded with oleanolic acid or gentiopicrin alone, NLCs loaded with both oleanolic acid and gentiopicrin produced drug concentrations which persisted for a significantly longer time in plasma, with a linear decrement following second-order kinetics. Aspartate and alanine aminotransferase levels were significantly lower on exposure to NLCs loaded with both oleanolic acid and gentiopicrin than in negative controls. Conclusion: The results of this study confirm that oleanolic acid and gentiopicrin can be loaded simultaneously into NLCs. Compared with oleanolic acid and gentiopicrin loaded alone, sustained release and protective effects against hepatic injury were observed using NLCs loaded with both oleanolic acid and gentiopicrin. Keywords: nanostructured lipid carriers, central composite design, in vitro release, pharmacokinetics

Cui-yan Han,1,2 Li-ling Yue,2 Ling-yu Tai,1 Li Zhou,2 Xue-yan Li,2 Gui-hua Xing,2 Xing-gang Yang,1 Ming-shuang Sun,1 Wei-san Pan1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Qiqihar Medical University, Qiqihar, People’s Republic of China Abstract: The epidermal growth factor receptor (EGFR) serves an important function in the proliferation of tumors in humans and is an effective target for the treatment of cancer. In this paper, we studied the targeting characteristics of small peptides (AEYLR, EYINQ, and PDYQQD) that were derived from three major autophosphorylation sites of the EGFR C-terminus domain in vitro. These small peptides were labeled with fluorescein isothiocyanate (FITC) and used the peptide LARLLT as a positive control, which bound to putative EGFR selected from a virtual peptide library by computer-aided design, and the independent peptide RALEL as a negative control. Analyses with flow cytometry and an internalization assay using NCI-H1299 and K562 with high EGFR and no EGFR expression, respectively, indicated that FITC-AEYLR had high EGFR targeting activity. Biotin-AEYLR that was specifically bound to human EGFR proteins demonstrated a high affinity for human non-small-cell lung tumors. We found that AEYLR peptide-conjugated, nanostructured lipid carriers enhanced specific cellular uptake in vitro during a process that was apparently mediated by tumor cells with high-expression EGFR. Analysis of the MTT assay indicated that the AEYLR peptide did not significantly stimulate or inhibit the growth activity of the cells. These findings suggest that, when mediated by EGFR, AEYLR may be a potentially safe and efficient delivery ligand for targeted chemotherapy, radiotherapy, and gene therapy. Keywords: EGFR, small peptide, tumor targeting, lung cancer, NLC