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Jing Wang,1 Xintian Wang,1 Yuyang Li,1 Xin Yao,1 Yuanyuan Shen,1 Ziling Song,1 Peihua Zhang,2 Xiaoqiong Huang2 1School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of ChinaCorrespondence: Xiaoqiong Huang, Email 13906632387@eye.ac.cnPurpose: Exploring the mechanisms of fear of negative evaluation (FNE) and self-esteem between family functioning and social avoidance and distress (SAD) to inform the promotion of social functioning in people with strabismus.Patients and Methods: Convenience sampling was used to select 249 strabismus patients attending a tertiary-level ophthalmology hospital in Wenzhou City from July 2023 to February 2024. The Social Avoidance and Distress Scale, Rosenberg Self-Esteem Scale, Brief Fear of Negative Evaluation Scale, and Family APGAR Index Questionnaire were utilized to assess levels of social avoidance and distress, self-esteem, fear of negative evaluation, and family functioning. Structural equation modeling (SEM) was employed to explore the sequential mediating role of FNE and self-esteem in the relationship between family functioning and SAD.Results: Family functioning negatively predicted SAD directly (β=− 0.14, P< 0.01). Additionally, family functioning predicted FNE (β=− 0.19, P< 0.01) and self-esteem (β=0.41, P< 0.01). FNE positively predicted SAD (β=− 0.38, P< 0.01) and negatively predicted self-esteem (β=− 0.22, P< 0.01). Moreover, self-esteem negatively predicted SAD (β=− 0.33, P< 0.01). FNE and self-esteem mediated the relationship between family functioning and SAD, with a combined mediating effect of − 0.249, explaining 63.52% of the total variance.Conclusion: This study examined how FNE and self-esteem affect the link between family functioning and SAD in patients with strabismus. These findings complement our understanding of SAD mechanisms in strabismus patients, encompassing familial, cognitive, and emotional perspectives, and offer theoretical insights for enhancing social functioning in this population.Keywords: strabismus, social avoidance and distress, family functioning, fear of negative evaluation, self-esteem, chain mediation

Shichun Huang,1,2 Xuejie Yao,2 Xueqin Chen,2 Xiuli Chen,3 Yanxia Li,3 Yashpal Kanwar,4 Faith Ka Shun Chan,5 Ping Ye,2 Ming Zhan2,6 1School of Medicine, Ningbo University, Ningbo, 315211, People’s Republic of China; 2Department of Medicine, The First Affiliated Hospital, Ningbo University, Ningbo, 315000, People’s Republic of China; 3Department of Medicine, Ningbo Baiyun Community Healthcare Center, Ningbo, 315000, People’s Republic of China; 4Department of Pathology and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA; 5School of Geographical Sciences, University of Nottingham Ningbo China, Ningbo, 315100, People’s Republic of China; 6China Health Institute, University of Nottingham Ningbo China, Ningbo, 315100, People’s Republic of ChinaCorrespondence: Ming Zhan, Department of Medicine, The First Affiliated Hospital, Ningbo University, 59 Liuting Street, Ningbo, Zhejiang Province, 315000, People’s Republic of China, Email stephen0726@163.comBackground: Metabolic syndrome (MS) and low socioeconomic status (SES) may increase the risk for chronic kidney disease (CKD). This study aimed to investigate the prevalence of MS and CKD and the association between MS, SES, and CKD among adults in Ningbo, a city in Eastern China.Methods: A cross-sectional survey of 3212 adults was conducted between July 2019 and February 2021 in Ningbo. MS was defined as the presence of three or more risk factors: elevated blood pressure, reduced high-density lipoprotein (HDL) cholesterol, elevated triglycerides, elevated plasma glucose, and abdominal obesity. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or the occurrence of albuminuria. SES was stratified according to personal education and income levels. Multivariate logistic regression was used to analyze the relationships among MS, sociodemographic factors, and CKD.Results: The age- and sex-adjusted prevalence of CKD was 9.1% (95% CI: 8.3– 10.0), the prevalence of eGFR less than 60 mL/min/per 1· 73 m² was 2.5% (95% CI 2.0– 3.0) and that of albuminuria was 7.9% (95% CI 7.0– 8.7), and the adjusted prevalence of MS was 23.1% (95% CI 21.7– 24.4). MS components, including elevated blood pressure, elevated fasting glucose, abdominal obesity, elevated serum triglyceride, or reduced serum HDL-C, were independent risk factors for CKD, and the adjusted prevalence of CKD proportionally increased with the number of MS-defined parameters. Participants with MS had 2.43-fold increased odds of developing CKD compared with those without MS. In addition, age, female sex, low SES including low educational level and low income were associated with increased odds of occurrence of albuminuria and CKD.Conclusion: The prevalence of metabolic syndrome and chronic kidney disease is high among adults in Ningbo. Metabolic syndrome and low socioeconomic status are associated with the high risk of developing chronic kidney disease.Keywords: chronic kidney disease, metabolic syndrome, socioeconomic status, prevalence, risk factors

Xiaobo Zhang,1,&ast; Xidan Gao,1,&ast; Xuefang Zhang,1 Xin Yao,1 Xin Kang2 1Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’An, Shaanxi, P.R. China; 2Department of Sports Medicine, Honghui Hospital, Xi’an Jiao Tong University, Xi’An, Shaanxi, P.R. China&ast;These authors contributed equally to this workCorrespondence: Xin Kang, Email honghuikangxin@163.comAbstract: Hydrogels are multifunctional platforms. Through reasonable structure and function design, they use material engineering to adjust their physical and chemical properties, such as pore size, microstructure, degradability, stimulus-response characteristics, etc. and have a variety of biomedical applications. Hydrogel three-dimensional (3D) printing has emerged as a promising technique for the precise deposition of cell-laden biomaterials, enabling the fabrication of intricate 3D structures such as artificial vertebrae and intervertebral discs (IVDs). Despite being in the early stages, 3D printing techniques have shown great potential in the field of regenerative medicine for the fabrication of various transplantable tissues within the human body. Currently, the utilization of engineered hydrogels as carriers or scaffolds for treating intervertebral disc degeneration (IVDD) presents numerous challenges. However, it remains an indispensable multifunctional manufacturing technology that is imperative in addressing the escalating issue of IVDD. Moreover, it holds the potential to serve as a micron-scale platform for a diverse range of applications. This review primarily concentrates on emerging treatment strategies for IVDD, providing an in-depth analysis of their merits and drawbacks, as well as the challenges that need to be addressed. Furthermore, it extensively explores the biological properties of hydrogels and various nanoscale biomaterial inks, compares different prevalent manufacturing processes utilized in 3D printing, and thoroughly examines the potential clinical applications and prospects of integrating 3D printing technology with hydrogels.Keywords: intervertebral disc degeneration, 3D bioprinting, hydrogel, novel therapy, challenges

Jie Zhang, Xuelin Yao, Yijing Chen, Qing Feng, Yi Zhang, Tian Jiang, Songtao Tang, Nan Zhang, Fang Dai, Honglin Hu, Qiu Zhang Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Qiu Zhang; Honglin Hu, Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Shushan District, 230032, People’s Republic of China, Email zhangqiu@ahmu.edu.cn; huhonglin@ahmu.edu.cnBackground: Diabetes mellitus and hypertension often coexist and share common risk factors. This study investigated the correlation between glycemic management and the prevalence of hypertension among Chinese adults diagnosed with type 2 diabetes mellitus (T2DM).Methods: This study included 1715 patients with T2DM from four cities in Anhui Province, China. Sociodemographic characteristics of the sample participants were collected via questionnaires. A univariate analysis of variance (ANOVA) was utilized for continuous variables, and chi-square testing was used for categorical variables. Binary logistic regression was utilized to examine the relationship between blood pressure and variables including fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), body mass index (BMI), waist circumference (WC), physical activity, dyslipidemia, and family history of hypertension.Results: FPG levels did not increase the risk of hypertension, while HbA1c was significantly and negatively associated with hypertension risk. HbA1c levels ranged from 7.2 to 8.6%, with odds ratios (OR) of 0.68 and 95% confidence intervals (CI) of 0.48 to 0.97 and a significant p value of less than 0.05. For the HbA1c levels above 8.6%, the OR was 0.58 with a 95% CI of 0.39 to 0.87 and a significant p value of less than 0.01. Furthermore, advanced age, higher BMI, greater waist circumference, presence of dyslipidemia, and positive family history of hypertension were all found to be significantly and independently linked to a heightened risk of developing hypertension. These associations remain significant after further adjustment.Conclusion: There was a negative association between HbA1c and the risk of hypertension, and the association remained significant after adjustment for antihypertensive drug use.Keywords: FPG, HbA1c, T2DM, hypertension

Wenze Han,1,2 Ran Zhang,1,2 Shuzhi Liu,1,2 Tong Zhang,1,2 Xuemin Yao,1,2 Yuxin Cao,1,2 Jiadi Li,1,2 Xiaoming Liu,1,2 Bing Li1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, People’s Republic of ChinaCorrespondence: Xiaoming Liu; Bing Li, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China, Email lxming0912@163.com; libing1975vip@163.comAbstract: Whiskers are nanoscale, high-strength fibrous crystals with a wide range of potential applications in dentistry owing to their unique mechanical, thermal, electrical, and biological properties. They possess high strength, a high modulus of elasticity and good biocompatibility. Hence, adding these crystals to dental composites as reinforcement can considerably improve the mechanical properties and durability of restorations. Additionally, whiskers are involved in inducing the value-added differentiation of osteoblasts, odontogenic osteocytes, and pulp stem cells, and promoting the regeneration of alveolar bone, periodontal tissue, and pulp tissue. They can also enhance the mucosal barrier function, inhibit the proliferation of tumor cells, control inflammation, and aid in cancer prevention. This review comprehensively summarizes the classification, properties, growth mechanisms and preparation methods of whiskers and focuses on their application in dentistry. Due to their unique physicochemical properties, excellent biological properties, and nanoscale characteristics, whiskers show great potential for application in bone, periodontal, and pulp tissue regeneration. Additionally, they can be used to prevent and treat oral cancer and improve medical devices, thus making them a promising new material in dentistry.Keywords: whiskers, dentistry, growth mechanism, biomaterials

Yuan Yuan,1,&ast; Mingyi Hou,2,&ast; Xiaoning Song,1 Xintao Yao,1 Xuerui Wang,1 Xiangjun Chen,2 Shengnan Li1 1School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin, 300401, People’s Republic of China; 2School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, Yantai, 264003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengnan Li; Xiaoning Song, School of Chemical Engineering and Technology, Hebei University of Technology, Xiping Road, Tianjin, 300401, People’s Republic of China, Email lisn027@hebut.edu.cn; songxn123@hebut.edu.cnBackground: With the rapid development of nanotechnology, constructing a multifunctional nanoplatform that can deliver various therapeutic agents in different departments and respond to endogenous/exogenous stimuli for multimodal synergistic cancer therapy remains a major challenge to address the inherent limitations of chemotherapy.Methods: Herein, we synthesized hollow mesoporous Prussian Blue@zinc phosphate nanoparticles to load glucose oxidase (GOx) and DOX (designed as HMPB-GOx@ZnP-DOX NPs) in the non-identical pore structures of their HMPB core and ZnP shell, respectively, for photothermally augmented chemo-starvation therapy.Results: The ZnP shell coated on the HMPB core, in addition to providing space to load DOX for chemotherapy, could also serve as a gatekeeper to protect GOx from premature leakage and inactivation before reaching the tumor site because of its degradation characteristics under mild acidic conditions. Moreover, the loaded GOx can initiate starvation therapy by catalyzing glucose oxidation while causing an upgradation of acidity and H2O2 levels, which can also be used as forceful endogenous stimuli to trigger smart delivery systems for therapeutic applications. The decrease in pH can improve the pH-sensitivity of drug release, and O2 can be supplied by decomposing H2O2 through the catalase-like activity of HMPBs, which is beneficial for relieving the adverse conditions of anti-tumor activity. In addition, the inner HMPB also acts as a photothermal agent for photothermal therapy and the generated hyperthermia upon laser irradiation can serve as an external stimulus to further promote drug release and enzymatic activities of GOx, thereby enabling a synergetic photothermally enhanced chemo-starvation therapy effect. Importantly, these results indicate that HMPB-GOx@ZnP-DOX NPs can effectively inhibit tumor growth by 80.31% and exhibit no obvious systemic toxicity in mice.Conclusion: HMPB-GOx@ZnP-DOX NPs can be employed as potential theranostic agents that incorporate multiple therapeutic modes to efficiently inhibit tumors. Keywords: Prussian Blue, glucose oxidase, co-delivery system, photothermal therapy, chemotherapy

Chenguang Jia,1,&ast; Xiaowei Yao,1,&ast; Zhaoliang Dong,1 Lianbo Wang,1 Fangchao Zhao,2,&ast; Jianguo Gao,1,&ast; Tao Cai3,&ast; 1Department of Orthopedics, Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Cai, Hebei Chest Hospital, No. 372, Shengli North Street, Shijiazhuang, Hebei, People’s Republic of China, Tel/Fax +86-311-86911080, Email caitaoxiongke@163.comBackground: Post-translational modifications (PTM) significantly influence the pathogenesis and progression of diverse neoplastic conditions. Nevertheless, there has been limited research focusing on the potential of PTM-related genes (PTMRGs) as tumor biomarkers for predicting the survival of specific patients.Methods: The datasets utilized in this research were obtained from the TARGET and GEO repositories, respectively. The gene signature was constructed through the utilization of LASSO Cox regression method. GSEA and GO was used to identify hub pathways associated with risk genes. The functionality of risk genes in osteosarcoma (OS) cell lines was verified through the implementation of the CCK-8 assay, cell cycle analysis, and immunofluorescence assay.Results: Two distinct PTM patterns and gene clusters were finally determined. Significant differences in the prognosis of patients were found among two different PTM patterns and gene clusters, so were in the function enrichment and the landscape of TME immune cell infiltration. Moreover, we examined two external immunotherapy cohorts and determining that patients in the low-risk group was more likely to profit from immunotherapy. In addition, we mapped the expression of the genes in the signature in distinct cells using single-cell analysis. Finally, CCK-8 assay, cell cycle analysis, and immunofluorescence assay were utilized to confirm that RAD21 was expressed and functioned in OS.Conclusion: In conclusion, this study elucidated the potential link between PTM and immune infiltration landscape of OS for the first time and provided a new assessment protocol for the precise selection of treatment strategies for patients with advanced OS.Keywords: post-translational modifications, osteosarcoma, immune microenvironment, immune therapy, RAD21

Jianwen Zhao,1– 5,&ast; Xintian Cai,1– 5,&ast; Junli Hu,1– 5 Shuaiwei Song,1– 5 Qing Zhu,1– 5 Di Shen,1– 5 Wenbo Yang,1– 5 Qin Luo,1– 5 Xiaoguang Yao,1– 5 Delian Zhang,1– 5 Jing Hong,1– 5 Nanfang Li1– 5 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, People’s Republic of China; 2Xinjiang Hypertension Institute, Urumqi, Xinjiang, 830001, People’s Republic of China; 3NHC Key Laboratory of Hypertension Clinical Research, Urumqi, Xinjiang 830001 People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region ”Hypertension Research Laboratory”, Urumqi, Xinjiang, 830001, People’s Republic of China; 5Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, Xinjiang, 830001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumuqi, Xinjiang, 830001, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina.comBackground: A newly introduced obesity-related index, the weight-adjusted-waist index (WWI), emerges as a promising predictor of cardiovascular disease (CVD). Given the known synergistic effects of hypertension and obstructive sleep apnea (OSA) on cardiovascular risk, we aimed to explore the relationship between the WWI and CVD risk specifically within this high-risk cohort.Methods: A total of 2265 participants with hypertension and OSA were included in the study. Multivariate Cox regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD events. The restricted cubic spline (RCS) was used to further evaluate the nonlinear dose-response relationship.Results: During a median follow-up period of 6.8 years, 324 participants experienced a CVD event. Multivariate Cox regression analysis revealed that compared to the reference group, the HRs for the second, third, and fourth groups were 1.12 (95% CI, 0.79– 1.59), 1.35 (95% CI, 0.96– 1.89), and 1.58 (95% CI, 1.13– 2.22), respectively. Moreover, RCS analysis illustrated a clear J-shaped relationship between the WWI and CVD risk, particularly notable when WWI exceeded 11.5 cm/, signifying a significant increase in CVD risk.Conclusion: There was a J-shaped relationship between WWI and CVD in hypertensive patients with OSA, especially when the WWI was greater than 11.5 cm/, the risk of CVD was significantly increased.Keywords: hypertensive, obstructive sleep apnea, weight-adjusted-waist index, cardiovascular disease, visceral obesity

Yingzi Zhang,1 Xiajuan Yao,1 Yaoquan Zhang,1 Zhuyun Chen,1 Zhongke Qin,1 Ying Cai,2 Wenkai Xia,1 Hong Hu1 1Department of Nephrology, Jiangyin People’s Hospital Affiliated to Nantong University, Jiangyin, Jiangsu, 214400, People’s Republic of China; 2Department of Hematology, Jiangyin People’s Hospital Affiliated to Nantong University, Jiangyin, Jiangsu, 214400, People’s Republic of ChinaCorrespondence: Wenkai Xia; Hong Hu, Department of Nephrology, Jiangyin People’s Hospital Affiliated to Nantong University, 3 Yingrui Road, Jiangyin, Jiangsu, 214400, People’s Republic of China, Email xiawenkai.xia@gmail.com; huhong1523@163.comBackground: The albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) have been recently regarded as promising prognostic factors in various malignancies. The present study investigated the prognostic value of combining the AGR and NLR (ANS) for risk assessments in multiple myeloma (MM) with renal impairment (RI).Methods: From 2011 to 2018, 79 patients with MM and RI were enrolled in this study. Receiver operating curves (ROCs) were constructed to determine optimal AGR and NLR thresholds for predicting overall survival (OS) and progression-free survival (PFS) during follow up. The prognostic values of AGR, NLR, and ANS were evaluated with Cox regression and Kaplan-Meier methods. We also created a predictive nomogram for prognostic evaluations of OS and PFS, and the predictive accuracy was assessed with a concordance index (c-index).Results: The ROC curves analyses showed that the optimal cut-off levels were 2.27 for NLR and 1.57 for AGR. A high NLR and a high ANS were significantly associated with worse OS and PFS. However, a high NLR combined with a low AGR was associated with worse OS. Multivariate analyses demonstrated that both the NLR and ANS were independent predictors for both OS and PFS and that a low AGR was an independent predictor of a reduced OS. The nomogram accurately predicted OS (c-index: 0.785) and PFS (c-index: 0.786) in patients with MM and RI.Conclusion: ANS may serve as a potential prognostic biomarker in patients with MM and RI. The proposed nomograms may facilitate prognostic predictions for patients with MM and RI.Keywords: multiple myeloma, renal impairment, neutrophil–lymphocyte ratio, albumin-to-globulin ratio, prognosis

Jingwen Xu,1,2 Yue Zhang,1,2 Xiaolin Yao,1 Sijuan Wang,1,2 Kaiqiang Lv,1,2 Guangwen Luo,1,2 Jiaqi Wang,1,2 Guoliang Li1 1School of Food Science and Engineering, School of Biological and Pharmaceutical Sciences, Shaanxi University of Science & Technology, Xi’an, 710021, People’s Republic of China; 2Xi’an Key Laboratory of Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Xi’an, 710021, People’s Republic of ChinaCorrespondence: Guoliang Li, Email 61254368@163.comIntroduction: To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging.Methods: A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release.Results: Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1.Conclusion: This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res. Keywords: trans-resveratrol, seleno-alginate, synergistic antioxidant, mucoadhesion, intestinal targeted delivery

Xiaohong Yao,1 Min Feng,1,2 Wei Wang1,2 1Department of Pathology, West China Second University Hospital, Sichuan University, Sichuan, Chengdu, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Wei Wang, Email bearwin2000@126.comAbstract: Endometrial cancer shows high histological and molecular heterogeneity. The POLE mutation is a significant molecular alteration in endometrial cancer, leading to the identification of a specific subtype known as POLE-mutated endometrial cancer. This subtype exhibits a high tumor mutation burden, abundant lymphocyte infiltration, and a favorable prognosis, making it a promising candidate for immune checkpoint inhibitor therapy. This paper presents a comprehensive review of the clinical and pathological characteristics, outcomes, treatment advancements, pathogenic POLE gene detection, and alternative testing methods for POLE-mutated endometrial cancer.Keywords: endometrial cancer, molecular subtyping, POLE, POLE-mutated endometrial cancer, immunotherapy

Weiwei Xiang,1,&ast; Yifan Wu,2,&ast; Hongyan Li,1,&ast; Desheng Zhu,1 Xiaoying Yao,1 Jie Ding,1 Ze Wang,1 Yangtai Guan1 1Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangtai Guan, Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Shanghai, People’s Republic of China, Email yangtaiguan@sina.comBackground: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system. However, few biomarkers have been found to predict the outcome of immunotherapy. We investigated the relationship between the serum albumin (S-Alb) and response to immunotherapy in acute NMOSD patients.Methods: A total of 107 consecutive Chinese patients with acute NMOSD diagnosed between January 2013 and January 2022 were included in our prospective observational study. S-Alb was measured by the use of bromocresol green and immunoturbidimetric methods on admission. The immunotherapy response was assessed by the percentage change in the expanded disability status scale (EDSS) score from admission to discharge after treatment. We evaluated the association between S-Alb and immunotherapy response through multivariate logistic regression analysis.Results: S-Alb levels were significantly lower in patients who were resistant to immunotherapy than in those who were responsive to treatment (p< 0.001). S-Alb levels were positively related to a favorable response to immunotherapy (r=0.386, p< 0.001). The odds ratio (95% CI) for the association between S-Alb level and response to immunotherapy was 1.27 (95% CI=1.08, 1.50; p=0.004) after adjusting for potential factors. ROC analysis showed that patients with S-Alb levels lower than 40.85 g/L were likely to be resistant to immunotherapy.Conclusion: Our study indicated that a higher S-Alb was an independent indicator of response to immunotherapy in acute NMOSD patients.Keywords: immune diseases, NMOSD, immunotherapy, albumin, multivariate analysis

Kaiyuan Zhang,1,&ast; Ziyue Luo,1,&ast; Xinchao Zhu,1 Xinyi Yao,1 Dingqi Lu,2 Liying Chen,1 Tao Hong,1 Yating Ren,1 Xinchang Wang3 1Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 2First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 3Department of Rheumatology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinchang Wang, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86 13065714635, Email ossani@126.comPurpose: Sjogren’s Syndrome (SS) is a systemic autoimmune disease primarily characterized by dysfunction of the exocrine glands. Research into the etiology and pathogenesis of salivary glands (SG) inflammation of SS is very limited. The aim of this study was to identify potential pyroptosis-related genes in SG inflammation through bioinformatics analysis and validation of the SG in SS.Methods: GSE157159 dataset and GSE159574 dataset were downloaded from Gene Expression Omnibus (GEO). Differentially Expressed Genes (DEGs) analysis was used to screen DEGs from SS and non-SS SG samples. Pyroptosis-related genes were obtained from GeneCards. After intersecting DEGs with pyroptosis-related genes, the pyroptosis-related DEGs in SS were obtained. Subsequently, ClueGO enrichment analysis, Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis, Protein-protein Interaction (PPI), and identification and co-expression analysis of hub genes were performed. Subsequently, we collected SG samples from 17 SS patients and 17 non-SS patients and validated the expression of two hub genes (GZMA, GBP1) and characteristic genes (GSDMD) of pyroptosis through immunohistochemistry. The accuracy of hub genes as biomarkers for predicting SS was evaluated by receiver operating characteristic (ROC) curve.Results: 834 DEGs were selected from the GSE157159 dataset, and a total of 39 pyroptosis-related DEGs were obtained. Functional analysis showed that these DEGs were significantly enriched in some inflammatory signaling pathways. Through the intersection of seven algorithms proposed by CytoHubba and validation using the GSE159574 dataset, 11 hub genes were identified, including IL18, AIM2, CCL5, CD274, GBP1, GBP5, GZMA, GZMB, TLR8, TNFS13B, and ICAM1. Finally, the results of immunohistochemistry showed that GSDMD, GZMA and GBP1 were all significantly highly expressed in SG from SS. And ROC analysis showed a high combined diagnostic value of the 3 genes (AUC=0.8858).Conclusion: Our study revealed enhanced levels of pyroptosis in the SS. GZMA and GBP1 were identified as candidate genes for pyroptosis-induced inflammation of the SG in SS, which may be used as biomarkers or potential therapeutic targets for SS.Keywords: Sjogren’s syndrome, pyroptosis, bioinformatics analysis, salivary gland, immunology

Xuemei Yao,1 Beibei Liu,2 Nan Hua,2 Jiaoling Huang,2 Xin Zhao1 1Neurosurgical Intensive Care Unit, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi Province, People’s Republic of China; 2Xiangya School of Nursing, Central South University, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Xin Zhao, Tel +86-173-9387-4096, Email 1157340236@qq.comPurpose: Sarcopenia and physical activity are significant factors influencing cognitive function. However, few studies have examined their underlying mechanisms between the three conditions. The aim of the study is to examine the mediating role of physical activity in the relationship between sarcopenia and cognitive function in elderly nursing home residents.Materials and Methods: A total of 420 older adults aged 60 years and above in nursing homes participated in this study. Sarcopenia was defined following the Asian Sarcopenia Working Group (AWGS) 2019 criteria. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). Multiple linear regression analysis was employed to explore the relationships between sarcopenia, cognitive function and physical activity. Mediation analyses were performed to examine whether physical activity moderates the relationship between sarcopenia and cognitive function, with the use of PROCESS macro version 4.0.Results: A total of 386 older adults were included in the analysis (mean age 80.30 years), 175 (45.3%) were assessed as cognitive impairment, and sarcopenia was more common in those with cognitive impairment (p < 0.01). The linear regression analysis indicated that there were significant associations between sarcopenia and physical activity (β = − 0.285, p = 0.012), physical activity and cognitive function (β = 0.218, p < 0.001), and sarcopenia and cognitive function (β = − 0.245, p = 0.021). Mediating effects of physical activity on the association between sarcopenia and cognitive function were observed in participants, with 20.2% of partial mediating effect.Conclusion: The results of the study suggest physical activity may partially buffer the adverse effects of sarcopenia on cognitive impairment among the older adults in nursing homes. Accordingly, engagement in physical activity can help to preserve cognitive function among those with sarcopenia.Keywords: cognitive impairment, sarcopenia, physical activity, older adults

Xue Wang,1,&ast; Chenghua Gao,2,&ast; Yuan Xia,1 Xiaoqian Xu,1 Lehui Li,1 Yan Liu,1 Xing Yao,3 Ning Cao,1 Zichao Li,1 Xin Fang1 1Public Health College, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 2School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, 518055, People’s Republic of China; 3Infection Control Department, Inner Mongolia People’s Hospital, Hohhot, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Fang, Public Health College, Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China, Tel +86 18686066179, Email 18686066179@163.comObjective: There is limited evidence that atmospheric pollutants are associated with the number of allergic rhinitis (AR) visits. This study aimed to investigate the relationship between atmospheric pollutants and meteorological factors and the number of daily visits for AR in Hohhot City, providing a theoretical basis for further research on the effects of atmospheric pollutants on AR.Methods: Microsoft Excel 2016 was used to collect and organize the AR outpatient consultation data, air pollution and meteorological data in Hohhot City during 2018– 2020, and the data were descriptively analyzed and Spearman correlation test was performed using SPSS22.0; A generalized additive model was built in R4.2.3 to analyze the effect of air pollution on the number of AR visits and its lagged and cumulative effects, while the robustness of the model was tested using a two-pollutant analysis. Finally, we analyzed the effects of the interaction of temperature, relative humidity and pollutants on the number of AR visits.Results: The daily average concentrations of PM2.5, PM10, SO2, NO2, CO, and O3 in Hohhot during 2018– 2020 were 38.1 μg/m3, 83.3 μg/m3, 36.1 μg/m3, 15.1 μg/m3, 14.2 mg/m3, and 99.95 μg/m3, respectively, with the concentrations of PM2.5 and PM10 exceeding the secondary limit of the national standard. The results of the generalized additive model analysis showed that the RR and 95% CI of the effect of each 10 μg/m3 increase in pollutant concentration (1 mg/m3 increase in CO) on the number of AR outpatient clinics were 1.008 (1.001– 1.016), 1.002 (1– 1.005), 1.072 (1.033– 1.113), 1.020 (1007– 1.034), 1.033 (1.014– 1.052), 0.987 (0.9804– 0.9936).Conclusion: Short-term exposure to PM2.5, PM10, SO2, NO2, and CO was significantly associated with an increase in AR clinic visits, and short-term exposure to O3 was significantly associated with a decrease in allergic rhinitis clinic visits.Keywords: allergic rhinitis, air pollutants, time series study, interaction effect

Yang Zhang,1,2,&ast; Jiahao Chu,2,&ast; Yunfan Xia,2 Yuepeng Xie,1 Ruikun Zhang,2 Xiaogang Chen,1 Zhineng Chen,1 Xinmiao Yao1,2 1The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinmiao Yao, Department of Orthopedics, the Third Affiliated Hospital of Zhejiang Chinese Medical University, 219 Moganshan Road, Xihu District, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 571-87238254, Fax +86 571-87238005, Email yxmzcmu@163.comObjective: This study aimed to explore the research trends of percutaneous endoscopic lumbar discectomy in treating lumbar disc herniation using bibliometrics over the past ten years.Methods: Relevant publications on the clinical application of percutaneous endoscopic lumbar discectomy in lumbar disc herniation were searched in the Web of Science Core Collection. Subsequently, the characteristics of all these articles were collected. Visualizing data of annual publications, journals, cited journals, authors, cited authors, countries, institutions, keywords, and cited references was performed by using CiteSpace (6.1.R6).Results: A total of 642 publications were extracted between 2013 and 2022. The number of publications peaked in the year 2020. The most prolific journal was World Neurosurgery (81), and Spine (597) as the cited journal was the most popular one. China (393) was the most prolific country, followed by South Korea (100). The institution with the most productivity was Tongji University (35). Yue Zhou (20) was the most prolific author, and Sebastian Ruetten (310) was the most cited author. The keyword “interlaminar” was top of research developments with the highest citation burst (8.69). “Lumbar disc herniation”, “surgical technique”, and “complication” were popular keywords. The surgical procedures and complications of percutaneous endoscopic lumbar discectomy have been the hot topics of recent research.Conclusion: This study summarized the current situation and development trends of percutaneous endoscopic lumbar discectomy clinical research in the form of visualization, and these findings may help researchers explore new directions in the future.Keywords: percutaneous endoscopic lumbar discectomy, lumbar disc herniation, bibliometric analysis, complication

Yuan Li,1,2,&ast; Gaihe Chen,3,&ast; Xin Zhou,4,&ast; Xiaole Zheng,1,&ast; Ming Zhang,3 Xiaojuan Yao,1 Jiejie Lu,1 Xiaohuan Hu1 1Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 4Medical Administration Department, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohuan Hu; Jiejie Lu, Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, 570100, People’s Republic of China, Email 872114382@qq.com; lujiejie677@163.comAbstract: We conducted a retrospective analysis of clinical and pathologic data from January 2020 to June 2023, focusing on 10 patients diagnosed with eosinophilic pustular folliculitis at our dermatology clinic. Four of the ten patients had the first rash on the face, five on the trunk, and one on the palms and feet, all of which were initially scattered papules that gradually increased and fused into erythematous plaques with a circular distribution. Seven had pustules with small surface desquamation, and three cases had micro swelling on the face. The rash involved only the face in 5 cases, the face and trunk in 5 cases, and the face, trunk, hands, and feet in 1 case. Seven of the ten patients were pruritic, and 3 had no obvious pruritus. The histopathological features were mild epidermal hyperplasia, lymphocytic and eosinophilic infiltration around the superficial middle dermal vessels and appendages, and eosinophilic and neutrophilic abscesses in the local hair follicles. Treatment with oral indomethacin, prednisone, and minocycline was effective.Keywords: eosinophilic pustular folliculitis, eosinophils, indomethacin

We present a framework to simulate the dynamics of hard probes such as heavy quarks or jets in a hot, strongly coupled quark-gluon plasma (QGP) on a quantum computer. Hard probes in the QGP can be treated as open quantum systems governed in the Markovian limit by the Lindblad equation. However, due to large computational costs, most current phenomenological calculations of hard probes evolving in the QGP use semiclassical approximations of the quantum evolution. Quantum computation can mitigate these costs and offers the potential for a fully quantum treatment with exponential speed-up over classical techniques. We report a simplified demonstration of our framework on IBM Q quantum devices and apply the random identity insertion method to account for cnot depolarization noise, in addition to measurement error mitigation. Our work demonstrates the feasibility of simulating open quantum systems on current and near-term quantum devices, which is of broad relevance to applications in nuclear physics, quantum information, and other fields.

Dingqi Lu,1,&ast; Xinchao Zhu,2,&ast; Tao Hong,2 Xinyi Yao,2 Zhiming Xie,3 Liying Chen,2 Yihan Wang,2 Kaiyuan Zhang,2 Yating Ren,2 Yi Cao,4 Xinchang Wang3 1First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 2Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 3The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 4The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinchang Wang, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86 13065714635, Email ossani@126.comPurpose: Systemic lupus erythematosus is a heterogeneous autoimmune disease in which skin involvement is a common manifestation. It is currently thought that the photosensitivity of SLE skin involvement is associated with anti-SSA antibodies. This study aimed to expand the current state of knowledge surrounding the molecular pathophysiology of SLE skin photosensitivity through Serum metabolomics analysis.Patients and Methods: The serum metabolites of 23 cases of skin-involved SLE (SI) group, 14 cases of no SI (NSI) group, and 30 cases of healthy controls (HC) were analyzed by using UPLC-MS/MS technology, and subgroup analysis was performed according to the expression of anti-SSA antibodies in SI. MetaboAnalyst 5.0 was used for enrichment analysis and ROC curve construction, identifying serum metabolic markers of skin-involved SLE associated with anti-SSA antibodies.Results: We identified several metabolites and metabolic pathways associated with SLE photosensitivity. Two metabolites, SM (d18:1/24:0) and gamma-CEHC can distinguish between anti-SSA antibody-positive and negative SI, with AUC of 0.829 and 0.806. These two photosensitization-related substances may be potential markers of skin involvement in SLE associated with anti-SSA antibody.Conclusion: This study provides new insights into the pathogenesis of SI patients, and provides a new molecular biological basis for the association between anti-SSA antibodies and skin photoallergic manifestations of SLE.Keywords: systemic lupus erythematosus, metabolomics, biomarkers, anti-SSA antibodies, photosensitivity

Yuan Li,1,2,&ast; Miaoting Wu,1,&ast; Xiaohuan Hu,1,&ast; Gaihe Chen,1,&ast; Xiaojuan Yao,1 Xin Zhou,3 Jiejie Lu1 1Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Medical Administration Department, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiejie Lu, Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, 570100, People’s Republic of China, Email lujiejie677@163.com Xin Zhou, Medical Administration Department, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, 570100, People’s Republic of China, Email zx5575759@126.comAbstract: Eosinophilic pustular folliculitis (EPF) is a rare skin disease for which the gold standard of diagnosis relies on the invasive examination of pathological tissue sections. However, due to its invasive nature, many patients tend to refuse this diagnostic test. In such situations, reflectance confocal microscopy (RCM) can be a valuable diagnosis tool. Reflectance confocal microscopy (RCM) can accurately identify the specific structures for biopsy and provide objective imaging data to evaluate clinical symptoms following treatment. Therefore, we present a case report demonstrating the utility of RCM in diagnosing and assessing the treatment of the rare disease EPF for reference.Keywords: eosinophilic pustular folliculitis, minocycline, reflectance confocal microscopy, non-invasive detection

Xin Yao,1 Qingyu Wang,1 Changge Han,1 Jiaojiao Nie,1 Yaotian Chang,1 Lipeng Xu,1 Bingya Wu,1 Jingtian Yan,1 Zhiyuan Chen,1 Wei Kong,1,2 Yuhua Shi,1 Yaming Shan1,2 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, 130012, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, 130012, People’s Republic of ChinaCorrespondence: Yaming Shan, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, Jilin, 130012, People’s Republic of China, Tel +86 133 2446 4361, Email shanym@jlu.edu.cnIntroduction: Broadly neutralizing antibodies (bNAbs) have the ability to neutralize a considerable breadth of genetically diverse human immunodeficiency virus (HIV) strains. Passive immunization can potentially provide protection against HIV infection in animal models. However, the direct antibody infusion effect is limited due to the short half-life and deficient immunogenicity of the antibody. As an alternative strategy, we propose the use of nano viral vectors, specifically the adeno-associated virus (AAV), to continuously and systematically produce bNAbs against HIV.Methods: Plasmids expressing bNAbs PG9, PG16, 10E8, and NIH45-46 antibodies were constructed, targeting three different epitopes of HIV. Additionally, the bNAbs gene mediated by rAAV8 was administered to generate long-term expression with a single injection. We established both single and combined immunization groups. The neutralizing activity of antibodies expressed in mice sera was subsequently evaluated.Results: The expression of bNAbs in BALB/c mice can last for > 24 weeks after a single intramuscular injection of rAAV8. Further studies show that neutralization of the HIV pseudovirus by sera from co-immunized mice with rAAV8 expressing 10E8 and PG16 was enhanced compared with mice immunized with 10E8 or PG16 alone.Conclusion: The prolonged expression of neutralizing antibodies can be maintained over long periods in BALB/c mice. This combined immunization is a promising candidate strategy for HIV treatment.Graphical Abstract: Keywords: AAV delivery, HIV therapy, passive immunotherapy, combined immunotherapy

Minglei Ma, Tao Jiang, Dongxue Zhang, Xiaoai Yao, Zhen Wen, Lei Xiu Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaCorrespondence: Tao Jiang, Email jiangtao@bjsjth.cnObjective: To investigate the association of bedtime with the risk of early-onset diabetes mellitus (DM) and islet beta cell function.Methods: 138 participants with treat-naïve DM were included in this study. All participants underwent a 75g oral glucose tolerance test. Sleep habit was obtained through a standardized questionnaire. Bedtime was categorized as < 22:00, 22:00– 24:00, and ≥ 24:00 in this study. Multivariate logistic regression and multiple linear regression were used to estimate the association between bedtime and risk of early-onset DM and islet beta cell function, respectively.Results: Patients with early-onset DM had a later bedtime than those with late-onset DM. Individuals with bedtime ≥ 24:00 had a higher prevalence of early-onset DM than those with bedtime at 22:00– 24:00 and < 22:00 (51.2% vs 29.3% vs 14.3%, respectively, p = 0.028). The multivariate logistic regression showed that per hour later in bedtime was associated with a 52% increased risk of early-onset DM (p = 0.023). Patients with bedtime after 24:00 had a 146% increased risk of early-onset DM compared to those went to bed between 22:00 to 24:00 (OR = 2.46, 95% CI 1.05 to 5.77, p = 0.039). The multiple linear regression showed that bedtime was independently negatively correlated with late-phase insulin secretion (assessed by disposition index, DI120).Conclusion: Later bedtime was associated with worse late-phase insulin secretion and may be a risk factor for early-onset DM. Proper bedtime to lower risk of early-onset DM deserves further investigation.Keywords: diabetes mellitus, early-onset, sleep, bedtime, islet beta cell function

Yan Wu,1 Shan Liu,1 Dongmei Wang,1 Xinjie Yao2 1Department of Hematology, The Harison International Peace Hospital Affiliated to Hebei Medical University, Hengshui, Hebei, 053000, People’s Republic of China; 2Department of Clinical Laboratory, The Harison International Peace Hospital Affiliated to Hebei Medical University, Hengshui, Hebei, 053000, People’s Republic of ChinaCorrespondence: Dongmei Wang, Department of Hematology, The Harison International Peace Hospital Affiliated to Hebei Medical University, No. 180 Renmin East Road, Hengshui, Hebei, 053000, People’s Republic of China, Tel/Fax +86-318-2187163, Email wdmys1970@163.comBackground: This study aimed to improve the understanding of acute myeloid leukemia (AML) secondary to chronic lymphocytic leukemia (CLL), and to explore the sequence of occurrence and clonal origin of the two diseases.Case Report: We reported a case of a 71-year-old man with a history of CLL. The patient was administrated with chlorambucil for 19 years and was admitted to our hospital due to fever. Then he was subjected with routine blood tests, bone marrow smear examination, flow cytometric immunophenotyping and cytogenetic analysis. A final diagnosis of AML-M2 secondary to CLL with -Y,del(4q),del(5q),-7,add(12p),der(17),der(18),-22,+mar was made. After rejecting the therapy with Azacitidine combined with B-cell lymphoma-2 (Bcl-2) inhibitor, the patient died of pulmonary infection.Conclusion: This case highlights the rare occurrence of AML secondary to CLL after prolonged chlorambucil therapy and the poor prognosis of such cases, underscoring the importance of enhanced assessment of these patients.Keywords: acute myeloid leukemia, chronic lymphocytic leukemia, Bcl-2 inhibitor, Azacitidine

Mingxun Wang,1,&ast; Xinfei Yao,2,&ast; Zhiyuan Bo,3,4,&ast; Jiuyi Zheng,3 Haitao Yu,3 Xiaozai Xie,3 Zixia Lin,3 Yi Wang,5 Gang Chen,3,4 Lijun Wu3 1Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2The First Clinical College, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 5Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lijun Wu; Gang Chen, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Fuxue Road, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86 577 55579-453, Fax +86 577 55579-555, Email wumolijun@163.com; chen.gang@wmu.edu.cnPurpose: The current study aimed to evaluate the synergistic efficacy of lenvatinib and FOLFOX (infusional fluorouracil (FU), folinic acid, and oxaliplatin) in hepatocellular carcinoma (HCC) using patient-derived xenograft (PDX) and PDX-derived organotypic spheroid (XDOTS) models in vivo and in vitro.Methods: PDX and matched XDOTS models originating from three patients with HCC were established. All models were divided into four groups and treated with drugs alone or in combination. Tumor growth in the PDX models was measured and recorded, and angiogenesis and phosphorylation of the vascular endothelial growth factor receptor (VEGFR2), rearranged during transfection (RET), and extracellular signal-regulated kinase (ERK) were detected using immunohistochemistry and Western blot assays. The proliferative ability of XDOTS was evaluated through active staining and immunofluorescence staining, and the effect of the combined medication was evaluated using the Celltiter-Glo luminescent cell viability assay.Results: Three PDX models with genetic characteristics similar to those of the original tumors were successfully established. Combining lenvatinib with FOLFOX led to a higher tumor growth inhibition rate than individual therapies (P < 0.01). Immunohistochemical analysis demonstrated that the combined treatment significantly inhibited the proliferation and angiogenesis of PDX tissues (P < 0.05), and Western blot analysis showed that the combined treatment significantly inhibited the phosphorylation of VEGFR2, RET, and ERK compared with single-agent treatment. Additionally, all three matched XDOTS models were successfully cultured with satisfactory activity and proliferation, and the combined therapies led to better suppression of XDOTS growth compared with individual therapy (P < 0.05).Conclusion: Lenvatinib combined with FOLFOX had a synergistic antitumor effect in HCC PDX and XDOTS models by inhibiting the phosphorylation of VEGFR, RET, and ERK.Keywords: hepatocellular carcinoma, lenvatinib, chemotherapy, patient-derived xenografts, angiogenesis

Wenbo Yang,1,&ast; Xintian Cai,1,2,&ast; Junli Hu,1 Wen Wen,1 Heizhati Mulalibieke,1 Xiaoguang Yao,1 Ling Yao,1 Qing Zhu,1 Jing Hong,1 Qin Luo,1 Shasha Liu,1 Nanfang Li1 1Hypertension Center, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China; 2Graduate School, Xinjiang Medical University, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, NO. 91 TianChi Road, Urumqi, 830001, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina.comObjective: We aimed to evaluate the METS-IR (metabolic score for insulin resistance) index for the prediction of incident cardiovascular disease (CVD) and its subtypes (coronary artery disease and stroke) in patients with hypertension and obstructive sleep apnea (OSA).Methods: A retrospective cohort study was conducted with 2031 adults with hypertension and OSA, participants from the Urumqi Research on Sleep Apnea and Hypertension study (UROSAH). The hazard ratios and 95% CIs (credibility interval) for CVD and its subtypes were estimated using multivariate Cox proportional hazards regression models.Results: After a median follow-up of 6.80 years (interquartile range: 5.90– 8.00 years), a total of 317 (15.61%) participants developed new-onset CVD, including 198 (9.75%) incident coronary heart disease (CHD) and 119 (5.86%) incident stroke. After adjusting for as many relevant confounding factors as possible, each SD increase in METS-IR was associated with a 30% increased risk of new onset overall CVD events, a 32% increased risk of new onset CHD, and a 27% increased risk of new onset stroke. When METS-IR was assessed as tertiles, after adjustment for fully confounding factors, the highest tertiles versus the lowest tertiles were associated with a greater hazard of CVD (HR 2.05; 95% CI 1.52,-2.77), CHD (HR 1.96; 95% CI 1.35– 2.84), and stroke (HR 2.24; 95% CI 1.35– 3.72). The results of various subgroups and sensitivity analyses were similar. When METS-IR was added, CVD predictions were reclassified and identified more accurately than baseline models for the C-index, continuous net reclassification improvement, and integrated discrimination index. CHD and stroke showed similar results.Conclusion: METS-IR is a powerful predictor of CVD and its subtypes in patients with hypertension and OSA, which can facilitate the identification of high-risk individuals and provide individualized CVD prevention.Keywords: cohort study, METS-IR, cardiovascular disease, hypertension, obstructive sleep apnoea

Zhijie Li,1,2,&ast; Mengnan Li,1,&ast; Xiaowei Yao,3 Bo Liu,1 Sikai Liu,1 Zeming Liu,1 Binquan Zhang,1 Yongtai Han1 1Department of Osteonecrosis and Hip Surgery, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, People’s Republic of China; 2Orthopedics Department, Affiliated Hospital of Hebei Engineering University, Handan, People’s Republic of China; 3Orthopedics Department, Hebei Provincial Chest Hospital, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongtai Han, Email yongtaihan@foxmail.comBackground: Whether hip revision with a metaphyseal-fixation femoral stem component can restore the bone mass of the proximal femur remains unclear. The aims of this study were to identify whether the bone mineral density (BMD) of the proximal femur increases following hip revision with a metaphyseal-fixation femoral stem and to identify the factors associated with BMD recovery.Methods: This was a retrospective study involving 36 patients who underwent hip arthroplasty with a metaphyseal-diaphyseal fixation stem (standard length stem) and had indications for hip revision, which was performed with a proximal press-fit short-stem prosthesis for each patient. Dual-energy X-ray absorptiometry (DEXA) was used to obtain, evaluate, and compare the BMD at baseline and one year and two years postoperatively. The proximal femur was divided into several independent areas according to the Gruen zone (Gruen 1 to Gruen 7 from the greater trochanter counterclockwise to the lesser trochanter). Logistic regression analyses were used to assess potential factors significantly associated with an increase in BMD.Results: An increased BMD was obviously identified in the proximal femur. Two years after the surgery, the BMD of the Gruen 1, Gruen 2, Gruen 6, and Gruen 7 areas had increased by 22.6%, 12.6%, 16.2% and 24.2%, respectively, relative to baseline. Three independent risk factors associated with bone mineral density recovery were identified: age (OR=1.100, 95% CI=1.005– 1.203, P=0.038), osteoporosis (OR=14.921, 95% CI=1.223– 182.101, P=0.034) and fair to poor hip function (OR=13.142, 95% CI=1.024– 168.582, P=0.048).Conclusion: This study confirms that metaphyseal-fixation stem hip revision can indeed help restore bone mass in the proximal femur, especially in the Gruen 1, Gruen 2, Gruen 6 and Gruen 7 zones. It was also found that advanced age, osteoporosis, and fair to poor hip joint function were three important risk factors affecting the recovery of proximal femur bone mass after surgery.Trial Registration: Retrospectively registered.Keywords: uncemented fixation, hip revision, bone mineral density, metaphyseal-fixation femoral stem component

Jie Ren,1,&ast; Jingzhou Wang,2,&ast; Xingchen Yao,1 Yue Wu,1 Ming Shi,1 Xiangjun Shi,3 Xinru Du1 1Department of Orthopaedics, Beijing Chao-yang Hospital, Beijing, 100020, People’s Republic of China; 2Department of Orthopaedics, Beijing Daxing District People’s Hospital, Beijing, 102600, People’s Republic of China; 3Department of Hematology, Beijing Chao-yang Hospital, Beijing, 100020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinru Du, Department of orthopaedics, Beijing Chao-yang Hospital, No. 8 of Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 13683156652, Email duxinru@163.comObjective: To explore the role of sclerosteosis (SOST) gene expression in the occurrence and development of multiple myeloma (MM) complicated with sarcopenia.Methods: Analysis of the SOST expression in skeletal muscle tissue of patients with MM using high-throughput sequencing combined with transcriptomics; observation of morphological changes of the mouse C2C12 myoblasts co-cultured with SP2/0 myeloma cells in Transwell; observation of the SOST expression in the C2C12 myoblasts using the immunofluorescence labeling method; and assessment of the changes in exercise capacity of mice with MM using ethology; and the measurement of the SOST expression in muscles of mice using immunohistochemistry.Results: The transcription level of the SOST gene in the muscle tissue was significantly higher in patients with MM and sarcopenia than in patients with MM without sarcopenia and elderly patients with sarcopenia; the area of C2C12 mouse myoblasts co-cultured with SP2/0 myeloma cells was 167,904 ± 8653.7 pix; this was significantly lower than the area of 402,994 ± 13,575.0 pix in the control group (CG); the fluorescence intensity of SOST in the cells of the experimental group (EG) was 159,389 ± 10,534 AU; this was significantly higher than the intensity of 26,338 ± 6059 AU in the CG; the differences in results of the coat-hanger test, the tail suspension test, the weight-bearing forced swimming test, and the grip strength test between the tumor-bearing mice in the EG and the CG were statistically significant; and the quantitative result of SOST expression in the muscle tissue of the EG mice was 11,515 ± 1573 pix; this was significantly higher than the result of 3399 ± 798.8 pix in the CG.Conclusion: The SOST gene expression was significantly higher in muscle of mice in EG than in CG; and increased SOST gene expression might be a pathogenesis of MM complicated with sarcopenia.Keywords: multiple myeloma, SOST, multiple myeloma mouse model, ethology, sarcopenia, myoblast differentiation

Yuan Li,1,2 Xiaole Zhen,1 Xiaojuan Yao,1 Jiejie Lu1 1Dermatology Department, the Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Jiejie Lu, Dermatology Department, the Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, 570100, People’s Republic of China, Email lujiejie677@163.comAbstract: Minocycline is a tetracycline derivative antibiotic commonly used to treat acne, rosacea, and other inflammatory skin conditions. Taking minocycline risks inducing skin pigmentation. If minocycline-induced hyperpigmentation is not treated, it may take months to years for the symptoms to subside after discontinuation of the drug, or the hyperpigmentation may never disappear completely, which can lead to cosmetic anxiety and affect people’s quality of life. Previous treatment options for hyperpigmentation were mainly q-switched nd: YAG, ruby, and alexandrite lasers. This article reports a case of facial hyperpigmentation caused by minocycline using a combination of chemical peel and intense pulsed light in a patient with eosinophilic cellulitis (Wells syndrome) who was taking oral minocycline. This case suggests combining chemical peel and intense pulsed light is an effective treatment option for minocycline-induced hyperpigmentation.Keywords: minocycline, pigmentation, chemical peel, intense pulsed light