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Zhenkang Liang,* Zehong Chen,* Chaowei Zhang, Cui Chen, Wende Yang, Yuxuan Zhang, Hongbo Wei Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongbo Wei, Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road 600, Guangzhou, 510630, People’s Republic of China, Tel +86-020-85253000, Email weihb@mail.sysu.edu.cnPurpose: Erectile dysfunction (ED) frequently arises as a complication of pelvic surgeries, including rectal and prostate surgery, and has no definitive cure. This study explored whether mitochondria-rich microvesicles (MVs) can be used to treat ED stemming from cavernous nerve injury (CNI) and investigated its potential mechanisms.Methods: We isolated MVs and mitochondria (MT) from PC12. The apoptosis rate, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial derived reactive oxygen species (mtROS), iron content, malondialdehyde (MDA) content and endogenous antioxidant system activity of corpus cavernosum smooth muscle cells (CCSMCs) cultured with MVs and MT were detected in vitro. In vivo, twenty-four male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI group were injected with PBS, MVs and MT respectively. After fourteen days of treatment, the erectile function was measured and penile tissues were collected for histological analysis. Subsequently, inhibition of mitochondria in MV was performed to explore the mechanism of the rescue experiment.Results: The CCSMCs, PC12-MVs and PC12-MT were successfully isolated and identified. After MVs culture, apoptosis rate, ROS, mtROS, iron content and MDA content of CCSMCs were significantly decreased, while MMP and the activities of endogenous antioxidant system were increased. MVs transplantation can significantly restore erectile function and smooth muscle content in CNIED rats. The rescue experiment suggested that MVs exerted the above therapeutic effect by transferring mitochondria within it.Conclusion: MVs transplantation significantly improve erectile function in CNI ED rats. MVs may play a role in anti-OS and anti-ferroptosis at the transplant site through efficient transfer of mitochondria, providing a potential treatment vehicle for CNI ED.Keywords: cavernous nerve injury, erectile dysfunction, microvesicles, oxidative stress, ferroptosis

Rongrong Zhang,1,* Wenjun Xu,1,* Hongquan Wei,1,* Boshi Li,1 Yaoxing Wang,1 Xueqing He,1 Jun Cao,1 Xinyu He,1 Mingxiang Xu,1,2 Wenjie Lu,1 Youzhi Xu1 1College of Basic Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Center for Scientific Research, Anhui Medical University, Hefei, 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Youzhi Xu; Wenjie Lu, Email xuyouzhi@ahmu.edu.cn; wenjie63136@163.comPurpose: Currently, there is still no clear treatment for polycystic ovary syndrome (PCOS). YJKL has better therapeutic effects and lower toxic side effects for PCOS type infertility. This study aims to clarify the potential mechanism of YJKL Decoction in the treatment of PCOS based on network pharmacology and experiments verification.Patients and Methods: Network pharmacology and experimental validation approach were used to investigate the bioactive ingredients, critical targets and potential mechanisms of YJKL Decoction against PCOS. Firstly, we use network pharmacology methods to collect core targets, and then validate their effects on diseases through experiments.Results: Five core targets were screened, Threonine kinase 1 (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Albumin (ALB) and Vascular endothelial growthfactor A (VEGFA). KEGG analysis showed that YJKL treatment for PCOS mainly include AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway and HIF-1 signaling pathway. The molecular docking results showed that compounds have higher affinity with targets. Finally, experimental results had shown that YJKL Decoction had an better therapeutic effects in the treatment of PCOS.Conclusion: Based on a systematic network pharmacology approach and experimental verification, our results comprehensively illustrated the active ingredients, potential targets, and molecular mechanism of YJKL for application to PCOS and helps to illustrate mechanism of action on a comprehensive level.Keywords: traditional Chinese Medicine, YJKL, polycystic ovary syndrome, PCOS, molecular docking, experimental validation

Hongtao Liu, Xiao Huang, Hongji Wei, Yanchang Nong Clinical Medical School, Guangxi Health Science College, Nanning, People’s Republic of ChinaCorrespondence: Yanchang Nong, Clinical Medical School, Guangxi Health Science College, Nanning, People’s Republic of China, Email nongyanchang@live.cnBackground: Non-scarring hair loss (NSHL) is a global health concern with increasing prevalence due to lifestyle changes and an aging population. It can cause psychological distress and affect quality of life.Objective: This study aimed to identify the associations between NSHL and immune cell phenotypes using a two-sample Mendelian randomization (MR) analysis, offering insights for future immune-based therapies for NSHL.Methods: We obtained immunocyte data from the IEU Open GWAS Project and NSHL data from the same database and used MR analysis to evaluate the causal association between each immunophenotype and NSHL. Three statistical methods were employed: the MR-Egger regression, weighted median estimation, and inverse variance weighting (IVW).Results: The MR resonance imaging identified 31 immunocyte phenotypes associated with NSHL. Among these, 19 immunocyte phenotypes were negatively associated with NSHL, indicating their protective effects. The remaining 12 immunocyte phenotypes were positive association. Sensitivity analyses suggested the robustness of all MR findings.Conclusion: These findings highlight a clear correlation between NSHL and immunity, demonstrating the significant role of certain immune cell phenotypes. This study offers a new direction for immune-based therapies in the treatment of NSHL.Keywords: non-scarring hair loss, immune cell, Mendelian randomization, immunotherapy

Ying Zhang,&ast; Sainan Liu,&ast; Qi Miao, Xu Zhang, He Wei, Shuang Feng, Xiaofei Li The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofei Li, Transplantation and Hepatobiliary Department, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China, Tel +15940564748, Email lixiaofei0603@aliyun.comPurpose: Kidney transplant recipients (KTRs) may experience symptoms that increase their fear of progression (FoP), but a dearth of research examines the issue from a patient-centered perspective. Our study aimed to first determine the category of symptom burden, then to explore the differences in characteristics of patients in different subgroups, and finally to analyze the impact of symptom subgroup on FoP.Patients and Methods: Sociodemographic and Clinical Characteristics, Symptom Experience Scale, and Fear of Progression Questionnaire-Short Form were used. Latent class analysis was used to group KTRs according to the occurrence of symptoms. We used multivariate logistic regression to analyze the predictors of different subgroups. The differences in FoP among symptom burden subgroups were analyzed by hierarchical multiple regression.Results: Three subgroups were identified, designated all-high (20.5%), moderate (39.9%), and all-low (39.6%) according to their symptom occurrence. Multivariate logistic regression showed that gender, post-transplant time, per capita monthly income, and hyperuricemia were the factors that distinguished and predicted the all-high subgroup (P < 0.05). Hierarchical multiple regression showed that symptom burden had a significant effect on FoP (class1 vs class3: β = 0.327, P < 0.001; class2 vs class3: β = 0.104, P = 0.046), explaining the 8.0% variance of FoP (ΔR2 = 0.080).Conclusion: KTRs generally experience moderate or low symptom burden, and symptom burden is an influencing factor in FoP. Identifying the traits of KTRs with high symptom burden can help clinicians develop targeted management strategies and ease FoP of KTRs.Keywords: kidney transplant, symptom burden, fear of progression, latent class analysis

Zhen Yuan,1,2 Fan Zhang,3 Zhiguang Li,1,2 Hua Wei1,2 1School of Economics and Management, Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 2Key Laboratory of Data Science & Innovative Development of Traditional Chinese Medicine, Philosophy and Social Sciences of Anhui Province, Hefei, Anhui, People’s Republic of China; 3School of Finance, Nanjing Agricultural University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Zhiguang Li; Hua Wei, Email lizhiguang0731@163.com; weihua@ahtcm.edu.cnBackground: A linchpin to realizing the internal circulation (referring to the domestic cycle of production, distribution and consumption) is reducing residents’ saving rate and expanding the domestic needs. However, rural residents in China demonstrate a strong propensity to save money.Methods: In light of practical characteristics of urban-rural health integration promoted in different places, the three-phase data (from 2014 to 2018) and the dual difference-in-differences model of the China Labor-force Dynamics Survey (CLDS) are used to empirically investigate the impact of urban-rural health insurance integration on rural household savings.Results: Research reveals that urban-rural health integration can reduce the health risks and medical risks facing rural households, thus weakening the motivation of precautionary savings. The analysis of heterogeneity reveals that the integration of urban-rural health insurance significantly influences the savings rates of households headed by older individuals, particularly women, with lower levels of educational attainment. Besides, the single-tier health insurance system can have a more significant impact, whereas the multi-tier insurance system may not significantly affect the savings rate.Conclusion: Based on the aforesaid research conclusions, this article believes that in order to reduce the savings rate of rural households and expand consumption, the health insurance system should be further improved.Keywords: urban-rural health insurance integration, rural household, savings rate, health risks, medical risks

Huamei Wei,1,&ast; Xianjian Wu,2,&ast; Lizheng Huang,3,&ast; Chen Long,3 Qi Lu,3 Zheng Huang,3 Yanyan Huang,3 Wenchuan Li,2 Jian Pu2 1Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China; 3Graduate College of Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Pu, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Two Road, Baise, Guangxi, 533000, People’s Republic of China, Email Pujianym@163.comObjective: Tumor-associated macrophages play a crucial role in the development of hepatocellular carcinoma (HCC). Our study aimed to investigate the relationship between long coding RNA (lncRNA) maternally expressed gene 3 (MEG3), RNA-binding protein human antigen R (HuR), and messenger RNA C–C motif chemokine 5 (CCL5) in the modulation of M1 and M2 macrophage polarization in HCC.Methods: To induce M1 or M2 polarization, LPS/IFNγ- or IL4/IL13 were used to treat bone marrow derived macrophages (BMDMs). The localization of MEG3 in M1 and M2 macrophages was assessed using fluorescence in situ hybridization assay. Expression levels of MEG3, HuR, CCL5, M1, and M2 markers were measured by RT-qPCR or immunofluorescence staining. Flow cytometry was performed to determine the proportion of F4/80+CD206+ and F4/80+CD68+ cells. RNA pulldown assay was performed to detect the binding of lncRNA MEG3 and HuR. The impacts of HuR on CCL5 stability and activity of CCL5 promoter were evaluated using actinomycin D treatment and luciferase reporter assay. Cell migration, invasiveness, and angiogenesis were assessed using transwell migration and invasion assays and a tube formation assay. A mixture of Huh-7 cells and macrophages were injected into nude mice to explore the effect of MEG3 on tumorigenesis.Results: MEG3 promoted M1-like polarization while dampening M2-like polarization of BMDMs. MEG3 bound to HuR in M1 and M2 macrophages. HuR downregulated CCL5 by inhibiting CCL5 transcription in macrophages. In addition, overexpression of MEG3 suppressed cell metastasis, invasion, and angiogenesis by obstructing macrophage M2 polarization. MEG3 inhibited tumorigenesis in HCC via promotion of M1-like polarization and inhibition of M2-like polarization. Rescue experiments showed that depletion of CCL5 in M2 macrophages reversed MEG3-induced suppressive effect on cell migration, invasion, and tube formation.Conclusion: MEG3 suppresses HCC progression by promoting M1-like while inhibiting M2-like macrophage polarization via binding to HuR and thus upregulating CCL5.Keywords: hepatocellular carcinoma, maternally expressed gene 3, macrophage polarization, human antigen R, C-C motif chemokine 5

Haijun Wei,&ast; Ke Wang,&ast; Wei Huang, Yang Liu Department of Vascular Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Liu, Department of Vascular Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email zjobliu@163.comAbstract: Pyoderma gangrenosum (PG) is a rare autoinflammatory neutrophilic dermatosis clinically characterized by painful nodules, red papules or plaques that rapidly erode into ulcers. We report a 53-year-old febrile male patient with acute peripheral arterial disease who underwent transtibial amputation after failed thrombolysis. Five days after amputation, an ulcer developed around the cannulation site of the right internal jugular vein that was indicative of pathergy. The patient’s fever did not improve after surgery, and purpuric discoloration and punctate ulcers of the skin near the amputation site became apparent, leading to re-debridement. Finally, consultation with a dermatologist raised the possibility of postoperative PG, and additional laboratory tests revealed positive anticardiolipin autoantibodies consistent with antiphospholipid syndrome. The patient was treated with intravenous glucocorticosteroids and antibiotics, and the amputation wound and cannulation site ulcer were found to have healed at the 2-month follow-up. The current report raises the need for vascular surgeons to be aware of this uncommon etiology of arterial thrombosis, and the postoperative appearance of dermatosis and pathergy should alert for PG.Keywords: antiphospholipid syndrome, case report, peripheral artery disease, pyoderma gangrenosum

Li-Jen Cheng,1 Benfa Gong,2 Christopher H Young,3 Prabhuram Krishnan,1 Ying Wang,2 Hui Wei,2 Chunlin Zhou,2 Shuning Wei,2 Yan Li,2 Qiuyun Fang,2 Jia Zhong,4 Eric Q Wu,5 Yingchang Mi,2 Jianxiang Wang2 1Medical Affairs, Astellas Pharma Singapore Pte. Ltd., Singapore; 2Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People’s Republic of China; 3Advanced Informatics & Analytics, Astellas Pharma US Inc., Northbrook, IL, USA; 4Analysis Group, Inc., Beijing, People’s Republic of China; 5Analysis Group, Inc., Boston, MA, USACorrespondence: Jianxiang Wang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, People’s Republic of China, Tel +86 13821389157, Email wangjx@ihcams.ac.cnIntroduction: For acute myeloid leukemia (AML), prognosis is particularly poor in patients harboring FMS-like tyrosine kinase 3 (FLT3) gene mutations, though routine screening for these mutations at diagnosis has been shown to be insufficient. The understanding of the impact of FLT3 mutations on treatment decisions is limited.Methods: In this retrospective, observational study, we investigated the key epidemiological characteristics, treatment patterns and responses among adult patients with newly diagnosed (ND) AML in China, who initiated treatment from January 1, 2015, to December 31, 2019, or progressed to relapsed/refractory (R/R) AML by December 31, 2020.Results: Of the 853 ND AML patients included, 63.4% were screened for FLT3 status, and 20.1% tested positive (FLT3MUT) at initial diagnosis. Of 289 patients who progressed to R/R AML during the study period, 24.9% were screened at the diagnosis of R/R AML, and 19.4% tested positive; 20.5% of screened patients changed FLT3 status at first diagnosis of R/R AML. Initial treatment regimens or treatment responses did not seem to differ in patients with ND AML by FLT3 mutation status. In patients with R/R AML, there was an apparent difference in second-line treatment choices by FLT3 mutation status; however, the number of FLT3-mutated patients were limited to demonstrate any meaningful distinction. FLT3-mutated R/R AML was associated with shorter relapse time.Conclusion: Study findings showed that there was a lack of routine testing for FLT3 mutations at first diagnosis of R/R AML, and initial treatment decisions did not differ by FLT3 mutation status. Given the clinical burden of FLT3MUT, likelihood of FLT3 status changes, and emerging FLT3 inhibitors, further routine FLT3 screening is needed to optimize treatment of R/R AML. Keywords: acute myeloid leukemia, epidemiology, real-world, retrospective study

Jiaxin Zeng,1,&ast; Chen Zhou,2,&ast; Qun Yi,1,3 Yuanming Luo,4 Hailong Wei,5 Huiqing Ge,6 Huiguo Liu,7 Jianchu Zhang,8 Xianhua Li,9 Pinhua Pan,10 Mengqiu Yi,11 Lina Cheng,11 Liang Liu,12 Jiarui Zhang,1 Lige Peng,1 Jiaqi Pu,1 Haixia Zhou1 On behalf of the MAGNET AECOPD Registry Investigators1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Center of Infectious Diseases, Division of Infectious Diseases in State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3Sichuan Cancer Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Neijiang City, Neijiang, Sichuan Province, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 11Department of Emergency, First People’s Hospital of Jiujiang, Jiu jiang, Jiangxi Province, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cnBackground: The Rome severity classification is an objective assessment tool for the severity of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on readily measurable variables but has not been widely validated. The aim of this study is to evaluate the validity of the Rome classification in distinguishing the severity of AECOPD based on short-term mortality and other adverse outcomes.Methods: The Rome severity classification was applied to a large multicenter cohort of inpatients with AECOPD. Differences in clinical features, in-hospital and 60-day mortality, intensive care unit (ICU) admission, mechanical ventilation (MV) and invasive mechanical ventilation (IMV) usage were compared among the mild, moderate and severe AECOPD according to the Rome proposal. Moreover, univariate logistic analysis and Kaplan Meier survival analysis were also performed to find the association between the Rome severity classification and those adverse outcomes.Results: A total of 7712 patients hospitalized for AECOPD were included and classified into mild (41.88%), moderate (40.33%), or severe (17.79%) group according to the Rome proposal. The rate of ICU admission (6.4% vs 12.0% vs 14.9%, P < 0.001), MV (11.7% vs 33.7% vs 45.3%, P < 0.001) and IMV (1.4% vs 6.8% vs 8.9%, P < 0.001) increased significantly with the increase of severity classification from mild to moderate to severe AECOPD. The 60-day mortality was higher in the moderate or severe group than in the mild group (3.5% vs 1.9%, 4.3% vs 1.9%, respectively, P < 0.05) but showed no difference between the moderate and severe groups (2.6% vs 2.5%, P > 0.05), results for in-hospital mortality showed the same trends. Similar findings were observed by univariate logistic analysis and survival analysis.Conclusion: Rome severity classification demonstrated excellent performance in predicting ICU admission and the need for MV or IMV, but how it performs in differentiating short-term mortality still needs to be confirmed.Keywords: AECOPD, the Rome severity classification, short-term mortality, intensive care unit admission, mechanical ventilation, multicenter cohort

Objective: The objective of this systematic review is to analyse the randomised control trials (RCTs) comparing the self-gripping mesh (SGM) with sutured mesh fixation (SMF) in open inguinal hernia repair. Materials and methods: RCTs comparing SGM with SMF in open inguinal hernia repair were selected from medical electronic databases and analysis was performed using the principles of meta-analysis with RevMan version 5 statistical software. Results: Seventeen RCTs involving 3863 patients were used for the final analysis. In the random effect model analysis, the operative time [mean difference − 7.72, 95 %, CI (−9.08, −6.35), Z = 11.07, P = 0.00001] was shorter for open inguinal hernia repair with SGM. However, there was noteworthy heterogeneity (Tau2 = 4.24; Chi2 = 1795.04, df = 12; (P = 0.00001; I2 = 99 %) among the included studies. The incidence of chronic groin pain [odds ratio 1.17, 95 %, CI (0.88, 1.54), Z = 1.09, P = 0.28], postoperative complications [odds ratio 0.92, 95 %, CI (0.73, 1.16), Z = 0.71, P = 0.48] and recurrence [odds ratio 1.31, 95 %, CI (0.80, 2.12), Z = 1.08, P = 0.28] were statistically similar between both groups, without heterogeneity. Conclusion: SGM failed to demonstrate a clinical advantage over SMF in terms of perioperative outcomes although the duration of surgery was shorter in SGM.

Although it is true that women have received much attention since the mid-twentieth century and some have held major positions in public domains, not many theatrical works have given women a full spotlight on their less perceivable experiences, particularly those who are disadvantaged or struggling on the social margins. In those works that do indeed do so, descriptions of women’s conditions do not always reflect their exact experiences and challenges. This paper will explore Frank McGuiness’s Baglady (1985), which centres on a woman protagonist who discloses her painful memories and tries to cope with her suffering. In this play, the protagonist, stuck in the past, reveals her dark secrets in a narrative that is not always in a regular time sequence. Incidentally, by hearing how she makes sense of her troubles in everyday life, the audience seems to participate in the process of her self-examination and possible healing. This essay will also investigate how the character struggles with oppression in more radical ways, and how she fails or succeeds in breaking free from her hidden constraints.

Aijun Zheng,1 Fangfang Zheng,1 Kai Jin,1 Ming Chi,1 Jiajia Mu,1 Hongxia Wei,2 Jian Lei,2 Chao Xu3 1Department of Acupuncture and Moxibustion, Peking University Third Hospital Yanqing Hospital, Beijing, 102100, People’s Republic of China; 2Department of Traditional Chinese Medicine, Nancaiyuan Community Hospital, Beijing, 102100, People’s Republic of China; 3Department of Pharmacy, Peking University Third Hospital Yanqing Hospital, Beijing, 102100, People’s Republic of ChinaCorrespondence: Aijun Zheng, Email zaj1970@163.comObjective: Knee osteoarthritis (KOA) is a common chronic degenerative joint disease, and acupuncture is an alternative therapy for KOA. This study aims to detect the effectiveness of acupuncture at LI11 in improving pain and function for KOA patients.Methods: A total of 108 patients with KOA were randomly allocated to Control Group (local points), Treatment Group A (LI11), and Treatment Group B (local points and LI11) with a treatment phase of 4 weeks and a follow-up phase of 4 weeks. Primary outcome was response rate. Secondary outcomes included Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and recurrence rate. Study was registered on Chinese Clinical Trial Registry (Registered number: ChiCTR2000034926).Results: The response rate in Treatment Group A, Treatment Group B, and Control Group was 71.43%, 85.29%, and 51.53%, respectively, at Week 4, and Treatment Group B was significantly higher than Control Group (difference[98.3% CI]: 33.86[0.135,0.543], P = 0.003). Although no significant difference was found, Treatment Group A had a better response rate compared with Control Group (difference[98.3% CI]: 20.00 [− 0.072, 0.472], P = 0.086). For VAS and WOMAC, there were significant differences within 3 groups at Week 4 compared with the baseline. There was a significant improvement in VAS scores and WOMAC function and pain subscales at Week 4 in Treatment Group B compared with Control Group and Treatment Group A.Conclusion: LI11 is an effective point for patients with KOA, and it could be a selection for young acupuncturists and acupuncturists who work in rural areas; however, large-sample studies are necessary to further verify results in the future.Keywords: knee osteoarthritis, manual acupuncture, Quchi, LI11, pilot randomized controlled trial

Huamei Wei,1,&ast; Lizheng Huang,2,&ast; Qi Lu,2,&ast; Zheng Huang,2 Yanyan Huang,2 Zuoming Xu,3 Wenchuan Li,3 Jian Pu3,4 1Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 2Graduate College of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 3Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 4Guangxi Clinical Medical Research Center of Hepatobiliary Disease, Baise, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Pu, Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Two Road, Baise, 533000, People’s Republic of China, Email jian_pu@126.comPurpose: N6-methyladenosine (m6A) modification plays an important role in regulating RNA maturation, stability, and translation. Thus, m6A modification is involved in various pathophysiological processes including hepatocellular carcinoma (HCC). However, the direct contribution of m6A modifications to RNA function in HCC remains unclear. Here, we identified LEAWBIH (long non-coding RNA epigenetically activating Wnt/β-catenin signalling in HCC) as an m6A-modified long non-coding RNA (lncRNA) and investigated the effects of m6A on the function of LEAWBIH in HCC.Methods: Quantitative polymerase chain reaction was performed to measure the gene expression in tissues and cells. The level of m6A modification was detected using a methylated RNA immunoprecipitation assay and single-base elongation- and ligation-based qPCR amplification method. Cell proliferation was evaluated using the Glo cell viability and CCK-8 assays. Cell migration and invasion were evaluated using Transwell migration and invasion assays. The mechanisms of m6A modified LEAWBIH were investigated using chromatin isolation by RNA purification, chromatin immunoprecipitation, and dual-luciferase reporter assays.Results: LEAWBIH was highly expressed and correlated with poor survival in HCC patients. LEAWBIH was identified as a m6A-modified transcript. m6A modification increased LEAWBIH transcript stability. The m6A modification level of LEAWBIH was increased in HCC, and a high m6A modification level of LEAWBIH predicted poor survival. LEAWBIH promotes HCC cell proliferation, migration, and invasion in an m6A modification-dependent manner. Mechanistic investigations revealed that m6A-modified LEAWBIH activated Wnt/β-catenin signaling. m6A-modified LEAWBIH binds to the m6A reader YTHDC1, which further interacts with and recruits H3K9me2 demethylase KDM3B to CTNNB1 promoter, leading to H3K9me2 demethylation and CTNNB1 transcription activation. Functional rescue assays showed that blocking Wnt/β-catenin signaling abolished the role of LEAWBIH in HCC.Conclusion: m6A-modified LEAWBIH exerts oncogenic effects in HCC by epigenetically activating Wnt/β-catenin signaling, highlighting m6A-modified LEAWBIH as a promising therapeutic target for HCC.Keywords: hepatocellular carcinoma, N6-methyladenosine, histone methylation, Wnt/β-catenin signaling

Na Wang,1 Pei Li,1 Dandan Suo,1 Hongyan Wei,1 Huanhuan Wei,2 Run Guo,2 Wen Si2 1Department of Infectious Diseases, Tangdu Hospital, Air Force Medical University, Xi’an, People’s Republic of China; 2Department of General Practice Medicine, Tangdu Hospital, Air Force Medical University, Xi’an, People’s Republic of ChinaCorrespondence: Wen Si, Department of General Practice Medicine, Tangdu Hospital, Air Force Medical University, 569 Xinsi Road, Baqiao District, Xi’an, Shaanxi Province, People’s Republic of China, Tel +86 15829643781, Email 15829643781@163.comPurpose: This study aims to identify the novel risk predictors of low medication adherence of cirrhosis patients in a large cohort and construct an applicable predictive model to provide clinicians with a simple and precise personalized prediction tool.Patients and Methods: Patients with cirrhosis were recruited from the inpatient populations at the Department of Infectious Diseases of Tangdu Hospital. Patients who did not meet the inclusion criteria were excluded. The primary outcome was medication adherence, which was analyzed by the medication possession ratio (MPR). Potential predictive factors, including demographics, the severity of cirrhosis, knowledge of disease and medical treatment, social support, self-care agency and pill burdens, were collected by questionnaires. Predictive factors were selected by univariable and multivariable logistic regression analysis. Then, a nomogram was constructed. The decision curve analysis (DCA), clinical application curve analysis, ROC curve analysis, Brier score and mean squared error (MSE) score were utilized to assess the performance of the model. In addition, the bootstrapping method was used for internal validation.Results: Among the enrolled patients (460), most had good or moderate (344, 74.78%) medical adherence. The main risk factors for non-adherence include young age (≤ 50 years), low education level, low income, short duration of disease (< 10 years), low Child-Plush class, poor knowledge of disease and medical treatment, poor social support, low self-care agency and high pill burden. The nomogram comprised these factors showed good calibration and good discrimination (AUC = 0.938, 95% CI = 0.918– 0.956; Brier score = 0.14). In addition, the MSE value was 0.03, indicating no overfitting.Conclusion: This study identified predictive factors regarding low medication adherence among patients with cirrhosis, and a predictive nomogram was constructed. This model could help clinicians identify patients with a high risk of low medication adherence and intervention measures can be taken in time.Keywords: medication adherence, cirrhosis, nomogram, prediction model

Xiao-Yu Wang,1– 3,&ast; San-Hua Xu,3,&ast; Hong Wei,3,&ast; Min Kang,3 Jie Zou,3 Qian Ling,3 Hui Huang,3 Xu Chen,4 Yi-Xin Wang,5 Yi Shao,3 Yao Yu1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, Jiangxi, 330006, People’s Republic of China; 2The First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Branch of National Clinical Research Center for Ocular Disease, Nanchang, Jiangxi, 330006, People’s Republic of China; 4Department of Ophthalmology and Visual Sciences, Maastricht University, Maastricht, Limburg Province, 6200MA, Netherlands; 5School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF244HQ, UK&ast;These authors contributed equally to this workCorrespondence: Yi Shao, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email freebee99@163.com Yao Yu, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email yuyao1234562023@163.comPurpose: This study aimed to explore the spontaneous brain activity in patients with diabetic optic neuropathy (DON) by using the amplitude of low-frequency fluctuation (ALFF) technique.Methods: Sixteen DON patients and 16 age- and sex-matched healthy controls (HCs) were recruited. ALFF along with functional MRI method was used to detect the intrinsic brain activity alterations. The mean values of ALFF in DON patients and HCs were analyzed by receiver operating characteristic (ROC) curves. Pearson’s correlation analysis was used to determine the correlation between Hospital Anxiety and Depression Scale (HADS) and ALFF values of DONs.Results: The DON group showed significantly increased ALFF values in the fusiform gyrus, and decreased ALFF values in the medial frontal gyrus/left frontal superior orbit/right frontal medial orbit, and left frontal inferior triangle. ROC curve analysis indicated that the accuracy of AUC was good. The anxiety scale and depression scale of the DON group were negatively correlated with the ALFF values of the medial frontal gyrus.Conclusion: DON is a neurodegenerative disease involving multiple brain regions. The abnormal activity of neurons in these brain regions helps to reveal the underlying neural mechanisms of brain activity related to DON.Keywords: ALFF, fMRI, diabetic optic neuropathy, spontaneous brain activity

Keyu Ren,1 Chunming Yong,2 Yanting Wang,1 Hongyun Wei,1 Kun Zhao,1 Baoguo He,1 Mingjuan Cui,1 Yunqing Chen,3 Jin Wang4 1Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 2Department of Emergency, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 4Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, 266000, People’s Republic of ChinaCorrespondence: Jin Wang, Department of Pathology, School of Basic Medicine, Qingdao University, No. 308, Ningxia Road, Qingdao, Shandong, 266000, People’s Republic of China, Email jinsmile@126.comAim: The objective was to elucidate the correlation between CMVP and immunosuppressive therapy in IBD patients, we hope this review could expand on the significance of CMV as an opportunistic pathogen and the potential impact on morbidity and mortality in IBD patients.Methods: Records and clinical trajectories linked to CMVP in IBD patients were extracted from the PubMed database, irrespective of language barriers. The reference lists incorporated in these studies were manually inspected. Conclusions were generated using straightforward descriptive analysis.Results: In total, 18 IBD patients, including Crohn’s disease (CD, 67%) and Ulcerative Colitis (UC, 33%), affected by CMVP were identified from 17 published articles. A minority of these patients (17%) exhibited active disease, whereas the majority (83%) presented with quiescent disease. Fever (100%) and dyspnea (44%) emerged as the most prevalent clinical symptoms. All the patients had undergone immunosuppressive therapy. A significant proportion, up to 89%, had received thiopurine treatment prior to the CMVP diagnosis. Interestingly, none of the patients were subjected to biological therapy. Half of the patients manifested with Hemophagocytic Lymphohistiocytosis (HLH). Almost all patients (94%) were administered antiviral treatment and a substantial 83% experienced full recovery. Immunosuppressive agents were either tapered or discontinued altogether. A subset of patients, 17%, suffered fatal outcomes.Conclusion: Our findings underscore the need for heightened suspicion of CMVP in IBD patients who exhibit symptoms such as fever and dyspnea. During the COVID-19 pandemic, CMVP should be considered a potential differential diagnosis. It was observed that CMVP primarily transpires during CD remission. Azathioprine emerged as the predominant immunosuppressant linked to CMV reactivation. The prompt application of effective antiviral therapy can substantially enhance patient outcomes. CMV vaccine might serve as a viable prevention strategy.Keywords: CMV, cytomegalovirus pneumonia, inflammatory bowel disease, ulcerative colitis, Crohn’s disease

Chuan Tan,1,&ast; Yanyan Huang,2,&ast; Zheng Huang,2,&ast; Yuanjia Ning,2 Lizheng Huang,2 Xianjian Wu,1 Yuan Lu,1 Huamei Wei,3 Jian Pu1 1Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 2Graduate College of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Pu, Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Two Road, Baise, Guangxi, People’s Republic of China, Email jian_pu@126.comPurpose: N6-methyladenosine (m6A) modification has shown critical roles in regulating mRNA fate. Non-coding RNAs also have important roles in various diseases, including hepatocellular carcinoma (HCC). However, the potential influences of m6A modification on non-coding RNAs are still unclear. In this study, we identified a novel m6A-modified ATP8B1-AS1 and aimed to investigate the effects of m6A on the expression and role of ATP8B1-AS1 in HCC.Methods: qPCR was performed to measure the expression of related genes. The correlation between gene expression and prognosis was analyzed using public database. m6A modification level was measured using MeRIP and single-base elongation- and ligation-based qPCR amplification method. The roles of ATP8B1-AS1 in HCC were investigated using in vitro and in vivo functional assays. The mechanisms underlying the roles of ATP8B1-AS1 were investigated by ChIRP and ChIP assays.Results: ATP8B1-AS1 is highly expressed in HCC tissues and cell lines. High expression of ATP8B1-AS1 is correlated with poor overall survival of HCC patients. ATP8B1-AS1 is m6A modified and the 792 site of ATP8B1-AS1 is identified as an m6A modification site. m6A modification increases the stability of ATP8B1-AS1 transcript. m6A modification level of ATP8B1-AS1 is increased in HCC tissues and cell lines, and correlated with poor overall survival of HCC patients. ATP8B1-AS1 promotes HCC cell proliferation, migration, and invasion, which were abolished by the mutation of m6A-modified 792 site. Mechanistic investigation revealed that m6A-modified ATP8B1-AS1 interacts with and recruits m6A reader YTHDC1 and histone demethylase KDM3B to MYC promoter region, leading to the reduction of H3K9me2 level at MYC promoter region and activation of MYC transcription. Functional rescue assays showed that depletion of MYC largely abolished the oncogenic roles of ATP8B1-AS1.Conclusion: m6A modification level of ATP8B1-AS1 is increased and correlated with poor prognosis in HCC. m6A-modified ATP8B1-AS1 exerts oncogenic roles in HCC via epigenetically activating MYC expression.Keywords: hepatocellular carcinoma, N6-methyladenosine, noncoding RNA, histone methylation, MYC signaling

Jiarui Zhang,1,&ast; Yichun Qin,2,&ast; Chen Zhou,3 Yuanming Luo,4 Hailong Wei,5 Huiqing Ge,6 Hui-Guo Liu,7 Jianchu Zhang,8 Xianhua Li,9 Pinhua Pan,10 Mengqiu Yi,11 Lina Cheng,11 Liang Liu,12 Adila Aili,1 Lige Peng,1 Yu Liu,1 Jiaqi Pu,1 Qun Yi,1,13,&ast; Haixia Zhou1,&ast; 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Neijiang City, Neijiang, Sichuan Province, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 11Department of Emergency, First People’s Hospital of Jiujiang, Jiujiang, Jiangxi Province, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, Sichuan Province, People’s Republic of China; 13Sichuan Cancer Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou; Qun Yi, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cn; yiqun925@126.comBackground: High blood urea nitrogen (BUN) is observed in a subset of patients with acute exacerbation of COPD (AECOPD) and may be linked to clinical outcome, but findings from previous studies have been inconsistent.Methods: We performed a retrospective analysis of patients prospectively enrolled in the MAGNET AECOPD Registry study (ChiCTR2100044625). Receiver operating characteristic (ROC) was used to determine the level of BUN that discriminated survivors and non-survivors. Univariate and multivariate Cox proportional hazards regression analyses were performed to assess the impact of BUN on adverse outcomes.Results: Overall, 13,431 consecutive inpatients with AECOPD were included in this study, of whom 173 died, with the mortality of 1.29%. The non-survivors had higher levels of BUN compared with the survivors [9.5 (6.8– 15.3) vs 5.6 (4.3– 7.5) mmol/L, P < 0.001]. ROC curve analysis showed that the optimal cutoff of BUN level was 7.30 mmol/L for in-hospital mortality (AUC: 0.782; 95% CI: 0.748– 0.816; P < 0.001). After multivariate analysis, BUN level ≥ 7.3 mmol/L was an independent risk factor for in-hospital mortality (HR = 2.099; 95% CI: 1.378– 3.197, P = 0.001), also for invasive mechanical ventilation (HR = 1.540; 95% CI: 1.199– 1.977, P = 0.001) and intensive care unit admission (HR = 1.344; 95% CI: 1.117– 1.617, P = 0.002). Other independent prognostic factors for in-hospital mortality including age, renal dysfunction, heart failure, diastolic blood pressure, pulse rate, PaCO2 and D-dimer.Conclusion: BUN is an independent risk factor for in-hospital mortality in inpatients with AECOPD and may be used to identify serious (or severe) patients and guide the management of AECOPD.Clinical Trial Registration: MAGNET AECOPD; Chinese Clinical Trail Registry NO.: ChiCTR2100044625; Registered March 2021, URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.Keywords: AECOPD, inpatients, blood urea nitrogen, mortality, adverse outcomes

Qing Wei,1,&ast; Guoman Liu,1,&ast; Zihua Huang,1,&ast; Yanyan Huang,1 Lizheng Huang,1 Zheng Huang,1 Xianjian Wu,2 Huamei Wei,3 Jian Pu2 1Graduate College of Youjiang Medical University for Nationalities, Baise, Guangxi, 533099, People’s Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Pu, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan two Road, Baise, Guangxi, 533000, People’s Republic of China, Tel +86 776-2836646, Email Pujianym@163.comBackground: Hepatocellular carcinoma (HCC) is the predominant histological type of primary liver cancer, which ranks sixth among the most common human tumors. Tumor-associated macrophages (TAMs) are an important component of tumor microenvironment (TME) and the M2 macrophage polarization substantially contributes to tumor growth and metastasis. Long non-coding RNA (lncRNA) MEG3 was reported to restrain HCC development. However, whether MEG3 regulates macrophage phenotypic polarization in HCC remains unclear.Methods: Bone marrow derived macrophages (BMDMs) were treated with LPS/IFNγ and IL4/IL13 to induce the M1 and M2 macrophage polarization, respectively. M2-polarized BMDMs were simultaneously transfected with adenovirus vector overexpressing MEG3 (Adv-MEG3). Subsequently, M2-polarized BMDMs were cultured for 24 h with serum-free medium, the supernatants of which were harvested as conditioned medium (CM). HCC cell line Huh7 was cultured with CM for 24 h. F4/80+CD68+ and F4/80+CD206+ cell percentages in M1-and M2-polarized BMDMs were calculated using flow cytometry. Huh7 cell migration, invasion and angiogenesis were determined via Transwell assay and tube formation experiment. Nude mice were implanted with Huh7 cells and Adv-MEG3-transfected M2-polarizd BMDMs, and tumor growth and M2 macrophage polarization markers were assessed. The binding between miR-145-5p and MEG3 or disabled-2 (DAB2) was verified by luciferase reporter assay.Results: MEG3 presented lower expression in HCC tissues than in normal controls, and low expression of MEG3 was correlated to poorer prognosis of HCC patients. MEG3 expression was enhanced during LPS/IFNγ-induced M1 polarization, but was reduced during IL4/IL13-induced M2 polarization. MEG3 overexpression inhibited the expression of M2 polarization markers in both M2-polarized BMDMs and mice. Mechanically, MEG3 bound with miR-145-5p to regulate DAB2 expression. Overexpressing MEG3 suppressed M2 polarization-induced HCC cell metastasis and angiogenesis by upregulating DAB2 and inhibited in vivo tumor growth.Conclusion: LncRNA MEG3 curbs HCC development by repressing M2 macrophage polarization via miR-145-5p/DAB2 axis.Keywords: hepatocellular carcinoma, tumor microenvironment, macrophage polarization, MEG3, miR-145-5p, DAB2, metastasis

Xiaomin Ren,1 Dingqun Bai,2 Yuan Zhang,3 Haidan Lin,2 Shu Zhang,2 Danyang Li,1 Hui Wei,1 Shouwei Yue1 1Rehabilitation Center, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Department of Physical Medicine & Rehabilitation, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Shouwei Yue; Hui Wei, Rehabilitation Center, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China, Tel +18560086655 ; +18560083563, Fax +531 82166115, Email shouweiy@sdu.edu.cn; 83926275@qq.comBackground and Purpose: Epidemiological studies on low back pain in residents living in mountainous areas are scarce. The study was aimed at investigating the prevalence and associated factors of low back pain in Chongqing, relatively impoverished mountainous areas of China.Materials and Methods: This was a cross-sectional study conducted at selected community or village health service centers in Chongqing over a 2-month period (May 2021 to June 2021), which included adults of Chongqing aged > 18 years with or without low back pain (N=1820) chosen by stratified, cluster-sampling. Associated factors of low back pain including sociodemographic characteristics, lifestyle, and occupational features were collected, along with medical history, Oswestry Disability Questionnaire (ODI), and Numerical Rating Scale (NRS) of patients with low back pain, and carried out for at least 20 minutes per respondent. Univariate and multivariate logistic regression models were utilized for statistical analysis.Results: Overall, 30.5% of 1704 respondents presented with low back pain, with 26.3% living in flat areas and 35.6% in mountainous areas. The associated factors of low back pain were mountainous area residence (OR 1.4, 95% CI 1.1– 1.8), advanced age (OR 1.8, 95% CI 1.3– 2.5 for those aged 45– 59 years, OR 2.3, 95% CI 1.6– 3.4 for those aged 60– 74 years, and OR 2.1, 95% CI 1.2– 3.6 for those aged ≥ 75 years), married or remarried (OR 1.9, 95% CI 1.1– 3.2), divorced or widowed (OR 2.7, 95% CI 14– 5.4), moderate labor intensity (OR 1.4, 95% CI 1.1– 1.8), frequent stoop (OR 1.6, 95% CI 1.1– 2.4), and depressed mood (OR 1.6, 95% CI 1.2– 2.1). Residents in the mountainous areas had a higher score on Oswestry Disability Questionnaire (8.3 [SD 6.3] vs 6.2 [SD 4.3]) than those in flat areas.Conclusion: Mountainous areas in Chongqing had higher prevalence of low back pain as 35.6%, compared with 26.3% in flat areas, with more severe dysfunction in low back pain patients. Multifactorial analysis found that the factors associated with low back pain in Chongqing residents included mountain residence, labor intensity, stoop, psychological factors and frequency of exercise.Keywords: low back pain, prevalence, associated factors, China

Yichuan Ding,1– 3,&ast; Sihui Tang,1,2,4,&ast; Zihan Zhou,1– 3 Hui Wei,1– 3 Wanchun Yang1– 3 1Department of Respiratory and Critical Care Medicine, the Second People’s Hospital of Hefei, Hefei, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Hefei Hospital Affiliated to Anhui Medical University, Hefei, People’s Republic of China; 3The Fifth Clinical College of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, the Second People’s Hospital of Hefei Affiliated to Bengbu Medical University, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wanchun Yang, Department of Respiratory and Critical Care Medicine, the Second People’s Hospital of Hefei, Hefei, Anhui, 230011, People’s Republic of China, Tel +8662965684, Fax +8662965684, Email 1225399339@qq.comPurpose: To investigate the potential of plasma microRNA-150-5p (miR-150-5p) as a biomarker for chronic obstructive pulmonary disease (COPD) and its relationship with clinical indicators such as pulmonary function.Patients and Methods: Fifty-nine patients with COPD and twenty-six healthy control individuals were recruited in the Second People’s Hospital of Hefei from September 2021 to September 2022. The plasma expression level of miR-150-5p was measured by quantitative real-time polymerase chain reaction.Results: The miR-150-5p level in the COPD group was significantly lower than that in the control group, and the relative expression was lower in patients with severe airflow limitation than those with mild limitation. Plasma miR-150-5p levels were positively correlated with pulmonary function indicators and negatively correlated with the white blood cell count and C-reactive protein level. The receiver operating characteristic curve suggested that plasma miR-150-5p had predictive value for COPD (area under curve = 0.819, sensitivity 64.4%, specificity 92.3%).Conclusion: MiR-150-5p can be useful for the diagnosis and disease assessment of COPD, and has value as a biomarker for COPD.Keywords: chronic obstructive pulmonary disease, miR-150-5p, biomarker, miRNA

Jiaqi Pu,1,&ast; Qun Yi,1,2,&ast; Yuanming Luo,3 Hailong Wei,4 Huiqing Ge,5 Huiguo Liu,6 Xianhua Li,7 Jianchu Zhang,8 Pinhua Pan,9 Hui Zhou,10 Chen Zhou,11 Mengqiu Yi,12 Lina Cheng,12 Liang Liu,10 Jiarui Zhang,1 Lige Peng,1 Adila Aili,1 Yu Liu,1 Haixia Zhou1 On behalf of the MAGNET AECOPD Registry Investigators1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, Cancer Hospital Affiliate to School of Medicine, UESTC, Chengdu, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, the First People’s Hospital of Neijiang City, Neijiang, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, People’s Republic of China; 11West China School of Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 12Department of Emergency, First People’s Hospital of Jiujiang, Jiu Jiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cnPurpose: The prognostic value of blood eosinophils in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains controversial. This study aimed to evaluate whether blood eosinophils could predict in-hospital mortality and other adverse outcomes in inpatients with AECOPD.Methods: The patients hospitalized for AECOPD were prospectively enrolled from ten medical centers in China. Peripheral blood eosinophils were detected on admission, and the patients were divided into eosinophilic and non-eosinophilic groups with 2% as the cutoff value. The primary outcome was all-cause in-hospital mortality.Results: A total of 12,831 AECOPD inpatients were included. The non-eosinophilic group was associated with higher in-hospital mortality than the eosinophilic group in the overall cohort (1.8% vs 0.7%, P < 0.001), the subgroup with pneumonia (2.3% vs 0.9%, P = 0.016) or with respiratory failure (2.2% vs 1.1%, P = 0.009), but not in the subgroup with ICU admission (8.4% vs 4.5%, P = 0.080). The lack of association still remained even after adjusting for confounding factors in subgroup with ICU admission. Being consistent across the overall cohort and all subgroups, non-eosinophilic AECOPD was also related to greater rates of invasive mechanical ventilation (4.3% vs 1.3%, P < 0.001), ICU admission (8.9% vs 4.2%, P < 0.001), and, unexpectedly, systemic corticosteroid usage (45.3% vs 31.7%, P < 0.001). Non-eosinophilic AECOPD was associated with longer hospital stay in the overall cohort and subgroup with respiratory failure (both P < 0.001) but not in those with pneumonia (P = 0.341) or ICU admission (P = 0.934).Conclusion: Peripheral blood eosinophils on admission may be used as an effective biomarker to predict in-hospital mortality in most AECOPD inpatients, but not in patients admitted into ICU. Eosinophil-guided corticosteroid therapy should be further studied to better guide the administration of corticosteroids in clinical practice.Keywords: acute exacerbation of chronic obstructive pulmonary disease, peripheral blood eosinophils, inpatients, in-hospital mortality, clinical outcomes

Yifan Su,1 Mingxue Qi,1 Mingli Zhong,2 Nawei Yu,1 Chen Chen,1 Zi Ye,1 Cong Cheng,1 Zhiliang Hu,1 Hongying Zhang,3 Hongxia Wei1 1Department of Infectious Disease, The Second Hospital of Nanjing Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 3Nanjing Center for Disease Control and Prevention Affiliated with Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Hongxia Wei, Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, People’s Republic of China, Email wghongxia@sina.com Hongying Zhang, Email xiao99now@aliyun.comBackground: Transmitted drug resistance (TDR) is a major challenge in the clinical management of acquired immunodeficiency syndrome (AIDS). Therefore, this study aimed to investigate the epidemic characteristics of and risk factors for human immunodeficiency virus (HIV)-1 TDR in Nanjing from 2018 to 2021 to provide support for clinical management.Methods: The HIV-1 Pol gene was amplified by nested reverse transcription polymerase chain reaction from venous blood of 1190 HIV-infected patients who did not receive antiviral therapy, and the amplified product was sequenced using an in-house sequencing method. The sequencing result was compared with the HIV drug resistance database from Stanford University to elucidate the rates of antiviral drug resistance and distribution of drug-resistant mutation sites. Factors associated with TDR were evaluated using a logistic regression model.Results: Detection of drug resistance at the gene level was successful in 1138 of 1190 HIV-1-infected patients (95.6%), and the overall 4-year drug resistance rate was 8.2% (93/1138). The drug resistance rate was higher for non-nucleoside reverse transcriptase inhibitors (NNRTIs; 6.7%) than for nucleoside reverse transcriptase inhibitors (NRTIs; 2.5%) or protease inhibitors (PIs; 0.1%) (χ2 = 83.907, P< 0.0001). The most common NNRTI-related mutation was V179D/E followed by K103N. M184V was the dominant NRTI-associated mutation, and M46L/I was the most prevalent PI-associated mutation. A CD4+ T cell count of < 50 cells/μL was significantly associated with an increased risk of TDR (OR=3.62, 95% CI: 1.38– 9.51, P=0.009).Conclusion: The prevalence of TDR in the city of Nanjing from 2018 to 2021 was at a moderate epidemic risk according to World Health Organization standards. Continuous monitoring of TDR can inform clinical diagnosis and treatment. Patients with advanced disease and a low CD4+ T lymphocyte count are more likely to have TDR in Nanjing.Keywords: HIV-1, transmitted drug resistance, mutation sites

Dong Liu,1,&ast; Huanhuan Wei,2,&ast; Jinyu Huang,1 Hailin Shen,3 Ximing Wang,1 Chunhong Hu1 1Radiological Department, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Academy of Medical Sciences, the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Radiology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhong Hu, Email 239847878@qq.comBackground: Endometriosis developing in a cesarean section (CS) scar is an unusual event. Malignant transformation arising on the background of scar endometriosis in the abdominal wall is extremely rare. Herein we report a case of clear cell carcinoma (CCC) arising in the abdominal wall from endometriosis tissues following CS and review previous literature.Case Presentation: A 48-year-old gravida 2 para 1 female presented with an abdominal wall mass at her CS scar, which increased in size and became painful in the last 2 years. Physical examination showed a multilocular solid mass of about 13 cm, at the previous CS scar. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a 12.8cm × 7.7cm multi-septate cystic lesion on the anterior abdominal wall, and histological examination showed that CCC was caused by the transformation of abdominal wall endometriosis (AWE).Conclusion: An endometriosis-associated malignancy should be considered in the differential with any enlarging mass in the abdominal wall scar.Keywords: cesarean section, abdominal wall endometriosis, case report

Rui Song,1,2,&ast; Hanghang Ni,1,&ast; Juntao Huang,1,&ast; Chenglei Yang,1 Shangdong Qin,1,3 Huaning Wei,1 Jiefu Luo,1 Yuxiang Huang,1 Bangde Xiang1– 3 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China; 3Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangde Xiang, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-7715301253, Email xiangbangde@gxmu.edu.cnPurpose: The study aimed to investigate the ability of inflammation-immunity-nutrition score (IINS) and inflammatory burden index (IBI), individually or in combination, to predict prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy.Methods: A total of 701 patients who underwent HCC resection at Guangxi Medical University Cancer Hospital were enrolled in the study. An IINS ranging from 0 to 3 was defined based on preoperative C-reactive protein (CRP), lymphocyte count, and serum albumin level, while an IBI was based on CRP and neutrophil-to-lymphocyte ratio. The prognostic value of IINS and IBI was assessed using univariate and multivariate Cox regression and Kaplan–Meier survival curves. The concordance index and calibration curve were used for internal validation of models. Decision curve analysis, net reclassification index and integrated discrimination improvement were used to compare the predictive performance of the models with traditional staging systems.Results: IINS and IBI were able to predict poor prognosis in HCC patients after hepatectomy, and a nomogram based on the IINS predicted survival at 1, 3, and 5 years better than other models or traditional staging systems.Conclusion: IINS may be accurate predictors of survival in HCC patients after hepatectomy, with potentially greater prognostic value than conventional markers.Keywords: hepatocellular carcinoma, inflammation-immunity-nutrition score, inflammatory burden index, prognosis, hepatectomy

Chen Zhou,1,&ast; Yujie Guang,1,&ast; Yuanming Luo,2 Huiqing Ge,3 Hailong Wei,4 Huiguo Liu,5 Jianchu Zhang,6 Pinhua Pan,7 Jiarui Zhang,8 Lige Peng,8 Adila Aili,8 Yu Liu,8 Jiaqi Pu,8 Xia Zhong,1 Yixi Wang,1 Qun Yi,8,9 Haixia Zhou8 On behalf of the MAGNET AECOPD Registry Investigators1West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 9Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, Cancer Hospital Affiliate to School of Medicine, UESTC, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel +86-28-85422571, Fax +86-28-85422571, Email zhouhaixia@wchscu.cnBackground: The optimal tool for risk prediction of venous thromboembolism (VTE) in inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is still unknown. This study aimed to evaluate whether D-dimer could predict the risk of VTE in inpatients with AECOPD compared to the Padua Prediction Score (PPS).Methods: Inpatients with AECOPD were prospectively enrolled from seven medical centers in China between December 2018 and June 2020. On admission, D-dimer was detected, PPS was calculated for each patient, and the incidence of 2-month VTE was investigated. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of D-dimer and PPS on VTE development, and the best cut-off value for both methods was evaluated through the Youden index.Results: Among the 4468 eligible patients with AECOPD, 90 patients (2.01%) developed VTE within 2 months after admission. The area under the receiver operating characteristic curves (AUCs) of D-dimer for predicting VTE were significantly higher than those of the PPS both in the overall cohort (0.724, 95% CI 0.672– 0.776 vs 0.620, 95% CI 0.562– 0.679; P< 0.05) and the subgroup of patients without thromboprophylaxis (0.747, 95% CI 0.695– 0.799 vs 0.640, 95% CI 0.582– 0.698; P< 0.05). By calculating the Youden Index, the best cut-off value of D-dimer was determined to be 0.96 mg/L with an AUC of 0.689, which was also significantly better than that of the PPS with the best cut-off value of 2 (AUC 0.581, P=0.007). After the combination of D-dimer with PPS, the AUC (0.621) failed to surpass D-dimer alone (P=0.104).Conclusion: D-dimer has a superior predictive value for VTE over PPS in inpatients with AECOPD, which might be a better choice to guide thromboprophylaxis in inpatients with AECOPD due to its effectiveness and convenience.Clinical Trial Registration: Chinese Clinical Trail Registry NO. ChiCTR2100044625; URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.Keywords: acute exacerbation of chronic obstructive pulmonary disease, inpatients, D-dimer, Padua Prediction Score, venous thromboembolism

Hong Wei,1 Dandan Liu,1,2 Leiyu Geng,1 Yun Liu,1 Huiqin Wang,1 Fuling Yan1 1Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Neurology, The People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Zhenjiang, People’s Republic of ChinaCorrespondence: Fuling Yan, Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Dingjiaqiao 87, Nanjing, 210009, People’s Republic of China, Email yanfuling218@163.comBackground and Study Aims: Elderly epilepsy is the third most common chronic disease that affects metabolism either alone or through antiepileptic drugs (AEDs). Here, we focus on whether neurocognitive profiles in elderly epilepsy and its treatment are linked to metabolic conditions.Patients and Methods: Elderly patients with epilepsy without cognitive impairment (n = 78) and with cognitive impairment (n = 75) were enrolled. C-reactive protein (CRP) and metabolic markers (triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), albumin, fasting glucose (Glu) and glycosylated hemoglobin (HbA1c)) were measured. Serum markers were modeled using logistic regression analysis.Results: TG, TC, fasting glucose, HbA1c and CRP were significantly increased (p < 0.05, 0.05, 0.001, 0.001, 0.01, respectively) in elderly epilepsy, whereas HDL-c, LDL-c and serum albumin were decreased (p < 0.001, 0.001, 0.001) in elderly epilepsy. TG, TC, fasting Glu, HbA1c and CRP were significantly elevated (p < 0.05, 0.001, 0.001, 0.001, 0.001, respectively) in epilepsy with cognitive impairment, whereas HDL-c, LDL-c and serum albumin were decreased (p < 0.001, 0.001, 0.001). The abnormal glycolipid profile was predominated in AED-treated patients. The regression model combined with TG, LDL-c, HDL-c and albumin performed better (area under the ROC curve was 0.824) in AED-treated patients.Conclusion: The relevant relationship between glycolipid profile and cognitive impairment with epilepsy was described, and the logistic regression model based on serum TG, LDL-c, HDL-c and albumin is reported and may serve as promising diagnostic markers for elderly epilepsy with cognitive impairment. Additionally, a specific emphasis on the complex role of altered lipid metabolism and AEDs is made.Keywords: elderly epilepsy, glycolipid metabolic, logistic regression, AED

Hongxiang Wei,1,&ast; Fei Chen,1,&ast; Jinyuan Chen,2,&ast; Huangfeng Lin,1 Shenglin Wang,1 Yunqing Wang,1 Chaoyang Wu,1 Jianhua Lin,1 Guangxian Zhong1 1Department of Orthopaedics, Fujian Institute of Orthopaedics, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2The Centralab, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangxian Zhong; Jianhua Lin, Tel/Fax +86 591 87981029, Email zhongguangxian@163.com; jianhual@126.comPurpose: The objective of this study was to investigate the antitumor activity, targeting capability, and mechanism of the developed nanodrug consisting of doxorubicin and exosome (Exo-Dox) derived from mesenchymal stem cells in vitro and in vivo.Methods: The exosomes were isolated with Exosome Isolation Kit, and the Exo-Dox was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The exosome and Exo-Dox were examined by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). The antitumor activity, targeting capability, and mechanism of the developed Exo-Dox were evaluated by cell viability assay, histological and immunofluorescence analysis and in vivo imaging system.Results: NTA results showed the size of the exosomes had increased from 141.6 nm to 178.1 nm after loading with doxorubicin. Compared with free Dox, the Exo-Dox exhibited higher cytotoxicity against osteosarcoma MG63 cells, HOS cells, and 143B cells than free Dox, the half-maximal inhibitory concentrations (IC50) of Dox, Exo-Dox were calculated to be 0.178 and 0.078 μg mL− 1 in MG63 cells, 0.294 and 0.109μg mL− 1 in HOS cells, 0.315 and 0.123 μg mL− 1 in 143B cells, respectively. The in vivo imaging showed that MSC derived Exo could serve as a highly efficient delivery vehicle for targeted drug delivery. The immunohistochemistry and histology analysis indicated that compared with the free Dox group, the Ki67-positive cells and cardiotoxicity in Exo-Dox group were significantly decreased.Conclusion: Our results suggested that MSC-derived Exo could be excellent nanocarriers used to deliver chemotherapeutic drug Dox specifically and efficiently in osteosarcoma, resulting in enhanced toxicity against osteosarcoma and less toxicity in heart tissue. We further demonstrated the targeting capability of Exo was due to the chemotaxis of MSC-derived exosomes to osteosarcoma cells via SDF1-CXCR4 axis.Keywords: targeted therapy, exosome, doxorubicin, osteosarcoma, nanocarrier

Qiang Cai,1,&ast; Guoqing Liu,2,&ast; Linsheng Huang,3,&ast; Yuting Guan,2,&ast; Huixia Wei,4 Zhiqian Dou,5 Dexi Liu,6 Yang Hu,1 Meiling Gao4 1Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, People’s Republic of China; 2Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Department of Hepatobiliary Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 4Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 5Department of Obstetrics, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 6Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meiling Gao, Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China, Tel +86-15971849819, Email mlgdoctor@163.com Yang Hu, Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441000, People’s Republic of China, Tel +86-13995744850, Email huyang1983919@163.comAbstract: Dexmedetomidine, a specific α 2 adrenergic receptor agonist, is highly frequently used in the perioperatively for its favorable pharmacology, such as mitigating postoperative cognitive dysfunction. Increasing attention has been recently focused on the effect of whether dexmedetomidine influences cancer recurrence, which urges the discussion of the role of dexmedetomidine in tumor-progressive factors. The pharmacologic characteristics of dexmedetomidine, the tumor-progressive factors in the perioperative period, and the relationships between dexmedetomidine and tumor-progressive factors were described in this review. Available evidence suggests that dexmedetomidine could reduce the degree of immune function suppression, such as keeping the number of CD3+ cells, NK cells, CD4+/CD8+ ratio, and Th1/Th2 ratio stable and decreasing the level of proinflammatory cytokine (interleukin 6 and tumor necrosis factor-alpha) during cancer operations. However, dexmedetomidine exhibits different roles in cell biological behavior depending on cancer cell types. The conclusions on whether dexmedetomidine would influence cancer recurrence could not be currently drawn for the lack of strong clinical evidence. Therefore, this is still a new area that needs further exploration.Keywords: dexmedetomidine, cancer recurrence, surgery, immune, inflammation

Ruoyao Xu,1 Jie Wang,1 Huimin Nie,1 Danyi Zeng,1 Chengyu Yin,1 Yuanyuan Li,1 Huina Wei,1 Boyu Liu,1 Yan Tai,2 Qimiao Hu,1 Xiaomei Shao,1 Jianqiao Fang,1 Boyi Liu1 1Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, 310053, People’s Republic of China; 2Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of ChinaCorrespondence: Boyi Liu; Jianqiao Fang, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, 310053, People’s Republic of China, Email boyi.liu@foxmail.com; fangjianqiao7532@163.comBackground: Chronic postsurgical pain (CPSP) is common among patients receiving major surgeries. CPSP produces suffering in patients, both physically and mentally. However, the mechanisms underlying CPSP remain elusive. Here, a genome-wide expression profiling of ipsilateral spinal cord dorsal horn (SCDH) was performed to identify potential genes related with CPSP.Methods: A rat skin/muscle incision and retraction (SMIR) model was established to induce CPSP. Immunostaining was used to study glial cell and neuron activation in ipsilateral SCDH of SMIR model rats. RNA sequencing (RNA-Seq), combined with bioinformatics analysis, was undertaken to explore gene expression profiles. qPCR was applied to validate the expression of some representative genes.Results: The SMIR model rats developed persistent mechanical allodynia in ipsilateral hindpaw for up to 14 days. Ipsilateral SCDH of SMIR rats showed remarkable glial cell and neuron activation. A number of differentially expressed genes (DEGs) were identified in ipsilateral SCDH of SMIR rats by RNA-Seq. qPCR confirmed expression of some representative DEGs. Bioinformatics indicated that chemical synaptic transmission, sensory perception of pain and neuroactive ligand-receptor interaction were predominant functions. We compared our dataset with human pain-related genes and found that several genes exclusively participate in pain modulation and mechanisms.Conclusion: Our study provided novel understandings of the molecular mechanisms possibly contributing to CPSP. These findings may offer new targets for future treatment of CPSP.Keywords: postsurgical pain, spinal cord dorsal horn, RNA-Seq, microglia, genome

Hainan Wen,1 Shoujun Xie,2 Yueyi Liang,2 Yanchao Liu,2 Honglian Wei,1 Qian Sun,1 Weigang Wang,1,3 Baojiang Wen,1,3 Jianhong Zhao1,3 1The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Clinical Laboratory, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei, People’s Republic of China; 3Hebei Provincial Center for Clinical Laboratories, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Jianhong Zhao, The Second Hospital of Hebei Medical University, 215 West Heping Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel +86 158 03210790, Fax +86 311 66002851, Email zhaojh_2002@yahoo.comPurpose: To shorten the turnaround time for blood culture (BC) analyses, a rapid method was developed for the direct identification, antimicrobial susceptibility testing (AST), and multidrug resistance testing of bacteria-positive BCs.Materials and Methods: The mixtures in BC bottles were treated with the multistep centrifugation method developed here and the conventional culture-based method. The bacterial sediment obtained after centrifugation was analyzed directly with MALDI-TOF MS and Vitek 2 Compact, and AST was performed directly with the Kirby–Bauer (K–B) disk diffusion, VITEK 2 Compact, and E-test methods. Extended spectrum lactamases (ESBLs) were detected with discs containing cefotaxime, cefotaxime/clavulanate, ceftazidime, and ceftazidime/clavulanate, and carbapenemase was detected with the modified carbapenem inactivation method (mCIM) and EDTA-mCIM (eCIM).Results: All the results of direct testing were compared to those of the conventional methods, to evaluate the accuracy of the direct methods. The accuracies of the direct Vitek 2 Compact and MALDI-TOF MS methods were 95.5% (214/224) and 90.2% (202/224), respectively. Direct AST with K–B, Vitek 2, and E-test showed category agreement of 96.0% (2611/2721), 96.1% (2614/2721), and 97.4% (2650/2721), respectively, and the major errors and very major errors were < 2% for all three methods. In the direct determination of ESBLs, the results for cefotaxime combined with cefotaxime/clavulanate were completely consistent with those after the standard isolation method. The carbapenemase detection rate with direct mCIM and eCIM was exactly the same as that with the standard method.Conclusion: These direct procedures based on multistep centrifugation are not only highly accurate but are appropriate for clinical laboratory use because the turnaround time is shorter.Keywords: blood culture, direct identification, direct antimicrobial susceptibility testing, extended-spectrum β-lactamase, carbapenemase, multistep centrifugation

Dingli Xu,1,2,&ast; Kaifeng Gan,3,&ast; Yang Wang,1 Zeting Wu,1 Yulong Wang,1 Song Zhang,1 Yujie Peng,2 Xuguang Fang,4 Hua Wei,5 Yansheng Zhang,5 Weihu Ma,2 Jing Chen5 1The Affiliated Hospital of Ningbo University Medical School, Ningbo, 315000, People’s Republic of China; 2Ningbo No.6 Hospital, Ningbo, 315000, People’s Republic of China; 3The Affiliated Lihuili Hospital of Ningbo University, Ningbo, 31500, People’s Republic of China; 4The First Affiliated Hospital of Xi ‘an Medical University, Xi’an, 710082, People’s Republic of China; 5Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology, Zhejiang Engineering Research Center for Biomedical Materials, Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weihu Ma; Jing Chen, Email 944973034@qq.com; jing.chen@nimte.ac.cnIntroduction: Bone delay union is mostly caused by lack of blood supply. Although autografts, allografts and artificial bone have been widely used to treat bone delay union, the bone regeneration fails in the ischemic site accompanied by the bone donor site complications and disease transmission. Recently, there is a growing recognition of the importance of hydrogel scaffolds which are regarded as an eligible engineer tissue for bone repair. However, hydrogel is still limited in improving neovascularization.Methods: In this work, black phosphorus nanosheet and deferoxamine (BPN-DFO) were loaded in the gelatin hydrogel to overcome the high risk of bone delay union and systemically investigated the regeneration capability of BPN-DFO hydrogel in vitro and vivo.Results: The resulting BPN-DFO hydrogel scaffold showed superior swollen, degradation and release rate, as well as satisfied biocompatibility. BPN-DFO hydrogel shown the significant up-expression of mRNA related to bone regeneration and cell proliferation. In vivo, the proposed BPN-DFO hydrogel significantly improved osteogenesis and neovascularization in the ischemic tibial bone site of SD rats with acute femoral artery occlusion. Both macroscopic and histological evaluation of new regenerated bone showed newly formed blood vessel and collagen using BPN-DFO hydrogel. The immunohistochemistry and RT-PCR revealed that the bone regeneration could be improved via BMP/Runx2 pathway.Conclusion: The BPN-DFO hydrogel possesses potential tissue engineer material for ischemic bone defect treatment. However, furthermore studies are needed to testify the safety and efficacy of BPN-DFO hydrogel.Keywords: ischemic bone defect regeneration, hydrogel scaffolds, black phosphorus nanosheets, deferoxamine

Zhuo Li,1 Hongrui Wei,1 Siyan Li,1 Pei Wu,2 Xiaoyun Mao1 1Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of China; 2Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of ChinaCorrespondence: Xiaoyun MaoDepartment of Breast Surgery, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang City, Liaoning Province, 110001, People’s Republic of China, Tel/Fax +86 24 83282618, Email xymao@cmu.edu.cnAbstract: The progesterone receptor (PR) modulates estrogen receptors α (ERα) action in breast cancer; it is an upregulated target gene of ER, and its expression is dependent on estrogen. PR is also a valuable prognostic biomarker in breast cancer, especially in hormone-positive breast cancer. High expression of PR is more frequently observed in tumors with a better baseline prognosis (ie, luminal A) than tumors with a poor baseline prognosis (ie, luminal B). In the following review, we present the role of PR in breast cancer, including the genomic characteristics and pathways in breast cancer, PR and endocrine therapy.Keywords: progesterone receptor, breast cancer, endocrine therapy

Na Lv,1 Ying Wang,2 Min Zhao,2 Lina Dong,3 Hongen Wei2 1Department of Physiology, Basic Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Neurology, Shanxi Provincial People’s Hospital, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Central Laboratory, Shanxi Provincial People’s Hospital, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Hongen WeiDepartment of Neurology, Shanxi Provincial People’s Hospital, The Fifth Clinical Medical College of Shanxi Medical University, 29 Shuangta Road, Taiyuan, 030012, People’s Republic of ChinaTel +86 351 4960173Fax +86 351 4961994Email hongen.wei@sxmu.edu.cnAbstract: In developmental biology, transcription factors are involved in regulating the process of neural development, controlling the differentiation of nerve cells, and affecting the normal functioning of neural circuits. Transcription factors regulate the expression of multiple genes at the same time and have become a key gene category that is recognized to be disrupted in neurodevelopmental disorders such as autism spectrum disorders. This paper briefly introduces the expression and role of PAX2 in neurodevelopment and discusses the neurodevelopmental disorders associated with Pax2 mutations and its possible mechanism. Firstly, mutations in the human Pax2 gene are associated with abnormalities in multiple systems which can result in neurodevelopmental disorders such as intellectual disability, epilepsy and autism spectrum disorders. Secondly, the structure of Pax2 gene and PAX2 protein, as well as the function of Pax2 gene in neural development, was discussed. Finally, a diagram of the PAX2 protein regulatory network was made and a possible molecular mechanism of Pax2 mutations leading to neurodevelopmental disorders from the perspectives of developmental process and protein function was proposed.Keywords: PAX2, neural development, disorders, mechanism

Jianchun Yang,1 Hongming Wei,2 Ying Wu2 1Business Administration, Guizhou University of Finance and Economics, the Guizhou Key Laboratory of Big Data Statistical Analysis, Guiyang, Guizhou, 550025, People’s Republic of China; 2Business Administration, Guizhou University of Finance and Economics, Guiyang, Guizhou, 550025, People’s Republic of ChinaCorrespondence: Jianchun Yang Email 772957289@qq.comPurpose: Based on the theory of social identity, this study focuses on the influence mechanism of self-sacrificing leadership on employees’ pro-organization unethical behaviors, as well as the moderating effect of power distance and the mediating effect of organizational identity between self-sacrificing leadership and employees’ pro-organization unethical behaviors.Methods: This work surveyed 286 employees in 12 companies in Guizhou province to test the research hypothesis model. Statistical analysis methods were used for data analysis.Results: The results reveal that self-sacrificial leadership has an indirect positive influence on unethical pro-organizational behavior of employees by positively influencing organizational identification. The higher the power distance of employees, the weaker the positive correlation between self-sacrificing leaders and organizational identity, and the lower the power distance of employees, the stronger the positive correlation between self-sacrificing leaders and organizational identity.Conclusion: This study reveals the influence mechanism of self-sacrificing leadership on employees’ pro-organization non-ethical behaviors from a new perspective and confirms the effects of power distance and organizational identity on creative performance. Unethical behavior under the cloak of “pro-organization” has a potential destructive effect on stakeholders, organizations and even the whole society. It is of great practical significance to identify its influencing factors and effectively avoid them.Keywords: unethical pro-organizational behavior, self-sacrificial leadership, organizational identification, power distance, the theory of social identity

Abstract Better models to identify individuals at low risk of ventricular arrhythmia (VA) are needed for implantable cardioverter-defibrillator (ICD) candidates to mitigate the risk of ICD-related complications. We designed the CERTAINTY study (CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia) with deep learning for VA risk prediction from cine cardiac magnetic resonance (CMR). Using a training cohort of primary prevention ICD recipients (n = 350, 97 women, median age 59 years, 178 ischemic cardiomyopathy) who underwent CMR immediately prior to ICD implantation, we developed two neural networks: Cine Fingerprint Extractor and Risk Predictor. The former extracts cardiac structure and function features from cine CMR in a form of cine fingerprint in a fully unsupervised fashion, and the latter takes in the cine fingerprint and outputs disease outcomes as a cine risk score. Patients with VA (n = 96) had a significantly higher cine risk score than those without VA. Multivariate analysis showed that the cine risk score was significantly associated with VA after adjusting for clinical characteristics, cardiac structure and function including CMR-derived scar extent. These findings indicate that non-contrast, cine CMR inherently contains features to improve VA risk prediction in primary prevention ICD candidates. We solicit participation from multiple centers for external validation.

Guangxian Zhong,1,&ast; Yunqing Wang,1,&ast; Hongxiang Wei,1 Meifang Chen,2 Huangfeng Lin,1 Zhen Huang,1 Jinlong Huang,3 Shenglin Wang,1 Jianhua Lin1 1Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 2The Health Management Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 3Department of Hematology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, People’s Republic of China&ast;These authors contributed equally to this work.Correspondence: Jianhua Lin; Shenglin Wang Tel/Fax +86 591 87981029Email jianhual@126.com; Shenglinwang0216@163.comPurpose: The aim of this research was to investigate the clinical significance of the expression of flap structure-specific endonuclease 1 (FEN1) in primary osteosarcoma.Methods: The expression of FEN1 was detected by immunohistochemistry analysis. The association of the expression of FEN1 in osteosarcoma with clinicopathological parameters was analyzed by using χ2 test or Fisher’s exact test. Survival analyses were performed by Kaplan–Meier method and Cox proportional hazards regression model.Results: Of the 40 osteosarcoma patients, 19 (47.5%) patients presented with FEN1 high expression, while in the non-neoplastic bone specimens, the FEN1 high expression was observed in 10% (3/30), the positive expression rate in osteosarcoma patients was significantly higher than that of non-neoplastic bone specimens (P< 0.01). Univariate analysis indicated that the progression-free survival (PFS) and overall survival (OS) were correlated with the expression level of FEN1 (PFS, P < 0.001; OS, P = 0.002), Enneking staging (PFS, P = 0.026; OS, P = 0.044) and chemotherapy response (PFS, P = 0.019; OS, P = 0.031). Multivariate analysis demonstrated that FEN1 expression was an independent prognostic factor for the PFS (HR = 4.73, P = 0.002) and OS (HR = 4.01, P = 0.038) of osteosarcoma patients.Conclusion: This study showed that FEN1 was overexpressed in osteosarcoma patients and positively associated with poor prognosis of osteosarcoma patients. Further studies should focus on the relative mechanisms and the targeted FEN1 therapies for osteosarcoma.Keywords: osteosarcoma, flap endonuclease 1, immunohistochemistry, prognosis

Jiahong Guo,1 Junying Li,2 Hua Wei,1 Zhaozhi Liang1 1Department of Nephrology, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, Xinxiang, 453000, People’s Republic of China; 2Department of Nephrology, The Affiliated Hospital of Qingdao University Pingdu district, Pingdu City, Qingdao, Shandong, 266000, People’s Republic of ChinaCorrespondence: Junying LiDepartment of Nephrology, The Affiliated Hospital of Qingdao University Pingdu District, No.369 Shanghai Road, Qingdao, Pingdu City, Shandong, 266000, People’s Republic of ChinaEmail lijunying2020@sina.cnBackground: Type 2 diabetes (T2D) is aglobal health burden that accounts for about 90% of all cases of diabetes. Injury to the kidneys is aserious complication of type 2 diabetes. Maackiain, apterocarpan extracted from roots of Sophora flavescens, has been traditionally used for various disease conditions. However, nothing is known about its possible potential effect on HFD/STZ-T2D-induced nephrotoxicity.Methods: In this study, T2D rat model is created by high-fat diet (HFD) for 2 weeks with injection of asingle dose of streptozotocin (35mg/kg body weight). T2D rats were orally administered with maackiain (10 and 20mg/kg body weight) for 7 weeks.Results: Maackiain suppressed T2D-induced alterations in metabolic parameters, lipid profile and kidney functionality markers. By administering 10 and 20mg/kg maackiain to T2D rats, it was able to reduce lipid peroxidation while improving antioxidant levels (SOD, CAT, and GSH). Furthermore, the present study demonstrated the molecular mechanisms through which maackiain attenuated T2D-induced oxidative stress (mRNA: Nrf2, Nqo-1, Ho-1, Gclc and Gpx-1; protein: NRF2, NQO-1, HO-1 and NOX-4), inflammation (mRNA: Tlr, Myd88, IκBα, Mcp-1, Tgf-β, col4, Icam1, Vcam1 and E-selectin; Protein: TLR4, MYD88, NF-κB, IκBα, MCP-1; levels: TNF-α and MCP-1) and apoptosis (mRNA: Bcl-2, Bax, Bad, Apaf-1, Caspase-9 and Caspase-3; protein: Bcl-2, Bax, Caspase-3 and Caspase-9) mediated renal injury. Additionally, significant improvement in kidney architecture was observed after treatment of diabetic rats with 10 or 20mg/kg maackiain.Conclusion: Maackiain protects the kidney by decreasing oxidative stress, inflammation, and apoptosis to preserve normal renal function in type 2 diabetes.Keywords: high-fat diet, streptozotocin, oxidative stress, inflammation, apoptosis, kidney

Zhiguang Li,1 Xu Si,1 Zhiyuan Ding,1 Xiao Li,1 Shuai Zheng,1 Yuxin Wang,1 Hua Wei,1 Yige Guo,2 Wei Zhang3 1School of Economics and Management, Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 2King’s Business School, King’s College London, London, UK; 3School of Information Engineering, Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Hua WeiSchool of Economics and Management, Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of ChinaTel +86 551-68129006Email weihua@ahtcm.edu.cnWei ZhangSchool of Information Engineering, Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of ChinaTel +86 551-68129224Email zhangwei900316@163.comPurpose: This paper aims to measure the operating efficiency of China’s basic pension insurance from 2014 to 2019 in 31 provinces.Methods: The three-stage DEA model was used to evaluate the operating efficiency of basic pension insurance in 31 provinces.Results: On the whole, the operating efficiency of China’s basic pension insurance was at a high level, but there was still room for improvement. GDP, urbanization level and scale of government public expenditure had a positive impact on the operating efficiency of regional basic pension insurance. In contrast, the old-age dependency ratio had a significant negative effect. There were noticeable regional differences in the operating efficiency of China’s basic pension insurance, which showed a pattern of Central (0.742) >Eastern (0.689) >Western (0.505) after removing the influence of environmental variables.Conclusion: This study systematically analyzes the impact of external environmental regulations on China’s basic pension insurance’s operating efficiency and provides decision-making references for further improving the operating efficiency of China’s basic pension insurance. In order to further optimize the allocation of basic endowment insurance, this paper proposes the following countermeasures and suggestions: (1) broaden investment channels and improve the investment efficiency; (2) increase supervision of social security departments and strengthen information disclosure; (3) unify the management of social basic pension insurance.Keywords: three-stage DEA, China’s pension insurance, operating efficiency, technical efficiency

Hao Wei,1,&ast; Yangnan Hu,2,3,&ast; Junguo Wang,1 Xia Gao,1 Xiaoyun Qian,1 Mingliang Tang2– 4 1Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, 210008, People’s Republic of China; 2State Key Laboratory of Bioelectronics, School of Life Sciences and Technology, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, People’s Republic of China; 3Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, People’s Republic of China; 4Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Medical College, Soochow University, Suzhou, 215000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyun Qian; Mingliang Tang Email qxy522@163.com; mltang@suda.edu.cnAbstract: Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely investigated and applied in the field of biomedicine due to their excellent superparamagnetic properties and reliable traceability. However, with the optimization of core composition, shell types and transfection agents, the cytotoxicity and metabolism of different SPIONs have great differences, and the labeled cells also show different cellular behaviors. Therefore, a holistic review of the construction and application of SPIONs is desired. This review focuses the advances of SPIONs in the field of biomedicine in recent years. After summarizing the toxicity of different SPIONs, the uptake, distribution and metabolism of SPIONs in vitro were discussed. Then, the regulation of labeled-cells behavior is outlined. Furthermore, the major challenges in the optimization process of SPIONs and insights on its future developments are proposed.Keywords: superparamagnetic iron oxide nanoparticles, stem cells, cytotoxicity, biological behavior

Yangnan Hu,1,&ast; Dan Li,2,&ast; Hao Wei,3,&ast; Shan Zhou,1 Wei Chen,1 Xiaoqian Yan,1 Jaiying Cai,1 Xiaoyan Chen,1 Bo Chen,4 Menghui Liao,1 Renjie Chai,1,5 Mingliang Tang1,5,6 1State Key Laboratory of Bioelectronics, School of Life Sciences and Technology, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, People’s Republic of China; 2School of Biology, Food and Environment, Hefei University, Hefei, 230601, People’s Republic of China; 3Department of Otorhinolaryngology Head and Neck Surgery, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 4Materials Science and Devices Institute, Suzhou University of Science and Technology, Suzhou, 215009, People’s Republic of China; 5Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, People’s Republic of China; 6Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Medical College, Soochow University, Suzhou, 215000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Renjie Chai; Mingliang Tang Email renjiec@seu.edu.cn; mltang@suda.edu.cnIntroduction: Neuroregeneration is a major challenge in neuroscience for treating degenerative diseases and for repairing injured nerves. Numerous studies have shown the importance of physical stimulation for neuronal growth and development, and here we report an approach for the physical guidance of neuron orientation and neurite growth using superparamagnetic iron oxide (SPIO) nanoparticles and magnetic fields (MFs).Methods: SPIO nanoparticles were synthesized by classic chemical co-precipitation methods and then characterized by transmission electron microscope, dynamic light scattering, and vibrating sample magnetometer. The cytotoxicity of the prepared SPIO nanoparticles and MF was determined using CCK-8 assay and LIVE/DEAD assay. The immunofluorescence images were captured by a laser scanning confocal microscopy. Cell migration was evaluated using the wound healing assay.Results: The prepared SPIO nanoparticles showed a narrow size distribution, low cytotoxicity, and superparamagnetism. SPIO nanoparticles coated with poly-L-lysine could be internalized by spiral ganglion neurons (SGNs) and showed no cytotoxicity at concentrations less than 300 μg/mL. The neurite extension of SGNs was promoted after internalizing SPIO nanoparticles with or without an external MF, and this might be due to the promotion of growth cone development. It was also confirmed that SPIO can regulate cell migration and can direct neurite outgrowth in SGNs preferentially along the direction imposed by an external MF.Conclusion: Our results provide a fundamental understanding of the regulation of cell behaviors under physical cues and suggest alternative treatments for sensorineural hearing loss caused by the degeneration of SGNs.Keywords: physical cues, neurites orientation, hearing loss, cochlear implants, migration

Kun He,1,2,&ast; Chunke Dong,3,&ast; Hongyu Wei,2,&ast; Feng Yang,2 Haoning Ma,2 Xiangsheng Tang,2 Mingsheng Tan,2 Ping Yi2 1Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Department of Orthopaedic Surgery, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 3Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Yi; Mingsheng Tan Email zryiping@163.com; zrtanms@163.comPurpose: Revision surgery for adjacent segment degeneration (ASD) commonly requires exposing and removing the original fixation. To minimize trauma and to reduce the operation time and blood loss, we introduced a minimally invasive lumbar revision technique using cortical bone trajectory (CBT) screws assisted by three-dimensional (3D)-printed navigation templates.Methods: From April 2017 to October 2019, 18 patients with ASD underwent revision surgery with CBT screws assisted by 3D-printed templates in our hospital. All surgical data, including the operation time, blood loss, and incision length, were recorded. We evaluated the clinical efficacy using the visual analog scale (VAS), the Oswestry Disability Index (ODI), and the Japanese Orthopedic Association (JOA) score. X-ray and computed tomography (CT) scans were used to evaluate the stability of CBT screw fixation, the accuracy of screws, and the fusion rate.Results: The mean follow-up was 22.4± 4.7 months (12– 31 months). The VAS, ODI, and JOA scores were analyzed by SPSS 21.0 and showed significant improvement at 2 weeks and the last follow-up compared with preoperative data (P< 0.05). Seventy-six CBT screws were inserted with navigation templates; 2 screws were Grade B, and the other screws were Grade 0 or A. Changes in intervertebral height showed good stability of CBT screw fixation (P> 0.05). All the patients exhibited satisfactory fusion results.Conclusion: Revision surgery for ASD with CBT screws assisted by 3D-printed navigation templates has satisfactory clinical efficacy with the advantages of a short operation time, a small incision, and less blood loss.Keywords: adjacent segment degeneration, cortical bone trajectory, revision surgery, 3D printing, navigation template

Yanhui Tang,1,2,* Qi Tang,1,2,* Haicheng Wei,1,2,* Pinzhang Hu,1,2 Donghua Zou,3 Rixiong Liang,1,2 Yu Ling1,2 1Department of Ophthalmology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 2Department of Ophthalmology, The First People’s Hospital of Nanning, Nanning, Guangxi, 530022, People’s Republic of China; 3Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rixiong Liang; Yu LingDepartment of Ophthalmology, The Fifth Affiliated Hospital of Guangxi Medical University, 89 Qixing Road, Nanning, Guangxi, 530022, People’s Republic of ChinaTel +86 7713919709; +86 7712636273Email lrx4896@163.com; lingyu3919709@163.comPurpose: This study aimed to identify genes that may be effective in diagnosing or treating diabetic retinopathy (DR), the most common complication of diabetes mellitus (DM).Methods: Differentially expressed genes (DEGs) were identified between DR and DM in GSE146615 dataset. DEGs that were consistently up- or down-regulated under both standard glucose and high glucose conditions were identified as common genes and used to generate a protein–protein interaction network and modules. The module genes were assessed for the area under the receiver operating characteristic curve (AUC), leading to the identification of hub genes. Differentially methylated probes in GSE76169 were also compared with common DEGs to identify specific methylation markers of DR. Enrichment analysis was used to explore the biological characteristics. The Short Time-series Expression Miner algorithm was used to identify genes that were progressively dysregulated in the sequence: healthy controls < DM < DR.Results: A total of 1917 common genes were identified for seven modules. The eight genes with AUC > 0.8 under high glucose and standard glucose conditions were considered as hub genes. The module genes were significantly enriched during vascular smooth muscle cell development and regulation of oxygen metabolism, while 92 methylation markers were involved in the similar terms. Among the progressively dysregulated genes, three intersection genes under both standard glucose and high glucose conditions were found to be module genes and were considered as key genes.Conclusion: We identified eight potential DR-specific diagnostic and therapeutic genes, whose abnormal expression can cause oxidative stress, thus favoring the course of the disease.Keywords: diabetic retinopathy, oxidative stress, glucose, cluster analysis, hub genes

Jun Shao,1,* Rongpu Liang,1,* Dongbing Ding,1,* Xiaoming Zheng,1 Xudong Zhu,1 Shengxue Hu,2 Hongbo Wei,1 Bo Wei1 1Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People’s Republic of China; 2College of Biological Science and Engineering, Fuzhou University, Fujian, 350108, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongbo Wei; Bo WeiDepartment of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People’s Republic of ChinaTel +86-20-85252228Email weihb@mail.sysu.edu.cn; weibo3@mail.sysu.edu.cnBackground: Surgery is considered to be a potentially curative approach for gastric cancer. However, most cases are diagnosed at a very advanced stage for the lack of typical symptoms in the initial stage, which makes it difficult to completely surgical resect of tumors. Early diagnosis and precise personalized intervention are urgent issues to be solved for improving the prognosis of gastric cancer. Herein, we developed an RGD-modified ROS-responsive multifunctional nanosystem for near-infrared (NIR) imaging and photothermal therapy (PTT) against gastric cancer.Methods: Firstly, the amphiphilic polymer was synthesized by bromination reaction and nucleophilic substitution reaction of carboxymethyl chitosan (CMCh) and 4-hydroxymethyl-pinacol phenylborate (BAPE). Then, it was used to encapsulate indocyanine green (ICG) and modified with RGD to form a smart multifunctional nanoparticle targeted to gastric cancer (CMCh-BAPE-RGD@ICG). The characteristics were determined, and the targeting capacity and biosafety were evaluated both in vitro and in vivo. Furthermore, CMCh-BAPE-RGD@ICG mediated photothermal therapy (PTT) effect was studied using gastric cancer cells (SGC7901) and SGC7901 tumor model.Results: The nanoparticle exhibited suitable size (≈ 120 nm), improved aqueous stability, ROS-responsive drug release, excellent photothermal conversion efficiency, enhanced cellular uptake, and targeting capacity to tumors. Remarkably, in vivo studies suggested that CMCh-BAPE-RGD@ICG could accurately illustrate the location and margin of the SGC7901 tumor through NIR imaging in comparison with non-targeted nanoparticles. Moreover, the antitumor activity of CMCh-BAPE-RGD@ICG-mediated PTT could effectively suppress tumor growth by inducing necrosis and apoptosis in cancer cells. Additionally, CMCh-BAPE-RGD@ICG demonstrated excellent biosafety both in vitro and in vivo.Conclusion: Overall, our study provides a biocompatible theranostic nanoparticle with enhanced tumor-targeting ability and accumulation to realize NIR image-guided PTT in gastric cancer.Keywords: gastric cancer, nanoparticle, indocyanine green, near-infrared imaging, photothermal therapy

Hongli Zhao,1,* Ying Zhang,2,* Jianhong Ye,3 Hongjiang Wei,4 Zhengping Huang,5 Xiaoyan Ning,6 Xiaoying Fu1 1Department of Endocrinology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, 510317, People’s Republic of China; 2Department of Endocrinology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, People’s Republic of China; 3Department of Endocrinology, Foshan Hospital of Traditional Chinese Medicine, Foshan, 528000, People’s Republic of China; 4Outpatient Department, Guangdong Second Provincial General Hospital, Guangzhou, 510317, People’s Republic of China; 5Department of Rheumatology and Immunology, Guangdong Second Provincial General Hospital, Guangzhou, 510317, People’s Republic of China; 6Department of Gastroenterology, Guangdong Second Provincial General Hospital, Guangzhou, 510317, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianhong YeDepartment of Endocrinology, Foshan Hospital of Traditional Chinese Medicine, No. 6, Qinren Road, Chancheng District, Foshan, Guangdong Province, 528000, People’s Republic of ChinaTel/Fax +86 0757-83066101Email jhy_ye@outlook.comObjective: The incidence of Hashimoto’s thyroiditis (HT) in patients with polycystic ovary syndrome (PCOS) is significantly higher than in normal controls, and there is a risk of more severe metabolic symptoms when the two diseases occur together. This study compares insulin secretion, insulin resistance (IR) and thyroid function in patients with PCOS with and without HT.Methods: A total of 164 patients (52 patients with HT (HT+) and 112 patients without HT diagnosed PCOS at our hospital were enrolled for testing of oral glucose tolerance, insulin release, thyroid function, the presence of thyroglobulin and thyroid peroxidase antibodies, and blood lipid levels.Results: Patients with PCOS and HT had higher insulin secretion and IR levels than those without HT, while free thyroxine and thyrotropin levels were significantly lower. The ratio of free thyroxine to thyrotropin was higher in patients with HT.Conclusion: HT may related with IR and relatively low thyroid function in patients with PCOS. Thus, thyroid function and autoimmune status in patients with PCOS should be evaluated in clinical practice.Keywords: polycystic ovary syndrome, Hashimoto’s thyroiditis, insulin resistance, oral glucose tolerance test

Hang Zhou,1,2,* Jiawei Sun,1,* Jiaqi Wu,1 Hong Wei,1 Xianli Zhou1 1In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Ultrasound, Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, 310058, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianli ZhouIn-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of ChinaTel/Fax +86-0451-86605362Email hrbzhouxl@163.comBackground: The specific microenvironment of solid tumors, which is characterized by hypoxia, overexpression of glutathione (GSH), and high accumulation of anti-inflammatory tumor-associated macrophages (TAMs), limits the efficiency of sonodynamic therapy (SDT).Method and Results: Herein, a multifunctional nanoplatform was engineered to modulate the tumor microenvironment for highly efficient SDT. In this system, sonosensitizers and catalase were encapsulated in disulfide-bridged mesoporous organosilicon nanoparticles with high loading, which protected the activity of catalase and ensure the stability of sonosensitizers and enzyme. Subsequently, hyaluronic acid was grafted onto the nanoplatform to reeducate TAMs and induce the secretion of exogenous hydrogen peroxide. Due to the good protection of enzyme, the catalase within the nanoplatform efficiently produced the mount of O2 through decomposing the hydrogen peroxide in tumor tissues, which remarkably alleviated tumor hypoxia. Furthermore, degradation of the nanoparticles was observed in response to GSH, which effectively decreased the intracellular GSH level, further favoring SDT-triggered anticancer effect.Conclusion: Based on the multiple adjustments to tumor microenvironment, our nanoplatform displayed extraordinary sonodynamic therapeutic effect with low systemic toxicity.Keywords: sonodynamic therapy, hypoxia, tumor-associated macrophages, catalase, glutathione depletion