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Cunxin Zhang,1,* Qian Wang,1,* Kang Li,1 Maoqing Fu,1 Kai Gao,2 Chaoliang Lv1 1Department of Spine Surgery, Jining No. 1 People’s Hospital, Jining, 272011, People’s Republic of China; 2Department of Orthopaedics, Jining No. 1 People’s Hospital, Jining, 272011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaoliang Lv, Department of Spine Surgery, Jining No. 1 People’s Hospital, No. 6 Healthy Road, Rencheng District, Jining, 272011, People’s Republic of China, Tel +86 15265775628, Fax +86-0537- 2253252, Email lvchaolianggk@163.com Kai Gao, Department of Orthopaedics, Jining No. 1 People’s Hospital, Jining, No. 6 Healthy Road, Rencheng District, Jining, 272011, People’s Republic of China, Tel +86 15853760330, Fax +86-0537- 2253252, Email gaohaikai88@126.comBackground: Intervertebral disc degeneration (IDD) underlies the pathogenesis of degenerative diseases of the spine; however, its exact molecular mechanism is unclear.Purpose: To explore the molecular mechanism of mechanical pressure (MP)-induced IDD and to assess the role and mechanism of Rosuvastatin (RSV) inhibits MP-induced IDD.Methods: SD rat nucleus pulposus cells (NPCs) were cultured in vitro and an apoptosis model of NPCs was constructed using MP. Proliferative activity, reactive oxygen species content, apoptosis, and wound healing were detected in each group of NPCs, respectively. The expression of relevant proteins was detected by qPCR and Western Blot techniques. 18 SD rats were randomly divided into control, pressure and RSV groups. Elisa, qPCR, Western Blot and immunohistochemical staining techniques were used to detect changes in the content of related proteins in the intervertebral discs of each group. HE staining and Modified Saffron-O and Fast Green Stain Kit were used to assess IDD in each group.Results: MP treatment at 1.0 MPa could significantly induce apoptosis of NPCs after 24 h. MP could significantly inhibit the proliferative activity and wound healing ability of NPCs, and increase the intracellular reactive oxygen species content and apoptosis rate; pretreatment with RSV could significantly activate the Nrf2/HO-1 signaling pathway and reverse the cellular damage caused by MP; when inhibit the Nrf2/HO-1 signaling pathway activation, the protective effect of RSV was reversed. In vivo MP could significantly increase the content of inflammatory factors within the IVD and promote the degradation of extracellular matrix, leading to IDD. When the intervention of RSV was employed, it could significantly activate the Nrf2/HO-1 signaling pathway and improve the above results.Conclusion: RSV may inhibit MP-induced NPCs damage and IDD by activating the Nrf2/HO-1 signaling pathway.Keywords: rosuvastatin, intervertebral disc, nucleus pulposus cells, oxidative stress, nuclear factor E2-related factor 2, heme oxygenase-1, quinone oxidoreductase 1

Mingyue Fu,1,2,* Diliaremu Aihemaiti,1,2,* Haowen Fu,1,2,* Na Li,1,2 Yifan Yuan,3 Mei Ye1,2 1Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Hubei Clinical Centre and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yifan Yuan; Mei Ye, Email yifanyuan95@163.com; wumeiye08@163.comBackground: Crohn’s disease (CD) is a persistent inflammatory condition that impacts the gastrointestinal system and is characterized by a multifaceted pathogenesis involving genetic, immune, and environmental components. This study primarily investigates the relationship between gene expression and immune cell infiltration in CD, focusing on disulfidptosis—a novel form of cell death caused by abnormal disulfide accumulation—and its impact on various immune cell populations. By identifying key disulfidptosis-related genes (DRGs) and exploring their association with distinct gene expression subtypes, this research aims to enhance our understanding of CD and potentially other autoimmune diseases.Methods: Gene expression data from intestinal biopsy samples were collected from both individuals with CD and healthy controls, and these data were retrieved from the GEO database. Through gene expression level comparisons, various differentially expressed genes (DEGs) were identified. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to reveal the biological processes and pathways linked to these DEGs. Later, immune cell infiltration was evaluated. Hub candidate DRGs were identified using machine learning algorithms. Validation of the expression of hub DRGs was carried out using quantitative real-time polymerase chain reaction. The hub DRGs were subjected to unsupervised hierarchical clustering to classify CD patients into subtypes. The characteristics of each subtype were then analyzed.Results: Two hub DRGs (NDUFA11 and LRPPRC) were identified. NDUFA11 showed a significantly positive association with the abundance of Th17 cells. Conversely, higher expression levels of LRPPRC were associated with a reduced abundance of various immune cells, particularly monocytes. CD patients were classified into two disulfidptosis-related subtypes. Cluster B patients exhibited lower immune infiltration and milder clinical presentation.Conclusion: LRPPRC and NDUFA11 are identified as hub DRGs in CD, with potential roles in disulfidptosis and immune regulation. The disulfidptosis subtypes provide new insights into disease progression.Keywords: Crohn’s disease, disulfidptosis, machine learning, expression pattern, immune cell infiltration

Changjin Wang,1,* Xiaolu Hu,1,2,* Songyuan Luo,1,* Yinghao Sun,1 Bangyuan Yang,1 Shengneng Zheng,3 Jiaohua Chen,1 Ming Fu,1 Ruixin Fan,4 Jie Li,1 Jianfang Luo1,2 1Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 2School of Medicine South China University of Technology, Guangzhou, People’s Republic of China; 3Department of Radiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Cardiac Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Li; Jianfang Luo, Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, #96 Dongchuan Road, Yuexiu District, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86-20-83827812, Fax +86-20-83875453, Email leomoku1981@163.com; jianfangluo@sina.comPurpose: In mixed aortic valve disease (MAVD), the results of transcatheter aortic valve replacement (TAVR) are conflicting. There is limited data on the outcomes of TAVR in patients with bicuspid aortic valve (BAV) and MAVD. The objective of this study is to compare outcomes after TAVR in BAV patients with MAVD and predominant aortic stenosis (PAS).Patients and Methods: Patients with BAV who underwent TAVR between January 2016 and April 2023 were included. The primary outcome was device success. The secondary endpoints were periprocedural mortality and other complications as defined by the Valve Academic Research Consortium-3 (VARC-3). Propensity score matching was used to minimize potential confounding.Results: A total of 262 patients were included in this study, 83 of whom had MAVD. The median age was 72 years, and 55.7% were male. The baseline comorbidity risk files were comparable between the two groups. Patients with MAVD had more mitral regurgitation, tricuspid regurgitation and pulmonary hypertension, larger annular and left ventricular outflow tract dimensions, and more severe calcification than PAS. In the unmatched population, MAVD patients had similar device success rate (69.9% vs 79.9%, P=0.075) and 30-day mortality (3.6% vs 3.4%, P=1) compared to PAS. Propensity score matching resulted in 66 patient pairs. Device success rate were still comparable in the matched population. Other clinical outcomes, including stroke, bleeding (type 2– 4), major vascular complications, acute kidney injury (stage 2– 4) and permanent pacemaker implantation, were comparable between the two groups. Multivariable logistic regression analysis did not show MAVD to be an independent negative predictor of device success. At one year, survival was similar between patients with MAVD and those with PAS.Conclusion: For the bicuspid valve, patients with MAVD had a more challenging anatomy. MAVD patients associated with comparable 30-day clinical outcomes after TAVR compared to PAS patients in patients with BAV.Keywords: transcatheter aortic valve replacement, mixed aortic valve disease, bicuspid aortic valve, device success, propensity score match

Saidi Ran,1 Zhiqian Wang,1 Mingming Fu,1 Zhiyong Hou2 1Department of Geriatric Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Zhiqian Wang, Department of Geriatric Orthopedics, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email w18533112890@163.com Zhiyong Hou, Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email drzyhou@gmail.comIntroduction: Older patients combined with coronary heart disease (CHD) develop acute heart failure (AHF) after hip fracture surgery is common, and this study aimed to investigate the risk factors of postoperative AHF in older hip fracture patients and to construct a nomogram prediction model.Methods: We retrospectively collected older hip fracture patients with CHD who underwent hip fracture surgery at the Third Hospital of Hebei Medical University from January 2017 to December 2021. We divided them into a training set and a validation set. We collected the demographic data, laboratory indicators and imaging examination results. We identified risk factors for postoperative AHF and used R language software to establish a nomogram prediction model, plot ROC curves, calibration curves and DCA decision curves.Results: We retrospectively collected 1288 older hip fractures patients with CHD. After excluding 214 patients who did not meet the criteria, 1074 patients were included in our research and we divided them into the training set and the validation set. In the training set, a total of 346 (42.8%) patients developing postoperative AHF. Through univariate and multivariate logistic regression analysis, we identified the risk factors for postoperative AHF and constructed a nomogram prediction model. The AUC of the prediction model is 0.778. The correction curve shows that the model has good consistency. The decision curve analysis shows that the model has good clinical practicality.Conclusion: There were 42.8% older patients combined with CHD develop postoperative AHF. Among them, fracture type, age, anemia at admission, combined with COPD, ASA ≥ 3, and preoperative waiting time > 3 days are risk factors for postoperative AHF. We constructed a nomogram prediction model that can effectively predict the risk of postoperative AHF in older hip fracture patients combined with CHD.Keywords: coronary heart disease, acute heart failure, Hip fracture, cardiovascular disease

Xiaoxi Li, Ling Yu, Miao Fu, Jiaonan Yang, Hongyu Tan Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Anesthesiology, Peking University Cancer Hospital & Institute, Beijing, ChinaCorrespondence: Hongyu Tan, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Anesthesiology, Peking University Cancer Hospital & Institute, &num;52 Fucheng Street, Haidian District, Beijing, 100142, China, Tel/Fax +8610-88196107, Email maggitan@yeah.netBackground: Postoperative pulmonary complications (PPCs) are the most prevalent complication after esophagectomy and are associated with a worse prognosis. This study aimed to investigate the perioperative risk factors for PPCs after minimally invasive esophagectomy (MIE).Methods: Seven hundred and sixty-seven consecutive patients who underwent McKeown MIE via thoracoscopy and laparoscopy were retrospectively studied. Patient characteristics, perioperative data, and postoperative complications were analyzed.Results: The incidence of PPCs after MIE was 25.2% (193/767). Univariate analysis identified age (odds ratio [OR] 1.022, P = 0.044), male sex (OR 2.955, P < 0.001), pulmonary comorbidities (OR 1.746, P = 0.032), chronic obstructive pulmonary disease (COPD) (OR 2.821, P = 0.003), former smoking status (OR 1.880, P = 0.001), postoperative albumin concentration (OR 0.941, P = 0.007), postoperative creatinine concentration (OR 1.011, P = 0.019), and perioperative transfusion (OR 2.250, P = 0.001) as risk factors for PPCs. In multivariate analysis, the independent risk factors for PPCs were male sex (OR 3.135, P < 0.001), body mass index (BMI) (OR 1.088, P = 0.002), COPD (OR 2.480, P = 0.012), neoadjuvant chemoradiotherapy (OR 2.057, P = 0.035), postoperative albumin concentration (OR 0.929, P = 0.002), and perioperative transfusion (OR 1.939, P = 0.013). The area under the receiver operating characteristic curve for the predictive model generated by multivariate logistic regression analysis was 0.671 (95% confidence interval 0.628– 0.713).Conclusions: Male sex, BMI, COPD, neoadjuvant chemoradiotherapy, postoperative albumin concentration, and perioperative transfusion were independent predictors of PPCs after MIE.Keywords: esophageal cancer, minimally invasive esophagectomy, postoperative pulmonary complications, perioperative risk factors, predictive model

Sicheng Zhao, Tingyan Wu, Mingjing Fu, Zhe Zhang Department of Dermatology, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, People’s Republic of ChinaCorrespondence: Sicheng Zhao, Department of Dermatology, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, No. 118 Wansheng Street, Suzhou Industrial Park, Suzhou, Jiangsu, 215028, People’s Republic of China, Email zscba@163.comBackground: Psoriasis is a chronic inflammatory skin disease characterized by erythema, papules, and plaques. Adiponectin (ADIPOQ) is an important protein hormone secreted by adipose tissue. Here, we aimed to explore the expression of ADIPOQ in psoriasis patients and the moderation effect of histone lactylation on ADIPOQ.Methods: The GSE78097 data set was downloaded from GEO database to analyze the differentially expressed genes (DEGs) in psoriasis. A total of 36 psoriasis patients were recruited to obtain the skin samples. The ADIPOQ protein levels, global lactylation and histone lactylation (H3K18lac) levels were detected by Western blot assay. Chromatin immunoprecipitation (CHIP) assay was performed to detect the combination between H3K18lac and promoter regions of the ADIPOQ. The receiver operating curve (ROC) analysis was used to evaluate the diagnostic value of ADIPOQ in psoriasis.Results: ADIPOQ was decreased in the skin tissues of psoriasis patients. In addition, the global lactylation and H3K18lac levels were significantly decreased in the skin tissues of psoriasis patients. In HaCaT cells, promoting the global lactylation and H3K18lac levels increased the ADIPOQ protein levels, while si-LDHA transfection decreased the ADIPOQ protein levels. The CHIP results indicated that lactylation promoted the binding of promoter regions of the ADIPOQ and H3K18lac. Finally, the ROC analysis showed that ADIPOQ exhibited diagnostic value in psoriasis.Conclusion: This study demonstrated ADIPOQ was decreased in the skin tissues of psoriasis patients, and ADIPOQ has diagnostic value for psoriasis. Furthermore, down-regulation of H3K18lac levels inhibited the transcription of ADIPOQ, which was the key factor of decrease of ADIPOQ levels in psoriasis patients.Keywords: psoriasis, ADIPOQ, histone, lactylation

Hanyu Fang,1,2 Tairan Dong,1 Shanlin Li,1 Yihan Zhang,1 Zhuojun Han,1 Mingfei Liu,1,2 Wenjun Dong,1,2 Zheng Hong,1,2 Min Fu,3 Hongchun Zhang1,2 1Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, 100029; 2Department of Traditional Chinese Medicine for Pulmonary Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 3Department of Infectious Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100029, People’s Republic of ChinaCorrespondence: Hongchun Zhang, Department of Traditional Chinese Medicine for Pulmonary Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China, Tel +86 13701226664, Email 13701226664@139.com Min Fu, Department of Infectious Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100029, People’s Republic of China, Tel +86 13366093706, Email bdfumin@126.comObjective: Although studies on the association between COPD and lung cancer are of great significance, no bibliometric analysis has been conducted in the field of their comorbidity. This bibliometric analysis explores the current situation and frontier trends in the field of COPD and lung cancer comorbidity, and to lay a new direction for subsequent research.Methods: Articles in the field of COPD and cancer comorbidity were retrieved from Web of Science Core Collections (WoSCC) from 2004 to 2023, and analyzed by VOSviewer, CiteSpace, Biblimatrix and WPS Office.Results: In total, 3330 publications were included. The USA was the leading country with the most publications and great influence. The University of Groningen was the most productive institution. Edwin Kepner Silverman was the most influential scholar in this field. PLOS One was found to be the most prolific journal. Mechanisms and risk factors were of vital importance in this research field. Environmental pollution and pulmonary fibrosis may be future research prospects.Conclusion: This bibliometric analysis provided new guidance for the development of the field of COPD and lung cancer comorbidity by visualizing current research hotspots, and predicting possible hot research directions in the future.Keywords: COPD, lung cancer, bibliometric analysis, VOSviewer, CiteSpace

Yaqian Zhang,1,&ast; Yan Liu,2,&ast; Mingming Fu,1 Zhiqian Wang,1 Zhiyong Hou2,3 1Department of Geriatric Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3NHC Key Laboratory of Intelligent Orthopaedic Equipment (The Third Hospital of Hebei Medical University), Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqian Wang, Third Hospital of Hebei Medical University Department of Geriatric Orthopedics, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email w18533112890@163.com Zhiyong Hou, Third Hospital of Hebei Medical University Department of Orthopaedic Surgery, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email drzyhou@gmail.comBackground: The prognosis of elderly patients with acute myocardial infarction (AMI) is poor, and this study aimed to investigate the characteristics and predictors of preoperative AMI in elderly hip fracture patients and to propose a valid clinical prediction model.Methods: We collected clinical data of older hip fracture patients from January 2019 to December 2020. The data collected include demographic and clinical characteristics, underlying diseases and laboratory results. In AMI patients, we further collected type of myocardial infarctions, clinical symptoms, electrocardiogram (ECG), Killip class and diagnosis method. The prediction model was constructed by using Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analyses. In addition, the constructed prediction model was transformed into a nomogram. The performance of the model was evaluated using the area under receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Bootstrapping was used for validation.Results: There are 40 (4.2%) cases developed AMI in all 958 patients. There were 685 (71.5%) female patients and 273 (28.5%) male patients. Among 40 AMI patients, 38 (95.0%) had Type 2 myocardial infarction (T2MI) and 2 (5.0%) had Type 1 myocardial infarction (T1MI). The majority of these ECG were ST segment depression (57.5%). Most elderly AMI patients (67.5%) presented asymptomatic. Predictors for preoperative AMI were higher age (OR 2.386, 95% CI 1.126– 5.057), diabetes (OR 5.863, 95% CI 2.851– 12.058), Hb≤ 100 g/L (OR 3.976, 95% CI 1.478– 10.695), CRP≥ 40 mg/L (OR 6.998, 95% CI 2.875– 17.033), and ALB≤ 35 g/L (OR 2.166, 95% CI 1.049– 4.471). Good discrimination and calibration effect of the model was showed. Interval validation could still achieve the C-index value of 0.771. DCA demonstrated this nomogram has good clinical utility.Conclusion: This model has a good predictive effect on preoperative AMI in elderly patients with hip fracture, which can help to better plan clinical evaluation.Keywords: hip fracture, myocardial infarction, characteristics, prediction model

Gongbiao Lu,1,2,&ast; Cunxin Zhang,2,&ast; Kang Li,2 Kai Gao,3 Maoqing Fu,2 Chaoliang Lyu,2 Zhengxue Quan1 1Department of Spine Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400042, People’s Republic of China; 2Department of Spine Surgery, Jining No.1 People’s Hospital, Jining, 272011, People’s Republic of China; 3Department of Orthopaedics, Jining No.1 People’s Hospital, Jining, 272011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengxue Quan, Department of Spine Surgery, the First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Tel +86 13608321800, Fax +86-023-68811360, Email Quanzx18@126.com Chaoliang Lyu, Department of Spine Surgery, Jining No.1 People’s Hospital, No. 6 Healthy Road, Rencheng District, Jining, 272011, People’s Republic of China, Tel +86 15265775628, Fax +86-0537- 2253252, Email lvchaolianggk@163.comPurpose: To investigate the molecular mechanism underlying the inhibitory effect of sinomenine (SN) on interleukin-1β (IL-1β)-induced apoptosis in nucleus pulposus cells (NPCs), and to evaluate the potential role of SN in preventing intervertebral disk degeneration (IDD).Methods: The Rat NPCs were cultured in vitro and identified using Hematoxylin-Eosin (HE) staining, toluidine blue staining, and immunofluorescence analysis. NPCs were pretreated with or without SN, then induced with IL-1β to assess cell viability, ROS levels, apoptotic rates, and wound healing ability. Relevant protein expression was detected using Elisa, qPCR and Western Blot techniques. NPCs were pretreated with SN, either alone or in combination with Nrf2-IN-1 or SC, before being induced to undergo apoptosis by IL-1β. Apoptosis was detected using Hoechst staining, while qPCR and Western Blot techniques assessed protein expression. Rat caudal intervertebral discs were induced with IDD, with or without SN injection, and then co-injected with IL-1β. The levels of IDD were evaluated using HE staining and modified saffron-O-fix green cartilage staining. Relevant protein expression was detected using Elisa, qPCR, and Western Blot techniques.Results: IL-1β significantly reduced NPC activity, induced ROS accumulation and apoptosis, decreased cell healing rate, promoted the expression and secretion of inflammatory factors, and inhibited extracellular matrix synthesis. However, pretreatment with SN effectively reversed these effects. Inhibition of the Keap1/Nrf2 signaling pathway or activation of the NF-κB signaling pathway significantly attenuated the cytoprotective effects of SN and increased apoptosis. Acupuncture combined with IL-1β injection markedly induced intervertebral disc degeneration in rat caudal spine, upregulated inflammatory factors expression and secretion, and downregulated extracellular matrix synthesis. SN intervention notably enhanced antioxidant enzyme expression and reversed these outcomes.Conclusion: SN can prevent IL-1β-induced apoptosis of NPCs and ameliorate IDD by activating the Keap1/Nrf2 pathway and inhibiting the NF-κB signaling pathway.Keywords: sinomenine, intervertebral disc degeneration, nucleus pulposus cells, apoptosis, Nrf2, NF-κB

Jiongchao Guo,1,2 Min Chen,3 Yu Hong,1,2 Yating Huang,1,4 Haiyan Zhang,2 Yuan Zhou,1,2 Bingfeng Zhou,1,5 Minmin Fu1 1Department of Cardiology, The Third Affiliated Hospital of Anhui Medical University (The First People’s Hospital of Hefei), Hefei, Anhui, 230000, People’s Republic of China; 2Graduate School, Anhui Medical University, Hefei, Anhui, 230000, People’s Republic of China; 3Department of Cardiology, the Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230000, People’s Republic of China; 4Department of Endocrinology department, the Third Affiliated Hospital of Anhui Medical University (The First People’s Hospital of Hefei), Hefei, Anhui, 230000, People’s Republic of China; 5Department of Cardiology, Hefei BOE Hospital, Hefei, Anhui, 230000, People’s Republic of ChinaCorrespondence: Minmin Fu, Department of Cardiology, the Third Affiliated Hospital of Anhui Medical University (The First People’s Hospital of Hefei), Hefei, Anhui, 230000, People’s Republic of China, Email fuminmin@126.com Bingfeng Zhou, Department of Cardiology, The Third Affiliated Hospital of Anhui Medical University (The First People’s Hospital of Hefei), Hefei BOE Hospital, Hefei, Anhui, 230000, People’s Republic of China, Email xnkzbf@126.comBackground: Neutrophil to high-density lipoprotein cholesterol ratio (NHR) has demonstrated predictive value for coronary artery disease (CAD). However, few research has been conducted on the predictive capacity of NHR for Major Adverse Cardiovascular Events (MACE) following Percutaneous Coronary Intervention (PCI) or the degree of coronary artery stenosis in hospitalized ST-segment elevation myocardial infarction (STEMI) patients.Methods: The study involved 486 patients diagnosed with STEMI between the years 2020 and 2023. Univariate and multivariate logistic regression analyses were conducted to evaluate the risk factors for MACE after PCI and severe coronary artery stenosis during hospitalization. Receiver operating characteristic (ROC) curves were generated to determine predictive power of NHR and MHR. Spearman correlation analysis was performed to assess the correlation between NHR, MHR and the Gensini score (GS).Results: Multivariate logistic regression analysis showed that the NHR and MHR were the independent risk factor for MACE during hospitalization in STEMI patients (MHR: the odds ratio (OR)=2.347, 95% confidence interval (CI)=1.082– 5.089, P=0.031) (NHR: OR=1.092, 95% CI=1.025– 1.165, P=0.004). In addition, NHR was also an independent risk factor for high GS (NHR: OR=1.103, 95% CI=1.047– 1.162, P< 0.001), and the MHR was not an independent risk factor. The ROC curve analysis was performed to evaluate the predictive ability of NHR and MHR for in-hospital MACE in STEMI patients after primary PCI. The area under the curve (AUC) for NHR was 0.681. The AUC for MHR was 0.672. Regarding the prediction of high GS, the AUC for NHR was 0.649. The AUC for MHR was 0.587. Spearman correlation analysis showed that NHR exhibited stronger correlation with GS, while MHR was lower (NHR: r=0.291, P< 0.001) (MHR: r=0.156, P< 0.001).Conclusion: These findings highlight the potential clinical utility of NHR as a predictive indicator in STEMI patients after PCI during hospitalization, both for MACE events and the degree of coronary artery stenosis.Keywords: neutrophil to high-density lipoprotein cholesterol ratio, monocyte to high-density lipoprotein cholesterol ratio, acute myocardial infarction, coronary artery disease, cardiovascular disease

Hanyu Fang,1,2,&ast; Tairan Dong,1,&ast; Zhuojun Han,1 Shanlin Li,1 Mingfei Liu,1 Ying Liu,3 Qiwen Yang,1 Min Fu,4 Hongchun Zhang1,2 1Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Department of Traditional Chinese Medicine for Pulmonary Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 3The Second Health and Medical Department, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 4Department of Infectious Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongchun Zhang, Department of Traditional Chinese Medicine for Pulmonary Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China, Tel +86 13701226664, Email 13701226664@139.com Min Fu, Department of Infectious Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100029, People’s Republic of China, Tel +86 13366093706, Email bdfumin@126.comObjective: The comorbidity of pulmonary fibrosis and COPD/emphysema has garnered increasing attention. However, no bibliometric analysis of this comorbidity has been conducted thus far. This study aims to perform a bibliometric analysis to explore the current status and cutting-edge trends in the field, and to establish new directions for future research.Methods: Statistical computing, graphics, and data visualization tools such as VOSviewer, CiteSpace, Biblimatrix, and WPS Office were employed.Results: We identified a total of 1827 original articles and reviews on the comorbidity of pulmonary fibrosis and COPD/emphysema published between 2004 and 2023. There was an observed increasing trend in publications related to this comorbidity. The United States, Japan, and the United Kingdom were the countries with the highest contributions. Professor Athol Wells and the University of Groningen had the highest h-index and the most articles, respectively. Through cluster analysis of co-cited documents, we identified the top 17 major clusters. Keyword analysis predicted that NF-κB, oxidative stress, physical activity, and air pollution might be hot spots in this field in the future.Conclusion: This bibliometric analysis demonstrates a continuous increasing trend in literature related to the comorbidity of pulmonary fibrosis and COPD/emphysema. The research hotspots and trends identified in this study provide a reference for in-depth research in this field, aiming to promote the development of the comorbidity of pulmonary fibrosis and COPD/emphysema.Keywords: COPD, pulmonary fibrosis, bibliometric analysis, VOSviewer, CiteSpace

Maria Liljeroos,1,2,&ast; Björn Agvall,3,&ast; Daniel Eek,4,&ast; Michael Fu5,&ast; 1Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; 2Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden; 3Department of Research and Development, Region Halland, Halmstad, Sweden; 4Cardiovascular, Renal and Metabolism, Medical Department, BioPharmaceuticals, AstraZeneca, Stockholm, Sweden; 5Section of Cardiology, Department of Medicine, Geriatrics and Emergency Medicine Sahlgrenska University Hospital-Östra Hospital, Gothenburg, Sweden&ast;These authors contributed equally to this workCorrespondence: Daniel Eek, AstraZeneca AB, Karlebyhus B674, Södertälje, SE-15185, Sweden, Tel +46 31 776 3659, Email Daniel.Eek@astrazeneca.comPurpose: Qualitative studies that highlight the patient perspective of heart failure (HF) and its impact on the lives of patients are limited. Our study objective was to describe the patient’s perspective on HF, including the diagnosis, treatment journey and healthcare interactions, and how HF impacts patients’ lives and specifically their health-related quality of life (HRQoL) and work capacity.Patients and Methods: This cross-sectional, non-interventional, mixed-methods patient experience study comprised: (i) a quantitative online survey with study-specific questions and assessments of HRQoL and work impairment among 101 patients with HF in Sweden and (ii) 35 qualitative interviews to gain in-depth understanding of the patients’ experiences.Results: Patients were found to experience a highly symptomatic and detrimental impact of HF on their HRQoL and work capacity. Fatigue was the most frequently reported symptom, and it was detrimental to all areas of patients’ lives limiting them mentally, socially, and physically. Two-thirds of patients were not aware of the type of HF they had, one-third did not check their body weight regularly, and around half did not increase their physical exercise as recommended by both guidelines and healthcare practitioners. Patients preferred specialist to primary care, desired greater access to healthcare, and continuity in whom they interact with in primary care.Conclusion: Patients with HF experience a highly symptomatic burden that affects them physically, mentally, and socially. Our study highlights a major gap in patients’ knowledge about HF and HF-related healthcare. These results demonstrate a challenge for the Swedish healthcare system particularly as regards providing patients with continuity, accessibility, and proximity to primary care.Graphical Abstract: Keywords: chronic heart failure, health-related quality of life, patient-reported outcomes, qualitative interviews, patient experience

Manru Fu,1,2,&ast; Anqi Li,2,&ast; Futing Zhang,3 Li Lin,3 Chuning Chen,2 Ying Su,2 Yunshao Ye,4 Dong Han,1,5 Jinghui Chang2 1The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2School of Health Management, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Oncology, Southern Hopital of Southern Medical University, Guangzhou, People’s Republic of China; 4Guangzhou Health Technology Identification & Human Resources Assessment Center, Guangzhou, People’s Republic of China; 5School of Public Health, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinghui Chang, School of Health Management, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Tel +86 19898199912, Fax +86 020-61648573, Email erin2007@foxmail.comPurpose: The purpose of this study was to investigate the current state of eHealth literacy among cancer patients in a grade A tertiary hospital in Guangzhou, Guangdong Province, and to identify the factors that influence it, in order to provide a basis for improving the eHealth literacy of cancer patients.Patients and Methods: From September to November 2021, a convenience sampling method was employed to survey cancer patients in the oncology department of a grade A tertiary hospital in Guangzhou, using a self-administered general information questionnaire and the eHealth literacy scale (eHEALS). A total of 130 questionnaires were distributed, and 117 valid questionnaires were returned.Results: The mean total score of eHealth literacy among cancer patients was 21.32± 8.35. Multiple linear regression analysis revealed that the frequency of searching for health information and education level were significant factors influencing eHealth literacy (p< 0.05). Specifically, the education level (junior high school vs primary school or below) was found to have a significant association with eHealth literacy (beta=0.26, p=0.039).Conclusion: The results of this study suggest that the eHealth literacy of cancer patients is relatively low, with low scores on the dimensions of judgment and decision-making ability. The government and relevant regulatory authorities should focus on strengthening the reliability of online health information and implementing targeted e-interventions to enhance the eHealth literacy of cancer patients.Keywords: health literacy, neoplasms, information seeking behavior, eHEALS

Peilin Dai,1,2,&ast; Guoguo Yi,3,4,&ast; Dandan Qian,5,&ast; Zhe Wu,2 Min Fu,6 Hui Peng1 1School of Nursing, Hunan University of Medicine, Huaihua, Hunan, People’s Republic of China; 2The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Ophthalmology, The Sixth Affiliated Hospital, Sun-Yat-sen University, Guangzhou, People’s Republic of China; 4Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Department of Clinical Skills Training Center, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 6Department of Ophthalmology, Zhujiang Hospital of Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Fu, Department of Ophthalmology, Zhujiang Hospital of Southern Medical University, No. 253, Industrial Avenue Middle, Haizhu, Guangzhou, People’s Republic of China, Tel +86 18665621066, Email min_fu1212@163.com Hui Peng, School of Nursing, Hunan University of Medicine, No. 492, Jinxi South Road, Huaihua, Hunan, People’s Republic of China, Email pengh533@163.comPurpose: This study aimed to explore the impact that coping styles and social support have on the mental health of medical students by constructing a corresponding structural situation model that reveals the complex relationship between these three factors. In doing so, it seeks to help medication students better manage mental health problems.Patients and Methods: The online study was conducted between March 6, 2021 and May 6, 2021. A total of 318 participants from multiple medical schools were involved. The general information questionnaire, simple coping style questionnaire (SCSQ), perceived social support scale (PSSS) and symptom checklist 90 (SCL-90) were used to collect relevant information from the subjects by snowball sampling. An independent t-test, ANOVA, Pearson correlation coefficient analysis, and intermediary effect analysis were all used to analyze the relevant data and construct the structural equation model.Results: There was a significant difference in SCL-90 between medical students and national college students (1.78± 0.70, P < 0.001), and the positive rate of mental health status was as high as 40.3%. Sleep quality, regular diet, and positive coping style were positively correlated with mental health (P < 0.01), while negative coping styles and total scores of coping style as well as family, friends, and other sources of social support and total scores of social support were negatively correlated with mental health problems (P < 0.01). Positive and negative coping styles have an impact on mental health through the mediating effect of between social support and coping styles, as well as in the direct pathway.Conclusion: The mental health status of medical students was significantly poor. Medical schools should thus pay close attention to the mental health status of students and encourage them to develop healthy living habits, optimize coping styles, and establish stable sources of social support to improve their psychological wellbeing.Keywords: mediating effect, structural equation model, questionnaire investigation, psychological wellbeing

Yifan Yuan,1,2,&ast; Na Li,1,2,&ast; Mingyue Fu,1,2,&ast; Mei Ye1,2 1Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, China; 2Hubei Clinical Centre and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, China&ast;These authors contributed equally to this workCorrespondence: Mei Ye, Email wumeiye08@163.comBackground: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon and rectum that has no exact cause and is characterized by relapsing and remitting episodes. We aimed to find biomarkers of UC and its causes.Methods: We got GSE73661 from the GEO database and used WGCNA to find DEGs that were expressed in the same way in both normal and UC samples. To identify the co-expression modules, we used Weighted Gene Co-Expression Network Analysis. Next, we selected genes that were both DEGs and parts of main modules. Later, three datasets were used to find the hub genes, and qRT-PCR was utilized to confirm the in-silico findings. Additionally, we analyzed the connection between the hub genes and the filtration of immune cells in UC. Using the databases, we made predictions about the miRNAs and lncRNAs that regulate the hub genes and predicted possible therapeutic drugs.Results: We found 822 DEGs and three main modules related to immunity, endoplasmic reticulum, and metabolism. Using another three datasets and human samples to confirm the mRNA expression of these genes in UC patients, XBP1 and PLPP1 were selected as hub genes, and had excellent diagnostic potential. According to the findings of the immune infiltration, patients with UC exhibited a larger proportion of immune cells. And hub genes, particularly XBP1, were closely linked to a number of immune cell infiltrations. Based on the databases and hub genes, a lncRNA-miRNA-mRNA network, including two miRNAs (miR-214-3p and miR-93-5p), two hub genes, and 124 lncRNAs, and potential therapeutic medicine were identified.Conclusion: We found two new genes, XBP1 and PLPP1, that are involved in UC and can help diagnose and measure the disease. XBP1 also relates to clinical scores and immune cells. We suggested a gene network and possible drugs based on them.Keywords: ulcerative colitis, hub genes, biomarkers, bioinformatics analysis, ceRNA regulatory network

Mei Fu,1 Jun Li,2 Mingchong Liu,1 Chensong Yang,1 Qidong Wang,1 Hongrui Wang,3 Bingdi Chen,2 Qingge Fu,3 Guixin Sun1 1Department of Traumatic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Institute for Regenerative Medicine, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3Department of Orthopedic Trauma, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, People’s Republic of ChinaCorrespondence: Guixin Sun; Qingge Fu, Email sunguixin@tongji.edu.cn; fqg7821@163.comBackground: Immune responses and osteogenesis differentiation induced by implants are crucial for bone tissue regeneration. Consideration of only one of those properties is not sufficient. To investigate the synergistic actions, we designed alginate/graphene oxide/sericin/nanohydroxyapatite (Alg/GO/Ser/nHAP) nanocomposite hydrogels with both osteoimmunomodulatory and osteoinductive activities. This study aimed to explore the effect of hydrogel with osteoimmunomodulatory properties on promoting osteogenesis of bone marrow stem cells (BMSCs).Methods: Alg/GO/Ser/nHAP nanocomposite hydrogel was fabricated and was characterized by SEM, FTIR, XRD, stress-strain, rheology, swelling and degradation. After the impact of sericin on M2 macrophage polarization was identified, the BMSCs viability and adhesion were evaluated by CCK8 assay, live/dead staining, cytoskeleton staining. The cell osteogenic differentiation was observed by ALP/ARS staining, immunofluorescence staining, RT-PCR, and Western blotting, respectively. Rat cranial defect model was used to assess osteoimmunomodulatory effects of scaffolds in vivo by micro‑computed tomographic, histological, and immunohistochemical analyses after 8 weeks of healing.Results: In vitro experiments revealed that the hydrogel presented desirable mechanical strength, stability, porosity, and biocompatibility. Significantly, sericin and nHAP appeared to exert synergistic effects on bone regeneration. Sericin was observed to inhibit the immune response by inducing macrophage M2-type polarization to create a positive osteoimmune microenvironment, contributing to improving osseointegration at the bone-implant interface to promote osteogenesis. However, the osteogenic differentiation in rat BMSCs was further enhanced by combining nHAP and sericin in the nanocomposite hydrogel. Eventually, the hydrogel was implanted into the rat cranial defect model, assisting in the reduction of local inflammation and efficient bone regeneration.Conclusion: The nanocomposite hydrogel stimulated bone formation by the synergistic effects of immunomodulation of macrophage polarization by sericin and direct osteogenic induction by nHAP, demonstrating that such a scaffold that modulates the osteoimmune microenvironment to promote osteogenesis is a promising approach for the development of bone tissue engineering implants in the future.Graphical Abstract: Keywords: hydrogel, nano-hydroxyapatite, sericin, osteoimmunomodulation, osteoinduction, bone regeneration

Jin Liang,1,&ast; Yuanfang Hu,1,&ast; Mingxia Fu,2 Na Li,1 Fengxia Wang,1 Xiaojun Yu,1 Bing Ji1 1Department of Laboratory Medicine, Binzhou Medical University Hospital, Binzhou, People’s Republic of China; 2Department of Laboratory Medicine, Binzhou People’s Hospital, Binzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bing Ji, Email bingji1218@163.comObjective: To investigate the molecular epidemiology of Staphylococcus aureus (S. aureus) isolated from patients in the Yellow River Delta region and to construct antibiotic resistance profiles in different genetic backgrounds.Methods: Antibiotics susceptibility testing, staphylococcal protein A (spa) typing and accessory gene regulator (agr) typing were performed for all the 204 strains. Isolates with the positive mecA gene and heterogeneous vancomycin-intermediate S. aureus (hVISA) were subjected to multilocus sequence typing (MLST) and Staphylococcal chromosomal cassettes mec (SCCmec) typing.Results: Thirty-nine MRSA strains were identified by mecA gene. Twenty-two hVISA isolates including 9 MRSA and 13 methicillin-sensitive S. aureus (MSSA) strains were confirmed, the rest isolates (n = 182) were vancomycin-susceptible S. aureus (VSSA). 94.9% of MRSA and 63.6% of hVISA belonged to agrI. Fifty-seven distinct spa types including 5 novel types were mainly t309 (30.9%), t078 (11.8%) and t437 (11.8%). Fourteen sequence types (STs) containing 3 new STs were classified into 3 clone complexes (CCs) and 7 singletons among MRSA and hVISA isolates. Most MRSA isolates (87.2%) belonged to type Ⅳ SCCmec.Conclusion: The predominant genotype among MRSA population was ST59-t437-agrI-IVa (53.8%), followed by ST72-t2431-agrI-IVF (15.4%). ST72 and CC5 (ST5/965/7197) were the most common hVISA clones. Both CC59 (ST59/7437) and ST72 clones were resistant to erythromycin and clindamycin among MRSA population. Strains of MSSA with phenotypic hVISA (MS-hVISA) exhibited a striking genetic diversity accompanied by the diversification of drug resistance patterns.Keywords: Staphylococcus aureus, heterogeneous vancomycin-intermediateS. aureus, accessory gene regulator, multilocus sequence typing, erythromycin

Mengyue Fu,1,&ast; Shi Chen,2,&ast; Rui Xu,1 Jie Chen,1 Xuehan Chen,1 Wanxia Gan,1 He Huang,1 Guangyou Duan1 1Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Anesthesiology, Chongqing Beibu Maternity Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangyou Duan; He Huang, Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China, Email duangy@hospital.cqmu.edu.cn; huanghe@cqmu.edu.cnPurpose: This study aimed to explore the effects of intravenous analgesia using tramadol on postoperative depression, anxiety, and sleep in women undergoing abdominal endoscopic surgery.Patients and Methods: Two hundred female patients (100 in each group) who underwent abdominal endoscopic surgery were recruited to randomly receive intravenous analgesia with sufentanil combined with tramadol (tramadol group) or sufentanil (control group). The primary outcome was the incidence of postoperative depression, which was assessed at 1, 2, and 3 days after surgery using the 13-item Beck Depression Inventory. The secondary outcomes were the incidence of anxiety and sleep quality, which were assessed using the 20-item Self-Rating Anxiety Scale and Richards–Campbell Sleep Questionnaire.Results: The incidence of depression (Beck depression scale≥ 4) during the 3-day follow-up in the control group was 51%, which was significantly higher than that in the tramadol group of 28% (relative risk [RR]=0.55; 95% confidence interval [CI], 0.38– 0.79; P=0.001). No difference was found in the incidence of anxiety state (Self-Rating Anxiety Scale≥ 40) between the tramadol and control groups (7%vs 5%; RR=1.40; 95% CI, 0.46– 4.25; P=0.552). All of the Richards–Campbell sleep scales of patients in the tramadol group at 1 (77.4± 15.2 vs 64.2± 20.1, P< 0.001), 2 (84.1± 14.9 vs 71.8± 18.8, P< 0.001), and 3 days (87.0± 12.2 vs 70.3± 21.0, P< 0.001) after surgery were higher than those in the control group.Conclusion: Intravenous analgesia using tramadol can effectively improve the postoperative depression and sleep status of women undergoing abdominal endoscopic surgery. Tramadol is recommended for use in postoperative analgesia when improving postoperative mood, and sleep is needed in clinical practice.Keywords: women, depression, anxiety, sleep, abdominal surgery

Jing Zhou,1 Miao Fu,2 Dehe Zhang,1 Yejin Xu,1 Jiangshan Lian,3 Hanglu Xu,1 Yang Zhang,1 Haijun Chen1 1Department of Infectious Disease, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China; 2Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China; 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of ChinaCorrespondence: Haijun Chen, Department of Infectious Disease, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 365 Renmin East Road, Jinhua, Zhejiang, 32100, People’s Republic of China, Email jhchenhaijun@sina.comBackground: Although individuals infected with HIV for the first time manifest a series of acute syndromes, most patients show mild or no symptoms, which complicates the initial clinical diagnosis. Early diagnosis is important for effective prevention and management of patients. Metagenomic next-generation sequencing technology (mNGS) can rapidly detect a wide range of pathogenic microorganisms, even in atypical cases. However, to date, few studies have reported the application of mNGS to diagnose acute HIV infection with aseptic meningitis.Case Presentation: A 38-year-old man was admitted to the Department of Infectious Diseases due to repeated fever, headache, and scattered rashes on his limbs. Routine blood analysis revealed elevated absolute lymphocytes and monocytes. Moreover, monocytes were found to be significantly increased following a lumbar puncture and cerebrospinal fluid detection. mNGS results revealed the presence of the human immunodeficiency virus (HIV-1), with HIV RNA of 910 copies/mL in his cerebrospinal fluid. The HIV antigen/antibody test was negative. According to a study by Fie Big et al, a clear diagnosis of acute HIV infection at Fiebig stage I. The patient’s condition improved after treatment, and he was prescribed antiretroviral therapy (ART) after discharge.Conclusion: Aseptic meningitis is easily misdiagnosed during the initial stages of acute HIV infection. mNGS can be used to identify the pathogen early, rapidly, and accurately, thereby improving the treatment of acute HIV infections.Keywords: acute HIV infection, aseptic meningitis, Fiebig stage I, mNGS

Jinghui Chang,1,&ast; Manru Fu,1,2,&ast; Peihua Cao,3 Changhai Ding,3,4,&ast; Dong Wang1,&ast; 1School of Health Management, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510282, People’s Republic of China; 3Clinical Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, People’s Republic of China; 4Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia&ast;These authors contributed equally to this workCorrespondence: Dong Wang, School of Health Management, Southern Medical University of China, Guangzhou, 510515, People’s Republic of China, Tel +86 18620089545, Email dongw96@smu.edu.cnPurpose: To compare patients’ self-reported health-related quality of life (HRQoL) before and after total knee arthroplasty (TKA) and determine factors contributing to any heterogeneity in HRQoL.Patients and Methods: This prospective multicenter observational study included 404 patients with knee osteoarthritis who underwent TKA between April 1, 2019 and December 30, 2019 and whose HRQoL was assessed preoperatively and 7 days and 1, 3, and 6 months postoperatively. Sociodemographic characteristics were assessed using a General Information Questionnaire, disability using the Knee Injury and Osteoarthritis Outcome Score (KOOS-PS), resting pain using the visual analogue scale (Pain-VAS), and HRQoL using the European Quality of Life Five Dimension Five Level (EQ-5D-5L) scale. The growth mixture model was used to identify group heterogeneity in the developmental trajectories of KOOS-PS, Pain-VAS, and EQ5D5L. Logistic regression was used to explore the factors influencing the developmental trajectories of factors affecting the developmental trajectory of HRQoL.Results: The mean EQ-5D-5L score improved from 0.69 preoperatively to 0.90 at 6 months postoperatively. Longitudinal heterogeneity in HRQoL was observed in patients during recovery: 1) patients with a small and slow improvement in HRQoL and 2) patients who showed marked and rapid improvement in HRQoL. The main characteristics of the latter group were decreasing VAS pain scores, a monthly family income > 2000 CNY (100 CNY equals approximately 14.9 USD), exercising for < 30 min daily, and better knee function at baseline. Baseline knee function and change in knee function were significantly associated with the percentage change in HRQoL.Conclusion: HRQoL improved considerably after TKA. However, there was heterogeneity in the changes in HRQoL depending on patients’ socioeconomic status, exercise, and baseline knee function. Dynamic tracking of the HRQoL of TKA patients and timely provision of rehabilitation guidance will promote continuous improvement of the HRQoL of TKA patients.Keywords: knee osteoarthritis, knee replacement, knee function

Jinfeng Zhang,1,2 Na Ta,3 Meng Fu,1,2 Fan Hua Tian,1,2 Jie Wang,1,2 Tianyou Zhang,1,2,* Baojun Wang1,2,* 1Department of Neurology, Baotou Central Hospital, Baotou, Inner Mongolia, People’s Republic of China; 2Cerebrovascular Disease Research Institute of Inner Mongolia Autonomous Region, Baotou, Inner Mongolia, People’s Republic of China; 3Practical Teaching Skills Center, Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tianyou Zhang; Baojun Wang, Department of Neurology, Baotou Central Hospital, Baotou, Inner Mongolia, People’s Republic of China, Tel +86-472-6955178 ; +86-472-6955346, Email jbwwbj@126.com; 2533784284@qq.comPurpose: To compare the MRI characteristics of patients with wake-up ischemic stroke (WUS) and with ischemic stroke with known onset time (clear-onset-time stroke, COS) to clarify the role of diffusion-weighted imaging–fluid-attenuated inversion recovery (DWI-FLAIR) mismatch in estimating the onset time of WUS patients.Patients and Methods: Two hundred patients with acute ischemic stroke were selected for complete brain MRI within six hours of symptom onset, including DWI and FLAIR sequences. The patients were divided into WUS (n = 78) and COS (n = 122) groups, based on whether the time of onset was known. The general conditions and imaging characteristics were collected to compare the DWI-FLAIR mismatch features between the two groups at different time intervals.Results: There was no significant difference in the DWI-FLAIR mismatch on MRI within 2 hour after the first found abnormality between the two groups (50.0% vs 71.8%, p = 0.180). With increasing time, the DWI-FLAIR mismatch decreased substantially in the WUS group, while a higher DWI-FLAIR mismatch presence persisted in the COS group within a four-hour interval from the onset of symptoms to the MRI. The DWI-FLAIR mismatch was significantly lower in the WUS group than in the COS group from symptom identification to MRI at 2– 3 h, 3– 4 h, and 4– 5 h intervals (15% vs 60%, 10.5% vs 48%, 6.7% vs 45.4%; p < 0.01).Conclusion: Our results suggest that the presence of DWI-FLAIR mismatch within 2 h of the first found abnormality was not significantly different between WUS and COS. Therefore, Patients with WUS within 2 hours after the first detected abnormality may be suitable for intravenous thrombolysis.Keywords: acute ischemic stroke, diffusion-weighted imaging, fluid-attenuated inversion recovery image, mismatch

Mingming Fu,1,&ast; Junfei Guo,2,&ast; Yaqian Zhang,1 Yuqi Zhao,1 Yingze Zhang,2– 4 Zhiqian Wang,1 Zhiyong Hou2,3 1Department of Geriatric Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Orthopaedic Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 3NHC Key Laboratory of Intelligent Orthopaedic Equipment (The Third Hospital of Hebei Medical University), Shijiazhuang, China; 4Chinese Academy of Engineering, Beijing, 100088, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingze ZhangThird Hospital of Hebei Medical University, Department of Orthopaedic Surgery, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaEmail dryzzhang@126.comZhiqian WangThird Hospital of Hebei Medical University, Department of Geriatric Orthopedics, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaEmail w18533112890@163.comPurpose: Respiratory complication is one of the major challenges in the treatment of older adults with hip fractures. However, no study so far has investigated the effect of wearing medical masks on the prevention of perioperative respiratory complications in these patients.Patients and Methods: In this retrospective cohort study, 1016 consecutive patients aged ≥ 65 years with hip fractures were included and assigned to two groups: the control group and the observation group. The two groups received the same perioperative management modalities. In addition, patients in the observation group were asked to wear medical masks for protection. Data of patients’ demographics, fracture type, surgical methods, comorbidities, the incidence of perioperative respiratory and other complications, and hospital outcomes were collected and compared between the two groups. Subgroup analyses were also performed stratified by fracture types.Results: A total of 1016 patients (292 females and 724 males) with a mean age of 79.4± 7.3 years were analyzed in the study, including 533 in the control group and 483 in the observation group. The overall incidence of perioperative respiratory complication, and the incidence of pulmonary infection, respiratory failure and arrhythmia in the observation group were significantly lower than the control group, especially in winter and spring. There was no difference in other complications, hospital length of stay, and total hospital costs. Further subgroup analyses showed that the incidence of heart failure and arrhythmia in the observation group was lower than that in the control group for patients with femoral neck fractures, which was different from patients with intertrochanteric fractures.Conclusion: The incidence of perioperative respiratory complications, including pulmonary infection and respiratory failure, could be reduced in older adults with hip fractures by strengthening personal protection, including wearing medical masks, especially in winter and spring. Wearing medical masks could also effectively reduce the incidence of perioperative heart failure and arrhythmia in femoral neck fracture patients and do not increase the incidence of other complications and the burden of hospitalization.Keywords: masks, aged, hip fractures, perioperative period, respiratory system

Mingming Fu,1,&ast; Junfei Guo,2,&ast; Yuqi Zhao,1 Yaqian Zhang,1 Yingze Zhang,2– 4 Zhiqian Wang,1 Zhiyong Hou2,3 1Department of Geriatric Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 3NHC Key Laboratory of Intelligent Orthopeadic Equipment (The Third Hospital of Hebei Medical University), Shijiazhuang, Hebei, 050051, People’s Republic of China; 4Chinese Academy of Engineering, Beijing, 100088, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqian WangDepartment of Geriatric Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaEmail w18533112890@163.comZhiyong HouDepartment of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaEmail drzyhou@gmail.comPurpose: Limited information exists on fall-related fractures in older adults with cerebrovascular disease. This study aimed to determine the characteristics of older adults with cerebrovascular disease who sustained fall-related fractures and identify the associated risk factors for perioperative complications.Patients and Methods: This was a cross-sectional study, which included patients with cerebrovascular disease who sustained fractures between Jan. 2017 and Dec. 2019. The collected data included demographics (age and gender), time and place of fracture occurrence, mechanism of injury, fracture location, type of cerebrovascular disease, complications, and comorbidities.Results: A total of 768 patients with 815 fractures were included; there were 253 males and 515 females, with an average age of 78.3 years. For either males or females, 80– 84 years was the most commonly involved age group. Most (61.0%) patients had their fractures occurring at home and most fractures (70.7%) occurred during the daytime. Most were hip fractures and limb weakness; instability-related falls were the most common cause of fracture, making a proportion of 34.5%. Patients who suffered falls were mainly combining ischemic cerebrovascular disease. Most (85.9%) patients presented with at least one comorbid disease and the perioperative complication rate was 76.9% in total cases. Age≥ 80 (OR: 1.772, 95% CI: 1.236– 2.540) and the number of comorbidities≥ 3 (OR: 1.606, 95% CI: 1.035– 2.494) were found independently associated with complications, while the type of cerebrovascular disease, fracture location, and comorbidities of prior fragility fracture and respiratory disease were not significantly correlated with complications.Conclusion: Our findings highlighted that more focus on improved physical function explored in intervention setting and the importance of primary home prevention measures seems justified in China and maybe other countries as well. It is the first study that presented the epidemiological characteristics of older adults with cerebrovascular disease who later experienced a fracture.Keywords: cross-sectional study, epidemiology, fall-related fracture, cerebrovascular disease, older adults

Wenqing Zhu,1,2 Xiangmei Kong,1,2,* Ying Huang,1,2,* Mingshui Fu,3 Xi Shen,4 Fang Wang,5 Xinghuai Sun1,2,6 1Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, People’s Republic of China; 3Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 4Ruijin Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5Shanghai Tenth People’s Hospital, Tongji University, Shanghai, People’s Republic of China; 6State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangmei Kong; Ying HuangDepartment of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of ChinaTel +86-21-64377134Email kongxm95@163.com; 13661763815@163.comPurpose: To investigate the agreement of optic nerve head evaluations and initial diagnoses of primary open-angle glaucoma (POAG) by general ophthalmologists and glaucoma specialists in Shanghai, China.Methods: This multicenter, cross-sectional study involved the outpatients from the general ophthalmology departments of four top eye hospitals in Shanghai. The participants underwent ocular examinations, including intraocular pressure, fundus photography, corneal thickness, refractometry, visual acuity, visual field and gonioscopy. General ophthalmologists and glaucoma specialists performed the diagnoses and classified them as non-glaucoma, POAG suspects, and POAG. The consistency of initial diagnosis between general ophthalmologists and glaucoma specialists was measured using the weighted kappa coefficient. Logistic regression analysis was used to detect the risk factors for the reliability of POAG diagnosis.Results: In 922 participants, the initial diagnosis rates of POAG and non-glaucoma were much higher in the glaucoma specialist group than in the general ophthalmologist group, while the initial diagnosis rates of POAG suspects were higher in the general ophthalmologist group. The weighted kappa coefficient between the two groups was 0.831± 0.027 (95% confidence interval, 0.779– 0.884). Logistic regression analysis of the risk factors for the reliability of POAG diagnosis showed that the independent risk factors were intraocular pressure (OR 8.363, 95% CI: 4.27– 16.37) and vertical cup-to-disc ratio (OR 3.459, 95% CI: 1.54– 7.76).Conclusion: The diagnosis consistency between the general ophthalmologists and the glaucoma specialists was similar among outpatients in the area of Shanghai. However, general ophthalmologists tended to classify the indefinite subjects as POAG suspects, and their accuracy in diagnosing POAG was low. By paying more attention to the risk factors of POAG diagnosis, general ophthalmologists could improve the diagnosis accuracy.Keywords: primary open-angle glaucoma, initial diagnosis, risk factor, intraocular pressure, vertical cup-to-disc ratio

Chengbin Liu,1 Ning Huang,1 Mingqi Fu,2 Hui Zhang,1 Xing Lin Feng,3 Jing Guo3 1School of Sociology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Center for Social Security Studies, Wuhan University, Wuhan, People’s Republic of China; 3Department of Health Policy and Management, School of Public Health, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Jing GuoDepartment of Health Policy and Management, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, People’s Republic of ChinaTel +86-18086471505Email jing624218@163.comBackground: The Coronavirus Diseases (COVID-19) pandemic is a global public health challenge and provides an opportunity to investigate the unclear relationship between risk perception, social support, and mental health. This study aims to examine the association between risk perception and mental health while taking social support as a moderator.Methods: An online cross-sectional study recruiting 2993 participants was conducted in China, from 1st to 10th, February 2020. The relationship between risk perception, social support, and mental health was examined using multivariate linear regression analyses.Results: This study indicated that risk perception was associated with a higher level of mental health symptoms. The subscale “Perceived uncontrollability” seemed to present a stronger correlation with depressive symptoms (Beta=0.306) and post-traumatic stress disorder (PTSD) symptoms (Beta=0.318) than the subscale “Perceived Severity” did. Moreover, social support moderated the relationship between perceived uncontrollability and mental health symptoms.Conclusion: In the context of the COVID-19 pandemic, it is necessary to design mental health strategies and programs from a risk perception perspective (more mental health strategies should be delivered to build reasonable risk perception), while social support from family and friends may be protective to against depressive symptoms and PTSD symptoms. There is a demand for mental health intervention from a risk perception perspective.Keywords: risk perception, social support, depressive symptoms, PTSD symptoms, SARS-CoV-2

Ming Fu,1,* Xiangming Hu,2,* Shuo Sun,1 Shixin Yi,1 Ying Zhang,1 Yingqing Feng,1 Yingling Zhou,1 Qingshan Geng,1 Haojian Dong1 1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China; 2The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.; Department of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haojian DongDepartment of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of ChinaEmail donghaojian@sina.comPurpose: Masked hypertension (MHT), as an independent clinical entity, the cardiac dysfunction caused by it can be early detected through left ventricular global longitudinal strain (GLS), yet the quantitative relation between MHT and GLS is still unclear. Therefore, we tried to conduct a community-based retrospective study to define this relationship.Patients and Methods: A total of 308 enrolled participants from Dongguan, China, were divided into non-hypertension (NHT) and MHT groups. Baseline characteristics were recorded, and echocardiography and 24-hour ambulatory blood pressure monitoring were performed. Linear regression analysis and receiver-operating characteristic (ROC) curve analysis were used to assess the associations between MHT and GLS in univariate and multivariate models, and the dose–response curve was plotted to demonstrate their relationship.Results: The mean age of the NHT and MHT groups was 57 and 60 years, respectively. Signs of left ventricular diastolic function, E/A was reduced and E/e’ was increased in the MHT group while those of the NHT group were nearly normal. The MHT group also showed a significantly lower (“worse”) GLS than NHT (− 15.2% vs − 19.9%, P < 0.001) while left ventricular ejection fraction (LVEF) did not differ between the groups. Worse GLS was independently and significantly associated with MHT both in univariate (odds ratio [OR]: 1.97, P < 0.001) and stepwise multivariate regression analysis (OR: 1.99, P < 0.001). Comparison of ROC curve results showed that area under curve of GLS was larger than that of E/e’ both in unadjusted (0.8673 vs 0.6831) and adjusted model (0.9178 vs 0.8284). Further analysis showed adjusted nonlinear correlation between MHT and GLS.Conclusion: Based on the relationship between MHT and GLS, in clinical practice, GLS measurement could facilitate diagnosis for suspected MHT patients and could define the extent of left ventricular dysfunction for diagnosed MHT patients.Keywords: masked hypertension, left ventricular dysfunction, global longitudinal strain, nonlinear relation

Yubei He,1 Mengzhu Wang,2 Ming Fu,2 Xun Yuan,3 Yuanli Luo,2 Bin Qiao,2 Jin Cao,2 Zhigang Wang,2 Lan Hao,2,* Gengbiao Yuan1,* 1Department of Nuclear Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 3Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lan Hao; Gengbiao Yuan Email lanhao5@cqmu.edu.cn; 300784@hospital.cqmu.edu.cnPurpose: A multi-functional nanoplatform with diagnostic imaging and targeted treatment functions has aroused much interest in the nanomedical research field and has been paid more attention in the field of tumor diagnosis and treatment. However, some existing nano-contrast agents have encountered difficulties in different aspects during clinical promotion, such as complicated preparation process and low specificity. Therefore, it is urgent to find a nanocomplex with good targeting effect, high biocompatibility and significant therapeutic effect for the integration of diagnosis and treatment and clinical transformation.Materials and Methods: Nanoparticles (NPs) targeting breast cancer were synthesized by phacoemulsification which had liquid fluorocarbon perfluoropentane(PFP) in the core and were loaded with Iron(II) phthalocyanine (FePc) on the shell. The aptamer (APT) AS1411 was outside the shell used as a molecular probe. Basic characterization and targeting abilities of the NPs were tested, and their cytotoxicity and biological safety in vivo were evaluated through CCK-8 assay and blood bio-chemical analysis. The photoacoustic (PA) and ultrasound (US) imaging system were used to assess the effects of AS1411-PLGA@FePc@PFP (A-FP NPs) as dual modal contrast agent in vitro and in vivo. The effects of photothermal therapy (PTT) in vitro and in vivo were evaluated through MCF-7 cells and tumor-bearing nude mouse models.Results: A-FP NPs, with good stability, great biocompatibility and low toxicity, were of 201.87 ± 1.60 nm in diameter, and have an active targeting effect on breast cancer cells and tissues. With the help of PA/US imaging, it was proved to be an excellent dual modal contrast agent for diagnosis and guidance of targeted therapy. Meanwhile, it can heat up under near-infrared (NIR) laser irradiation and has achieved obvious antitumor effect both in vitro and in vivo experiments.Conclusion: As a kind of nanomedicine, A-FP NPs can be used in the integration of diagnosis and treatment. The treatment effects and biocompatibility in vivo may provide new thoughts in the clinical transformation of nanomedicine and early diagnosis and treatment of breast cancer.Keywords: poly (lactic-co-glycolic) acid, theranostics, phase transition, photoacoustic imaging, ultrasound imaging, near infrared

Liang Kong,1 Xue-tao Li,1 Ying-nan Ni,1 Hong-he Xiao,1 Ying-jia Yao,2 Yuan-yuan Wang,3 Rui-jun Ju,4 Hong-yan Li,1 Jing-jing Liu,1 Min Fu,1 Yu-tong Wu,1 Jing-xian Yang,1 Lan Cheng1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, People’s Republic of China; 2College of Life and Health Sciences, Northeastern University, Shenyang 110819, People’s Republic of China; 3Department of Pharmacy, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, People’s Republic of China; 4Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, People’s Republic of ChinaCorrespondence: Jing-xian Yang; Lan Cheng Email jingxianyang0520@163.com; sychenglan@163.comIntroduction: Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aβ oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer’s disease (AD). However, the effectiveness of the drug is limited by its solubility and bioavailability, as well as by the low permeability of the blood-brain barrier (BBB). In this study, a kind of transferrin-modified Ost liposomes (Tf-Ost-Lip) was constructed, which could improve the bioavailability and enhance brain targeting.Methods: Tf-Ost-Lip was prepared by thin-film hydration method. The ability of liposomal formulations to translocate across BBB was investigated using in vitro BBB model. And the protective effect of Tf-Ost-Lip was evaluated in APP-SH-SY5Y cells. In addition, we performed pharmacokinetics study and brain tissue distribution analysis of liposomal formulations in vivo. We also observed the neuroprotective effect of the varying formulations in APP/PS-1 mice.Results: In vitro studies reveal that Tf-Ost-Lip could increase the intracellular uptake of hCMEC/D3 cells and APP-SH-SY5Y cells, and increase the drug concentration across the BBB. Additionally, Tf-Ost-Lip was found to exert a protective effect on APP-SH-SY5Y cells. In vivo studies of pharmacokinetics and the Ost distribution in brain tissue indicate that Tf-Ost-Lip prolonged the cycle time in mice and increased the accumulation of Ost in the brain. Furthermore, Tf-Ost-Lip was also found to enhance the effect of Ost on the alleviation of Alzheimer’s disease-related pathology.Conclusion: Transferrin-modified liposomes for delivery of Ost has great potential for AD treatment.Keywords: transferrin, osthole, liposomes, blood-brain barrier, Alzheimer’s disease

Nan Wang,1 Chaochao Zhong,2 Mingti Fu,3 Lin Li,1 Fang Wang,1 Pengwei Lv,1 Mingzhi Zhu,1 Youyi Xiong,1 Hailong Mi,1 Yuanting Gu1 1Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of China; 2Department of Emergency, The First People’s Hospital of Zhengzhou, Zhengzhou 450052, Henan, People’s Republic of China; 3Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of ChinaCorrespondence: Yuanting GuDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Erqi District, Zhengzhou 450052, People’s Republic of ChinaEmail yuantinggu@126.comIntroduction: Long non-coding RNAs (lncRNAs) were found to regulate many biological processes including cancer development, immunology and other diseases. LncRNA HULC was found to be oncogenes in many cancer progression. However, the role of HULC in the regulation of breast cancer remains unclear.Methods: The expression of HULC and miR-6754-5p was examined by RT-PCR. Through knockdown of HULC, we found that the proliferation abilities coupled with migration and invasion abilities were significantly decreased. And also, we verified that overexpression of miR-6754-5p significantly decreased the proliferation ability of breast cancer cells.Results: In this study, we found that lncRNA HULC was overexpressed in breast cancer tissues and cell lines compared to normal healthy breast tissues and normal breast cell line. Moreover, the high expression of HULC was associated with metastasis and malignancy of breast cancers. Mechanically, we found that HULC can bind to miR-6754-5p directly through complementary base pairing. Furthermore, we found that HULC regulates the expression of LYPD1 through sponging miR-6754-5p. Moreover, overexpression of LYPD1 can rescue the migration and invasion abilities of breast cancer cells decreased by knockdown of HULC or overexpression of miR-6754-5p.Conclusion: Our study showed the role of HULC in promoting breast cancer development and explained the detailed molecular mechanisms.Keywords: lncRNA HULC, breast cancer development, miR-6754-5p, LYPD1

Jing Guo,1 Mingqi Fu,1 Zhiyong Qu,2 Xiaohua Wang,2 Xiulan Zhang21School of Sociology, Huazhong University of Science and Technology, Wuhan 430074, People’s Republic of China; 2School of Social Development and Public Policy, China Institute of Health, Beijing Normal University, Beijing 100875, People’s Republic of ChinaObjectives: We aimed to investigate the prevalence of and risk factors associated with pain and to compare the correlation between depression and sleep quality and pain among adults in Northwest China, where health care resources are limited.Methods: In total, 7,602 subjects (age ≥40 years) participated in this survey. Using the Brief Pain Inventory-Chinese version, we evaluated the overall pain among respondents, including pain sites, pain intensity, and its interference in daily life. In addition, depression symptoms were measured using the Center for Epidemiologic Studies Depression Scale Chinese edition. Furthermore, the subjective sleep quality among participants was assessed using the Pittsburgh Sleep Quality Index.Results: Approximately 25.2% of the participants experienced pain, and 41.7% of those perceived the worst pain they had experienced as severe pain. Chronic disease exhibited the most robust correlation with severe pain, followed by poor sleep quality. Furthermore, the correlation between depression and pain was found only in the population with severe pain.Conclusion: The study reveals that pain affects a large proportion of Chinese adults, especially females, living in rural areas, having lower incomes, unemployed, and suffering from poor health status or mental illness. Furthermore, this study suggests we should have a screen and intervention for depression and poor sleep quality among pain suffers, which will be helpful for pain management in Northwest China.Keywords: pain, depression, sleep quality

Yuanyuan Wang,1 Min Fu,2 Jingjing Liu,2 Yining Yang,1 Yibin Yu,1 Jinyu Li,1 Weisan Pan,1 Lei Fan,3 Guiru Li,4 Xuetao Li,2 Xiaobo Wang1,31Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China; 2School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, People’s Republic of China; 3Department of Pharmacy, 210th Hospital of People’s Liberation Army, Dalian, Liaoning, People’s Republic of China; 4Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of ChinaBackground: Chemotherapy for non-small-cell lung cancer (NSCLC) still leads to unsatisfactory clinical prognosis because of poor active targeting and tumor metastasis.Purpose: The objective of this study was to construct a kind of PFV peptide modified targeted daunorubicin and dioscin codelivery liposomes, which could enhance tumor targeting and inhibit tumor cell metastasis.Methods and results: Targeted daunorubicin and dioscin codelivery liposomes were prepared by film dispersion and the ammonium sulfate gradient method. With the ideal physicochemical properties, targeted daunorubicin and dioscin codelivery liposomes exhibited enhanced cellular uptake and showed strong cytotoxicity to tumor cells. The encapsulation of dioscin increased the inhibitory effects of daunorubicin on A549 cells, vasculogenic mimicry (VM) channels and tumor metastasis. The enhanced antimetastatic mechanism of the targeted liposomes was attributed to the downregulation of matrix metalloproteinase-2 (MMP-2), vascular endothelial cadherin (VE-Cad), transforming growth factor-β1 (TGF-β1) and hypoxia inducible factor-1α (HIF-1α). Meanwhile, the targeted daunorubicin and dioscin codelivery liposomes exhibited significant antitumor effects in tumor-bearing mice. H&E staining, immunohistochemistry with Ki-67 and TUNEL assay also showed the promoted antitumor activity of the targeted liposomes.Conclusion: Targeted daunorubicin and dioscin codelivery liposomes may provide an effective strategy for the treatment of NSCLC.Keywords: daunorubicin, dioscin, liposomes, cell penetrating peptides, tumor metastasis, non-small-cell lung cancer

Song X, Ju R, Xiao Y, et al. Int J Nanomedicine. 2017;12:7433‒7451. The authors have advised due to an error at the time of figure assembly, Figure 5 on page 7442 is incorrect. The correct Figure 5 is shown in Download Article. The authors apologize for this error and advise it does not affect the results of the paper. Read the original article

Gang Guo,1,* Moushun Fu,2,* Shuxiang Wei,3 Ruiwan Chen4 1Department of Ophthalmology, Tongjiang Hospital of Guangdong, Foshan, 2Department of Otorhinolaryngology, Tongjiang Hospital of Guangdong, Foshan, 3Department of Endocrinology, Tongjiang Hospital of Guangdong, Foshan, 4Department of Radiotherapy, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Diabetes mellitus (DM) has been identified to be both a risk factor and a prognostic factor in a variety of malignancies, but its association with the risk and outcome of nasopharyngeal carcinoma (NPC) is still unclear. To elucidate this issue, we systematically reviewed the evidence concerning the association between DM status and NPC.Materials and methods: We identified studies by a literature search of PubMed, Embase, and ISI Web of Knowledge through May 31, 2017, and by searching the reference lists of pertinent articles. Odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were used to estimate the effect size. Heterogeneity across studies was evaluated by the Cochran’s Q and I2 statistics.Results: A total of nine studies were included. Four studies with a total sample size of 221,611 reported the effect of DM on NPC risk, and the other five studies with a sample size of 9,442 reported the impact of DM on survival in NPC patients. All included studies were retrospective, and mostly conducted in Asian populations. Meanwhile, condition of metformin usage was not considered in all studies. A pooled OR of 0.65 (95% CI: 0.43–0.98, P=0.04) revealed an inverse association between DM and NPC. Additionally, pooled analyses of studies investigating the prognosis value of DM revealed that preexisting DM had no effect on overall survival (HR =1.17, 95% CI: 0.94–1.46, P=0.16), local recurrence-free survival (HR =1.16, 95% CI: 0.80–1.67, P=0.44), and distant metastasis-free survival (HR =1.14, 95% CI: 0.92–1.40, P=0.22).Conclusion: Our results suggested that DM patients might have decreased NPC risk, and have little impact on prognosis of NPC patients. This conclusion should be limited to Asian population. Our results also suggest that more attention should be paid to metformin medication in further studies in order to clarify whether the effects of DM on NPC risk and prognosis are influenced by the anticancer effect of metformin. Keywords: diabetes mellitus, nasopharyngeal carcinoma, risk factor, prognosis factor, a meta-analysis, evidence based medicine

Xiao-li Song,1 Rui-jun Ju,2 Yao Xiao,1 Xin Wang,1 Shuang Liu,1 Min Fu,1 Jing-jing Liu,1 Li-yan Gu,1 Xue-tao Li,1 Lan Cheng1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 2Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing, China Abstract: Chemotherapy for aggressive non-small-cell lung cancer (NSCLC) usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM) channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC. Keywords: octreotide, honokiol, chemotherapy, vasculogenic mimicry, tumor metastasis, targeting drug delivery

Ai-Ling Liang,1–3,* Hai-Li Qian,4,* Ting-Ting Zhang,1–3 Ning Zhou,1–3 Hai-Juan Wang,4 Xi-Ting Men,4 Wei Qi,5 Ping-Ping Zhang,6 Ming Fu,4 Xiao Liang,4 Chen Lin,4 Yong-Jun Liu1–3 1Medical Molecular Diagnostics Key Laboratory of Guangdong, 2Department of Biochemistry and Molecular Biology, 3Department of Clinical Biochemistry, Guangdong Medical University, Dongguan, Guangdong, 4State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, 5Electroencephalogram Room, 6Department of Orthopedics, Guangdong Medical University Affiliated Hospital, Zhanjiang, Guangdong, People’s Republic of China *These authors contributed equally to this study Abstract: Breast cancer is the most common cancer and the leading cause of cancer-related death among women worldwide, with urgent need to develop new therapeutics. Targeted therapy is a promising strategy for breast cancer therapy. Stromal-derived factor-1/CXC chemokine receptor 4 (CXCR4) has been implicated in the metastasis of breast cancer, which renders it to be therapeutic target. This study aimed to evaluate the anticancer effect of fused TAT–DV1–BH3 polypeptide, an antagonist of CXCR4, and investigate the underlying mechanism for the cancer cell-killing effect in the treatment of breast cancer in vitro and in vivo. This results in a potent inhibitory effect of fused TAT–DV1–BH3 polypeptide on tumor growth and metastasis in nude mice bearing established MDA-MB-231 tumors. Fused TAT–DV1–BH3 polypeptide inhibited the proliferation of MDA-MB-231 and MCF-7 cells but did not affect that of HEK-293 cells. The fused TAT–DV1–BH3 polypeptide colocalized with mitochondria and exhibited a proapoptotic effect through the regulation of caspase-9 and -3. Furthermore, the fused TAT–DV1–BH3 polypeptide suppressed the migration and invasion of the highly metastatic breast cancer cell line MDA-MB-231 in a concentration-dependent manner. Notably, the DV1-mediated inhibition of the stromal-derived factor-1/CXCR4 pathway contributed to the antimetastasis effect, evident from the reduction in the level of phosphoinositide 3 kinase and matrix metalloproteinase 9 in MDA-MB-231 cells. Collectively, these results indicate that the apoptosis-inducing effect and migration- and invasion-suppressing effect explain the tumor regression and metastasis inhibition in vivo, with the involvement of caspase- and CXCR4-mediated signaling pathway. The data suggest that the fused TAT–DV1–BH3 polypeptide is a promising agent for the treatment of breast cancer, and more studies are warranted to fully elucidate the therapeutic targets and molecular mechanism. Keywords: bifunctional, fused polypeptide, CXCR4, breast cancer, apoptosis, transfer

Xiaoping Li,1–3,* Chi Cai,3,* Rong Luo,4 Rongjian Jiang,1 Jie Zeng,1 Yijia Tang,1 Yang Chen,1 Michael Fu,5 Tao He,1 Wei Hua31Department of Cardiology, Hospital of the University of Electronic Science and Technology of China, Sichuan Provincial People’s Hospital, Chengdu, Sichuan, 2School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 3Department of Clinical Electrophysiology, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 4Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 5Department of Medicine, Sahlgrenska University Hospital/Östra Hospital, Gothenburg, Sweden*These authors contributed equally to this workObjective: Recent studies have shown that sex and age are associated with outcomes in patients with cardiomyopathy. The purpose of this study was to determine the all-cause mortality of dilated cardiomyopathy (DCM) by age and sex.Methods and results: The patients were divided into non-elderly (age

Chengxue Yi,* Hui Zhong,* Shanshan Tong,* Xia Cao,* Caleb K Firempong, Hongfei Liu, Min Fu, Yan Yang, Yingshu Feng, Huiyun Zhang, Ximing Xu, Jiangnan Yu Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, People's Republic of China*These authors contributed equally to this workPurpose: To investigate the growth inhibition activity of Flammulina velutipes sterol (FVS) against certain human cancer cell lines (gastric SGC and colon LoVo) and to evaluate the optimum microemulsion prescription, as well as the pharmacokinetics of encapsulated FVS.Methods: Molecules present in the FVS isolate were identified by gas chromatography/mass spectrometry analysis. The cell viability of FVS was assessed with methyl thiazolyl tetrazolium (MTT) bioassay. Based on the solubility study, phase diagram and stability tests, the optimum prescription of F. velutipes sterol microemulsions (FVSMs) were determined, followed by FVSMs characterization, and its in vivo pharmacokinetic study in rats.Results: The chemical composition of FVS was mainly ergosterol (54.8%) and 22,23-dihydroergosterol (27.9%). After 72 hours of treatment, both the FVS (half-maximal inhibitory concentration [IC50] = 11.99 µg • mL-1) and the standard anticancer drug, 5-fluorouracil (IC50 = 0.88 µg • mL-1) exhibited strong in vitro antiproliferative activity against SGC cells, with IC50 > 30.0 µg • mL-1; but the FVS performed poorly against LoVo cells (IC50 > 40.0 µg • mL-1). The optimal FVSMs prescription consisted of 3.0% medium chain triglycerides, 5.0% ethanol, 21.0% Cremophor EL and 71.0% water (w/w) with associated solubility of FVS being 0.680 mg • mL-1 as compared to free FVS (0.67 µg • mL-1). The relative oral bioavailability (area-under-the-curve values of ergosterol and 22,23-dihydroergosterol showed a 2.56-fold and 4.50-fold increase, respectively) of FVSMs (mean diameter ~ 22.9 nm) as against free FVS were greatly enhanced.Conclusion: These results indicate that the FVS could be a potential candidate for the development of an anticancer drug and it is readily bioavailable via microemulsion formulations.Keywords: Flammulina velutipes sterol, microemulsions, pharmacokinetics, bioavailability