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Shanshan Chen,1,2 Youjia Duan,2 Yongchao Zhang,2 Long Cheng,2 Liang Cai,2 Xiaopu Hou,2 Xiaojun Wang,3 Wei Li1,2 1Cancer Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Integrated Traditional Chinese and Western Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wei Li, Cancer Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China, Email weili8989@ccmu.edu.cn Xiaojun Wang, Department of Integrated Traditional Chinese and Western Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email w_xiaojun@ccmu.edu.cnPurpose: To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation.Methods: A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed.Results: A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1− 14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5− 11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1− 95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7− 64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (P = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (P = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups.Conclusion: Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.Keywords: thermal ablation, aspirin, hepatocellular carcinoma, survival analysis, retrospective study

Libin Liu,1,&ast; Chuyan Wang,2 Bin Mei,1 Jing Wang,1 Xiaoqun Xu,1 Hongjuan Zhou,1 Long Cai1,&ast; 1Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Clinical Laboratory, The Third People’s Hospital of Lin’an District, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Long Cai, Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, No. 208 East Huancheng Road, Hangzhou, 310003, People’s Republic of China, Email cailong317@hotmail.comPurpose: This study aimed to establish and validate a diagnostic nomogram for identifying false positives in the Xpert MTB/RIF (Xpert) for detection of rifampicin resistance (RIF-R).Patients and Methods: In this retrospective study, we collected basic patient characteristics and various clinical information from the electronic medical record database. Patients were randomly divided into training and validation groups in a 7:3 ratio. LASSO regression was used to screen variables and construct a diagnostic nomogram. The ROC curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram.Results: A total of 384 patients were included in the study, with 268 and 116 patients in the training and validation cohorts, respectively. Finally, probe mutations and probe delay were identified as the independent influencing factors. Using the mutation of probe E as a reference, probes A or C (OR = 51.07, P< 0.001), probe D (OR = 7.48, P< 0.001), and multiple probes (OR = 4.42, P=0.029) were identified as factors influencing false positives in Xpert for detection of RIF-R. Taking probe delay ΔCT < 4 as a reference, ΔCT (4– 5.9) (OR = 17.06, P=0.005) and ΔCT (6– 7.9) (OR = 36.67, P< 0.001) were noted to be the factors influencing false positives in Xpert for detection of RIF-R. Based on these two variables, we constructed a diagnostic nomogram. The area under the curve of the nomogram model was 0.847 and 0.850 for the training and validation groups, respectively. The calibration curves were consistent. The DCA revealed that the model achieved the greatest net benefit when the threshold probability was set between 6% and 71% in the training cohort and 6% and 70% in the validation cohort.Conclusion: The nomogram constructed can identify false positives in Xpert for detection of RIF-R and provides basis for clinicians to formulate diagnosis and treatment plans.Keywords: nomogram, probe mutation, probe delay, calibration curve

Tongfei Feng,1– 3,&ast; Yanlin Zhou,1,3,&ast; Bin Lv,1,3 Lijun Cai1,3 1Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hubin Campus, Hangzhou, 310006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lijun Cai; Bin Lv, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel +86-571-86613545, Fax +86-571-87073763, Email 20051018@zcmu.edu.cn; lvbin@medmail.com.cnPurpose: Through network pharmacology combined with molecular docking and in vivo validation, the study examines the unexplored molecular mechanisms of Tongxieyaofang (TXYF) in the treatment of irritable bowel syndrome (IBS). In particular, the potential pharmacological mechanism of TXYF alleviating IBS by regulating CHRM3 and intestinal barrier has not been studied.Patients and Methods: LC-MS technique and TCMSP database were used in combination to identify the potential effective components and target sites of TXYF. Potential targets for IBS were obtained from Genecards and OMIM databases. PPI and cytoHub analysis for targets. Molecular docking was used to validate the binding energy of effective components with related targets and for visualization. GO and KEGG analysis were employed to identify target functions and signaling pathways. In the in vivo validation, wrap restraint stress-induced IBS model was employed to verify the change for cytoHub genes and CHRM3 expression. Furthermore, inflammatory changes of colon were observed by HE staining. The changes of Ach were verified by ELISA. IHC and WB validated CHRM3 and GNAQ/PLC/MLCK channel variations. AB-PAS test and WB test confirmed the protection of TXYF on gut barrier. The NF-κB/MLCK pathway was also verified.Results: In TXYF decoction, LC-MS identified 559 chemical components, with 23 remaining effective components after screening in TCMSP. KEGG analysis indicated that calcium plays a crucial role in TXYF treated for IBS. Molecular docking validated the binding capacity of the effective components Naringenin and Nobiletin with cytoHub-gene and CHRM3. In vivo validation demonstrated that TXYF inhibits the activation of Ach and CHRM3 in IBS, and inhibits for the GNAQ/PLC/MLCK axis. Additionally, TXYF downregulates TNF-α, MMP9, and NF-κB/MLCK, while modulating goblet cell secretion to protect gut barrier.Conclusion: TXYF inhibits Ach and CHRM3 expression, regulating the relaxation of intestinal smooth muscle via GNAQ/PLC/MLCK. Additionally, TXYF inhibits NF-κB/MLCK activated and goblet cell secretion to protect gut barrier. Keywords: irritable bowel syndrome, tongxieyaofang decoction, Ach, CHRM3, GNAQ/PCL/MLCK, gut barrier

Jieyang Yu,1,2 Yanan Zhang,1 Lijia Cai,1 Qingqing Sun,1 Wanru Li,1 Junfang Zhou,1 Jianmin Liang,2 Zan Wang1 1Sleep Centre, Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Jianmin Liang, Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, People’s Republic of China, Email liangjm@jlu.edu.cn Zan Wang, Sleep Centre, Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, People’s Republic of China, Email wangzan@jlu.edu.cn; wangzanprof@163.comPurpose: This study aimed to evaluate nocturnal sleep structure and anxiety, depression, and fatigue in patients with narcolepsy type 1 (NT1).Methods: Thirty NT1 patients and thirty-five healthy controls were enrolled and evaluated using the Epworth sleepiness scale (ESS), Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Fatigue Severity Scale (FSS), polysomnography, multiple sleep latency test, and brain function state monitoring. Statistical analyses were performed using SPSS Statistics for Windows, version 23.0. Benjamini-Hochberg correction was performed to control the false discovery rate.Results: Apart from typical clinical manifestations, patients with NT1 are prone to comorbidities such as nocturnal sleep disorders, anxiety, depression, and fatigue. Compared with the control group, patients with NT1 exhibited abnormal sleep structure, including increased total sleep time (Padj=0.007), decreased sleep efficiency (Padj=0.002), shortening of sleep onset latency (Padj< 0.001), elevated wake after sleep onset (Padj=0.002), increased N1% (Padj=0.006), and reduced N2%, N3%, and REM% (Padj=0.007, Padj< 0.001, Padj=0.013). Thirty-seven percent of patients had moderate to severe obstructive sleep apnea-hypopnea syndrome. And sixty percent of patients were complicated with REM sleep without atonia. Patients with NT1 displayed increased anxiety propensity (Padj< 0.001), and increased brain fatigue (Padj=0.020) in brain function state monitoring. FSS scores were positively correlated with brain fatigue (Padj< 0.001) and mean sleep latency was inversely correlated with FSS scores and brain fatigue (Padj=0.013, Padj=0.029). Additionally, ESS scores and brain fatigue decreased after 3 months of therapy (P=0.012, P=0.030).Conclusion: NT1 patients had abnormal nocturnal sleep structures, who showed increased anxiety, depression, and fatigue. Excessive daytime sleepiness and fatigue improved after 3 months of treatment with methylphenidate hydrochloride prolonged-release tablets in combination with venlafaxine.Keywords: narcolepsy, sleep structure, excessive daytime sleepiness, anxiety, depression, fatigue

Kaixin Bao,1 Xiaobin Zhang,1,2 Lianyu Cai1 1College of Education, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of China; 2Taizhou University, School of Life Science, Taizhou, People’s Republic of ChinaCorrespondence: Xiaobin Zhang; Lianyu Cai, College of Education, Zhejiang Normal University, No. 688 Yingbin Avenue, Jinhua, Zhejiang, 321004, People’s Republic of China, Tel +86 1 365 586 3110 ; +86 1 516 794 4636, Fax +86-0576-88660338, Email zhangxiaobin611@126.com; cailianyu@zjnu.cnPurpose: With the rapid development of information, digital networks, and artificial intelligence technologies, the new generation of children growing up with electronic products faces the dilemma of addiction to online games. There is a significant correlation between the addiction of rural children to online games and the lack of proper parental upbringing.Patients and Methods: Based on purposive sampling, the research selected 41 sixth-grade rural children, 20 parents, and 14 teachers from three cities in Zhejiang Province, China. Three rounds of semi-structured, in-depth interviews were conducted.Results: The research portrayed that the parental upbringing styles of rural children addicted to online games could be categorized into four types: conflict and chaos type, indulgent and permissive type, disciplinary neglect type, and coercive and brutal type. All four parenting styles were related to emotional involvement and value guidance.Discussion: Both the parenting styles of rural parents and the children’s addiction to online games were difficult to self-update and change, and they mutually “affirmed” and even reinforced each other. Insufficient cultural capital was found in rural families, resulting in a closed loop between parental upbringing and online game addiction. Introducing professional expertise, increasing cultural capital, and promoting improvement in rural parenting styles are crucial.Keywords: rural children, online game addiction, parental upbringing, closed-loop effect, narrative research

Ying Chen,1,2,&ast; Wen-Xia Li,1,2,&ast; Jia-Hua Wu,1,2 Geng-Hang Chen,2 Chun-Min Yang,1,2 Hai Lu,1,2 Xi Wang,3 Shu-Sen Wang,4 Heng Huang,5 Li Cai,6 Li Zhao,7 Rou-Jun Peng,8 Ying Lin,9 Jun Tang,3 Jian Zeng,10 Le-Hong Zhang,11 Yong-Li Ke,12 Xian-Ming Wang,13 Xin-Mei Liu,14 An-Qin Zhang,15 Fei Xu,4 Xi-Wen Bi,4 Jia-Jia Huang,4 Ji-Bin Li,16 Dan-Mei Pang,17 Cong Xue,4 Yan-Xia Shi,4 Zhen-Yu He,18 Huan-Xin Lin,18 Xin An,4 Wen Xia,4 Ye Cao,16 Ying Guo,16 Ruo-Xi Hong,4 Kui-Kui Jiang,4 Yong-Yi Zhong,4 Ge Zhang,19 Piyawan Tienchaiananda,20 Masahiro Oikawa,21 Zhong-Yu Yuan,4 Qian-Jun Chen22,23 1Department of Breast Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Breast Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Breast Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 4Department of Medical Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 5Department of Breast Oncology, Lianjiang People’s Hospital, Lianjiang, People’s Republic of China; 6Department of Medical Oncology, The Affiliated Tumour Hospital of Harbin Medical University, Harbin, People’s Republic of China; 7Department of Breast Oncology, Guangzhou First People Hospital, Guangzhou, People’s Republic of China; 8Department of Integrated Therapy in Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 9Department of Breast Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 10Department of Breast Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 11Department of Breast Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 12Department of Breast Oncology, General Hospital of PLA Guangzhou Military Area, Guangzhou, People’s Republic of China; 13Department of Breast Oncology, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China; 14Department of Breast Oncology, Haikou People’s Hospital, Haikou, People’s Republic of China; 15Department of Breast Oncology, Maternal and Child Health Care Hospital of Guangdong Province, Guangzhou, People’s Republic of China; 16Department of Good Clinical Practice, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 17Department of Medical Oncology, Foshan First People’s Hospital, Foshan, People’s Republic of China; 18Department of Radiotherapy, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 19Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong; 20Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Rangsit University, Rajavithi Hospital, Bangkok, Thailand; 21The Department of Breast Surgery, New-wa-kai Oikawa Hospital, Fukuoka, Japan; 22State Key Laboratory of Traditional Chinese Medicine Syndrome/Departments of Gynecologic Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 23State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian-Jun Chen, 55N, Neihuanxi Road, Guangzhou, Guangdong, 510006, People’s Republic of China, Tel +86 1868883505, Email cqj55@163.com Zhong-Yu Yuan, 651 Dongfeng Road, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86 13798027658, Email yuanzhy@sysucc.org.cnPurpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not.Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into “consistent” (standard acceptable dose) and “inconsistent” (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes.Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the “inconsistent” dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the “inconsistent” dose of anthracycline and taxane did not affect DFS compared with the “consistent” dose. Moreover, in the capecitabine group, the “inconsistent” anthracycline dose did not affect DFS compared with the “consistent” dose. However, patients with “consistent” taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06).Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.Keywords: adjuvant chemotherapy, capecitabine, SYSUCC-001, triple-negative breast cancer, TNBC

Aiming Lv,1,2 Bian Ba Zhuo Ma,3 De Qiong,2 Da Wa Zhuo Ma,2 Pu Bu Zhuo Ma,3 Donghua Yao,4 Da Zhen,2 Chunxiu Tang,2 Bian Ba Zhuo Ma,2 Youzhi Lu,2 Long Cai,2 Yutong Zhang,2 Jinyu Yin,2 Tong Ding,2 Lang Ji Qu Zhen,2 Da Wa Cang,5 Meng Wu,5 Yulan Chen,5 Ye Li1 1Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Tibet Autonomous Region, Lhasa City, TB, People’s Republic of China; 3Department of Obstetrics and Gynecology, Lhasa People’s Hospital, Lhasa, TB, 850000, People’s Republic of China; 4Department of Obstetrics and Gynecology, Nyingchi People’s Hospital, Nyingchi City, TB, People’s Republic of China; 5Department of Obstetrics and Gynecology, Tibet University Medical School, Lhasa City, TB, People’s Republic of ChinaCorrespondence: Ye Li, Department of Obstetrics and Gynecology, Beijing Hospital, National center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China, No. 1 DaHua Road, Dong Dan, Beijing, 100730, People’s Republic of China, Tel +86 13611118475, Fax +86 10 85136220, Email liyewtfy@126.comPurpose: To explore the effect of coronavirus disease 2019 (COVID-19) infection on neonates in plateau regions.Methods: Cases of newborns born to pregnant women infected with COVID-19 who received prenatal care or treatment at the Women and Children’s Hospital of the Tibet Autonomous Region and the Lhasa People’s Hospital between January 2020 and December 2022 (infected group) and newborns born to healthy pregnant women (non-infected group) who were included by age, underlying disease and length of hospital stay were retrospectively collected. According to the inclusion and exclusion criteria, 381 patients in the infected group and 314 patients in the non-infected group were included in the study.Results: The results of multivariate analysis showed that admission to the neonatal intensive care unit (OR = 3.342, 95% CI = 1.564– 6.764), shortness of breath (OR = 2.853, 95% CI = 1.789– 3.154), irregular breathing (OR = 2.465, 95% CI = 1.879– 4.112) and neonatal jaundice (OR = 2.324, 95% CI = 1.989– 2.445) were the factors influencing the low Apgar scores of neonates in the infected group (all P < 0.05).Conclusion: Neonates born to pregnant women infected with COVID-19 had lower Apgar scores and higher incidences of complications, such as shortness of breath, groaning, irregular breathing and neonatal jaundice, than newborns born to pregnant women not infected with COVID-19.Keywords: COVID-19, pregnant women, newborn

Xiaoqun Xu,1,&ast; Xinyu Zhu,2,&ast; Hanxin Wang,3 Xiao Liu,3 Chao Yang,3 Libin Liu,1 Tielong Chen,4 Long Cai,1 Houyong Zhu4 1Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houyong Zhu, Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, 310007, People’s Republic of China, Email houyongzhu@foxmail.com Long Cai, Department of Clinical Laboratory, Hangzhou Red Cross Hospital, NO. 208 East Huancheng Road, Hangzhou, 310003, People’s Republic of China, Email cailong317@hotmail.comAim: The purpose of this study was to investigate the role of neutrophil-lymphocyte ratio (NLR), C-reactive protein-albumin ratio (CAR), and platelet-lymphocyte ratio (PLR) in the prognosis of patients with coronary artery disease (CAD) complicated with coronavirus disease 2019 (COVID-19).Methods: This study included 265 patients. A receiver operating characteristic (ROC) curve analysis was performed to preliminarily evaluate the predictive ability of NLR, CAR, and PLR for all-cause death. The primary outcome was all-cause death during hospitalization, while the secondary outcomes were cardiovascular death and respiratory failure death. The Cox proportional hazard model with adjusted covariates was used to analyze the cumulative risk of outcomes. We also conducted subgroup analyses based on the acute and chronic characteristics of CAD. Propensity score matching (PSM) was used to further evaluate the robustness of the primary outcome.Results: The ROC curve analysis results showed that the area under curve (AUC) values were 0.686 (95% CI 0.592– 0.781, P< 0.001) for NLR, 0.749 (95% CI 0.667– 0.832, P< 0.001) for CAR, and 0.571 (95% CI 0.455– 0.687, P=0.232) for PLR. The Cox proportional hazard model showed that trends in NLR and PLR did not affect the risk of all-cause death (P=0.096 and P=0.544 for trend, respectively), but a higher CAR level corresponded to a higher risk of all-cause death (P< 0.001 for trend). Similarly, The trends of NLR and PLR did not affect the risk of cardiovascular death and respiratory failure death, while a higher CAR level corresponded to a higher risk of cardiovascular death and respiratory failure death. The results of subgroup analyses and PSM were consistent with the total cohort.Conclusion: In patients with CAD complicated with COVID-19, a higher CAR level corresponded to a higher risk of all-cause death, cardiovascular death, and respiratory failure death, while trends in NLR and PLR did not.Keywords: coronary artery disease, coronavirus disease 2019, neutrophil-lymphocyte ratio, C-reactive protein-albumin ratio, platelet-lymphocyte ratio

Jun Zhang,1 Yu Wang,1 Wei Zhang,1 Linglong Cai,1 Jianglong Feng,2 Yiwei Zhu,1 Hongguang Lu1 1Department of Dermatology, the Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 2Department of Pathology, the Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of ChinaCorrespondence: Hongguang Lu, Department of Dermatology, the Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Guiyang, Guizhou, 550001, People’s Republic of China, Tel +86-13885144269, Fax +86-851-86820346, Email hongguanglu@hotmail.com; luhongguang@gmc.edu.cnPurpose: The rising incidence and mortality associated with cutaneous malignant tumours highlight the importance of early diagnosis of these tumors. In clinical practice, these tumors are often misdiagnosed as benign skin lesions such as melanocytic nevi (MN) and seborrheic keratosis (SK) because of their similar morphologic features. The incidence and clinicopathological subtypes of cutaneous malignancies in East Asia populations significantly differ from those in fair-skinned groups. However, studies on misdiagnoses in Eastern countries are lacking. Therefore, this study focused on the clinical and pathological features of cutaneous malignant tumors misdiagnosed as MN or SK in a Chinese population.Patients and Methods: A total of 4592 samples clinically diagnosed as MN (n = 3503) or SK (n = 1089) from July 2014 to June 2022 were collected and evaluated retrospectively. The clinical and pathological data were analyzed to identify associated factors.Results: Pathological assessments showed that 2.5% (86/3503) of the specimens clinically diagnosed as MN were malignancies, predominantly basal cell carcinoma (BCC, 84.9%, 73/86), followed by malignant melanoma (MM, 8.1%, 7/86) and squamous cell carcinoma (SCC, 7.0%, 6/86). Similarly, 5.7% (62/1089) of the specimens clinically diagnosed as SK were malignant tumors, of which BCC (50.0%, 31/62) was the most common, followed by SCC (41.9%, 26/62) and MM (8.1%, 5/62). In both types of specimens, advanced age and facial lesions were risk factors for malignancy misdiagnosis. The malignancy rate, mean age, and proportion of SCC in the specimens clinically diagnosed as SK were higher than those in the specimens clinically diagnosed as MN. Dermoscopy significantly reduced the rate of misdiagnosis of these tumors as MN or SK.Conclusion: In China, cutaneous malignant tumors misdiagnosed as MN or SK are not uncommon in clinical practice, and active introduction of noninvasive diagnostic techniques is essential to distinguish them.Keywords: malignant melanoma, squamous cell carcinoma, basal cell carcinoma, skin benign neoplasms, dermoscopy, China

Ling Wang,1,&ast; Yuee Guan,2,&ast; Xu Lin,3,&ast; Jie Wei,4 Qinghuan Zhang,4 Limei Zhang,5 Jing Tan,1 Jie Jiang,1 Caiqin Ling,1 Lei Cai,1 Xiaobin Li,5 Xiong Liang,1 Wei Wei,6 Rui-Man Li7 1Department of Obstetrics, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, 519000, People’s Republic of China; 2Department of Cardiology, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, 519000, People’s Republic of China; 3Department of Gastrointestinal Surgery, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, 519000, People’s Republic of China; 4Department of Clinical Laboratory, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, 519000, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, 519000, People’s Republic of China; 6Department of Cardiothoracic Surgery, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, 519000, People’s Republic of China; 7Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui-Man Li; Wei Wei, Email hqyyck@126.com; Weiweidr001@163.comObjective: Escherichia coli is a common Gram-negative human pathogen. The emergence of E. coli with multiple-antibiotic-resistant phenotypes has become a serious health concern. This study reports the whole-genome sequences of third-generation cephalosporin-resistant (3GC-R) and multidrug-resistant (MDR) E. coli EC6868 and explores the acquired antibiotic-resistance genes (ARGs) as well as their genetic contexts.Methods: E. coli EC6868 was isolated from a vaginal secretion sample of a pregnant patient in China. The antimicrobial susceptibility was assessed, and whole-genome sequencing was conducted. The acquired ARGs, insertion sequence (IS) elements, and integrons within the genome of E. coli EC6868 were identified, and the genetic contexts associated with the ARGs were analyzed systematically.Results: E. coli EC6868 was determined to belong to ST69 and harbored a 144.9-kb IncF plasmid (pEC6868-1) with three replicons (Col156, IncFIBAP001918, and IncFII). The ESBL gene blaCTX-M-27 was located on the structure “∆ISEcp1-blaCTX-M-27-IS 903B”, which was widely present in the species of Enterobacteriales. Other ARGs carried by plasmid pEC6868-1 were mainly located on the 18.9-kb IS 26-composite transposon (five copies of intact IS 26 and one copy of truncated IS 26) composing of IS 26-mphA-mrx(A)-mphR(A)-IS 6100, ∆TnAs3-eamA-tet(A)-tetR(A)-aph(6)-Id-aph(3”)-Ib-sul2-IS 26, and a class 1 integron, which was widely present on IncF plasmids of E. coli, mainly distributed in ST131, ST38, and ST405. Notably, pEC6868 in our study was the first report on a plasmid harboring the 18.9-kb structure in E. coli ST69 in China.Conclusion: The 3GC-R E. coli ST69 strain with an MDR IncF plasmid carrying blaCTX-M-27 and other ARGs, conferring resistance to aminoglycosides, macrolides, sulfonamides, tetracycline, and trimethoprim, was identified in a hospital in China. Mobile genetic elements including ISEcp1, IS 903B, IS 26, Tn 3, IS 6100 and class 1 integron were found within the MDR region, which could play important roles in the global dissemination of these resistance genes.Keywords: Escherichia coli, vaginal secretion, plasmid, blaCTX-M-27, genetic context

Aiming Lv,1,2 Tong Ding,2 DeQiong,2 DaWaZhuoMa,2 Long Cai,2 Yutong Zhang,2 Jinyu Yin,2 SeZhen,2 Qiubo Lv1 1Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Women and Children’s Hospital of Tibet Autonomous Region, Lhasa, Tibet Autonomous Region, People’s Republic of ChinaCorrespondence: Qiubo Lv, Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 DaHua Road, Dong Dan, Beijing, 100730, People’s Republic of China, Tel +86 13801192185, Fax +86 10 85136220, Email lvqiubo@yeah.netPurpose: Pelvic floor disorder (PFD) seriously affects the everyday life of women. This cross-sectional study aimed to evaluate the prevalence and risk factors for postpartum PFD in women living in the Tibet Autonomous Region (TAR).Methods: Parous women who attended the outpatient gynaecology clinic at our hospital between June 2022 and August 2022 were screened in this study. The demographic and clinical data of these women were collected. Their pelvic floor functions were evaluated via a pelvic organ prolapse (POP) quantification examination, the Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) and the Overactive Bladder Symptom Score (OABSS).Results: A total of 201 women were included in this study, of whom 81.09% (163/201) were Tibetan. Twenty-seven women (13.43%) were diagnosed with POP stage ≥ 2 and 27 women (13.43%) with an OABSS score ≥ 3. The median PFDI-20 total score was 4.17 (range 0– 43.75). Han women (n = 38) in the TAR had much lower PFDI-20 total scores, compared with Tibetan women (n = 163) (p < 0.05). The results of the multiple linear regression models showed that the PFDI-20 scores obtained from women living in the TAR were closely related to parity, history of heavy weight lifting, age, history of instrumental deliveries, ethnicity and number of caesarean sections.Conclusion: Pelvic floor disorder is common among parous women living in the TAR. Ethnicity, parity, history of heavy weight lifting, age, history of instrumental deliveries and number of caesarean sections are the factors closely related to the PFDI-20 scores.Keywords: pelvic floor disorder, Tibet Autonomous Region, pelvic organ prolapse, urinary incontinence, overactive bladder symptoms

Mingxiang Cai,1,&ast; Huizhen Peng,1,&ast; Minyi Liu,1,&ast; Maohua Huang,2,3 Wen Zheng,1 Guilan Zhang,1 Wenjia Lai,1 Chufang Liao,1 Lizhao Cai,1 Dongmei Zhang,2,3 Xiangning Liu1 1The First Affiliated Hospital of Jinan University, School of Stomatology, Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, 510630, People’s Republic of China; 2College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China; 3Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou, 510632, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangning Liu, The First Affiliated Hospital of Jinan University, School of Stomatology, Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, 510630, People’s Republic of China, Email liuxiangning@jnu.edu.cn Dongmei Zhang, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China, Email dmzhang701@jnu.edu.cnPurpose: Blood vessels distribute cells, oxygen, and nutrients throughout the body to support tissue growth and balance. Pericytes and endothelial cells form the inner wall of blood vessels, crucial for organ development and tissue homeostasis by producing paracrine signaling molecules. In the skeletal system, pericyte-derived vascular factors along with angiogenic factors released by bone cells regulate angiogenesis and bone formation. Although the involvement of angiogenic factors and skeletal blood vessels in bone homeostasis is relatively clear, the role of pericytes and the underlying mechanisms remain unknown. Here, our objective was to elucidate the significance of pericytes in regulating osteoclast differentiation.Methods: We used tissue staining to detect the coverage of pericytes and osteoclasts in femoral tissues of osteoporotic mice and mice of different ages, analyzing their correlation. We developed mice with conditionally deleted pericytes, observing changes in bone mass and osteoclast activity using micro-computer tomography and tissue staining to detect the regulatory effect of pericytes on osteoclasts. Pericytes-derived exosomes (PC-EVs) were collected and co-cultured with monocytes that induce osteoclast differentiation to detect the effect of the former on the exosomes. Finally, the specific mechanism of PC-EVs regulating osteoclast differentiation was verified using RNA sequencing and Western blotting.Results: Our study indicates a significant correlation between pericytes and age-related bone resorption. Conditional deletion of pericytes activated bone resorption and led to osteopenia in vivo. We discovered that PC-EVs inhibited the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, which is mediated by tumor necrosis factor receptor-associated factor 3 (Traf3), negatively regulating osteoclast development and bone resorption. Silencing Traf3 in PC-EVs canceled their inhibitory effect on osteoclast differentiation.Conclusion: Our study provides a novel perspective into the regulatory role of pericytes on bone resorption and may provide potential strategies for developing novel anti-bone resorption therapies. Keywords: pericytes, exosomes, bone resorption, Traf3

Hongjuan Zhou, Wenli Wang, Long Cai, Tingting Yang Clinical Laboratory Experiment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Tingting Yang; Long Cai, Clinical Laboratory Experiment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, 310003, People’s Republic of China, Email yang1989tingitng@126.com; cailong317@hotmail.comAbstract: The growing global apprehension towards multi-drug resistant (MDR) bacteria necessitates the development of innovative strategies to combat these infections. Berberine (BER), an isoquinoline quaternary alkaloid derived from various medicinal plants, has surfaced as a promising antibiotic adjuvant due to its ability to enhance the effectiveness of conventional antibiotics against drug-resistant bacterial strains. Here, we overview the augmenting properties and mechanisms of BER as an adjunctive antibiotic against MDR bacteria. BER has been observed to exhibit synergistic effects when co-administered with a range of antibiotics, including β-lactams, quinolones, aminoglycosides, tetracyclines, macrolides, lincosamides and fusidic acid. The adjunctive properties of BER led to an increase in antimicrobial effectiveness for these antibiotics against the corresponding bacteria, a decrease in minimal inhibitory concentrations, and even the reversal from resistance to susceptibility sometimes. The potential mechanisms responsible for these effects included the inhibition of antibiotic efflux, the disruption of biofilm formation, the modulation of host immune responses, and the restoration of gut microbiota homeostasis. In brief, BER demonstrated significant potential as an antibiotic adjuvant against MDR bacteria and is a promising candidate for combination therapy. Further research is necessary to fully elucidate its mechanism of action and address the challenges associated with its clinical application.Keywords: berberine, antibiotic adjuvant, multidrug-resistant bacteria, efflux pump, biofilm

Shanshan Chen,1,2,&ast; Youjia Duan,2,&ast; Yongchao Zhang,2 Long Cheng,2 Liang Cai,2 Xiaopu Hou,2 Wei Li1,2 1Cancer Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li, Cancer Center, Beijing Tongren Hospital, Capital Medical University, 2 West Ring South Road, Daxing District, Beijing, 100176, People’s Republic of China, Tel +86 15811029005, Email weili8989@ccmu.edu.cnPurpose: Tumor capsule is an independent prognostic factor for patients with hepatocellular carcinoma (HCC) and used increasingly to guide clinical decision-making. Considering the genetic complexity for capsule formation and its potential association with hypoxia, the significance of the polymorphisms of hypoxia-related genes in capsule formation and HCC prognosis remains to be elucidated.Patients and Methods: Peripheral blood samples from HCC patients were collected in this study. Single nucleotide polymorphism (SNP) genotyping was conducted by the iPLEX chemistry on a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (Sequenom, Inc.). The demographic and clinical data for the patients were obtained through medical chart review and/or consultation with the treating physicians. SPSS 25.0, R 4.1.1, and PLINK toolset were used to perform statistical analysis.Results: A total of 183 patients were enrolled, including 88 patients assigned to the capsule group and 95 to the non-capsule group. SLC2A1 rs841858 T allele, SLC2A1 rs2297977 T allele, STAT1 rs1547550 C allele, and STAT1 rs34997637 G allele were associated with significantly increased risk of capsule formation. The genotypes of SLC2A1 rs841858, SLC2A1 rs2297977, STAT1 rs34997637, and STAT1 rs1914408 were significantly associated with the formation of HCC capsule. The polymorphisms of STAT1 rs2066802, STAT1 rs12693591, and HIF1A rs2057482 showed close relationship with the prognosis of HCC patients in the capsule group, while the genotype distributions of CTNNB1 rs4135385, IFNG rs1861494, and SERPINE1 rs2227631 were closely related to the survival of patients in the non-capsule group. Further haplotype analysis suggested that SLC2A1 block 1 and STAT1 block 2 were related to the susceptibility of HCC capsule.Conclusion: The polymorphisms of the hypoxia-related genes (HIF1A, SERPINE1, IFNG, STAT1, CTNNB1, and SLC2A1) were correlated with the formation of HCC capsule. Several SNPs in these genes also showed association with HCC prognosis except SLC2A1. Further functional studies are warranted to explore the underlying mechanisms.Keywords: single nucleotide polymorphism, hypoxia, capsule formation, hepatocellular carcinoma

Wenqi Shen,&ast; Lingli Cai,&ast; Bin Wang, Yuying Wang, Ningjian Wang, Yingli Lu Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingli Lu, Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Tel +86 136 3635 2507, Email luyingli2008@126.comPurpose: This study aimed to determine the associations of relative fat mass (RFM), a novel adiposity indicator, with the prevalence of non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) and compared the disease discriminative ability of RFM with other common adiposity indicators in the general Chinese population.Patients and Methods: This cross-sectional study consisted of 11,532 adult participants from the SPECT-China study (2014– 2016). We included RFM and six other adiposity indicators, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), visceral adiposity index (VAI), and lipid accumulation product (LAP). Binary logistic regression analysis was used to assess the relationship between adiposity indicators and the prevalence of NAFLD and CVD. The receiver operating characteristic (ROC) curve was used to evaluate the ability to screen NAFLD and CVD.Results: After adjusting for confounding variables, RFM showed a strong association with the prevalence of NAFLD and CVD. In men, each 1-SD (standard deviation) increase in RFM was associated with more than 3-fold increased risk of NAFLD (OR: 4.33, 95% CI: 3.79– 4.93) and 66% increased risk of CVD (OR: 1.66, 95% CI: 1.36– 2.02); in women, per 1-SD increase in RFM was associated with about 4-fold increased risk of NAFLD (OR: 5.16, 95% CI: 4.62– 5.77) and 26% increased risk of CVD (OR: 1.26, 95% CI: 1.08– 1.47). ROC analysis showed that RFM and WHtR were the strongest predictors for CVD.Conclusion: RFM was significantly associated with prevalent NAFLD and CVD in Chinese adults and might be considered a simple tool for disease prediction. Further large longitudinal studies are needed to verify our findings.Keywords: relative fat mass, obesity, anthropometric measures, non-alcoholic fatty liver disease, cardiovascular disease

Hazrat Bilal,1 Dongxing Zhang,2,3 Muhammad Shafiq,4 Muhammad Nadeem Khan,5 Canhua Chen,6 Sabir Khan,1 Qian Wang,1,7 Lin Cai,1 Muhammad Awais,8 Haibin Hu,9 Yuebin Zeng1,10 1Department of Dermatology, Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China; 2Department of Dermatology, Meizhou Dongshan Hospital, Meizhou, Guangdong Province, 514023, People’s Republic of China; 3Department of Dermatology, Meizhou People’s Hospital, Meizhou, Guangdong Province, 514023, People’s Republic of China; 4Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, People’s Republic of China; 5Faculty of Biological Sciences, Department of Microbiology, Quaid-I-Azam University, Islamabad, 45320, Pakistan; 6Clinical Laboratory, Meizhou People’s Hospital, Meizhou, Guangdong Province, 514023, People’s Republic of China; 7Department of Medical-Surgical and Experimental Sciences University of Sassari Neurology Unit, Azienda Ospedaliera Universitaria (AOU), Sassari, Italy; 8Department of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 9The First Clinical Medical college, Guangdong Medical University, Zhanjiang, 523808, People’s Republic of China; 10Department of Dermatology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610021, People’s Republic of ChinaCorrespondence: Yuebin Zeng, Tel +8618607549813, Email zeng_yb@163.comObjective: Cryptococcosis is a fatal infection that can affect both immunocompetent and immunocompromised patients, and it is little understood in China’s various regions. This research aimed to look at the epidemiology, risk factors, and antifungal susceptibility pattern of Cryptococcus neoformans in eastern Guangdong, China.Methods: A six-year (2016– 2022) retrospective study was conducted at Meizhou People’s Hospital, China. Demographical, clinical, and laboratory data of cryptococcal patients were collected from hospital records and statistically analyzed using the chi-square and ANOVA tests.Results: Overall, 170 cryptococcal infections were recorded, of which meningitis accounted for 78 (45.88%), cryptococcemia for 50 (29.41%), and pneumonia for 42 (24.7%). The number of cases increased 8-fold during the study duration. The median age of patients was 58 years (Inter quartile range: 47– 66), and the high proportion of cases was from the male population (n = 121, 71.17%). The underlying diseases were identified only in 60 (35.29%) patients, of which 26 (15.29%) were severely immunocompromised, and 26 (15.29%) others were mildly immunocompromised. A statistically significant difference was reported for chronic renal failure, and anemia (p < 0.05) persisted in cases of three infection types. A high number of non-wild type (NWT) isolates were found against amphotericin B (n=13/145, 8.96%), followed by itraconazole (n=7/136, 5.15%) and voriconazole (n=4/158, 2.53%). Only six isolates (3.79%) were multidrug-resistant, four of which were from cryptococcemia patients. Compared to meningitis and pneumonia, cryptococcemia revealed a higher percentage of NWT isolates (p < 0.05).Conclusion: In high-risk populations, cryptococcal infections require ongoing monitoring and management.Keywords: cryptococcosis, Cryptococcus neoformans, epidemiology, risk factors, antifungal susceptibility

Honghong Liu,1 Peng Li,1 Dan Yu,1 Zhongxi Ma,2 Yu An,1 Si Li,1 Lin Cai1 1Department of Anesthesiology, Wuhan Fourth Hospital, Wuhan, 430033, People’s Republic of China; 2Department of Spine Surgery, Wuhan Fourth Hospital, Wuhan, 430033, People’s Republic of ChinaCorrespondence: Lin Cai, Department of Anesthesiology, Wuhan Fourth Hospital, No. 473, Hanzheng Street, Qiaokou District, Wuhan, 430033, People’s Republic of China, Tel +86 17764059606, Email Yellow0707@163.comObjective: This study explored the nursing effect of anesthesia care integration combined with preventive nursing on older patients with perioperative lumbar disc herniation (LDH).Methods: Clinical data of 100 older patients with LDH who were admitted to our hospital between May 2017 and May 2022 were used, and there were no patients who had not had surgery between January and May 2020 because of the COVID-19 pandemic. Based on the different nursing methods, the patients were divided into control and observation groups, with 50 cases each. The control group received anesthesia care integration, whereas the observation group received anesthesia care integration combined with preventive nursing. Lumbar spine function, pain score, anesthesia recovery assessment, and nursing effects were compared between the two groups.Results: The scores of the anesthesia recovery assessment of the two groups were compared, and the vital signs of the observation group during recovery from anesthesia were significantly better than those of the control group (P< 0.05). After nursing care, the Japanese Orthopaedic Association (JOA) score of the observation group was significantly higher than that of the control group; however, the numerical scale (NRS) score of the observation group was significantly lower than that of the control group (P< 0.05). After nursing care, the physical comfort, emotional state, psychological support, self-care ability, and pain scores were higher in the observation group than in the control group; however, the NRS score of the observation group was significantly lower than that of the control group (P< 0.05).Conclusion: Anesthesia care integration combined with preventive nursing has a positive effect on older patients with perioperative LDH, and it significantly improves lumbar spine function, reduces pain, shortens recovery time, and benefits physical and mental health.Keywords: anesthesia nursing, preventive nursing, lumbar disc herniation, nursing effect, lumbar spine function

Xiaoyang Liu,1 Yan Zhao,1 Zhanglei Mu,1 Yuan Jia,2 Chen Liu,3 Jianzhong Zhang,1 Lin Cai1 1Department of Dermatology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Lin Cai, Department of Dermatology, Peking University People’s Hospital, &num; 11. Xizhimen South St, Beijing, 100044, People’s Republic of China, Tel +8610 88325472, Fax +8610 88325474, Email scailin66@hotmail.comBackground: Early screening or timely prediction of psoriatic arthritis (PsA) are crucial. The study aimed to compare the clinical characteristics, cytokines and inflammation index between plaque psoriasis and PsA to explore their values in the early diagnosis of PsA.Methods: This was a case-control study in a single center from January 2021 to February 2023. The differences in clinical characteristics and laboratory examinations between PsA and plaque psoriasis were conducted. Patients with rheumatoid arthritis (RA) were used as a positive control. The correlation between variables were analyzed and multivariable logistic regression were performed by using the 10-fold cross-validation to find independently risk factors of plaque psoriasis that are developing PsA.Results: A total of 109 patients with plaque psoriasis (without joint damage), 47 patients with PsA and 41 patients with RA were enrolled in this study. The study found that the proportion of patients with elevated serum IL-6 levels, as well as the value of platelet to lymphocyte ratio (PLR) and systemic immune-inflammation index (SII), were significantly higher in patients with PsA and early PsA (PsA course ≤ 2 years) compared to those with plaque psoriasis (p< 0.05). After adjusting for age, gender, severity of skin lesions, and comorbidities (diabetes, hypertension, hyperlipidemia, hyperuricemia, and overweight/obesity), the study identified nail psoriasis (OR=4.35, 95% CI 1.67– 11.29, p< 0.002), elevated serum IL-6 (OR=6.78, 95% CI 2.34– 19.67, p< 0.001), and PLR (OR=8.37, 95% CI 2.97– 23.61, p< 0.001) as independent risk factors for PsA. A multivariable logistic regression analysis employing 10-fold cross-validation assessing the predictive association between the diagnosis of early PsA and the combination of IL-6, PLR, and nail psoriasis demonstrated that the area under the curve (AUC) was 0.84 (95% CI 0.77– 0.90) and the F1-score was 0.67 (95% CI 0.54– 0.80).Conclusion: The combination of elevated serum IL-6, PLR, and nail psoriasis can help to predict and screen the early stage of PsA.Keywords: biomarkers, IL-6, PLR, psoriasis, psoriatic arthritis

Libin Liu,1,2,&ast; Guihua Wu,1,2 Jing Wang,1,2 Lijun Peng,1,2 Xiaoqun Xu,1,2 Long Cai1,2,&ast; 1Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Long Cai, Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, 310003, People’s Republic of China, Email cailong317@hotmail.comPurpose: Exploring whether smoking is an influencing factor for the inconsistency between QuantiFERONTB Gold assay (QFT-GIT) and tuberculosis etiology.Patients and Methods: The clinical data of patients who were confirmed positive for Mycobacterium tuberculosis (MTB) after undergoing QFT-GIT testing from September 2017 to August 2021 were retrospectively analyzed. Chi-square and rank-sum tests were used to compare the differences in characteristics between smokers and non-smokers. Logistic regression was used to adjust for confounding factors affecting smoking. Propensity score matching (PSM) was used to verify the above conclusions again.Results: Positive results of tuberculosis etiology were adopted as the standard, the incidence of inconsistent results between QFT-GIT and tuberculosis etiology was 8.90% (108/1213), of which the false negative rate was 6.27% (76/1213) and the indeterminate rate was 2.64% (32/1213). In the overall population, the smokers had a lower level of basal IFN-γ (Z=− 2.079, P=0.038). Among 382 elderly (≥ 65 years old) patients, the smokers had lower levels of antigen-stimulated IFN-γ (Z=− 2.838, P=0.005). After performing BOX-COX transformation on all non-normally distributed data, logistic stepwise regression was used to adjust confounding factors. The results showed that smoking was an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiology results (OR=1.69, P=0.020). Using PSM for 1:2 matching, the results showed that smoking was still an independent risk factor for the inconsistent results of QFT-GIT and tuberculosis etiology (OR= 1.95, P=0.019). Age-stratified analysis showed that smoking was an independent risk factor in discordance between QFT-GIT and tuberculosis etiology in patients aged ≥ 65 years (OR=2.40, P=0.005), but not in patients aged < 65 years (P > 0.05).Conclusion: Smoking can reduce the body’s IFN-γ release ability, and smoking (especially the elderly) is an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiological results.Keywords: tuberculosis etiology, PSM, inconsistency, influencing factors

Rongping Ni,1,&ast; Lizhang Cai,2,&ast; Yingru Xing,3 Xiaoyun Fan1 1Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui People’s Republic of China; 2Department of Respiratory, Shanghai Nanxiang Hospital, Shanghai, People’s Republic of China; 3Department of Clinical Laboratory, Huainan Oriental Hospital Group of Anhui University of Science and Technology, Huainan, Anhui People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyun Fan, Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui, 230022, People’s Republic of China, Tel +86 13956988552, Email xiaoyunfan1201@163.comObjective: To investigate the effects of respiratory rehabilitation training combined with limb rehabilitation on sputum clearance and quality of life in patients with bronchiectasis.Methods: A retrospective analysis of 86 patients with bronchiectasis was divided into an intervention group and an observation group, with 43 cases in each group. All patients were above 18 years of age with no history of relevant drug allergies. Patients in the observation group were treated with conventional drugs, and those in the intervention group were given respiratory rehabilitation training and limb rehabilitation on this basis. After three months of treatment, the indexes of sputum discharge, sputum traits, lung function, and the 6-minute walk distance (6MWD) were compared and quality of life and survival skills were assessed using the Barthel index and a quality-of-life comprehensive assessment questionnaire (GQOLI-74).Results: The percentage of patients with mild Barthel index in the intervention group was higher than that in the observation group, and the difference between the groups was statistically significant (P < 0.05). After treatment, the scores of life quality and the lung function in the intervention group were higher than those in the observation group (both P < 0.05). After three months of treatment, the sputum volume and sputum viscosity scores of the two groups were higher than those before treatment (P < 0.05).Conclusion: Respiratory rehabilitation training with limb exercise rehabilitation can effectively improve the sputum clearance rate, lung function, and quality of life of patients with bronchiectasis and is thus worthy of clinical promotion and application.Keywords: bronchiectasis, respiratory rehabilitation training, limb exercise rehabilitation, lung function, quality of life

Yiwen Dong,1– 3 Litao Yao,2– 4,&ast; Lei Cai,1 Mi Jin,1 Tymour Forouzanfar,2,3 Lianjun Wu,1 Jinsong Liu,1,&ast; Gang Wu2,3 1School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Science, Amsterdam, Amsterdam, the Netherlands; 3Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam (UvA) and Vrije Universiteit Amsterdam (VU), Amsterdam, the Netherlands; 4Department of Dentistry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Litao Yao, Department of Dentistry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Zhejiang, Email yaolt@srrsh.com Jinsong Liu, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Email jinsong0719@wmu.edu.cnIntroduction: An antibacterial and pro-osteogenic coaxially electrospun nanofiber guided bone regeneration (GBR) membrane was fabricated to satisfy the complicated and phased requirements of GBR process.Methods: In this study, we synthesize dual-functional coaxially electrospun nanofiber GBR membranes by encapsulating parathyroid hormone (PTH) in the core layer and magnesium oxide nanoparticles (MgONPs) in the shell layer (MgONPs-PCL/PTH-PCL). Herein, the physicochemical characterization of MgONPs-PCL/PTH-PCL, the release rates of MgONPs and PTH, and antibacterial efficiency of the new membrane were evaluated. Furthermore, the pro-osteogenicity of the membranes was assessed both in-vitro and in-vivo.Results: We successfully fabricated a coaxially electrospun nanofiber MgONPs-PCL/PTH-PCL membrane with the majority of nanofibers (> 65%) ranged from 0.40~0.60μm in diameter. MgONPs-PCL/PTH-PCL showed outstanding antibacterial potential against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) through the release of MgONPs. We also discovered that the incorporation of MgONPs significantly prolonged the release of PTH. Furthermore, both the in-vivo and in-vitro studies demonstrated that high dosage of PTH promoted pro-osteogenicity of the membrane to improve bone regeneration efficacy with the presence of MgONPs.Conclusion: The new composite membrane is a promising approach to enhance bone regeneration in periodontitis or peri-implantitis patients with large-volume bone defects.Keywords: antibacterial property, pro-osteogenicity, coaxially electrospun, barrier membrane, guided bone regeneration

Xiaoqun Xu1,2 &ast;, Houyong Zhu3 &ast;, Long Cai1,2 &ast;, Xinyu Zhu,4 Hanxin Wang,5 Libin Liu,1,2 Fengwei Zhang,1,2 Hongjuan Zhou,1,2 Jing Wang,1,2 Tielong Chen,3 Kan Xu1,2 1Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Department of Cardiology, The Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kan Xu, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, 310003, People’s Republic of China, Email xukan3787@qq.com Tielong Chen, Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, 310007, People’s Republic of China, Email ctlppp@foxmail.comBackground: This study aimed to investigate whether nutrition levels in patients with active pulmonary tuberculosis (TB) affect their risk of all-cause mortality during hospitalization and to further evaluate the predictive ability of Geriatric Nutritional Risk Index (GNRI) and Body Mass Index (BMI) for risk of all-cause mortality.Methods: Patients from January 1, 2020 to December 31, 2021 were retrieved, and a total of 1847 were included. The primary outcome was all-cause mortality. Propensity score matching (PSM) was performed for risk adjustment, and receiver operating characteristic (ROC) curve analysis was performed to assess the predictive ability of GNRI and BMI for all-cause mortality.Results: Malnourished TB patients were older, had more congestive heart failure, and had more chronic obstructive pulmonary disease or asthma. Under the nutrition level grouping defined by GNRI, the all-cause mortality in the malnourished group did not appear to reach a statistical difference compared with the nonmalnourished group (P = 0.078). When grouped by level of nutrition as defined by BMI, the all-cause mortality was higher in the malnourished group (P = 0.009), and multivariate logistic regression analysis revealed that malnutrition was an independent risk factor for all-cause mortality. After propensity score matching, the results showed that the all-cause mortality was higher in the malnutrition group, regardless of BMI or GNRI defined nutrition level grouping, compared with the control group (both P < 0.001). The ROC curve analysis revealed that the area under the curve (AUC) was 0.811 ([95% confidence interval (CI) 0.701– 0.922], P < 0.001) for GNRI and 0.728 ([95% CI 0.588– 0.869], P = 0.001) for BMI.Conclusion: In the clinical treatment of patients with active TB, more attention should be paid to the management of nutritional risk. GNRI may be a highly effective and easy method for predicting short-term outcomes in patients with active pulmonary TB.Keywords: tuberculosis, malnutrition, Geriatric Nutritional Risk Index, body mass index

Zheng S, Zhang M, Bai H, et al. Int J Nanomedicine. 2019;14:9513–9524. The authors have advised due to an error at the time of figure assembly, the image of Spleen at 1 day in Figure 8B on page 9522 is incorrect. The correct Figure 8 is shown below. Figure 8 In vivo toxicity test of Mn-MoS2 QDs: (A(a–l)) Mouse serum biochemistry analysis and blood routine analysis before (0d, control) and after injection of Mn-MoS2 QDs for 1, 7, 21d. (B) Histological images of the heart, lungs, liver, spleen and kidneys of mice 1, 7 and 21 days post-intravenous injection of Mn-MoS2 QDs and in control mice. The organs were sectioned and stained with hematoxylin and eosin (H&E) and observed under a light microscope, scale bar = 100 μm. The authors apologize for this error and advise it does not affect the results of the paper.

Jianying Song,1,2,&ast; Lixin Hu,1,2,&ast; Bo Liu,2 Nan Jiang,3 Houqiang Huang,4 JieSi Luo,3 Long Wang,3 Jing Zeng,3 Feihong Huang,3 Min Huang,5 Luyao Cai,2 Lingyu Tang,2 Shunli Chen,2 Yinyi Chen,2 Anguo Wu,3 Silin Zheng,4 Qi Chen1,2,6,7 1Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2School of Nursing, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, People’s Republic of China; 4Department of Nursing, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 5Department of Respiratory and Critical Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 6Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, People’s Republic of China; 7Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Chen, Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China, Tel +0086-18383008873, Email qichen@swmu.edu.cn Silin Zheng, Department of Nursing, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China, Tel +86-13002866667, Email 1400223549@qq.comAbstract: Poor wound healing in individuals with diabetes has long plagued clinicians, and immune cells play key roles in the inflammation, proliferation and remodeling that occur in wound healing. When skin integrity is damaged, immune cells migrate to the wound bed through the actions of chemokines and jointly restore tissue homeostasis and barrier function by exerting their respective biological functions. An imbalance of immune cells often leads to ineffective and disordered inflammatory responses. Due to the maladjusted microenvironment, the wound is unable to smoothly transition to the proliferation and remodeling stage, causing it to develop into a chronic refractory wound. However, chronic refractory wounds consistently lead to negative outcomes, such as long treatment cycles, high hospitalization rates, high medical costs, high disability rates, high mortality rates, and many adverse consequences. Therefore, strategies that promote the rational distribution and coordinated development of immune cells during wound healing are very important for the treatment of diabetic wounds (DW). Here, we explored the following aspects by performing a literature review: 1) the current situation of DW and an introduction to the biological functions of immune cells; 2) the role of immune cells in DW; and 3) existing (or undeveloped) therapies targeting immune cells to promote wound healing to provide new ideas for basic research, clinical treatment and nursing of DW.Keywords: diabetic wounds, wound healing, immune cells, inflammation, targeted therapy

Li-Fei Cai,1,2 Shi-Bin Wang,2 Cai-Lan Hou,2 Ze-Bin Li,1 Yi-Jun Liao,1 Fu-Jun Jia1,2 1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2Guangdong Mental Health Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, People’s Republic of ChinaCorrespondence: Fu-Jun Jia, Guangdong Mental Health Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, People’s Republic of China, Tel +86-13609049731, Fax +86-02081884713, Email jiafujun@126.comPurpose: By exploring the gut-related microbiota differences of adolescents with non-suicidal self-injury (NSSI) and depression (without NSSI) and healthy volunteers, we provide a theoretical basis for the prevention and control of NSSI in adolescents through intestinal microecological regulation.Patients and Methods: A total of 99 subjects were recruited in Guangdong Province, China, including 51 adolescents with NSSI (KD), 24 healthy adolescents (NOR1), and 24 depression adolescents without NSSI (NOR2). General clinical data and fecal samples were collected from all subjects, who were assessed using the NSSI Behavioral Questionnaire and the 24-item Hamilton Depression Scale. The taxonomic composition of the gut microbiota was determined using the 16S rDNA gene sequencing method.Results: There were significant differences in diversity between the KD and NOR1, and the species uniformity index of the KD according to the Shannon and Simpson indices was significantly reduced compared with that of the NOR1 (4.81 vs 5.21, p< 0.01; 0.02 vs 0.01, p< 0.05). The relative abundances were different among the KD, NOR1 and NOR2, as reflected at the taxonomic levels of class, order, family, genus, and species. Bacteroides were the dominant flora of the KD and NOR2, while Mitsuokella was the dominant flora that distinguished the KD from the NOR2.Conclusion: We found that gut microbiota diversity was decreased in adolescents with NSSI, and the relative abundance was altered at different taxonomic levels. These results enrich the understanding of the relationship between NSSI and depression and the gut microbiota, Supporting that NSSI and depression are not homologous disorders. What is more, it establishes the basis for exploring the mechanisms of flora action in NSSI, providing a possible direction for NSSI to achieve a better prognosis and prevent relapse.Keywords: NSSI, gut microbiota, depression, adolescents

Ling-Yao Qi, Han-Xiong Liu, Lian-Chao Cheng, Yan Luo, Si-Qi Yang, Xu Chen, Lin Cai Department of Cardiology, The Third People’s Hospital of Chengdu Affiliated Hospital of Southwest Jiaotong University, Chengdu, People’s Republic of ChinaCorrespondence: Lin Cai, Department of Cardiology, The Third People’s Hospital of Chengdu Affiliated Hospital of Southwest Jiaotong University, 82 Qinglong St, Chengdu, Sichuan, People’s Republic of China, Tel/Fax +86 28-67575956, Email clin63@hotmail.comPurpose: The leuko-glycaemic index (LGI) is an index that combines white blood cell count and blood glucose and could be a marker of systemic inflammatory response syndrome. The prognostic value of the LGI in acute myocardial infarction (AMI) is still unclear. We aimed to investigate the prognostic value of the LGI for short- and long-term prognosis in AMI patients with different diabetic status.Patients and Methods: This was an observational, multicenter study involving 1256 AMI patients admitted in 11 hospitals between March 2014 and June 2019 in Chengdu. White blood cell count and blood glucose were measured on admission. The LGI was calculated by multiplying both values and dividing them by a thousand. Logistic regression was used to explore the predictive value of LGI in in-hospital mortality. Receiver operating characteristic curve was used to determine the optimal cut-off values of the LGI to predict in-hospital mortality. The patients were classified into diabetic and non-diabetic groups and further divided into higher and lower LGI subgroups according to the optimal cut-off values. The endpoints were all-cause mortality during the hospitalization and major adverse cardiovascular and cerebrovascular events (MACCE) during follow-up, including all-cause mortality, non-fatal myocardial infarction, vessel revascularization and non-fatal stroke.Results: LGI was an independent predictor of all-cause mortality during the hospitalization in non-diabetics, but not in diabetics. The optimal cut-off values of diabetics and non-diabetics were 3593 mg/dl. mm3 and 1402 mg/dl. mm3, respectively. Whether diabetics or not, in-hospital mortality was higher in the higher LGI subgroup (p-value < 0.001). And in the follow-up of 15 months (9 months, 22 months), we observed 99 (8.6%), 6 (0.5%), 54 (4.7%) and 29 (2.5%) cases of death, non-fatal MI, revascularization and non-fatal stroke, respectively. The cumulative incidence of MACCE during follow-up was higher in the higher LGI subgroup, both in the diabetics and non-diabetics (p-value < 0.05). In non-diabetics, higher LGI was an independent predictor of MACCE.Conclusion: LGI was an independent predictor for short- and long-term prognosis in AMI patients without diabetes, but had no prognostic value for short- and long-term prognosis of AMI patients with diabetes.Keywords: acute myocardial infarction, prediction, leuko-glycemic index, in-hospital mortality, long-term prognosis

Heng Zhang, Jiang Jin, Xue Chen, Lin Cai, Jianzhong Zhang, Guangdong Wen Department of Dermatology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaCorrespondence: Guangdong Wen, Department of Dermatology, Peking University People’s Hospital, # 11. Xizhimen South St, Beijing, 100044, People’s Republic of China, Tel +86 10 88325472, Fax +86 10 88325474, Email 163vip2008@163.comAbstract: Pilomatricoma, also known as “benign calcifying epithelioma”, is an uncommon slow-growing benign adnexal skin tumor, which originates from primitive cells of the hair matrix and usually appears as a solitary, firm, and asymptomatic nodule beneath the skin. Bullous pilomatricoma is a rare form of pilomatricoma, always presenting with firm subcutaneous nodules with a bullous appearance. In this study, we report a 9-year-old Chinese presenting girl with bullous pilomatricoma after influenza vaccination.Keywords: bullous pilomatricoma, calcifying epithelioma of Malherbe, influenza vaccination

Liang Gao, Weiling Huang, Laisheng Cai, Yufen Peng Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Yufen Peng; Liang Gao, Tel +86 791-88692511, Email 315989133@qq.com; gaoliang0123@sina.comPurpose: To assess Parkinson’s disease (PD)-related pain using the Chinese translation of King’s Parkinson’s disease Pain Scale (KPPS).Patients and Methods: A cohort of 200 patients with primary PD was recruited for this study. Their demographic and clinical features, including age, disease duration, levodopa equivalent daily dose (LEDD), and scores on the Unified Parkinson’s Disease Rating Scale-III (UPDRS III), Hoehn-Yahr Scale (H&Y), Mini-Mental State Examination (MMSE), Activities of Daily Living Scale (ADL), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Pittsburgh Sleep Quality Index (PSQI), Visual Analogue Scale (VAS) and KPPS, were recorded.Results: The prevalence of PD-related pain was 44.5%. Among the patients with PD-related pain, the average KPPS score was 41.2 ± 26.8. Pain was most commonly located in the lower limbs (60.7%), upper limbs (22.5%) and waist (21.3%). The most common pain type was musculoskeletal pain (68.5%). Compared with the PD group without pain, the PD group with pain had a longer disease duration (p = 0.022), higher LEDD (p = 0.008), higher UPDRSIII score (p = 0.018), higher H&Y stage (p = 0.003), higher HAMD score (p < 0.001), higher HAMA score (p < 0.001), lower ADL score (p = 0.046) and higher PSQI score (p < 0.001). PD-related pain was correlated with the H&Y stage and the PSQI score (p < 0.05). Cut-off points of 0, 34, and 70 were obtained to discriminate pain severity levels between no pain, mild, moderate, and severe pain, respectively.Conclusion: Chinese version of KPPS is not only an easy tool for characterization and scoring of pain in PD patients but also has the ability to distinguish between different levels of pain severity.Keywords: Parkinson’s disease, pain, clinical characteristics, King’s Parkinson’s disease Pain Scale

Ruibing Su,1,&ast; Lijun Cai,1,&ast; Pan Xiong,1,&ast; Zhiwei Liu,1,&ast; Shaobin Chen,2 Xi Liu,1 Runhua Lin,1 Zhijin Lei,1 Dongping Tian,1 Min Su1 1Institute of Clinical Pathology, Department of Pathology, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Su, Institute of Clinical Pathology, Department of Pathology, Shantou University Medical College, No. 22 Xinling Road, Shantou, Guangdong, People’s Republic of China, Tel/Fax +86-754-88900429, Email minsu@stu.edu.cnBackground: Toll-like receptor 3 (TLR3) not only plays a crucial role in innate immune and inflammation but also in anti-cancer immunity. Nevertheless, the clinicopathological outcome of TLR3 in ESCC is still ambiguous.Methods: Immunohistochemistry was performed to investigate TLR3 expression and its impact on survival in 137 ESCC patients (including paired esophageal tissues with different stages of early lesions from 37 patients). Furthermore, we downloaded ESCC RNA-seq datasets (including phenotype and survival data) from The Cancer Genome Atlas (TCGA). The relationship between TLR3 and prognosis, biological landscape, and immune infiltration was assessed to verify the immunohistochemical results of our tissue samples, explore the possible mechanism of prognostic outcomes, and predict the sensitivity of immunotherapy.Results: TLR3 protein expression displayed an increasing trend in the progression through different grades of cellular atypia, from normal, esophageal simple hyperplasia (ESSH), intraepithelial neoplasia (IEN) to ESCC (P < 0.0083). TLR3 protein had a positive association with inflammation level (Rho = 0.341, P < 0.001). TLR3 mRNA expression was significantly higher in comparison to adjacent normal tissues (P < 0.001). Cox regression analysis indicated high TLR3 protein and mRNA expression conferred good prognosis in our samples and TCGA, especially for advanced ESCC patients (TNM stage III and IV). Overexpression of TLR3 resulted in an immune-active microenvironment via the recruitment of immune-active cells including cytotoxic lymphocytes (CTLs), CD8+ T cells, NK cells, dendritic cells, and M1-type macrophages. TLR3 expression was correlated with the pro-inflammatory cytokines and chemokines relating to anti-tumor immunity. Moreover, GSEA analysis indicated upregulated expression of TLR3 could activate the apoptotic pathway.Conclusion: High TLR3 expression in ESCC patients was associated with a more favorable prognosis, immune-active cell infiltration, and an activated apoptotic pathway. TLR3 has potential applications for immunotherapy and immune response prediction in patients with ESCC.Keywords: esophageal squamous cell carcinoma, TLR3, prognosis, immune infiltrates, immunotherapy response

Li-Qiang Cai,1,2 Lei Huang,1,2 Li-Li Wei,1,2 Jia-Shu Yao,1,2 Luo-Yi Xu,1,2 Wei Chen1,2 1Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Center for Sleep Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Wei ChenDepartment of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3, Hangzhou, Zhejiang, 310016, People’s Republic of ChinaTel +86-571-87887800Email srrcw@zju.edu.cnObjective: This study aimed at investigating the correlation between estradiol and sleep apnea among women with major depressive disorders during the perimenopausal and postmenopausal periods.Methods: A total of 84 perimenopausal and postmenopausal women diagnosed with depression, and who had been subjected to whole-night polysomnography (PSG) were retrospectively studied. They were assigned into two groups based on the presence of OSA (apnea–hypopnea index (AHI)≥ 5) (OSA vs non-OSA). The correlation between estradiol levels and apnea–hypopnea index were assessed by logistic regression models after adjusting for age, body mass index (BMI), Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), apnea frequency and progesterone.Results: Among the 84 patients, 45.23% had OSA. Estradiol levels were significantly elevated in non-OSA than in OSA patients (p< 0.05). Univariate analysis revealed that elevated estradiol levels are associated with reduced odds of OSA (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.875– 0.966, p = 0.001). Multivariate analyses showed that low estradiol levels (OR = 0.859, 95% CI 0.826– 0.991, p = 0.031), higher HAMD scores (OR = 1.212, 95% CI 1.012– 1.453, p = 0.037), higher apnea frequency (OR = 2.493, 95% CI 1.389– 4.473, p = 0.002) and higher BMI (OR=1.635, 95% CI 1.136– 2.353, p = 0.008) are correlated with OSA.Conclusion: The ratio of depressed perimenopausal to postmenopausal women comorbid OSA was high. Higher BMI, low estradiol levels, high apnea frequency and high HAMD scores were correlated with OSA diagnosis and could be potential diagnostic markers for OSA in depressed perimenopausal and postmenopausal women. Reduced estradiol levels were correlated with an increased risk of OSA among depressed perimenopausal and postmenopausal women.Keywords: major depressive disorder, estradiol, obstructive sleep apnea, menopause, polysomnography

Kai Fang,&ast; Yiding Shen,&ast; Kendrick Hii Ru Yie, Zixin Zhou, Lei Cai, Shuyi Wu, Abdullrahman M Al-Bishari, Mohammed A Al-Baadani, Xinkun Shen, Pingping Ma, Jinsong Liu School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinkun Shen; Pingping MaSchool and Hospital of Stomatology, Wenzhou Medical University, 268#Xueyuan West Road, Lucheng District, Wenzhou City, 325000, People’s Republic of ChinaTel +86-577-88066010; +86-577-88066085Email 20111902015@cqu.edu.cn; ppma2012@sina.comBackground: Sandblasted/acid-etched titanium (SLA-Ti) implants are widely used for dental implant restoration in edentulous patients. However, the poor osteoinductivity and the large amount of Ti particles/ions released due to friction or corrosion will affect its long-term success rate.Purpose: Various zirconium hydrogen phosphate (ZrP) coatings were prepared on SLA-Ti surface to enhance its friction/corrosion resistance and osteoinduction.Methods: The mixture of ZrCl4 and H3PO4 was first coated on SLA-Ti and then calcined at 450°C for 5 min to form ZrP coatings. In addition to a series of physiochemical characterization such as morphology, roughness, wettability, and chemical composition, their capability of anti-friction and anti-corrosion were further evaluated by friction-wear test and by potential scanning. The viability and osteogenic differentiation of MC3T3-E1 cells on different substrates were investigated via MTT, mineralization and PCR assays.Results: The characterization results showed that there were no significant changes in the morphology, roughness and wettability of ZrP-modified samples (SLA-ZrP0.5 and SLA-ZrP0.7) compared with SLA group. The results of electrochemical corrosion displayed that both SLA-ZrP0.5 and SLA-ZrP0.7 (especially the latter) had better corrosion resistance than SLA in normal saline and serum-containing medium. SLA-ZrP0.7 also exhibited the best friction resistance and great potential to enhance the spreading, proliferation and osteogenic differentiation of MC3T3-E1 cells.Conclusion: We determined that SLA-ZrP0.7 had excellent comprehensive properties including anti-corrosion, anti-friction and osteoinduction, which made it have a promising clinical application in dental implant restoration.Keywords: titanium, zirconium hydrogen phosphate, anti-corrosion, anti-friction, osteoinduction

Jianwei Wang,1,2,&ast; Lili Yu,1,3,&ast; Yulong Sun,4,&ast; Liangming Zhang,1,3 Mingshu Tu,1,3 Liqing Cai,1,3 Xiaoqing Yin,3,5 Xiaojie Pan,1,6 Tao Wang,4 Yi Huang1,3,7,8 1Provincial Clinical College, Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 2Department of Clinical Laboratory, Fujian Provincial Hospital South Branch, Fuzhou, 350008, People’s Republic of China; 3Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 4Shanghai Liangrun Biomedicine Technology Limited Company, Shanghai, 200000, People’s Republic of China; 5Integrated Chinese and Western Medicine College, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, People’s Republic of China; 6Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 7Central Laboratory, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 8Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Huang; Tao Wang Email hyi8070@126.com; wangtao@microdiag.comPurpose: Our pilot study has shown that cystatin SN (CST1) protein is highly expressed in esophageal squamous cell carcinoma (ESCC) tissues. We intend to develop a chemiluminescent enzyme immunoassay (CLEIA) available for serum CST1 detection and define the diagnostic value of CST1 detection for early ESCC patients, and establish a panel of CST1 with traditional tumor markers to improve the diagnostic sensitivity for early ESCC.Methods: Detection performance of CLEIA for CST1 was evaluated by linearity, detection limit, accuracy, precision, anti-interference and stability. Diagnostic performance of CST1 for early ESCC was evaluated by detecting CST1 of 112 early ESCC, 107 esophageal benign lesions (EBL), and 151 healthy controls (HC). CEA, CYFRA21-1 and SCC-Ag were detected by chemiluminescence immunoassay (CLIA).Results: The linear range and detection limit of CLEIA for CST1 were 6.25– 400 pg/mL and 1.35 pg/mL, respectively; the average recovery rate was 102.65%; CVs of intra-batch precision and inter-batch precision were < 1/4 TEa and < 1/3 TEa, respectively; 8 interferents including 7 common interferents and CST4 had no interference on CST1 detection; stability evaluation showed good sample and reagent stability. The level and positive rate of CST1 in early ESCC group were significantly higher than those in EBL/HC groups (P< 0.05). The diagnostic sensitivity of CST1 for early ESCC was 31.25% (specificity 92.64%, AUC 0.654). The diagnostic sensitivity of traditional tumor markers ranged from 16.07% to 28.57%, at > 93.0% specificity, and SCC-Ag showed the highest AUC (0.709). Combination of CST1 and CEA, SCC-Ag exhibited the highest AUC up to 0.736 (sensitivity 49.11%, specificity 89.53%).Conclusion: CLEIA has excellent detection performance for CST1. CST1 might be a prospective serological biomarker for early diagnosis of ESCC, while combination of CST1 and CEA, SCC-Ag might improve the early diagnostic performance.Keywords: esophageal squamous cell carcinoma, cystatin SN, chemiluminescence enzyme immunoassay, methodological evaluation, early diagnosis

Lingyao Qi, Hanxiong Liu, Lianchao Cheng, Caiyan Cui, Xu Chen, Siqi Yang, Lin Cai Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Lin CaiDepartment of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaTel/Fax +86 28-67575956Email clin63@hotmail.comPurpose: Chronic kidney disease (CKD) is common in patients admitted with acute coronary syndrome (ACS), and it is associated with poor outcomes. However, data are limited. Hence, we examined the long-term prognostic significance of estimated glomerular filtration rate (eGFR) among Chinese patients hospitalized with ACS.Patients and Methods: This is a multicenter, observational study that included 1860 ACS patients enrolled between March 2014 and June 2019 from 11 hospitals in Chengdu. CKD-EPI equation was used to calculate the baseline eGFR. Patients were divided into three groups: eGFR ≥ 90 mL/min (normal renal function), eGFR 60 to < 90 mL/min (mild impaired renal function), and eGFR < 60 mL/min (moderate or severe renal dysfunction). The endpoint was all-cause death during follow-up.Results: At baseline, 714 patients had normal renal function, while 746 patients had mild impaired renal function, and 400 patients had moderate or severe renal dysfunction. In the follow-up of 15 months (10 months, 22 months), 261 (14.0%) patients died;, 139 (34.8%) in the moderate or severe renal dysfunction group, 94 (12.6%) in the mild impaired renal function group, and 28 (3.9%) in the normal renal function group (log-rank p-value from Kaplan–Meier analysis < 0.001). In multivariable Cox Proportional hazard analysis, age, systolic blood pressure (SBP), heart rate, eGFR, ST-elevation myocardial infarction (STEMI), and percutaneous coronary intervention (PCI) were independent predictors of all-cause death.Conclusion: In this study, among Chinese patients with ACS, renal insufficiency was associated with unfavorable long-term prognosis. Age, SBP, heart rate, eGFR, STEMI, and PCI could identify those at risk.Keywords: renal insufficiency, acute coronary syndrome, long-term prognosis, retrospective study

Yanglin Ni,1 Xuan Zhou,2 Ling Wu,3 Ping Wu,3 Ying Liu,3 Yinnan Li,3 Li Cai,3 Xueshu Fu,3 Chunhua Zhang3 1Department of Gynaecology, Huai’an Hospital of Traditional Chinese Medicine, Huai’an, Jiangsu Province, People’s Republic of China; 2MyGenostics Inc., Beijing, People’s Republic of China; 3Department of Gynaecology, Huai’an Maternal and Child Health Hospital, Huai’an, Jiangsu Province, People’s Republic of ChinaCorrespondence: Chunhua ZhangDepartment of Gynaecology, Huai’an Maternal and Child Health Hospital, Huai’an, Jiangsu Province, People’s Republic of ChinaTel +8613952326117Email hafyzch@yeah.netIntroduction: DICER1 syndrome is a rare tumor predisposition syndrome caused by germline DICER1 mutation, which is related to a variety of benign and malignant diseases. Our report is the first described case of these three disease phenotypes of DICER1 syndrome. The female patient with a novel germline DICER1 nonsense mutation (c.1088_1089delCTinsAA p.F363X) in exon 8 that was inherited from her mother. In addition to germline DICER1 mutation, two different hotspot somatic DICER1 mutations were detected in her ovarian tissue and goiter tissue. Our report will expand the report of DICER1 mutations in DICER1-syndrome-related diseases and provide case references for further research in the future.Conclusion: When the related disease phenotype appears in childhood, it should be considered whether it is DICER1 syndrome. Genetic testing can help diagnose DICER1 syndrome and develop related surveillance strategies. Awareness of the DICER1 syndrome may result in early recognition of these rare pediatric tumors and appropriate therapeutic management.Keywords: case report, DICER1, Sertoli-Leydig cell tumor, multinodular goiter, cystic nephroma

Jiandong Shi, Piaoyan Zhang, Huarong Su, Lingyi Cai, Liang Zhao, Haixia Zhou Department of Hematology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Haixia ZhouDepartment of Hematology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Xueyuanxi Load No. 109, Wenzhou City, Zhejiang Province, People’s Republic of ChinaEmail e-mail:zhxcrystal@126.comObjective: To analyze the changes in downstream genes, signaling pathways, and proteins based on the difference of microRNA (miRNA) expression in neuroblastoma (NB).Methods: GSE128004 second-generation sequencing expression data were downloaded from GEO, and Limma package of R language was used to analyze differential expression, and a volcano map and heat map were drawn; the target genes corresponding to the differential miRNA were found using the miWalk web tool, and GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were performed. The key genes were identified and verified in the TCGA database.Results: A total of 34 differentially expressed miRNAs were screened out. Among them, 22 up-regulated miRNAs predicted 1163 target genes and 12 down-regulated miRNAs predicted 1474 target genes. Target genes were enriched and analyzed by KEGG to find the FOXO signal pathway, mTOR signal pathway, AMPK signal pathway, and other signal pathways. After GO analysis, axon formation, regulation of chemical synaptic transmitters, regulation of nerve synapses, regulation of cross-synaptic signals, and other physiological processes were assessed. A total of 16 key genes were obtained by PPI analysis, and the survival analysis of TP53 and ATM genes verified in the TCGA database showed statistical significance.Conclusion: The 34 differential miRNAs may be related to the occurrence and development of NB. TP53 and ATM are related to the prognosis of NB. The role and mechanism of TP53 and ATM in NB need to be further verified.Keywords: neuroblastoma, miRNA, bioinformatics

Li Cai,1,2 Lixian Wang,3 Xuhua Guan,4 Lei Wang,4 Xinyi Hu,5 Yang Wu,4 Yeqing Tong,4 Peigang Wang1 1School of Health Sciences, Wuhan University, Wuhan, 430071, People’s Republic of China; 2Wuhan Center for Disease Control and Prevention, Wuhan, 430015, People’s Republic of China; 3Xiaonan Center for Disease Control and Prevention, Xiaogan, 432100, People’s Republic of China; 4Hubei Center for Disease Control and Prevention, Wuhan, Hubei, 430079, People’s Republic of China; 5Global Study Institute, University of Geneva, Geneva, SwitzerlandCorrespondence: Peigang Wang Email wpg926@163.comYeqing Tong Tel +8627 87652010Email t_yeqing@163.comObjective: The study aimed to timely grasp the epidemiologic status of rabies in Central China from 2013 to 2018 and provide scientific evidence for the implementation of follow-up prevention and control measures.Methods: We initiated a retrospective observational and descriptive study of bite-related injuries data and rabies disease data in Hubei province from 2013 to 2018, managed by the Center for Disease Control and Prevention.Results: A total of 2,028,691 individuals were exposed to bites from 2013 to 2018, of which 221 were diagnosed with rabies and deceased. Among those cases, the incubation periods of rabies varied from 3 days to 18,406 days, which has been shown to be statistically associated with where the infected person was exposed and whether the wound care has been conducted.Conclusion: Epidemiological studies have shown that from 2013 to 2018, the current situation of rabies in Central China is still severe. The case fatality rate keeps virtually 100%. The rural population is still the most vulnerable group to rabies, characterized by a high exposure ratio and low treatment rate as well as poor vaccination compliance. Hoewever, larger populations are warranted to validate our findings.Keywords: rabies, epidemiology, China

Meng-yuan Zhou,1,* Li Cai,1,2,* Xiao-wen Feng,1 Yu-rong Mu,1 Bo Meng,1 Fang-yuan Liu,1 Rong Li1 1Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, 230032, Anhui Province, People’s Republic of China; 2Department of Pathology, School of Basic Medicine, Anhui Medical University, Hefei, 230032, Anhui Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong LiSchool of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, People’s Republic of ChinaTel +86 551-65172132Email aydlirong@163.comIntroduction: Previous studies have confirmed the pathologic role of synovial aquaporin 1 (AQP1) in rheumatoid arthritis (RA), but its associations with the abnormal biologic behaviors of fibroblast-like synoviocytes (FLS) remain unclear. Herein, we examined the roles of AQP1 in the proliferation, migration and invasion of TNF-α-stimulated RA FLS (MH7A cells) and explored the underlying mechanisms.Materials and Methods: Lentivirus-mediated AQP1 overexpression or silencing MH7A cells was constructed. Assays of MTT, flow cytometry (PI staining and Annexin V-PE/7-AAD staining), TMRM staining, wound-healing, transwell and phalloidin staining were performed to detect cell proliferation, cycle distribution, apoptosis, migration and invasion. The involvement of Wnt/β-catenin pathway was revealed by Western blot and β-catenin immunofluorescence staining.Results: AQP1 overexpression promoted cell proliferation of TNF-α-stimulated MH7A by facilitating transformation from G0/G1 to S phase and inhibiting cell apoptosis (ie, reduced apoptosis rates, raised mitochondrial membrane potential, increased Bcl-2 protein level and decreased levels of Bax and cleaved caspase 3 protein). Also, AQP1 overexpression increased the migration index as well as the numbers of migrated and invasive cells. Furthermore, AQP1 overexpression promoted the activation of Wnt/β-catenin pathway, and XAV939, an inhibitor of Wnt/β-catenin, canceled the above effects of AQP1 overexpression on MH7A cells. As expected, AQP1 silencing exhibited the opposite effects on TNF-α-stimulated MH7A cells, which could be reversed by LiCl, an activator of Wnt/β-catenin.Conclusion: AQP1 can affect the proliferation, migration and invasion of MH7A cells by Wnt/β-catenin signaling pathway, and AQP1 can be as a crucial determiner that can regulate RA FLS biologic behaviors.Keywords: aquaporin 1, rheumatoid arthritis, fibroblast-like synoviocytes, Wnt/β-catenin signaling pathway, biologic behaviors

Lingli Cai,* Cheng Li,* Yufei Wang, Yifei Mo, Jun Yin, Xiaojing Ma Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital; Shanghai Clinical Center for Diabetes; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Yin; Xiaojing MaDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, People’s Republic of ChinaTel +86-21-64369181Fax +86-21-64368031Email yinjun@sjtu.edu.cn; maxiaojing@sjtu.edu.cnAim: Growth differentiation factor 15 (GDF15) is closely related to obesity. This study aimed to explore the influence of weight loss intervention on serum GDF15 levels and the relationship between GDF15 and metabolism.Materials and Methods: Forty-four overweight and obese adults either adopted a low-carbohydrate diet or performed moderate-to-vigorous exercise for 3 weeks. Weekly follow-ups were conducted to measure body composition, glucose and lipid metabolism and serum GDF15 levels.Results: After 3 weeks of intervention, body weight, fat mass and waist circumference in both groups decreased (P < 0.05). No significant change in GDF15 levels was observed in the two groups. Among all the subjects, 10 of them (22.7%, group of Down) showed a decrease in GDF15 and 34 (77.3%, group of Up) showed an increase in GDF15 after the intervention. We found that GDF15 increased significantly with the follow-up time in the UP group and waist circumference, fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and triglycerides (TG) decreased (P for trend < 0.05). However, no significant differences in all parameters were detected in Down group. In addition, GDF15 was elevated between 30 mins and 120 mins in a 75-g oral glucose tolerance test. Its trend was negatively correlated with plasma glucose and serum insulin.Conclusion: Increased serum GDF15 was associated with improvement in metabolism by lifestyle intervention among young overweight and obese adults. The increase of GDF15 could be an indicator to evaluate metabolic improvements in overweight and obese people.Clinical Trial Registration: www.chictr.org.cn, registration number ChiCTR1800016786.Keywords: growth differentiation factor 15, obesity, metabolism, low-carbohydrate diet, exercise

Yajing Gao,1 Yan Shan,2 Tingting Jiang,3 Li Cai,4 Fanliang Zhang,3 Xinxin Jiang,1 Xue Li,1 Hong Wang1 1Nursing and Health School of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Medical School of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Zhengzhou University First Affiliated Hospital, Zhengzhou, Henan, People’s Republic of China; 4Renji Hospital Affiliated to Shanghai Jiao Tong University, Shangai, People’s Republic of ChinaCorrespondence: Yan Shan Email sy110@sina.comPurpose: Little is known about factors that predict dietary adherence among Chinese patients undergoing peritoneal dialysis. We investigated whether self-regulatory fatigue and trait self-control influence dietary adherence among Chinese patients with peritoneal dialysis.Methods: A total of 192 Chinese patients undergoing peritoneal dialysis were recruited at two peritoneal dialysis centers. The dietary adherence, trait self-control and self-regulatory fatigue of these patients were assessed using self-administered questionnaires. Clinical data were extracted from the hospital medical records. The significance of several social demographic factors on dietary adherence was analyzed using One-way ANOVA was used to analyze, whereas the association between dietary adherence and self-regulatory fatigue as well as trait self-control were analyzed using Pearson correlation. The independence association between dietary adherence and other influencing factors was assessed using Multivariable linear regression analyses.Results: We found that peritoneal dialysis patients only moderately adhere to dietary prescriptions. The top three least adherences were observed for salt intake (1.89± 0.36), face of difficulty (2.86± 0.26) and fluid restriction adherence intake (2.97± 0.30). Multivariable linear regression analysis revealed that education level (β=0.339, P< 0.001), residence (β=− 0.151, P=0.015), self-regulatory fatigue (β= − 0.648, P< 0.001), and trait self-control (β=0.118, P=0.022) were independent predictors of dietary adherence.Conclusion: Education level and residence strongly influence dietary adherence among Chinese peritoneal dialysis patients. On the other hand, Self-regulatory fatigue and trait self-control are independent predictors of dietary adherence among peritoneal dialysis patients. These findings can guide the enhancement of dietary adherence of peritoneal dialysis patients.Keywords: peritoneal dialysis, dietary adherence, trait self-control, self-regulatory fatigue

Lixia Cai,1,* Yangji Xue,2,* Jianzu Ding,2,3 Bin Zheng2,3 1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Huanglong Science and Education Center, Hangzhou Medical College, Hangzhou, People’s Republic of China; 3Zhejiang Academy of Medical Sciences, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin ZhengHuanglong Science and Education Center, Hangzhou Medical College, Hangzhou, 310013 Zhejiang, People’s Republic of ChinaTel +86-571-88215606Fax +86-591-88215602Email bin_zheng@foxmail.comBackground: Gastric cancer (GC) is a highly occurring cancer with poor prognosis. Reports indicate that long non-coding RNA (LncRNA) potentially regulates tumor progression. Herein, we aim to explore the effect of LncRNA AC118344.1 on the progression of gastric cancer.Methods: Overexpression and knockout experiments were used to clarify the potential molecular signaling mechanisms induced by AC118344.1. CCK-8, transwell and in vivo metastasis assay were used to detect the function of AC118344.1 in AGS and SGC-7901 cells. Additionally, shRNA silencing techniques, qRT-PCR and Western blot assay were used to explore the relationship between AC118344.1, AKT2, and its downstream molecules.Results: Upregulating the expression of AC118344.1 induces cell proliferation, invasion in vitro, and lung metastasis in vivo whereas downregulating the expression of AC118344.1 inhibits these effects. Besides, silencing the expression of AC118344.1 downregulated the expression of AKT2 in both the two cells. On the other hand, silencing the expression of AKT2 by shRNA was unable to downregulate the expression of AC118344.1 in both the gastric cancer cells. Also, AC118344.1 regulated AKT2 via its downstream molecules including HK2 and MMP2.Conclusion: AC118344.1 promotes gastric cancer cell proliferation and invasion and lung metastasis in nude mice by upregulating the expression of AKT2 and its downstream molecules (HK2 and MMP2). Therefore, our findings provide a novel mechanism of the AC118344.1-AKT2-HK2/MMP2 axis in regulating the development of gastric cancer cells.Keywords: gastric cancer, lncRNA AC118344.1, AKT2, proliferation, invasion, metastasis

Liang Cai,1,* Ganlu Ouyang,2,* Xin Wang,2 Zhiping Li,3 Yali Shen2 1Lung Cancer Center, West China School of Medicine, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yali ShenDepartment of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37 of Wainan Guoxue Lane, Wuhou District, Chengdu 610041, People’s Republic of ChinaTel/Fax +86 2885422589Email sylprecious@163.comPurpose: Regional lymph node recurrence (RLNR) in gastric cancer is uncommon. We investigated the effects of radiotherapy combined with chemotherapy against limited RLNR and analyzed the regularity of regional lymph node recurrence and metastasis.Patients and Methods: This retrospective study included 34 gastric cancer patients with limited RLNR after D2 lymphadenectomy between January 2012 and May 2018. All patients received systemic chemotherapy and local radiotherapy with median dose of 52.5 Gy (30– 66 Gy in fractions of 1.8– 3.0 Gy daily, five times weekly). All sites of recurrent and metastatic lymph nodes were collected and analyzed.Results: The median follow-up was 19 months (range 7– 60 months). After treatment, complete response and partial response were observed in 32.4% and 55.9% of patients, respectively. The median overall survival (OS) and progression-free survival (PFS) were 18 months and 13 months. On multivariate analysis, age (≤ 60 vs > 60) was associated with a significantly better OS (p = 0.025) and radiation dose (< 54 Gy vs ≥ 54 Gy) was considered as an independent prognostic factor for PFS (p = 0.000). During radiotherapy, three patients developed grade 3 gastrointestinal toxicity, and no deaths were related to the treatments. The most commonly metastatic lymph nodes were the No. 4, No. 3, No. 6, No. 5, No. 7, No. 9, and No. 8 nodes; the recurrent lymph nodes were mainly located in the No. 16b, No. 16a, No. 9, No. 14, No. 7, No. 13, and No. 8 nodes.Conclusion: The selected gastric cancer patients with limited RLNR may benefit from radiotherapy combined with chemotherapy. High-dose radiotherapy (≥ 54 Gy) lead to better PFS and tend to extend OS. The major lymph node recurrence sites were in the gastric vascular region (especially No. 16a/b nodes).Keywords: gastric cancer, radiotherapy, regional lymph node, D2 lymphadenectomy, recurrence

Shilin He,1,* Tunan Yu,1,* Parikshit Asutosh Khadaroo,2,3 Liuxin Cai,1 Yeyuan Chu,4 Fangqiang Wei,5 Xiao Liang1 1Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Monash University, School of Medicine, Nursing and Health Sciences, Melbourne, Australia; 3School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 4School of Nursing, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao LiangDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang Province, People’s Republic of ChinaTel/Fax +86-571-8600-6605Email srrshlx@zju.edu.cnPurpose: Incidental gallbladder cancer (IGBC) is defined as gallbladder cancer (GBC) that is accidentally discovered during cholecystectomy to treat benign lesions. We aimed to compare the prognosis of IGBC patients who underwent simultaneous radical resection (SIR) vs salvage radical resection (SAR).Patients and Methods: We retrospectively reviewed data for IGBC patients admitted to Sir Run Run Shaw Hospital from January 2000 to May 2016. Survival analysis was performed using Kaplan–Meier (univariate) and COX regression (multivariate) analyses.Results: Eighty-four patients with IGBC underwent radical resection; 43/84 underwent SIR, and 41/84 underwent SAR. Compared with SIR, the SAR group was more likely to receive comprehensive preoperative radiographic evaluation, port-site excision, and have more lymph nodes excised (all P < 0.05). Kaplan–Meier analysis indicated that the prognosis in the SAR group was better than that in SIR (overall survival: P = 0.050, recurrence-free survival: P = 0.028). Regression analysis indicated that the type of radical resection (SIR/SAR) was not an independent prognostic factor (overall survival: P = 0.737, recurrence-free survival: P = 0.957).Conclusion: Patients undergoing SAR had non-inferior survival compared with SIR. It is possible that patients in SAR underwent preoperative radiographical evaluations more comprehensively and the surgical operations were more well performed.Keywords: incidental gallbladder carcinoma, simultaneous surgery, salvage surgery, prognosis

Meijuan Liu,1,* Li Cai,2,* Qifan Li,3 Xiaoran Chen,1 Lingyun Gao,1 Lei Jiang2 1Department of Ultrasound, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of China; 2Department of Pathology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of China; 3Department of Ultrasound, RongCheng Maternal and Child Care Service Centre, Weihai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei JiangDepartment of Pathology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of ChinaEmail yhdyylmj@163.comAim: To investigate the association of the blood flow parameters measured by transvaginal three-dimensional power Doppler ultrasound and the angiogenesis of endometrial cancer.Material and Methods: The expressions of vascular endothelial growth factor (VEGF) and CD31 in benign and malignant endometrial lesions, and in malignant lesions with different clinical and pathological features were analyzed. The correlations of the blood flow parameters (vascularization index [VI], blood flow index [FI], and vascularization-blood flow index [VFI]) of transvaginal 3D power Doppler ultrasound, and VEGF expressions, microvessel density (MVD) were also evaluated.Results: The VEGF-positive rates and the MVD values in benign and malignant endometrial lesions were significantly different (both P< 0.001). The differences of VEGF-positive rates (P < 0.001) and MVD values (P = 0.021) between type I and type II lesions of endometrial cancer were statistically significant. There was no significant difference in the VEGF-positive rate and MVD value between stage IA and IB (P=0.443, P=0.311). The difference of VEGF expression and MVD in stage IA, stage IB and stage II and above was statistically significant (P=0.003, P=0.017). The VEGF-positive rate and MVD value were not significantly different in IAG1 and IAG2 lesions of endometrioid adenocarcinoma (P=0.709, P=0.792). There was no significant correlation between VI, FI, VFI and VEGF expression and MVD in endometrial cancer.Conclusion: The VEGF-positive rates and MVD values were relatively high in malignant endometrial lesions, type II and stage II and above lesions of type I endometrial cancer, indicating that the angiogenesis of endometrial cancer tissues might play a crucial role in the tumor classification, and pelvic metastasis.Keywords: three-dimensional power Doppler ultrasound, VEGF, CD31

Yayu Wang,1,* Jie Yao,2– 4,* Lizhao Cai,2– 4,* Tong Liu,1 Xiaogang Wang,2,4 Ye Zhang,2– 4 Zhiying Zhou,2– 4 Tingwei Li,2– 4 Minyi Liu,2– 4 Renfa Lai,2– 4 Xiangning Liu2– 4 1Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, People’s Republic of China; 2Department of Stomatology Medical Center, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 3School of Stomatology, Jinan University, Guangzhou 510632, People’s Republic of China; 4Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangning Liu; Renfa LaiThe First Affiliated Hospital of Jinan University, Guangzhou 510632, People’s Republic of ChinaTel +86 20 3868 8109Fax +86 20 3868 8000Email liuxiangning2003@126.com; prof.dr.lai@163.comBackground: Current drugs used for osteoporosis therapy show strong adverse effects. Stem cell-derived extracellular vesicles (EVs) provide another choice for osteoporosis therapy. Mouse mesenchymal stem cells (mMSCs)-derived EVs promote bone regeneration; however, their clinical application is limited due to non-specific tissue targeting. Alendronate specifically targets bone tissue via hydroxyapatite. Therefore, EVs were combined with alendronate to generate Ale-EVs by “click chemistry” to facilitate EVs targeting bone via alendronate/hydroxyapatite binding.Methods: Ale-EVs were characterized based on size using dynamic light scattering analysis and morphology was visualized by transmission electron microscopy. Hydroxyapatite affinity of Ale-EVs was detected by flow cytometry. Bone targeting of Ale-EVs was tested by ex vivo fluorescent imaging. Cell viability was assessed by using WST-8 reduction assay kit for testing the ability of Ale-EVs to promote mMSCs proliferation. Alkaline phosphatase experiment was used to detect ability of Ale-EVs to promote differentiation of mouse mesenchymal stem cells in vitro. Western blotting and Q-PCR assay were used to detect the early marker of osteogenic differentiation. Antiosteoporotic effects of Ale-EVs were detected in ovariectomy (OVX)-induced osteoporosis rat model. The safety of the Ale-EVs in vivo was measured by H&E staining and serum markers assay.Results: In vitro, Ale-EVs had high affinity with hydroxyapatite. Also, ex vivo data indicated that Ale-EVs-DiD treatment of mice induced strong fluorescece in bone tissues compared with EVs-DiD group. Furthermore, results suggested that Ale-EVs promoted the growth and differentiation of mouse MSCs. They also protected against osteoporosis in ovariectomy (OVX)-induced osteoporotic rats. Ale-EVs were well tolerated and no side effects were found, indicating that Ale-EVs specifically target bone and can be used as a new therapeutic in osteoporosis treatment.Conclusion: We used the Ale-N3 to modify mouse mesenchymal stem cells-derived extracellular vesicles by copper-free “click chemistry” to generate a Ale-EVs system. The Ale-EVs had a high affinity for bone and have great potential for clinical applications in osteoporosis therapy with low systemic toxicity.Keywords: extracellular vesicles, EVs, mesenchymal stem cells, MSCs, bone-targeting, osteoporosis, click chemistry

Yu-rong Mu1,2 ,* Meng-yuan Zhou1,2 ,* Li Cai,3 Ming-ming Liu,1,2 Rong Li1,2 1School of Pharmacy, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, People’s Republic of China; 3Department of Pathology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong LiSchool of Pharmacy, Anhui Medical University, Hefei, Anhui Province, People’s Republic of ChinaEmail aydlirong@163.comIntroduction: Previous studies have confirmed that aquaporin 1 (AQP1) is up-regulated in synovium of rheumatoid arthritis (RA), but its exact pathogenic mechanisms in RA are unclear. This study revealed the pathogenic role of AQP1 in rat collagen-induced arthritis (CIA) and the underlying mechanisms related to β-catenin signaling.Materials and Methods: Secondary paw swelling and pathological changes of ankle joints were used to evaluate the severity of rat CIA. Synovial AQP1 and β-catenin expression were measured by immunohistochemistry (IHC) and Western blot assay. AQP1 siRNA was applied to knockdown AQP1 in cultured CIA fibroblast-like synoviocyte (FLS). Assays of MTT, PCNA immunofluorescence and transwell were performed to detect cell proliferation, migration and invasion. The protein levels of β-catenin pathway members and ratio of TOP/FOP luciferase activity were also measured.Results: In vivo, we revealed that synovial AQP1 and β-catenin expressions in CIA rats were higher than normal rats, and synovial AQP1 expression of CIA rats increased in parallel with secondary paw swelling and total pathological score on joint damage. Correlation analysis of IHC results indicated that synovial AQP1 expression positively correlated with β-catenin expression in CIA rat. In vitro, AQP1 siRNA apparently reduced the proliferation, migration and invasion of CIA FLS by inhibiting β-catenin signaling pathway. As an activator of β-catenin signaling, lithium chloride (an inhibitor of GSK-3β) reversed the inhibitory effects of AQP1 siRNA on the cultured CIA FLS.Conclusion: We concluded that the overexpression of synovial AQP1 aggravated rat CIA by promoting the activation of FLS through β-catenin signaling pathway.Keywords: aquaporin 1, collagen-induced arthritis, fibroblast-like synoviocyte, rheumatoid arthritis, β-catenin signaling

Yanling Lin,1,* Lingzhi Wang,2,* Wenxiao Luo,1,* Xiaohan Zhou,1 Yuting Chen,1 Kaifan Yang,3 Jinrong Liao,4 Dehua Wu,1 Longmei Cai1 1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2First Clinical Medical College, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Second Clinical Medical College, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dehua Wu; Longmei CaiDepartment of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of ChinaTel +86 186 0206 2748; +86 134 5020 5073Email wudehua.gd@gmail.com; cailongmeibestlove@163.comPurpose: Nasopharyngeal carcinoma (NPC) is among the most common malignancies derived from the epithelium of the nasopharynx. To date, the regulatory networks involved in NPC have not been fully identified. Previous studies revealed multiple loss-of-function mutations in NPC and specifically in cylindromatosis lysine 63 deubiquitinase (CYLD); however, the exact role of CYLD in NPC progression and its potential mechanism remains unclear.Methods: We performed immunohistochemical (IHC) staining and real-time quantitative polymerase chain reaction (qPCR) to measure CYLD expression in NPC tissues, and Western blot was conducted to determine CYLD levels in NPC cell lines. Cell proliferation was detected by CCK8 assay and colony formation analysis, and apoptosis was determined by Annexin V/propidium iodide staining. Potential targets of CYLD were verified by co-immunoprecipitation and mass spectrometry. Xenograft assay was conducted to confirm the role of CYLD in vivo.Results: We found that CYLD levels were significantly decreased in both NPC tissues and cell lines, and that CYLD overexpression inhibited NPC cell proliferation and promoted apoptosis. Additionally, we revealed that CYLD bound and upregulated N-Myc downstream regulated 1 (NDRG1), and that silencing NDRG1 abolished the tumor-suppressor effect of CYLD on NPC cells. Furthermore, CYLD suppressed tumor growth in xenograft mice models.Conclusion: These results suggest CYLD as a tumor suppressor, potential biomarker for diagnosing NPC, and therapeutic target.Keywords: NPC, CYLD, proliferation, apoptosis, NDRG1

ZhiBo Liu,* KangWen Xiao,* ZhiQiang Hou, FeiFei Yan, Yan Chen, Lin Cai Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Cai Tel +86 1388609 6467Email orthopedics@whu.edu.cnBackground: With excellent shape memory and superelastic properties, shape memory alloy (SMA) is an ideal actuator, and it can form smart structure for different applications in medical field. However, SMA devices cause apparent thermal damage to the surrounding tissues when it works in vivo, making the application of smart structure that is composed of SMA actuator in vivo is greatly limited.Methods: In this paper, coating (APA) with PLA as the main body to limit the heat conduction, a multifunctional Ag nanoparticles (AgNPs)/polylactic acid (PLA)/Al2O3 was synthesized. The Al2O3 layer was formed by micro-arc oxidation (MAO) and AgNPs were synthesized by silver nitrate and ethylene glycol. Scanning electron microscopy, transmission electron microscope, and Fourier transform infrared spectra were applied to analyze the morphology and characterization of APA coating. The antimicrobial activity, thermal insulation activity, and biocompatibility of APA coating were furtherly explored and verified through animal experiments and immunohistochemistry.Results: With different particle sizes and concentrations of AgNPs, APA multi-functional films were successfully prepared. The Al2O3 layer was closely combined with SMA and formed a porous surface, so the PLA and AgNPs layers can firmly adhere to SMA, thus reducing the release of nickel ions in SMA. AgNPs gave APA coating excellent antibacterial activity and effectively inhibited the growth of Staphylococcus aureus. In addition, coupled with the low thermal conductivity of PLA and Al2O3, AgNPs were tightly anchored on the surface of PLA, which has high infrared reflectivity, making the APA coating obtain good thermal insulation performance.Conclusion: We have successfully prepared the APA coating and obtained the optimum amount of AgNPs, which makes it have good thermal insulation performance, good antibacterial activity and good biocompatibility, which provides a new prospect for the application of SMA.Keywords: thermal insulation, nickel-titanium alloy, silver nanoparticles, micro-arc oxidation

Shaohui Zheng,1–3,* Min Zhang,2,* Hongyan Bai,2 Meijuan He,2 Lina Dong,2 Lulu Cai,2 Mingming Zhao,2 Qi Wang,2 Kai Xu,1–3 Jingjing Li1–3 1Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of China; 2School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, People’s Republic of China; 3Institute of Medical Imaging and Digital Medicine, Xuzhou Medical University, Xuzhou 221004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingjing Li; Kai Xu Email qingchao0124@163.com; xkpaper@163.comBackground: Early diagnosis of renal cell carcinoma is extremely significant for the effective treatment of kidney cancer. The development of AS1411 aptamer modified Mn-MoS2 QDs provides a promising fluorescence/magnetic resonance (MR) dual-modal imaging probe for the precise diagnosis of renal clear cell carcinoma.Methods: In this work, Mn-MoS2 QDs were synthesized through a simple “bottom-up” one-step hydrothermal method. AS1411 aptamer was modified on the Mn-MoS2 QDs to improve the specificity to renal cell carcinoma. The characteristics of Mn-MoS2 QDs were confirmed by transmission electronic microscopy (TEM), atomic force microscope (AFM), X-ray photoelectron spectrometer (XPS), photoluminescence (PL) emission spectra, etc. Cellular fluorescence labelling was investigated using the Mn-MoS2 QDs and AS1411-Mn-MoS2 QDs. The T1-weighted MR imaging was assessed by the in vitro MR cell imaging and in vivo MR imaging. Finally, the long-term toxicity of Mn-MoS2 QDs was investigated by the hematology and histological analysis.Results: The prepared Mn-MoS2 QDs exhibited excellent aqueous property, intense fluorescence, low toxicity, high quantum yield of 41.45% and high T1 relaxivity of 16.95 mM−1s−1. After conjugated with AS1411 aptamer, the AS1411-Mn-MoS2 QDs could specifically fluorescently label the renal carcinoma cells and present a specific MRI signal enhancement in the tumor region of mice bearing renal carcinoma tumors. Furthermore, Mn-MoS2 QDs revealed low toxicity to the mice via hematology and histological analysis.Conclusion: These results demonstrated the potential of AS1411-Mn-MoS2 QD as a novel nanoprobe for targeted MR imaging and fluorescence labelling of renal cell carcinoma.Keywords: manganese-doped molybdenum disulfide quantum dots, renal cell carcinoma, magnetic resonance imaging, cell fluorescence labelling

Yuanlong Xie,1,* Wenchao Sun,2,* Feifei Yan,1 Huowen Liu,1 Zhouming Deng,1 Lin Cai11Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, Wuhan City, Hubei Province, People’s Republic of China; 2Department of Pain Management, Wuhan Fourth Hospital, Wuhan City, Hubei Province, People’s Republic of China*These authors contributed equally to this workObjective: Icariin (IC) promotes osteogenic differentiation, and it may be a potential small molecule drug for local application in bone regeneration. Icariin-loaded hydroxyapatite/alginate (IC/HAA) porous composite scaffolds were designed in this study for the potential application of the sustainable release of icariin and subsequent bone regeneration.Methods: An icariin-loaded hydroxyapatite/alginate porous composite scaffold was prepared and characterized by SEM and HPLC for morphology and release behavior, respectively. The mechanical properties, degradation in PBS and cytotoxicity on BMSCs were also evaluated by MTT assay, compression strength and calculation of weight remaining ratio, respectively. Rabbit BMSCs were cocultured with IC/HAA scaffolds, and ALP activity and Alizarin Red staining were performed to evaluate osteogenic differentiation induction. The mRNA and protein expression level of an osteogenic gene was detected by RT-PCR and Western blotting, respectively. In vivo animal models of critical bone defects in the radius of rabbit were used. Four and 12 weeks after the implantation of IC/HAA scaffolds in the bone defect, radiographic images of the radius were obtained and scored by using the Lane and Sandhu X-ray scoring system. Tissue samples were also evaluated using H&E and Masson staining, and an osteogenic gene and Wnt signaling pathway genes were detected.Results: A hydroxyapatite/alginate (HAA) porous composite scaffold-loaded icariin was fabricated using a freeze-drying method. Our data indicated that the icariin was loaded in alginate scaffold without compromising the macro/microstructure or mechanical properties of the scaffold. Notably, the IC/HAA promoted the proliferation of rBMSCs without exerting cytotoxicity on rBMSCs. In vivo, rabbit radius bone defect experiments demonstrated that the IC/HAA scaffold exhibited better capacity for bone regeneration than HAA, and IC/HAA upregulated the relative expression levels of an osteogenic gene and the Wnt signaling pathway genes. Most notably, the IC/HAA scaffold also inhibited osteoclast activity in vivo.Conclusion: Our data suggests a promising application for the use of HAA scaffolds to load icariin and promote bone regeneration in situ through mediation of the coupling processes of osteogenesis induction and osteoclast activity inhibition.Keywords: icariin, bone regeneration, osteogenesis, osteoclastic activity, drug delivery

Muyu Wu,*,1,2 Pingfu Hou*,3, Lina Dong,1 Lulu Cai,1 Zhudian Chen,1 Mingming Zhao,1 Jingjing Li1–2,41School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, Jiangsu, People’s Republic of China; 2Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, Jiangsu, People’s Republic of China; 3Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221004, Jiangsu, People’s Republic of China; 4Institute of Medical Imaging and Digital Medicine, Xuzhou Medical University, Xuzhou 221004, Jiangsu, People’s Republic of China*These authors contributed equally to this workAbstract: Advancements in nanotechnology and molecular biology have promoted the development of a diverse range of models to intervene in various disorders (from diagnosis to treatment and even theranostics). Manganese dioxide nanosheets (MnO2 NSs), a typical two-dimensional (2D) transition metal oxide of nanomaterial that possesses unique structure and distinct properties have been employed in multiple disciplines in recent decades, especially in the field of biomedicine, including biocatalysis, fluorescence sensing, magnetic resonance imaging and cargo-loading functionality. A brief overview of the different synthetic methodologies for MnO2 NSs and their state-of-the-art biomedical applications is presented below, as well as the challenges and future perspectives of MnO2 NSs.Keywords: MnO2 nanosheets, synthetic methods, biocatalysis, fluorescence sensing, controlled drug delivery, stimuli-activated imaging