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Hao Wu, Yanna Shen, Li Zhang, Mouzhe Yang, Yougang Ren, Feng Mao, Zhongxiao Wu Department of Dermatology, Ningbo No.6 Hospital, Ningbo, People’s Republic of ChinaCorrespondence: Zhongxiao Wu, Department of Dermatology, Ningbo No.6 Hospital, No. 1059, Zhongshan East Road, Ningbo, People’s Republic of China, Email 2016123801@jou.edu.cnAbstract: Psoriasis is relatively common in clinical practice, whereas niacin deficiency is relatively rare. We describe the clinical case of a patient with plaque psoriasis for over 20 years who also had a concomitant latent tuberculosis infection. After secukinumab and anti-tuberculosis treatment for 1 year, the psoriatic rash mostly resolved, but atypical symptoms of niacin deficiency suddenly appeared. The patient’s symptoms rapidly subsided after experimental treatment with niacin. After 2 weeks, the patient suddenly developed an erythroderma-like rash, manifesting as large areas of erythema and plaque psoriasis throughout the body. The patient was admitted to the hospital and treated with an anti-inflammatory, biologic adalimumab, tripterygium glycoside, and sodium thiosulfate. The patient was discharged after a week. This case suggests the need for caution and to look out for the emergence of new symptoms when treating patients with moderate-to-severe plaque psoriasis, especially with biologics.Keywords: psoriasis, niacin deficiency, case report

Rui Wang,1– 4 Wei Zhang,1– 3 Yuanyuan Li,1– 3 Yuting Jiang,1– 3 Hongqi Feng,1– 3 Yang Du,1– 3 Zhe Jiao,1– 3 Li Lan,4 Xiaona Liu,1– 3 Bingyun Li,1– 3 Chang Liu,1– 3 Xingbo Gu,5 Fang Chu,1– 3 Yuncheng Shen,1– 3 Chenpeng Zhu,1– 3 Xinhua Shao,1– 3 Simeng Tong,1– 3 Dianjun Sun1– 3 1Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, 150081, People’s Republic of China; 2National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin, 150081, People’s Republic of China; 3Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, 150081, People’s Republic of China; 4Harbin Center for Disease Control and Prevention, Harbin, 150056, People’s Republic of China; 5Department of Biostatistics, School of Public Health, Hainan Medical University, Haikou, 571199, People’s Republic of ChinaCorrespondence: Dianjun Sun, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Baojian Road 157, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86-13313685318, Fax +86 45186612695, Email hrbmusdj@163.comPurpose: To investigate the environmental, immune, and inflammatory factors associated with chronic obstructive pulmonary disease (COPD) in middle-aged and older Chinese individuals.Patients and Methods: A community-based case–control study was conducted among 471 patients with COPD and 485 controls. The information on COPD of the participants was collected through face-to-face interviews, and serum samples were measured at the laboratory. The main risk factors for COPD were analyzed using principal component analysis (PCA) and logistic regression.Results: Nine hundred and fifty-six respondents were included in the analysis. The results of the PCA-logistic regression analysis showed significant differences in the environmental factors, medical history, and serum C-reactive protein (CRP) levels between patients and controls. COPD was markedly more usual in those with smoking index > 200 (OR, 1.42; 95% CI, 1.28– 1.57); exposure to outdoor straw burning (OR, 1.64; 95% CI, 1.47– 1.83); use of coal, wood, and straw indoors (OR, 2.31; 95% CI, 1.92– 2.78); history of respiratory disease and coronary heart disease (OR, 3.58; 95% CI, 3.12– 4.10), congestive heart failure (OR, 1.23; 95% CI, 1.09– 1.38), and cerebrovascular disease (OR, 1.15; 95% CI,1.02– 1.31); and higher serum level of CRP (OR, 1.20; 95% CI, 1.11– 1.30). Compared to the logistic regression analysis, PCA logistic regression analysis identified more important risk factors for COPD.Conclusion: PCA-logistic regression analysis was first utilized to explore the influencing factors among rural residents in Northeast China Environmental aged 40 years and above, it was found that environmental factors, medical history, and serum CRP levels mainly affected the prevalence of COPD.Keywords: chronic obstructive pulmonary disease, collinearity, principal component, logistic regression

Mingfang Li,1 Jiaojiao Shi,1 Ming Chu,1 Youmei Shen,1 Shimeng Zhang,1 Xingxing Sun,1 Hengli Zhang,1 Qing Yan,1 Jinlong Gong,2 Gregory YH Lip,3,4 Minglong Chen1,5 1Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Division of Cardiology, Jiangdu People’s Hospital, Yangzhou, People’s Republic of China; 3Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK; 4Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 5Division of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Minglong Chen, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-25-68303115, Fax +86-25-6813-6479, Email chenminglong@njmu.edu.cnAbstract: China has a large population of elderly in rural areas. Village doctors are acting as health-care gatekeepers for the rural elderly in China and are encouraged to provide more long-term care for patients with chronic diseases such as atrial fibrillation (AF). The data of AF registries from the rural elderly are limited. The present registry aims to provide contemporary data on the current AF-related health status of the rural elderly and the gaps in management of AF by village doctors. This study has two phases. The first phase is a cross-sectional study of AF screening in two rural towns of eastern China. All the residents aged ≥ 65 years are eligible and will be invited to attend a government-led health examination or an in-house AF screening program. The AF detection rate, the awareness of AF and the usage of oral anticoagulants and smartphones by AF patients, and the ability to diagnose and manage AF by village doctors will be assessed. Participants with AF detected in the first phase are eligible for the second phase. A variety of modes of intensified education will be provided to all AF patients and their family members to enrich their AF-related knowledge. Their village doctors will be offered a lecture-based training program focusing on Atrial fibrillation Better Care (ABC) pathway. Follow-up will be conducted for 1 year. The primary endpoint is the composite of all stroke and all-cause mortality. The first phase of AF screening was conducted between April 2019 and June 2019, and 18,712 participants with the mean age of 73.1± 5.8 years were enrolled. The second phase that includes 810 patients with AF, started on 1 May 2019. This study will provide a perspective of primary care system and would indirectly reflect the current status of chronic disease care in rural China.Keywords: atrial fibrillation, elderly, village doctors, rural China

Shengwei Meng,1,&ast; Derong Xu,1,&ast; Shuo Han,1 Guanghui Li,1 Yan Wang,1 Yanqing Shen,2 Kai Zhu,1 Antao Lin,1 Ruiting Wang,3 Xuexiao Ma,1 Chuanli Zhou1 1Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Operating Room, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 3Medical Insurance Audit Department, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanli Zhou; Xuexiao Ma, Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266000, People’s Republic of China, Tel +8618661809796 ; +8618661807895, Email justin_5257@hotmail.com; maxuexiaospinal@163.comPurpose: To evaluate the outcomes, feasibility, and safety of endoscopic unilateral laminectomy, bilateral decompression and discectomy (Endo-ULBDD) for central lumbar spinal stenosis (CLSS) combined with disc herniation (DH).Methods: This study includes 39 patients diagnosed with CLSS combined with DH who met the inclusion criteria and underwent surgery for Endo-ULBDD from April 2020 to March 2021. The mean age of the patients, operation time, hospitalization time, time in bed, and complications were recorded. Patients were followed up for at least 12 months. Visual analog scale (VAS) scores for low-back and lower-limb pain and Oswestry Disability Index (ODI) scores were evaluated preoperatively, before discharge, and at 3, 6, and 12 months postoperatively. To evaluate clinical effectiveness 12 months postoperatively, the modified MacNab criteria were used.Results: The mean age of the patients was 59.9 years, the mean operation time was 82.1 minutes, the mean hospitalization time was 3.7 days, and the mean time in bed was 20.9 hours. The mean VAS scores of low-back and lower-limb pain improved from 5.9 and 7.2 to 2.0 and 1.6, respectively (P < 0.05). The ODI score improved from 56.0 to 16.7 (P < 0.05). The overall excellent-good rate of the modified MacNab criteria was 89.7%. Two kinds of complications occurred in 4 patients (10.3%), including 1 patient whose inferior articular process was excessively removed and 3 patients who suffered from postoperative dysesthesia. No other severe complications were noted.Conclusion: Endo-ULBDD is a safe, feasible, efficient, and minimally invasive approach to treating CLSS combined with DH.Keywords: endoscopic spinal surgery, laminectomy, discectomy, lumbar spinal stenosis, intervertebral disc displacement

Yu Shen,1 Yilei Zheng,1 Daojun Hong1,2 1Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 2Department of Medical Genetics, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of ChinaCorrespondence: Daojun Hong, Department of Neurology, The First Affiliated Hospital of Nanchang University, 17# Yongwaizheng St, Nanchang, 330006, People’s Republic of China, Tel/Fax +86-791-8869-2511, Email hongdaojun@hotmail.comAbstract: Over the past decades, advances in genetic sequencing have opened a new world of discovery of causative genes associated with numerous pain-related syndromes. Familial episodic pain syndromes (FEPS) are one of the distinctive syndromes characterized by early-childhood onset of severe episodic pain mainly affecting the distal extremities and tend to attenuate or diminish with age. According to the phenotypic and genetic properties, FEPS at least includes four subtypes of FEPS1, FEPS2, FEPS3, and FEPS4, which are caused by mutations in the TRPA1, SCN10A, SCN11A, and SCN9A genes, respectively. Functional studies have revealed that all missense mutations in these genes are closely associated with the gain-of-function of cation channels. Because some FEPS patients may show a relative treatability and favorable prognosis, it is worth paying attention to the diagnosis and management of FEPS as early as possible. In this review, we state the common clinical manifestations, pathogenic mechanisms, and potential therapies of the disease, and provide preliminary opinions about future research for FEPS.Keywords: familial episodic pain syndromes, voltage-gated sodium channel, transient receptor potential A1, dorsal root ganglia, nociceptive pain

Haixin Luo,1,&ast; Bo Xie,2,&ast; Jinhui Xu,2 Yuqi Zhu,1 Jiayi Sun,1 Yuqing Shen,1 Xiuzu Song2 1Department of Dermatology, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Dermatology, Hangzhou Third People’s Hospital; Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuzu Song, Email songxiuzu@sina.comBackground: Vitiligo is an acquired skin depigmentation disease. It can be misdiagnosed at an early stage and tend to relapse. Serum markers are essential to monitoring the progression of vitiligo. Exosomal miRNAs act as the communication mediator between melanocytes and immune cells. Our study aimed to use serum exosomal miRNAs as a reference for evaluating vitiligo progression.Methods: The miRNAs were extracted from the serum exosomes of ten progressive vitiligo patients (before and after treatment) and ten healthy individuals. We profiled miRNAs expression by RNA sequencing and screened out potential miRNAs and plotted their receiver operating characteristic (ROC) curves to explore their sensitivity and specificity as prognostic biomarkers in vitiligo progression. We examined the correlation between miRNA expression and the lesion area. Different databases were used to predict gene targets of miRNAs, which were analyzed by gene ontology and Kyoto encyclopedia of genes and genomes (KEGG).Results: Our results showed that 141 miRNAs were differentially expressed in serum exosomes of progressive vitiligo patients, and 365 miRNAs were differentially expressed in these patients after treatment compared to healthy individuals. The expression of hsa-miR-487b-3p was significantly lower in these patients compared to healthy individuals. Still, there was no difference in its levels in patients after corticosteroid treatment compared to healthy controls. ROC curve analysis (area under curve = 0.840) indicated that hsa-miR-487b-3p could serve as a biomarker for the prognosis of vitiligo progression. Its expression positively correlated with the lesion area. A total of 41 target genes of hsa-miR-487b-3p were predicted via different databases. KEGG pathways were enriched in phenylalanine metabolism, glycan degradation, and protein export.Conclusion: Serum exosomal hsa-miR-487b-3p can be a biomarker to detect vitiligo progression. The predicted target genes of hsa-miR-487b-3p were enriched in catabolism. Thus, its in progressive vitiligo may accelerate catabolism in melanocytes and cause its impairment.Keywords: progressive vitiligo, exosome, miRNA, biomarker

Mingqiang Gong,1,2,&ast; Yunxia Shen,2,&ast; Wenbin Liang,2 Zhen Zhang,3 Chunxue He,4 Mingwu Lou,2 ZiYu Xu2 1Department of Acupuncture and Moxibustion, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Radiology, Longgang Central Hospital, Shenzhen, People’s Republic of China; 3Department of Radiology, The Third People’s Hospital of Longgang District, Shenzhen, People’s Republic of China; 4Department of Radiology, Shenzhen Clinical Medicine College, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwu Lou; ZiYu Xu, Department of Radiology, Longgang Central Hospital, No. 6082, Longgang Avenue, Longgang District, Shenzhen, 518000, People’s Republic of China, Tel +86 13808854650 ; +86 13824321925, Email mingwulou@sina.com; xuziyu82@163.comPurpose: Methamphetamine use may cause severe neurotoxicity and cognitive impairment, leading to addiction, overdose, and high rates of relapse. However, few studies have systematically focused on functional impairments detected by neuroimaging in methamphetamine abstainers (MAs) during short-term abstinence. This study aimed to investigate effective connectivity, resting-state networks, and internetwork functional connectivity in MA brains to improve clinical treatment.Methods: Twenty MAs and 27 age- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuations and Granger causality were analyzed to investigate disrupted brain regions and effective connectivity, respectively. Independent component analysis and functional network connectivity were used to identify resting-state networks and internetwork functional connectivity, respectively.Results: Compared with healthy controls, MAs demonstrated abnormal amplitudes of low-frequency fluctuations in the bilateral precuneus, left posterior cingulate cortex (PCC), left middle frontal gyrus (MFG), left superior parietal lobule, left supplementary motor area (SMA), and left inferior parietal lobule (IPL). Moreover, MAs showed decreased effective connectivity from the left PCC to the left precuneus, increased effective connectivity from the left precuneus to the left MFG and from the right precuneus to the left SMA, and altered functional connectivity within the default mode network (DMN), frontoparietal network, sensorimotor network, ventral attention network, cerebellar network, and visual network. Importantly, hyperconnectivity between the DMN and ventral attention network and hypoconnectivity between the DMN and cerebellar network as well as the DMN and frontoparietal network were demonstrated in MAs.Conclusion: Our study implies that in short-term methamphetamine abstinence, disruptions to the DMN and executive network may a play key role, providing new insights for early rehabilitation.Keywords: methamphetamine, abstinence, network, Granger causality analysis, independent component analysis

Ying Shi1– 3&ast;, Wenming Kong1 &ast;, Haiqin Jiang,2,3 Wenyue Zhang,2,3 Chen Wang,2– 4 Limei Wu,1 Yunliang Shen,1 Qiang Yao,1 Hongsheng Wang1– 3,5 1Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, Huzhou, People’s Republic of China; 2Hospital of Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, People’s Republic of China; 3National Centre for STD and Leprosy Control, China CDC, Nanjing, People’s Republic of China; 4Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 5Centre for Global health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China&ast; These authors contributed equally to this workCorrespondence: Qiang Yao, Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, St 61, Zhejiang, People’s Republic of China, Email 7793908@qq.com Hongsheng Wang, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 12 Jiangwangmiao Street, Nanjing, People’s Republic of China, Tel: +86 025 8547 8953, Email whs33@vip.sina.comPurpose: Reports on antimicrobial resistance (AMR) of Mycobacterium leprae (M. leprae) in Zhejiang Province are limited. Thus, this study aimed to investigate the drug resistance of new leprosy cases within several years and analyse the emergence of AMR mutations from Zhejiang Province.Methods: This study enrolled 34 leprosy cases in Zhejiang Province, China, from 2018 to 2021. Gene mutation of WHO-recommended DRDRs (folP1, rpoB and gyrA) and genes of compensatory AMR-associated DRDRs, including nth, rpoA, rpoC, gyrB and 23S rRNA, were detected by amplification. Clinical data analysis was performed to investigate the epidemiological association of leprosy.Results: Of the 34 samples, 2 (5.9%) strains showed drug resistance, which were mutated to dapsone and ofloxacin, separately. Two single mutations in gyrB were detected in different strains (5.9%), whereas one of the rpoC mutation was also detected in one strain each (2.9%), which were proved to be polymorphs. No correlation of drug resistance proportion was identified in male vs female, nerve vs no nerve involvement, deformity vs no deformity and reaction vs non-reaction cases.Conclusion: Results showed well control of leprosy patients in Zhejiang Province. Gene mutations of WHO-recommended DRDRs folP1 and gyrA confirmed the resistance to dapsone and ofloxacin. Compensatory AMR-associated mutations confirmed to be polymorphs still require further study to determine their phenotypic outcomes in M. leprae. The results demonstrated that drug-resistant strains are not epidemic in this area. Given the few cases of leprosy, analysing the AMR of M. leprae in Zhejiang Province more comprehensively is difficult. However, regular MDT treatment and population management in the early stage may contribute to the low prevalence of leprosy.Keywords: M. leprae, antimicrobial resistance, gene mutation

Ke Zhang,&ast; Songwei Feng,&ast; Yu Ge, Bo Ding, Yang Shen Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Shen, Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China, Email shenyang@seu.edu.cnPurpose: Mucinous ovarian cancer (MOC) is a rare histological type of EOC. In order to guide the clinical diagnosis and management of MOC patients, we constructed and verified a nomogram for the estimation of overall survival in patients with MOC.Patients and Methods: We collected 494 patients with MOC diagnosed from 2010 to 2015 in SEER database, and the following main inclusion criteria were used: (1) patients whose MOC was confirmed by pathology; (2) patients without a history of primary other cancer. Subsequently, we performed randomized grouping (6:4) and Cox hazard regression analysis in the training group. Subsequently, the nomogram was established. A variety of indicators were used to validate the prognosis value of nomogram, including the C-index, area under the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). Moreover, Kaplan–Meier analysis was used to compare the survival results among different risk subgroups.Results: Cox hazard regression analysis revealed that age, grade, FIGO stage and log odds of positive lymph nodes stage were independent risk factors for patients with MOC. In the training group, the C-index of the nomogram was 0.827 (95% CI: 0.791– 0.863) and the areas under the curve (AUC) predicting the 1-, 3- and 5-year survival rate were 0.853 (95% CI: 0.791– 0.915), 0.886 (95% CI: 0.852– 0.920) and 0.815 (95% CI: 0.766– 0.864), respectively. The calibration curve revealed that the nomogram of the 1-, 3- and 5-year survival rate was consistent with the actual fact. Patients with high risk had a poorer prognosis than those with low risk (P < 0.001). DCA revealed that the nomogram had the best clinical value than other classical prognostic markers. Similarly, nomogram had excellent prognostic ability in the testing group.Conclusion: The nomogram was constructed to predict overall survival in patients with MOC, which had the significance for clinical evaluation.Keywords: mucinous ovarian cancer, SEER database, nomogram, prognosis, log odds of positive lymph nodes (LODDS) stage

Qian Cao,1,&ast; Yu Shen,1,2,&ast; Zhuo Hou,1 Defu Li,3 Boji Tang,1 Lijun Xu,1 Yanping Li4 1Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Jiangxi Provincial Key Laboratory of Preventive Medicine, Nanchang University School of Public Health, Nanchang, Jiangxi, People’s Republic of China; 4Department of Neuroelectrophysiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lijun Xu, Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email xulijun20050901@sina.com Yanping Li, Department of Neuroelectrophysiology, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, Jiangxi, People’s Republic of China, Email 359173628@qq.comIntroduction: Patent foramen ovale (PFO) is potentially associated with abnormal embolisms, and it results in mixing of arteriovenous blood when its right-to-left shunt (RLS) emerges. Present studies have found that PFO is a risk factor that can lead to many diseases. However, few studies have examined the relationship between PFO and dizziness.Methods: This study was a large single-center, prospective, controlled study. From March 2019 to March 2021, we recruited patients with dizziness were divided into two groups: “explained” and “unexplained”. All patients were submitted to contrast-enhanced transcranial Doppler ultrasound and screened for PFO. Transesophageal heart ultrasound or right heart catheterization was used to confirm PFO. Additionally, multiple factors were collected and statistical analysis was performed between the two groups.Results: Among the 244 patients included, 123 were in the “explained” group and 121 were in the “unexplained” group. The prevalence of PFO in the “explained” group was 34 (27.4%) compared to 79 (64.7%) in the “unexplained” group. In the “explained” group, 7 were RLS level IV, 6 were level III, 7 were level II, and 14 were level I. For the “unexplained” group, the numbers of patients with levels IV, III, II and I were 27, 26, 12 and 14, respectively. Univariate analysis revealed that PFO (χ2= 34.77, P < 0.001) and age (t = − 3.49, P < 0.001) seemed to be potential risk factor candidates for “unexplained” dizziness. In multiple regression analysis, age (OR = 0.97; 95% CI 0.95– 0.99) and the prevalence of PFO (OR = 4.37; 95% CI 2.50– 7.63) were statistically significant. Massively shunted PFO showed more pronounced risk factors (OR = 8.76; 95% CI 4.04– 19.03).Conclusion: There was a high prevalence of PFO and a greater RLS level in unexplained dizziness. PFO and age were independent risk factors for unexplained dizziness. When treating with unexplained dizziness, especially among young people, we must pay attention to the presence of PFO.Keywords: patent foramen ovale, PFO, right to left shunt, RLS, unexplained dizziness, contrast-enhanced transcranial Doppler ultrasound, cTCD

Huan Tang, Yizhuo Xie, Ming Zhu, Juan Jia, Rui Liu, Yujia Shen, Yucui Zheng, Xin Guo, Dongfanghui Miao, Jin Pei Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Jin Pei, Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, 1163 Xinmin Street, Changchun, 130021, People’s Republic of China, Tel +86 431 85619725, Email peijin@jlu.edu.cnPurpose: Ovarian cancer is the most lethal gynecologic malignancy. The combination of paclitaxel (PTX) and carboplatin (CBP) is the first-line remedy for clinical ovarian cancer. However, due to the limitations of adverse reaction and lacking of targeting ability, the chemotherapy of ovarian cancer is still poorly effective. Here, a novel estrone (ES)-conjugated PEGylated liposome co-loaded PTX and CBP (ES-PEG-Lip-PTX/CBP) was designed for overcoming the above disadvantages.Methods: ES-PEG-Lip-PTX/CBP was prepared by film hydration method and could recognize estrogen receptor (ER) over-expressing on the surface of SKOV-3 cells. The characterizations, stability and in vitro release of ES-PEG-Lip-PTX/CBP were studied. In vitro cellular uptake and its mechanism were observed by fluorescence microscope. In vivo targeting effect in tumor-bearing mice was determined. Pharmacokinetics and biodistribution were studied in ICR mice. In vitro cytotoxicity and in vivo anti-tumor efficacy were evaluated on SKOV-3 cells and tumor-bearing mice, respectively. Finally, the acute toxicity in ICR mice was explored for assessing the preliminary safety of ES-PEG-Lip-PTX/CBP.Results: Our results showed that ES-PEG-Lip-PTX/CBP was spherical shape without aggregation. ES-PEG-Lip-PTX/CBP exhibited the optimum targeting effect on uptake in vitro and in vivo. The pharmacokinetics demonstrated ES-PEG-Lip-PTX/CBP had improved the pharmacokinetic behavior. In vitro cytotoxicity showed that ES-PEG-Lip-PTX/CBP maximally inhibited SKOV-3 cell proliferation and its IC50 values was 1.6 times lower than that of non-ES conjugated liposomes at 72 h. The in vivo anti-tumor efficacy study demonstrated that ES-PEG-Lip-PTX/CBP could lead strong SKOV-3 tumor growth suppression with a tumor volume inhibitory rate of 81.8%. Meanwhile, acute toxicity studies confirmed that ES-PEG-Lip-PTX/CBP significantly reduced the toxicity of the chemo drugs.Conclusion: ES-PEG-Lip-PTX/CBP was successfully prepared with an optimal physicochemical and ER targeting property. The data of pharmacokinetics, anti-tumor efficacy and safety study indicated that ES-PEG-Lip-PTX/CBP could become a promising therapeutic formulation for human ovarian cancer in the future clinic.Graphical Abstract: Keywords: ovarian cancer, combination therapy, drug delivery system, liposome, estrogen receptor

Ying Du,1,2 Shujun Wang,3 Jianfeng Luan,3 Meilin Zhang,1,2 Baoan Chen,1,2,&ast; Yanfei Shen2,&ast; 1Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Blood Transfusion, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoan Chen, Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China, Email cba8888@hotmail.com Yanfei Shen, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China, Email Yanfei.Shen@seu.edu.cnBackground: Glucose oxidase (GOx)-based starvation therapy is a new cancer treatment strategy. However, the characteristics such as limited curative effect and hypoxic tumor environment hinder its further application seriously.Methods: Herein, doxorubicin (DOX) loaded in hollow mesoporous copper sulfide (HMCuS) nanoparticles assembled with manganese dioxide (HMMD) as nanoshell was prepared. We developed a targeted enhanced cancer treatment method to camouflage HMMD by GOx-functionalized platelet (PLT) membranes (HMMD@PG).Results: GOx can be specially transported to the tumor site with PLT membrane for effective starvation treatment. Glucose and oxygen (O2) in the tumor were converted to H2O2 under the catalysis of GOx. HMMD can catalyze H2O2 to produce O2 and consume glutathione (GSH) in time, which regulates the tumor microenvironment (TME) and improves the adverse conditions of anti-tumor. In addition, DOX encapsulated in HMCuS-MnO2 release was accelerated from the nanoparticles after the “gatekeeper” MnO2 is consumed. The study of anti-tumor mechanism shows that the remarkable tumor suppressive ability of HMMD@PG comes from the three peaks synergy of starvation treatment, photothermal treatment (PTT), and chemotherapy. This nanoplatform disguised by PLT membrane has significant tumor inhibition ability, good biocompatibility and almost has no side effects in main organs.Conclusion: This work broadens the application mode of GOx and shows the new development of a multi-mode collaborative processing system of nanoplatforms based on cell membrane camouflage.Keywords: glucose oxidase, PLT membrane, nanoparticles, tumor microenvironment, tumor treatment

Xingyu Chang,1,&ast; Yuchen Kang,2,&ast; Yuxuan Yang,1,&ast; Yajie Chen,1 Yanyu Shen,1 Chenjun Jiang,1 Yi Shen3 1The First Clinical Medical College, Lanzhou University, Lanzhou, People’s Republic of China; 2The Second Clinical Medical College, Lanzhou University, Lanzhou, People’s Republic of China; 3Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Shen, Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-13517490910, Email shenyiak487@163.comAbstract: Osteoarthritis (OA) is one of the most common chronic joint diseases and is gradually becoming the main cause of disability and joint pain in the elderly worldwide. Pyroptosis is a regulated programmed cell death triggered by inflammasomes. It leads to cell swelling, lysis, and bioactive molecule secretion. Studies found that the damaged chondrocytes in OA joints had morphological characteristics of pyroptosis, and the cytokines associated with pyroptosis in synovial fluid increased, indicating that pyroptosis may have certain impacts on the pathological progression of OA. This review briefly summarizes the molecular mechanisms of pyroptosis and the epidemiology and pathogenesis of OA. Furthermore, we discussed the role of pyroptosis in articular cartilage and synovium during OA and reviewed the progress of pyroptosis-related molecules in the targeted therapy of OA joints, hoping to provide feasible directions for the diversified treatment of OA.Keywords: pyroptosis, osteoarthritis, articular cartilage, synovium, NLRP3 inflammasome, GSDMD

Yuhuan Shen,1,&ast; Xiaoyan Dong,2,&ast; Jinlin Liu,1 Huoyang Lv,1 Yumei Ge1,3 1Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 2Department of Clinical Laboratory, Ningbo Blood Centers, Ningbo, Zhejiang, People’s Republic of China; 3Key Laboratory of Biomarkers and in vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumei Ge, Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158, Shang-Tang Road, Gong-Shu District, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-0571-85893264, Email 11218070@zju.edu.cnBackground: Interleukin-26 (IL-26) is an atypical proinflammatory cytokine due to its binding to circulating double-stranded DNA and direct antibacterial activity. Although IL-26 has been confirmed to be involved in the pathophysiology of cancer, chronic inflammatory diseases and infections, the diagnostic and prognostic values of IL-26 levels in syphilis patients are not clear. This study aimed to investigate IL-26 levels in different stages of syphilis progression.Methods: A total of 30 healthy controls and 166 patients with syphilis at different stages of disease progression were enrolled. Serum IL-26 levels were quantified in accordance with the protocols of RayBio® Human Interleukin-26 Enzyme Linked Immunosorbent Assay (ELISA) kits. Clinical laboratory diagnostic parameters and blood analysis data were detected and collected according to clinical medical laboratory standards.Results: The levels of serum IL-26 were significantly higher in neurosyphilis patients than in healthy subjects (6.87 (4.36, 12.14) and 1.67 (0.09, 4.89) pg/μL, respectively; &ast;&ast;&ast;&ast;p < 0.0001), latent syphilis (1.48 (0.40, 2.05) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001), seroresistant syphilis (0.81 (0.20, 2.91) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001) and secondary syphilis (1.66 (0.41, 4.25) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001) with data presented as the median with interquartile range. The concentration of serum IL-26 was most sensitive to serum low-density lipoprotein concentration (r = − 0.438, &ast;&ast;p = 0.004) in latent syphilis, urine epithelial cells (r = 0.459, &ast;&ast;p = 0.003) in seroresistant syphilis, and serum creatinine levels (r = 0.463, &ast;&ast;p = 0.004) and urea creatinine ratio levels (r = 0.500, &ast;&ast;p = 0.008) in secondary syphilis patients. There was no significant correlation with the concentration of IL-26 and toluidine red unheated serum test (TRUST) titers in each type of syphilis patient.Conclusion: Circulating IL-26 in serum displays diagnostic potential in the progression of neurosyphilis and warrants further evaluation in clinical trials.Keywords: neurosyphilis, interleukin-26, IL-26, disease progression, biomarker, diagnosis

Yujuan Mao,1 Yumeng Chen,2 Chang Liu,2 Xingyue He,2 Yi Zheng,1 Xiaolan Chen,1 Ying Wang,1 Wei Chen,1 Yanling Wu,1 Yan Shen,2 Haifeng Yang,1 Songbo Ma3 1Jiangsu Animal Husbandry and Veterinary College, Taizhou, Jiangsu, 225300, People’s Republic of China; 2State Key Laboratory of Natural Medicines, Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, Taizhou People’s Hospital, Taizhou, Jiangsu, 225300, People’s Republic of ChinaCorrespondence: Haifeng Yang, Email yhf8142@sina.com; Songbo Ma, Email masongbo1978@163.comIntroduction: Cefquinome sulfate (CS) is the first fourth-generation antibiotic for animals, which has a wide antibacterial spectrum, strong antibacterial activity and low drug resistance. However, it is accompanied by problems of poor therapeutic efficacy. In this context, the use of nanosuspensions have been found to be an attractive strategy. The main objective of this work is to develop a new oily nanosuspension to improve bioavailability and stability of CS formulations.Methods: After screening the formulations, cefquinome sulfate oily nanosuspension (CS-NSP) was prepared by mortar grinding, using propylene glycol dicaprolate/dicaprate (Labrafac™ PG) as oil medium and caprylocaproyl polyoxyl-8 glycerides (Labrasol®) as stabilizer. The properties of CS-NSP were investigated by testing its physicochemical characteristics, stability, in vitro release, hemolysis, and muscle irritation. The in vivo pharmacokinetics of CS-NSP was studied using rats.Results: Results show that CS-NSP presents suitable stability, physicochemical properties and safety. Moreover, a rapid release and high bioavailability of CS-NSP have also been verified in the study. Pharmacokinetic experiments in vivo showed that the bioavailability of CS-NSP was about 1.6 times that of commercial cefquinome sulfate injection (CS-INJ, Chuangdao®) (p< 0.01). These advantages of CS-NSP were carried out by small particle size and low viscosity, being associated with the use of Labrafac PG and stabilizer Labrasol.Conclusion: The results proved that the new preparation is safe and effective and is expected to become a promising veterinary nanodelivery system.Keywords: cefquinome sulfate, oily nanosuspension, Labrafac PG, labrasol, pharmacokinetics

Lei Dong,1,&ast; Nana Li,1,&ast; Xixi Wei,2 Yongling Wang,2 Liansheng Chang,3 Hongwei Wu,4 Liujiang Song,5 Kang Guo,6 Yuqiao Chang,1 Yaling Yin,2 Min Pan,7 Yuanyuan Shen,8 Feng Wang1 1Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 2Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 3Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 4Department of Chemistry, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 5Department of Ophthalmology, Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27517, USA; 6Department of Oncology, The Third affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 7Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, 518034, People’s Republic of China; 8National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Wang, Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453002, People’s Republic of China, Email wfeng100@126.com Min Pan, Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, No. 6001 Beihuan Avenue, Shenzhen, 518034, People’s Republic of China, Email min.pan@siat.ac.cnBackground: The blood–brain barrier (BBB) inhibits the delivery of macromolecular chemotherapeutic drugs to brain tumors, leading to low utilization rates and toxic side effects to surrounding tissues and organs. Ultrasonic targeted microbubble destruction (UTMD) technology can open the BBB, leading to a new type of drug delivery system with particular utility in glioma.Purpose: We have developed a new type of drug-loaded microbubble complex based on poly(lactic-co-glycolic acid) (PLGA) that targets gambogic acid (GA) to the area of brain tumors through UTMD.Methods: GA/PLGA nanoparticles were prepared by the double emulsification method, and cationic microbubbles (CMBs) were prepared by a thin film hydration method. The GA/PLGA-CMB microbubble complex was assembled through electrostatic attractions and was characterized chemically. The anti-glioblastoma effect of GA/PLGA-CMB combined with focused ultrasound (FUS) was evaluated by biochemical and imaging assays in cultured cells and model mice.Results: GA/PLGA-CMB combined with FUS demonstrated a significant inhibitory effect on glioblastoma cell lines U87 and U251 as compared with controls (P< 0.05). Tumor access and imaging analyses demonstrated that administration of GA/PLGA-CMBs combined with FUS can open the BBB and target the treatment of glioblastoma in a mouse model, as compared with control groups (P< 0.05).Conclusion: The combination of PLGA-CMB with FUS provides an effective and biocompatible drug delivery system, and its application to the delivery of GA in a mouse glioblastoma model was successful.Keywords: microbubbles, cavitation effect, glioblastoma, focused ultrasound

Yanjun Shen, Yawen Xu, Jianying Wei, Wendong Li Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wendong Li, Department of Oncology, Beijing Ditan Hospital, Capital Medical University, 8 Jingshun East Street, Chaoyang District, Beijing, People’s Republic of China, Tel +86-010-84322470, Email dtzlcentre@sina.comBackground: This research aimed to comprehensively assess the prognostic role of fibrinogen to prealbumin ratio (FPR) in BCLC A-C HCC patients treated by TACE and RFA.Methods: The research included 240 patients at stage BCLC A-C treated by TACE and RFA at Beijing Ditan Hospital of Capital Medical University from May 2011 to November 2018.Results: The results showed that the size of the tumor, vascular invasion, α-foetoprotein, cirrhosis, NLR, LMR, and PLR showed prognostic value in predicting 5-year OS. Besides, FPR (95% confidence interval: 1.006– 1.013, hazard ratio: 1.009) was a prognostic factor for the prediction of 5-year OS in HCC.Conclusion: Our research indicated that FPR was a potential indicator for patients with BCLC A-C hepatocellular carcinoma after treatment of RFA and TACE.Keywords: FPR, hepatocellular carcinoma, prognosis, overall survival

Liwei Yao,1 Xudong Xu,2 Gang Chen,2 Yanqin Shen,2,* Weixian Jiang1,* 1Department of Nursing, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanqin Shen, Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, Zhejiang, People’s Republic of China, Email yanqinshen@yeah.net Weixian Jiang, Department of Nursing, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, Zhejiang, People’s Republic of China, Email jwxmed@163.comPurpose: To evaluate the diagnostic accuracy of the CapitalBio Mycobacterium real-time polymerase chain reaction assay (CapitalBio test) testing of core needle biopsy (CNB) specimens for tuberculous lymphadenitis (TBL) and to compare it with Xpert MTB/RIF.Methods: We retrospectively analyzed the medical data on patients with suspected peripheral TBL. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of the CapitalBio test, Xpert MTB/RIF, and parallel test (positive result for either of these two tests) were calculated to evaluate their diagnostic efficacy compared with the final clinical diagnosis.Results: The study included 114 patients. For diagnosing TBL using CNB samples, the sensitivity, specificity, PPV, NPV, and AUC were 65.0%, 100.0%, 100.0%, 28.6%, and 0.83, respectively, for the CapitalBio test; 72.0%, 100.0%, 100.0%, 33.3%, and 0.86, respectively, for Xpert MTB/RIF; and 82.0%, 100.0%, 100.0%, 43.8%, and 0.91, respectively, for the parallel test.Conclusion: The accuracy of the CapitalBio test and Xpert MTB/RIF for diagnosing TBL using CNB specimens was moderate, while the sensitivity and NPV of these two tests were relatively low. The diagnostic accuracy of the CapitalBio test was slightly lower than that of Xpert MTB/RIF, but the difference between the two was not statistically significant. Parallel test might improve the diagnostic accuracy but not substantially over a single test.Keywords: CapitalBio test, Xpert, tuberculous lymphadenitis, core needle biopsy, diagnostic accuracy

Guocan Yu,1,&ast; Linhua Wang,2 Yanqin Shen,1 Likui Fang,1 Jun Yang,1 Bo Ye,1 Kan Xu,1 Fangming Zhong1,&ast; 1Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hospital Infection, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guocan Yu; Fangming Zhong, Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China, Email dabaitwo@163.com; zhongfangm@126.comPurpose: We evaluated CapitalBio Mycobacterium RT-PCR assay diagnosing tuberculous pericarditis (TBP), performed a head-to-head comparison with Xpert MTB/RIF, and assessed the impact of a parallel test (positive result for either of these two tests).Methods: We reviewed suspected TBP patients with Xpert MTB/RIF, CapitalBio Mycobacterium RT-PCR assay, and Mycobacterium tuberculosis (MTB) culture. We analyzed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC).Results: Seventy-four patients were included. Overall sensitivity, specificity, PPV, NPV, and AUC of CapitalBio Mycobacterium RT-PCR assay compared with culture were 50%, 91.1%, 64.3%, 85%, and 0.71, respectively. Overall sensitivity, specificity, PPV, NPV, and AUC of Xpert MTB/RIF for TBP were 61.1%, 91.1%, 68.8%, 87.9%, and 0.76. Parallel test values were 72.2%, 91.1%, 72.2%, 91.1%, and 0.82. The diagnostic accuracy of Xpert MTB/RIF was higher than CapitalBio Mycobacterium RT-PCR assay but was not significant (P > 0.05). The parallel test could improve diagnostic accuracy, but it was not significant compared to single tests (P > 0.05).Conclusion: CapitalBio Mycobacterium RT-PCR assay had a moderate diagnostic accuracy, similar to Xpert MTB/RIF. The parallel test maximized diagnostic efficacy, but differences were not significant. CapitalBio Mycobacterium RT-PCR assay and Xpert MTB/RIF for TBP could be an initial option for early diagnosis.Keywords: tuberculosis pericarditis, polymerase chain reaction, Xpert MTB/RIF, CapitalBio, accuracy

Chang Zhang,1,2 Lijuan Shi,3 Tong Tian,3 Ziwei Zhou,3 Xiyuan Peng,3 Yidong Shen,4 Yamin Li,1,2 Jianjun Ou4 1Xiangya Nursing School, Central South University, Changsha, China; 2Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital of Central South University, Changsha, China; 3School of Education, Hunan University of Science and Technology, Xiangtan, China; 4National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, ChinaCorrespondence: Yamin Li; Jianjun Ou, The Second Xiangya Hospital of Central South University, No. 139 Renmin Road, Furong District, Changsha, 410011, People’s Republic of China, Tel +86-0731-85294072; +86 17775861486, Email aminny@csu.edu.cn; oujianjun@csu.edu.cnPurpose: Explore the potential mediating effects of anxiety symptoms and hopelessness on the relationship between academic stress and depressive symptoms among Chinese college students.Patients and Methods: A total of 1309 college students with informed consent were recruited from a local university in China. Academic stress, anxiety symptoms, hopelessness, and depressive symptoms were assessed by self-report scales. Haye’s PROCESS macro for SPSS was used to test the hypothesized mediation effect of anxiety symptoms and hopelessness in the relationship between academic stress and depressive symptoms.Results: Anxiety symptoms, hopelessness, and depressive symptoms were common among college students and were all significantly positively associated with academic stress levels. Academic stress could indirectly affect depressive symptoms by anxiety symptoms, hopelessness, and both anxiety symptoms and hopelessness. The total effect of academic stress on depressive symptoms was 0.063. The total effect of three indirect pathway was 0.039 which account for 62% of the total effect.Conclusion: The study detailed the specific process of depressive symptoms caused by academic stress in college students. Anxiety symptoms and hopelessness could mediate the relationship between academic stress and depressive symptoms. Paying attention to the anxiety levels and hopelessness levels of college students with high academic pressure is suggested as a means of preventing depression and promoting mental health.Keywords: academic stress, anxiety, hopelessness, depression, college students

Hui Zhang,1,&ast; Jinyi Lin,2,&ast; Yihui Shen,1 Jianan Pan,3 Chunhui Wang,4 Leilei Cheng1 1Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China; 2Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, People’s Republic of China; 3Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leilei Cheng, Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Shanghai, 200032, People’s Republic of China, Fax +86-21-51217561, Email cheng.leilei@zs-hospital.sh.cnPurpose: Immune checkpoint inhibitors (ICIs)-related myocarditis is now one of the most critical immune-related adverse effects (irAEs) in tumor immunotherapy, which has raised great concern in cardio-oncology. The pathogenesis involved in cardiac injury remains elusive. Crocin, the main component of saffron, has shown distinct functions in cardioprotective and anti-inflammation properties. We therefore aimed to investigate the potential effect of crocin on the protection of ICIs-related myocarditis and its underlying molecular mechanism.Methods: We immunized the BALB/c mice with murine cardiac troponin I (cTnI) peptide and additionally gave anti-mouse programmed death 1 (PD-1) to induce the mouse model of ICIs-related myocarditis. Mice were treated with crocin at different dosages. In vitro, HL-1 cells were pre-incubated with crocin at different concentrations and then stimulated with lipopolysaccharide (LPS). Myocardial contractile functions, myocardial inflammation and fibrosis, and myocardial injury were assessed. The expressions of pyroptosis-related proteins and nuclear factor-κB (NF-κB) pathway were evaluated.Results: Crocin treatment could partially reverse the ICIs-related myocarditis in terms of improving heart function, ameliorating inflammation and fibrosis in the myocardium, and alleviating myocardial injury. Mechanistically, ICIs administration significantly activated pyrin domain-containing protein 3 (NLRP3) inflammasome in cardiomyocytes. Crocin treatments significantly downregulated the expression of NLRP3, cleaved gasdermin D (GSDMD), cleaved caspase1, interleukin-1β (IL-1β), and IL-18. Besides, crocin inhibited the activation of NF-κB pathway, which performed as reducing the phosphorylation of p-NF-kappa-B inhibitor-α (p-IκBα), degradation of IκBα, phosphorylation of p65 and p65 DNA binding activity both in vivo and in vitro.Conclusion: By reversing the pyroptosis in cardiomyocytes, crocin treatment in a mouse model exerted great potential to aid in the prevention of ICIs-related myocarditis from a novel target.Graphical Abstract: Keywords: cardio-oncology, immune checkpoint inhibitors, autoimmune myocarditis, programmed death 1, immune-related adverse effects

Si-Yi Gong,1,&ast; Yun Shen,1,&ast; Han-Ying Gu,1 Sheng Zhuang,1 Xiang Fu,1,2 Qiao-Jun Wang,1 Cheng-Jie Mao,1 Hua Hu,1 Yong-Ping Dai,1 Chun-Feng Liu1– 3 1Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 3Department of Neurology, Suqian First Hospital, Suqian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun-Feng Liu; Yong-Ping Dai, Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +86 512-67783307 ; +86 512-67784179, Fax +86 512-68284303, Email liuchunfeng@suda.edu.cn; dai_yongping@163.comPurpose: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is the prodromal marker of α-synuclein degeneration with markedly high predictive value. We aim to evaluate the value of electroencephalography (EEG) data during rapid eye movement (REM) sleep and subjective RBD severity in predicting the conversion to neurodegenerative diseases in iRBD patients.Methods: At the baseline, iRBD patients underwent clinical assessment and video-polysomnography (PSG). Relative spectral power for nine frequency bands during phasic and tonic REM sleep in three regions of interest, slow-to-fast ratios, clinical and PSG variables were estimated and compared between iRBD patients who converted to neurodegenerative diseases (iRBD-C) and iRBD patients who remained disease-free (iRBD-NC). Receiver operating characteristic (ROC) curves evaluated the predictive performance of slow-to-fast ratios, and subjective RBD severity as assessed with RBD Questionnaire-Hong Kong.Results: Twenty-two (33.8%) patients eventually developed neurodegenerative diseases. The iRBD-C group showed shorter total sleep time (p < 0.001), lower stage 2 sleep percentage (p = 0.044), more periodic leg-movement-related arousal index (p = 0.004), increased tonic chin electromyelographic activity (p = 0.040) and higher REM density in the third REM episode (p = 0.034) than the iRBD-NC group. EEG spectral power analyses revealed that iRBD phenoconverters showed significantly higher delta and lower alpha power, especially in central and occipital regions during the phasic REM state compared to the iRBD-NC group. Significantly higher slow-to-fast ratios were observed in a more generalized way during the phasic state in the iRBD-C group compared to the iRBD-NC group. ROC analyses of the slowing ratio in occipital areas during phasic REM sleep yielded an area under the curve of 0.749 (p = 0.001), while no significant predictive value of subjective RBD severity was observed.Conclusion: Our study shows that EEG slowing, especially in a more generalized manner during the phasic period, may be a promising marker in predicting phenoconversion in iRBD, rather than subjective RBD severity.Keywords: idiopathic rapid eye movement sleep behavior disorder, neurodegenerative diseases, EEG slowing, RBD severity, phenoconversion, neuroprotective therapy

Chunxue He,1,2,&ast; Mingqiang Gong,3,4,&ast; Gengxiao Li,1,2 Yunxia Shen,2 Longyin Han,5 Bin Han,6 Mingwu Lou2 1Shenzhen Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Radiology, Longgang District Central Hospital of Shenzhen, Shenzhen, People’s Republic of China; 3The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 4Department of Acupuncture, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China; 5Department of Neurology, Beijing Longfu Hospital, Beijing, People’s Republic of China; 6Department of Rehabilitation Medicine, Longgang District Central Hospital of Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Han; Mingwu Lou, Tel +86 13928488998 ; +86 13808854650, Email hhbb08@163.com; mingwulou@sina.comPurpose: To investigate white matter alterations in post-stroke cognitive impairment (PSCI) patients at the subacute stage employing diffusion kurtosis and tensor imaging.Methods: Thirty PSCI patients at the subacute phase and 30 healthy controls (HC) underwent diffusion kurtosis imaging (DKI) scans and neuropsychological assessments. Based on the tract-based spatial statistics and atlas-based ROI analysis, fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), kurtosis fractional anisotropy (KFA), axial kurtosis (AK), and radial kurtosis (RK) were compared in specific white matter fiber bundles between the groups (with family-wise error correction). Adjusting for age and gender, a partial correlation was conducted between neurocognitive assessments and DKI metrics in the PSCI group.Results: In comparison with the HC, PSCI patients significantly showed decreased MK, RK, and FA and increased MD values in the genu of corpus callosum, anterior limb internal capsule, and left superior corona radiata. In addition, DKI detected more white matter region changes in MK (31/48), KFA (40/48), and RK (25/48) than DTI with FA (28/48) and MD (21/48), which primarily consisted of the right cingulum, right superior longitudinal fasciculus, and left posterior limb of internal capsule. In the left anterior limb of internal capsule, MK and RK values were significantly negatively correlated with TMT-B (r = − 0.435 and − 0.414, P < 0.05), and KFA values (r = − 0.385, P < 0.05) of corpus callosum negatively associated with TMT-B.Conclusion: Combing DTI, DKI, and neuropsychological tests, we found extensive damaged white matter microstructure and poor execution performance in subacute PSCI patients. DKI could detect more subtle white matter changes than DTI metrics. Our findings provide added information for exploring the mechanisms of PSCI and conducting cognitive rehabilitation in the subacute stage.Keywords: diffusion kurtosis imaging, diffusion tensor imaging, subacute ischemic stroke, cognitive impairment

Yanqin Shen, Likui Fang, Bo Ye, Xudong Xu, Guocan Yu,&ast; Lihong Zhou&ast; Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Zhejiang Chinese Medicine and Western Medicine Integrated Hospital, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guocan Yu; Lihong Zhou, Email dabaitwo@163.com; zhoulh198508@163.comBackground: Early lymph node tuberculosis (LNTB) diagnosis is still difficult. The majority of LN specimens require the undertaking of invasive and unpleasant procedures.Purpose: To evaluate the diagnostic efficacy of pathology when combined with molecular tests for the diagnosis of LNTB in core needle biopsy (CNB) specimens and to compare that diagnostic efficacy with that deriving from tissue specimens’ examination alone.Methods: We retrospectively analyzed the medical records of LNTB patients who met the inclusion criteria. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of pathology, molecular tests, and parallel test (positive result for either of these two assays) were calculated to evaluate their diagnostic efficacy compared with a composite reference standard.Results: A total of 289 patients were included in the study. The overall sensitivity, specificity, PPV, NPV, and AUC of pathology, molecular tests, and parallel test were 94.5%, 97.2%, 99.6%, 71.4%, 0.96; 73.1%, 100.0%, 100.0%, 34.6%, 0.87; and 98.4%, 97.2%, 99.6%, 89.7%, 0.98, respectively. For CNB specimens, these values for pathology, molecular tests, and parallel test were 93.3%, 96.2%, 99.4%, 69.4%, 0.95; 76.4%, 100.0%, 100.0%, 40.0%, 0.88; and 99.4%, 96.2%, 99.4%,96.2%,0.98, while those same values for the tissue were 96.6%, 100.0%, 100.0%, 76.9%, 0.98; 67.1%, 100.0%, 100.0%, 25.6%, 0.84; and 96.6%, 100.0%, 100.0%, 76.9%,0.98, respectively.Conclusion: The validity of pathology and molecular testing when using CNB specimens was similar to that of tissue specimens for relevant assessment approaches. For the LNTB diagnosis, CNB specimens were preferred for the simultaneous undertaking of pathological examination and molecular testing.Keywords: pathology, molecular tests, CapitalBio assay, Xpert, lymph node tuberculosis, CNB, tissue, accuracy

Hao Yang,1,&ast; Qing Xia,2,&ast; Yan Shen,2 Ting-Li Chen,3 Jing Wang,3 Ya-Yun Lu2 1Department of Stomatology, Huadong Sanatorium, Wuxi, 214065, People’s Republic of China; 2Health Examination Center, Huadong Sanatorium, Wuxi, 214065, People’s Republic of China; 3Department of Ophthalmology, Huadong Sanatorium, Wuxi, 214065, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ya-Yun LuHealth Examination Center, Huadong Sanatorium, Wuxi, 214065, People’s Republic of China, Tel +86 13763384379, Email luyy28@163.comBackground: Hashimoto’s thyroiditis (HT) is recognized as the most common autoimmune thyroid disease, often accompanied by the diffuse enlargement of thyroid with abundant blood flow and elevated level of thyroid autoantibodies. As obesity had a positive association with the risk of HT. Thus, this retrospective study was established to further explore the gender relationship between metabolic obesity phenotypes and the risk of Hashimoto’s thyroiditis (HT).Materials and Methods: Data for 3697 subjects aged ≥ 18 years were randomly collected from a Health check-up database from April to December 2019. Obesity was defined by general obesity (GO; body mass index [BMI] ≥ 28 kg/m2) and abdominal obesity (AO; waist circumstance, male ≥ 90 cm, female ≥ 85 cm). Metabolic unhealthy was defined as having at least one metabolic syndrome component and a homeostasis model assessment of insulin resistance ≥ 2.5. Obesity phenotypes were divided into three groups: GO, AO, compound obesity (GO+AO). After adjustment for potential confounding factors, multivariate logistic regression was used to assess the association between metabolic obesity phenotypes and risk of HT by sex and explore the correlation between different obesity patterns and HT risk by metabolic health status.Results: The incidence of HT was 23.5% and significantly higher among females than males with different metabolic phenotypes (26.2% vs 20.5%, p< 0.05), except metabolically healthy AO. Compared with non-obese subjects, different metabolic obesity phenotypes were independent risk factors among males (p< 0.05). Among females, unhealthy metabolic status with GO (adjusted odds ratio [OR]=2.62) or AO (adjusted OR=2.87) and metabolically healthy non-GO (adjusted OR=2.05) were risk factors of HT (p< 0.05). Increasing BMI categories and waist circumstance quartiles were positively correlated with HT risk (p for trend < 0.05). Subgroup analyses indicated that GO+AO (adjusted OR=2.52) or only AO (adjusted OR=2.41) were risk factors for HT for those with unhealthy metabolic status. Moreover, GO+AO (adjusted OR=2.37) was an independent risk factor for HT under healthy metabolic status.Conclusion: GO+AO was associated with an increased risk of HT, identifying higher BMI/WC as a significant risk factor for HT. Males with unhealthy metabolic state or obesity and metabolically unhealthy females with obesity are high-risk group for HT. Additionally, only AO and GO+AO conferred increased risk of HT for individuals with metabolic abnormalities.Keywords: Hashimoto’s thyroiditis, metabolic obesity phenotypes, general obesity, abdominal obesity, retrospective data

Nickel smelting produces a large amount of nickel slag which contains a lot of Fe in the form of FeO. The effect of FeO content on the melting properties and structure of nickel slag is investigated by thermodynamic calculations and experiments, using the nickel slag of water quenching furnace as raw material, which is simplified to CaO-SiO2-FeO-MgO slag system. The results are as follows: with increasing FeO content, the precipitated primary phase changes from melilite to olivine. The liquidus temperature, softening temperature, hemispherical temperature, flow temperature, viscosity, and critical viscosity temperature of the slag system tend to decrease gradually, but the solid phase temperature tends to decrease first and then increase. The centre of the symmetric stretching vibration band of the [SiO4]4 tetrahedron -in the slag system shifts to the low wavenumber region. The mole fraction of O0 in the slag continuously decreases, and the mole fraction of O- and O2- increases. The complex silicon-oxygen tetrahedron structure gradually disintegrates and the structural unit tends to be simple.

Hua Zou,&ast; Yan Shen,&ast; Chunli Li, Qiuhong Li Department of Laboratory Medicine, Chongqing Health Center for Women and Children, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunli Li; Qiuhong Li Tel +8615823827032; +8613212377189Email lcl518023@126.com; 1963163263@qq.comPurpose: Severe infection has been the leading causes of neonatal death, especially the emergency of multidrug-resistant bacteria such as carbapenem-resistant Enterobacteriaceae. This study aimed to investigate the outbreak of carbapenem-resistant Klebsiella pneumoniae (CR-KP) in neonatal wards and to explore the possible pathogenesis of Klebsiella pneumoniae.Materials and Methods: CR-KP were collected from neonatal ward of Chongqing Health Center for Women and Children between 2017 and 2019. Broth microdilution method was used to evaluate the antimicrobial activities in vitro, at the same time, the virulence of the strain was evaluated by in vitro and in vivo experiments. At last, prokaryotic chain specific transcriptome sequencing was conducted to explore the possible pathogenesis of CR-KP.Results: In this study, a total of 14 carbapenem-resistant-Klebsiella pneumoniae (CR-KP) strains were isolated from Chongqing Health Center for Women and Children, among which all CR-KP isolates were identified as NDM-1-producers. Molecular epidemiological studies revealed ST147 being the most common sequence type (ST). Moreover, we first found two phenotypes of K. pneumoniae with different virulence from the same specimen. Type I, which was a white and sticky colony had a slight increase in virulence with higher biofilm formation, serum resistance and virulence than Type II with gray colony. Compared with the Type II, 10 pathways were obviously changed in Type I especially amino acid metabolism, such as arginine and proline metabolism.Conclusion: Our findings revealed a new potential threat of NDM-1-positive CR-KP with higher virulence in neonatal ICU ward. We found two phenotypes of K. pneumoniae with different virulent, which may be due to the difference expression of arginine and proline metabolism.Keywords: neonates, carbapenem-resistant-Klebsiella pneumoniae, NDM-1, virulence

The aim of this study was to describe the authors' experience in head and neck reconstruction with the tensor fascia lata perforator flap (TFLPF). Between April 2009 and August 2020, 16 patients underwent head and neck reconstruction with a TFLPF. The flaps were designed in a vertical or transverse fashion based on perforators traveling along the medial or lateral aspect of the posterior edge of the tensor fascia lata muscle. Clinical details and postoperative results were recorded and analyzed. The size of the flap ranged from 7 × 5 cm2 to 25 × 9 cm2. The perforators were mostly septocutaneous (11 patients), allowing a simple and straightforward dissection of the perforator and TFLPF in most patients. There were either one or two perforators in all cases. The overall flap survival rate was 100%. All of the flaps healed uneventfully with no delayed wound healing or donor site dysfunction. Follow-up ranged from 18 to 120 months, during which all patients experienced satisfactory functional and aesthetic results, without serious complications at either the recipient or donor site. The TFLPF is a pliable and reliable flap that could be a first choice in selected head and neck reconstruction cases. [ABSTRACT FROM AUTHOR]

The facet-specific interaction between molecules and crystalline catalysts, such as titanium dioxides (TiO2), has attracted much attention due to possible facet-dependent reactivity. Using surface-sensitive sum-frequency vibrational spectroscopy, we have studied how methanol interacts with different common facets of crystalline TiO2, including rutile(110), (001), (100), and anatase(101), under ambient temperature and pressure. We found that methanol adsorbs predominantly in the molecular form on all of the four surfaces, while spontaneous dissociation into methoxy occurs preferentially when these surfaces become defective. Extraction of Fermi resonance coupling between stretch and bending modes of the methyl group in analyzing adsorbed methanol spectra allows determination of the methanol adsorption isotherm. The isotherms obtained for the four surfaces are nearly the same, yielding two adsorbed Gibbs free energies associated with two different adsorption configurations singled out by ab initio calculations. They are (i) ∼-20 kJ/mol for methanol with its oxygen attached to a low-coordinated surface titanium, and (ii) ∼-5 kJ/mol for methanol hydrogen-bonded to a surface oxygen and a neighboring methanol molecule. Despite similar adsorption energetics, the Fermi resonance coupling strength for adsorbed methanol appears to depend sensitively on the surface facet and coverage.

Xiaoyan Wang,1,* Yi Shen,1,* Xinying Zhuang,1 Na Wang,2 Qi Zhang,1 Lulin Zhu,1 Yuling Liu,1 Xinyu Lu,1 Luping Qin,1 Qiaoyan Zhang1 1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Ginwa Enterprise (Group) INC, Xi’an, 710069, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiaoyan Zhang; Luping Qin Tel +86 571-6176 8519Email zqy1965@163.com; lpqin@zcmu.edu.cnPurpose: Jintiange capsule (JTG), an approved drug developed as a substitute for tiger bone (TB), has been clinically applied for osteoporosis therapy since 2003. The drug is composed of bionic TB powder, in which peptides and proteins are primarily enriched from other bone extracts. However, as a precious material of traditional Chinese medicine (TCM), TB has been mainly understood and used in TCM to relieve osteoporosis, rheumatoid arthritis and bone injury. Inspired by those, the purpose of this study was to investigate whether JTG also had an effect on relieving rheumatoid arthritis in collagen-induced arthritic (CIA) rats and explore potential mechanism from the perspective of serum metabolic profile changes.Methods: JTG was analyzed using Nano LC-MS/MS and orally administered in CIA rats for 6 weeks. After administration, intervention effects of JTG on synovial inflammation, bone micro-architecture and bone metabolism were studied, and the impact of JTG on serum metabolic profiles in CIA rats was investigated by metabolomics.Results: Nine bioactive peptides were identified in JTG. In animal treatments, JTG alleviated paw swelling (P < 0.01), arthritic severity (P < 0.01) and synovial tissue proliferation, as well as inflammatory cell infiltration of ankle joint, decreased bone loss, improved microstructure of bone in CIA rats by regulating bone absorption and formation, specifically increasing bone mineral density (BMD) (P < 0.05), bone volume fraction (BVF) (P < 0.05), trabecular number (Tb.N) (P < 0.05) and decreasing trabecular separation (Tb.Sp) (P < 0.05). Besides, serum IL-6 was down-regulated remarkably in CIA rats (P < 0.05). Furthermore, metabolomics analysis revealed that 32 metabolites were regulated significantly (P < 0.05) by comparison between CIA model and JTG in 360 mg/kg dose. The pathway analysis implied that JTG was involved in regulation of biosynthesis of phenylalanine.Conclusion: JTG alleviates rheumatoid arthritis and reverses changes in serum metabolic profile in CIA rats.Keywords: bionic tiger bone powder, synovial inflammation, bone micro-architecture, bone metabolism, metabolomics

Mingxuan Li,1,&ast; Yutao Shen,1,&ast; Yujia Xiong,1,&ast; Jiwei Bai,2 Shuai Wang,1 Chuzhong Li,1 Yazhuo Zhang1– 5 1Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Institute for Brain Disorders Brain Tumor Center, Beijing, People’s Republic of China; 4China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 5Key Laboratory of Central Nervous System Injury Research, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yazhuo Zhang Email zyz2004520@yeah.netObjective: Accumulating studies report that levels of mean corpuscular volume (MCV) and red cell distribution width (RDW) are associated with outcomes in cancer patients, while studies including MCV and RDW in chordoma are lacking so far. Therefore, our study aims to investigate the prognostic impact of MCV and RDW on survival in skull base chordoma patients.Methods: Levels of preoperative MCV and RDW in 187 primary skull base chordoma patients were collected. X-tile software was used to find the cutoff values of MCV and RDW. Progression-free survival (PFS) and overall survival (OS) analyses were performed using the Kaplan–Meier methods, Cox analysis, and nomogram model.Results: Low MCV level (MCV < 84.2) was more commonly observed in classical chordoma patients (p=0.022). High RDW level (RDW≥ 12.7) was correlated with older patient age (p=0.022) and a tough tumor texture (p=0.035). Low MCV level and high RDW level were associated with poor PFS (p=0.045 and 0.007, respectively) and OS (p=0.023 and < 0.001, respectively). Multivariate Cox analysis demonstrated that RDW was an independent prognostic indicator for both PFS (p=0.001) and OS (p< 0.001). Importantly, a nomogram based on RDW and clinical predictors showed satisfactory performance for PFS and OS prediction (concordance index, C-index: 0.684 and 0.744, respectively).Conclusion: Our data was first to reveal the prognostic role of RDW in skull base chordoma, and identified the use of RDW may contribute to a more accurate prognosis judgment and personalized treatment decision.Keywords: skull base chordoma, mean corpuscular volume, red cell distribution width, survival analysis, biomarker

Qun Li,1 Yangli Jin,2 Zhisen Shen,1 Huigao Liu,3 Yi Shen,1 Zhenhua Wu1 1Department of Otorhinolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, People’s Republic of China; 2Department of Doppler Ultrasonic, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang, People’s Republic of China; 3Department of Otorhinolaryngology Head and Neck Surgery, Ningbo Zhenhai Longsai Hospital, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Zhenhua WuDepartment of Otorhinolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, No. 57 Xingning Road, Yinzhou District, Ningbo, 315040, People’s Republic of ChinaTel +86-574-87018634Fax +86-574-87018634Email wuzhenhua1975@126.comBackground: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers, and few studies have demonstrated the value of ferroptosis-related genes in prognosis.Methods: The original counts of RNA sequencing data and clinicopathological data were obtained from TCGA and GSE65858 datasets. Common ferroptosis-related genes related to prognosis were identified from the training set and were included in LASSO to determine the best prognosis. To evaluate the efficacy, time-dependent ROC and Kaplan–Meier (KM) survival analyses were applied. Moreover, univariate and multivariate Cox regression analyses were used to screen independent parameters of prognosis and build a nomogram. Eventually, possible biological pathways were proposed based on GSEA.Results: Among 242 ferroptosis-related genes, we identified that the FLT3, IL6, Keap1, NQO1, SOCS1 and TRIB3 genes were significantly connected with HNSCC patient prognosis as a six-gene signature. After, the patients were divided into high- and low-risk groups based on the six-gene signature. The KM survival curves demonstrated that the high-risk group had worse OS (p < 0.0001) and higher AUC values (0.654, 0.735, and 0.679 for 1-, 3-, and 5-year survival, respectively) for the prognostic signature of the six genes compared with other genes, which were also validated in the GSE65858 dataset. Moreover, GSEA suggested that the epithelial mesenchymal transition pathway was abundant and that the mesenchymal status in the high-risk group was substantially higher than that in the low-risk group. Finally, the immune microenvironment and differences in the content of immune cell types were demonstrated.Conclusion: We established a six-ferroptosis-related-gene model crossing clinical prognostic parameters that can predict HNSCC patient prognosis and provide a reliable prognostic evaluation tool to assist clinical treatment decisions.Keywords: head and neck squamous cell carcinoma, ferroptosis, prognosis, TCGA

Zixuan Ye,1,&ast; Lizhen Liang,1,&ast; Huazhen Lu,1 Yan Shen,2 Wenwu Zhou,3 Yanan Li1 1School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, People’s Republic of China; 2State Key Laboratory of Natural Medicines, Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 3National Experimental Teaching Demonstration Center of Pharmacy, School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanan LiSchool of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, People’s Republic of ChinaTel +8615051850598Email liyanan@njnu.edu.cnWenwu ZhouNational Experimental Teaching Demonstration Center of Pharmacy, School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of ChinaEmail dancingzww@163.comAbstract: Bacteria and their derivatives (membrane vesicles, MVs) exhibit great advantages for targeting hypoxic tumor cores, strong penetration ability and activating immune responses, holding great potential as auspicious candidates for therapeutic and drug-delivery applications. However, the safety issues and low therapeutic efficiency by single administration still need to be solved. To further optimize their performance and to utilize their natural abilities, scientists have strived to modify bacteria with new moieties on their surface while preserving their advantages. The aim of this review is to give a comprehensive overview of a non-genetic engineering modification strategy that can be used to optimize the bacteria with nanomaterials and the design strategy that can be used to optimize MVs for better targeted therapy. Here, the advantages and disadvantages of these processes and their applicability for the development of bacteria-related delivery system as antitumor therapeutic agents are discussed. The prospect and the challenges of the above targeted delivery system are also proposed.Keywords: bacteria, nanomaterial, targeted delivery, immune response, membrane vesicles

Yuxin Sun,&ast; Yizhuo Xie,&ast; Huan Tang, Zhihui Ren, Xue Luan, Yan Zhang, Ming Zhu, Zhe Lv, Han Bao, Yan Li, Rui Liu, Yujia Shen, Yucui Zheng, Jin Pei Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, ChangChun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jin PeiSchool of Pharmaceutical Sciences, Jilin University, 1163 Xinmin Street, ChangChun, 130021, Jilin Province, People’s Republic of ChinaTel +86 431 85619725Email peijin@jlu.edu.cnBackground: Chemotherapy is still the main first-line treatment for advanced metastatic gastric cancer, but it has the limitations of serious side effects and drug resistance. Conventional liposome has been substantially used as drug carriers, but they lack targeting character with lower drug bioavailability in tumor tissues. Based on the above problems, a novel estrogen-targeted PEGylated liposome loaded with oxaliplatin (ES-SSL-OXA) was prepared to further improve the metabolic behavior, the safety profile, and the anti-tumor efficacy of oxaliplatin.Methods: Four kinds of oxaliplatin (OXA) liposomes were prepared by film hydration method. The obtained formulations were characterized in terms of entrapment efficiency (EE), particle size, and so on by HPLC and DLS (dynamic light scanning). The morphology of ES-SSL-OXA was detected by transmission electron microscope (TEM). The in vitro and in vivo targeting effect of ES-SSL-OXA was verified by fluorescence microscopy and in vivo imaging system in gastric cancer cells (SGC-7901) and tumor-bearing athymic mice. The in vitro and in vivo antitumor efficacies of ES-SSL-OXA were investigated on SGC-7901 cells and athymic tumor-bearing mice. Pharmacokinetic, biodistribution, and acute toxicity tests of ES-SSL-OXA were performed on ICR mice.Results: The ES-SSL-OXA exhibited an average particle size of about 153.37 nm with an encapsulation efficiency of 46.20% and low leakage rates at 4°C and 25°C. In vivo and in vitro targeting study confirmed that ES-SSL-OXA could effectively target the tumor site. The antitumor activity demonstrated the strongest inhibition in tumor growth of ES-SSL-OXA. Pharmacokinetics and acute toxicity study showed that ES-SSL-OXA could significantly improve the metabolic behavior and toxicity profile of oxaliplatin.Conclusion: In this study, a novel estrogen-targeted long-acting liposomal formulation of OXA was successfully prepared. ES fragment effectively targeted the delivery system to tumor tissues which highly express estrogen receptor, providing a promising therapeutic method for gastric cancer in clinic.Keywords: estrogen receptors, chemotherapy, long-acting liposomes, targeted drug delivery, pharmacokinetics, antitumor activity