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Jingjing Wei,1,* Zhaoyang Liu,1,2,* Mingming Li,1 Lingyun Du,1 Xia Zhu,1 Yi Leng,1 Changyu Han,1 Qingqing Xu,1 Chunhong Zhang1 1Department of Dermato-Venereology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Dermato-Venereology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunhong Zhang, Department of Dermato-Venereology, the Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Dajie Street, Jinan, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email aliu133@163.comBackground: Psoriasis is an immune-mediated chronic inflammatory disease. Qingre Lishi Decoction (QRLSD) has achieved great clinical effect in the treatment of psoriasis. However, the potential bioactive components and the mechanisms are yet unclear.Aim: To analyze the serum parameters of rats fed with QRLSD, screen out the active components of QRLSD, and explore the potential targets and pathway of QRLSD in the treatment of psoriasis.Materials and Methods: The active components of serum containing QRLSD were analyzed using ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The targets of QRLSD in the treatment of psoriasis were predicted by network pharmacology and molecular docking. In vitro experiments verified the underlying mechanism.Results: By UPLC-Q-TOF/MS, 15 prototype components and 22 metabolites were identified in serum containing QRLSD. Subsequently, 260 chemical composition targets and 218 psoriasis targets were overlapped to obtain 23 intersection targets, including LGALS3, TNF, F10, DPP4, EGFR, MAPK14, STAT3 and others. TNF, IL-10, GAPDH, STAT3, EGFR, ITGB1, LGALS3 genes were identified as potential drug targets in the PPI network analyzed by CytoHubba. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that QRLSD may improve psoriasis by regulating immune and inflammatory pathways, the cytokine mediated signal transduction pathways and other signaling pathways. Molecular docking results showed that the main active components of the serum containing QRLSD had higher affinities for TNF and LGALS3. In vitro experiments confirmed that QRLSD may decrease levels of inflammatory cytokines by suppressing the NF-κB signaling pathway activated by TNF-α in human keratinocytes.Conclusion: This study explores the potential compounds, targets and signaling pathways of QRLSD in the treatment of psoriasis, which will help clarify the efficacy and mechanism of QRLSD.Keywords: qingre lishi decoction, psoriasis, UPLC-Q-TOF/MS, network pharmacology, molecular docking, NF-κB signaling pathway

Jingjing Wei,1 Chunhong Zhang,1 Yi Leng,1 Mingming Li,1 Lingyun Du,1 Zhiqiang Cao,2 Xia Zhu,1 Changyu Han,1 Liya Meng1 1Department of Dermato-Venereology, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Liya Meng, Department of Dermato-venereology, The Second Hospital of Shandong University, 247 Beiyuan Dajie Street, Jinan, 250033, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email mly0706@sina.comObjective and Design: The treatment of recurrent rosacea has always been a problem. Oral minocycline has been widely used in the treatment of rosacea. However, the efficacy and safety of ozonated hydrotherapy combined with LED yellow light irradiation and oral minocycline for mild to moderate papulopustular rosacea (PPR) has not been thoroughly studied.Methods: Patients with rosacea who met the criteria and had complete clinical statistic admitted to our hospital from April 2021 to September 2022 were retrospectively collected and divided into combined therapy group and oral only group. The patients in the two groups were treated with minocycline for 8 weeks. In addition, the patients in combined therapy group were treated with ozone hydrotherapy once a week, followed by LED yellow light irradiation for a total of 4 weeks. The Investigator’ s global assessment (IGA) score was used to assess the condition. The efficacy was evaluated using the patients’ subjective symptom scores. Skin lesion images and adverse reactions were recorded. The recurrence rate was observed after 24 weeks of follow-up.Results: A total of 39 patients included in the study. After 4 weeks of treatment, the effective rate was 90% in combined therapy group and 52.63% in oral only group (p< 0.05). After 8 weeks of treatment, the total score of the patients’ subjective symptom scores and the scores of itching and burning sensation in combined therapy group were lower than those in oral only group (p< 0.05). After 24 weeks of follow-up, the recurrence rate of combined therapy group was 5%, and that of oral only group was 26.32%. The mild adverse reactions experienced by both groups disappeared during follow-up.Conclusion: This combination therapy has a significant, rapid and safe therapeutic effect, especially in relieving itching and burning sensations, and may reduce the recurrence rate.Keywords: papulopustular rosacea, ozonated hydrotherapy, LED yellow light, minocycline, combined therapy

Mai Zhang,1 Yan Li,1,2 Chunli Han,3 Shiying Chu,1 Peng Yu,1 Wenbo Cheng1,2 1Mass Spectrometry Application Center, Tianjin Guoke Medical Technology Development Co., Ltd, Tianjin, People’s Republic of China; 2Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences (CAS), Suzhou, People’s Republic of China; 3Mass Spectrometry Application Center, Shandong CAS Intelligent Manufacturing Medical Device Technology Co., Ltd, Zaozhuang, People’s Republic of ChinaCorrespondence: Wenbo Cheng, Email chengwb@sibet.ac.cnBackground: Inhibition of amyloid β protein fragment (Aβ) aggregation is considered to be one of the most effective strategies for the treatment of Alzheimer’s disease. (-)-Epigallocatechin-3-gallate (EGCG) has been found to be effective in this regard; however, owing to its low bioavailability, nanodelivery is recommended for practical applications. Compared to chemical reduction methods, biosynthesis avoids possible biotoxicity and cumbersome preparation processes.Materials and Methods: The interaction between EGCG and Aβ 42 was simulated by molecular docking, and green tea-conjugated gold nanoparticles (GT-Au NPs) and EGCG-Au NPs were synthesized using EGCG-enriched green tea and EGCG solutions, respectively. Surface active molecules of the particles were identified and analyzed using various liquid chromatography-tandem triple quadrupole mass spectrometry methods. ThT fluorescence assay, circular dichroism, and TEM were used to investigate the effect of synthesized particles on the inhibition of Aβ 42 aggregation.Results: EGCG as well as apigenin, quercetin, baicalin, and glutathione were identified as capping ligands stabilized on the surface of GT-Au NPs. They more or less inhibited Aβ 42 aggregation or promoted fibril disaggregation, with EGCG being the most effective, which bound to Aβ 42 through hydrogen bonding, hydrophobic interactions, etc. resulting in 39.86% and 88.50% inhibition of aggregation and disaggregation effects, respectively. EGCG-Au NPs were not as effective as free EGCG, whereas multiple thiols and polyphenols in green tea accelerated and optimized heavy metal detoxification. The synthesized GT-Au NPs conferred the efficacy of diverse ligands to the particles, with inhibition of aggregation and disaggregation effects of 54.69% and 88.75%, respectively, while increasing the yield, enhancing water solubility, and decreasing cost.Conclusion: Biosynthesis of nanoparticles using green tea is a promising simple and economical drug-carrying approach to confer multiple pharmacophore molecules to Au NPs. This could be used to design new drug candidates to treat Alzheimer’s disease.Keywords: gold nanoparticles, green synthesis, (-)-epigallocatechin-3-gallate, liquid chromatography tandem triple quadrupole mass spectrometry, amyloid β protein, green tea

Pengzhu Huang,1,2,&ast; Rongrong Wu,1,2,&ast; Xin Guo,1,2,&ast; Xiaoli Gao,1,2 Ye Yan,1,2 Cha Han,1,2 Fengxia Xue1,2 1Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengxia Xue; Cha Han, Department of Gynecology and Obstetrics, Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China, Tel +86-22-60363769, Fax +86-22-27813550, Email xuefengxia@tmu.edu.cn; tjhancha@tmu.edu.cnObjective: This study aimed to evaluate the impact of twin pregnancies with antiphospholipid antibody (aPL) positivity, a rare and complex clinical condition that remains a huge challenge for management.Methods: This study enrolled twin-pregnant women at our hospital between January 2018 and August 2023. Women with and without aPL positivity were selected using propensity score matching (PSM). Clinical features and pregnancy outcomes were compared between the two groups in the PSM cohort. To analyze the effect of aPL positivity on pregnancy outcomes, multivariate logistic models were used to obtain adjusted odds ratios (aOR) with 95% confidence intervals (CI).Results: Among the 773 women with twin pregnancies, aPL positivity was found in 26 women (3.36%). In the PSM cohort, there were 24 twin-pregnant women with positive aPL, and 48 women without aPL were selected as controls. Twin-pregnant women with aPL positivity had a higher proportion of abortion (8.33% vs 0, P = 0.043), preterm birth < 34 weeks (33.33% vs 8.33%, P = 0.007) and very low birthweight (< 1500 g) (20.83% vs 4.17%, P = 0.016) than the control group. In addition, stillbirth of one fetus was observed in one twin-pregnant woman with positive aPL. Multivariate logistic regression analysis revealed that twin pregnancy with aPL positivity was associated with preterm birth < 34 weeks (aOR = 2.76, 95% CI: 0.83– 4.70, P = 0.005), very low birthweight (< 1500 g) (OR = 2.40, 95% CI: 0.18– 4.67, P = 0.034) and small for gestational age (SGA) (aOR = 1.66, 95% CI: 0.22– 3.10, P =0.024).Conclusion: Twin pregnancies with aPL positivity were correlated with obstetric complications, including abortion, preterm birth < 34 weeks and very low birthweight (< 1500 g). The detection of aPL may be of clinical significance for women with twin pregnancies and should be considered in future studies.Keywords: twin pregnancy, antiphospholipid antibody, pregnancy outcomes, propensity score matching

Feng Lu,1,&ast; Yangyang Wang,2,&ast; Fangyu Miao,3 Chengzhou Han,2 Xiangming Meng2 1Department of Emergency Medicine, Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, Wuxi, 214187, People’s Republic of China; 2Department of Otolaryngology, Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, Wuxi, 214187, People’s Republic of China; 3Information Centre, Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, Wuxi, 214187, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangming Meng, Department of Otolaryngology, Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, 2 Zhanqian North Road, Luoshe Town, Huishan District, Wuxi, 214187, People’s Republic of China, Email xiangming_meng@hotmail.comPurpose: This study aimed to investigate the clinical characteristics of acute epiglottitis (AE) patients in East China and examine the correlation between the incidence of AE and the 24 solar terms (24 STs).Methods: A retrospective, observational study was conducted on patients diagnosed with AE between January 2014 and December 2021 at a single-center medical institution in East China. The clinical characteristics of patients with AE and their correlation with the 24 STs were investigated.Results: A total of 287 patients with AE were included in this study, among which there were 179 males (62.37%) and 108 females (37.63%), with a mean age of 47.79 ± 13.83 years (range 16– 87 years). Of these patients, 100 (34.84%) had at least one comorbidity and the most common comorbidities were hypertension, smoking and type 2 diabetes. The duration of hospitalization was 3 days (IQR, 1– 16 days). All patients, except for one who required tracheal intubation, were cured with intravenous antibiotic administration and the combined use of corticosteroids. The incidence of AE showed significant fluctuations between the 24 STs and the highest number of cases occurred during the Summer solstice (24 cases, 8.36%).Conclusion: The incidence of AE was seen to increase annually in this study. The main features of AE are sore throat, dysphagia, odynophagia and fever, which may be accompanied by inflammation in surrounding areas. A clear correlation exists between the incidence of AE and the fluctuations within the 24 STs, notably with the peak incidence observed during the Summer solstice, which approximately corresponds to June 21 to July 7 in the Gregorian calendar.Keywords: acute epiglottitis, 24 solar terms, seasonal variations, incidence, summer solstice

Chunyi Lyu,1 Hongyan Xiao,1 Xuewei Yin,2 Zonghong Li,1 Chen Han,1 Ruirong Xu3,4 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 2Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250002, People’s Republic of China; 3Key Laboratory of Integrated Traditional Chinese and Western Medicine for Hematology, Health Commission of Shandong Province; Institute of Hematology, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 4Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of ChinaCorrespondence: Ruirong Xu, Email shandongxuruirong@163.comBackground: Peripheral neuropathy (PN) is a prevalent complication of multiple myeloma (MM), due to the disease itself or its treatment. Despite extensive research, the optimal treatment for multiple myeloma peripheral neuropathy (MMPN) remains unclear. Clinical practice has shown the potential efficacy of acupuncture in managing MMPN. This study aimed to conduct a comprehensive analysis of the literature to assess the effectiveness and safety of acupuncture as a treatment for MMPN.Methods: The PubMed, Web of Science, MEDLINE, Cochrane Library, and Embase databases were comprehensively searched from inception to November 1, 2023 to identify relevant studies pertaining to the use of acupuncture to treat MMPN.Results: A total of five studies, encompassing 97 patients diagnosed with drug-related PN, were ultimately included in this analysis. The literature lacks any reports pertaining to the utilization of acupuncture for disease-related PN. ST36, LI4, SP6, and EX-LE-10 were found to be the most frequently chosen acupoints. Following acupuncture treatment, there was a consistent reduction in scores on the Visual Analogue Scale (VAS), Neuropathic Pain Scale (NPS), Brief Pain Inventory-Short Form (BPI-SF), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) among MMPN patients. The results of Nerve Conduction Velocity (NCV) tests yielded conflicting results. No severe adverse effects were reported.Conclusion: The use of acupuncture for disease-related PN has not been studied to date. Acupuncture is safe for drug-related PN and is helpful for relieving pain. But uncertainty exists regarding the efficacy of this approach because there is substantial heterogeneity with respect to acupuncture treatment regimens, and more high-quality studies on this topic are warranted.Keywords: multiple myeloma peripheral neuropathy, acupuncture, pain, systematic review

Lingyun Du,1 Zhiqiang Cao,2 Changyu Han,1 Jingjing Wei,1 Mingming Li,1 Chunhong Zhang1 1Department of Dermato-venereology, the Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710004, People’s Republic of ChinaCorrespondence: Chunhong Zhang, Department of Dermato-venereology, the Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email aliu133@163.comObjective: Dermatological consultation plays an important role in diagnosing and treating skin diseases in the Department of Geriatrics. The objective of this study is to provide an analysis of the factors leading geriatric inpatients to seek dermatological consultation, aiming to facilitate accurate diagnosis and effective treatment of skin diseases by healthcare professionals specializing in geriatrics and dermatology.Methods: The electronic health records of hospitalized patients in the Department of Geriatrics who applied for dermatological consultation at the Second Hospital of Shandong University from June 1, 2022, to June 1, 2023, were retrieved. Sex, age, number of consultations, reason for dermatology consultation, and final diagnosis by dermatologists were reviewed.Results: A total of 216 consultations of 178 patients (n=178, 95 men and 83 women) were collected in this study, of whom 153 (86.0%) required only one consultation, 19 (10.7%) required two consultations, and 4 (2.2%) required three consultations. The reasons for dermatology consultations were divided into three categories: the first was for the definitive diagnosis of a new skin condition that developed during the patient’s hospitalization (n=165, 76.4%), the second was for the follow-up of the condition and adjustment of medication (n=40, 18.5%), and the third was for the evaluation of the patient’s disease that existed before admission to the hospital (n=11, 5.1%). In 165 consultations, most of these diseases (n=131, 79.4%) can be diagnosed by patients’ conscious symptoms and clinical manifestations. Some of them need to be diagnosed or differentially diagnosed with the help of supplementary examinations, such as microscopic examination of scabies or fungi, and pathological examination.Conclusion: This study summarized the reasons for dermatology consultations for geriatric inpatients and found that dermatitis/eczema and infectious diseases were the common types of diseases consulted. The findings of this study contribute to the enhanced comprehension and management of dermatological conditions in hospitalized patients by geriatricians, as well as facilitating more efficient diagnosis and treatment by dermatologists.Keywords: geriatrics, dermatology consultation, skin diseases

Changlin Han,1,&ast; Xueling Wang,1,&ast; Wenjia Zhang,2,&ast; Mingyue Liu,1,&ast; Yuhuan Xia3,&ast; 1School of Business, Qingdao University, Qingdao, Shandong, People’s Republic of China; 2School of Economics and Management, Beijing Jiaotong University, Beijing, People’s Republic of China; 3School of Innovation and Entrepreneurship, Shandong University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhuan Xia, School of Innovation and Entrepreneurship, Shandong University, No. 72 Binhai Road, Jimo District, Qingdao, Shandong, 266237, People’s Republic of China, Email xiayuhuan@sdu.edu.cnPurpose: In recent years, due to the increasingly prominent role of voice behavior in leader decision-making and organizational performance, such behavior has become a central topic for scholars. A majority of studies explore the “uphold” effects of multiple leader behavior toward the voice behavior; nonetheless, our study revealed the “undo” effect --- leader hypocrisy on voice behavior. Drawing on social cognitive theory, we investigated the relationship between leader hypocrisy and voice behavior, examined the mediating effects of cognition-based trust and affect-based trust, and the moderating effect of moral identity.Patients and Methods: We conducted a three-wave survey in a large Chinese corporation to test the hypothesized model. We collected 562 employees to participate in this survey.Results: The results show that leader hypocrisy negatively impacts employees’ cognition-based and affect-based trust, and both types of trust mediate the relationship between leader hypocrisy and voice behavior, respectively. In the meantime, moral identity manifested the negative effect of leader hypocrisy on cognition-based and affect-based trust.Conclusion: Our research not only enriches the related research on leader hypocrisy and voice behavior but also uncovers the underlying mechanism through which leader hypocrisy affects voice behavior and the boundary conditions of this effect. Meanwhile, our research provides a theoretical reference for increasing employees’ voice behavior and promoting the healthy development of enterprises.Keywords: leader hypocrisy, cognition-based trust, affect-based trust, voice behavior, moral identity, social cognitive theory

Min-Jie Wang,1– 3 Jiayu Wang,4 Houdi Zhang,2,3 Fang-Bin Hao,1– 3 Gan Gao,1– 3 Si-Meng Liu,1– 3 Xiao-Peng Wang,1– 3 Jing-Jie Li,1– 3 Zheng-Xing Zou,2,3 Qing-Bao Guo,1– 3 He-Guan Fu,2,3 Yi-Qin Han,2,3 Cong Han,2,3 Lian Duan2,3 1Chinese PLA Medical School, Beijing, People’s Republic of China; 2Department of Neurosurgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Neurosurgery, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lian Duan; Cong Han, Department of Neurosurgery, Department of Neurosurgery, the Fifth Medical Centre (South Campus), Chinese PLA General Hospital, No. 8 Dong-Da Street, Fengtai District, Beijing, 100071, People’s Republic of China, Tel +86-10-66947389 ; +86-13466346163 ; +86-10-66947388, Fax +86-10-62177976, Email duanlian307@sina.com; hc82225@126.comBackground: The immune system plays an important role in the onset and development of moyamoya disease (MMD), but the specific mechanisms remain unclear. This study aimed to explore the relationship between the expression of complements and immunoglobulin in serum and progression of MMD.Methods: A total of 84 patients with MMD and 70 healthy individuals were enrolled. Serum immunoglobulin and complement C3 and C4 expression were compared between healthy individuals and MMD patients. Follow-up was performed at least 6 months post-operation. Univariate and multivariate analysis after adjusting different covariates were performed to explore predictive factors associated with vasculopathy progression. A nomogram basing on the results of multivariate analysis was established to predict vasculopathy progression.Results: Compared to healthy individuals, MMD patients had significantly lower expression of serum complements C3 (P = 0.003&ast;). Among MMD patients, C3 was significantly lower in those with late-stage disease (P = 0.001&ast;). Of 84 patients, 27/84 (32.1%) patients presented with vasculopathy progression within a median follow-up time of 13.0 months. Age (P=0.006&ast;), diastolic blood pressure (P=0.004&ast;) and serum complement C3 expression (P=0.015&ast;) were associated with vasculopathy progression after adjusting different covariables.Conclusion: Complement C3 is downregulated in moyamoya disease and decreases even further in late–Suzuki stage disease. Age, diastolic blood pressure and serum complement C3 expression are associated with vasculopathy progression, suggesting that the complement might be involved in the development of moyamoya disease.Keywords: moyamoya disease, complement, Suzuki stage, nomogram

Junhao Wu,&ast; Caihan Duan,&ast; Chaoqun Han, Xiaohua Hou Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoqun Han; Xiaohua Hou, Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of China, Email hcq1987912@hotmail.com; houxh@medmail.com.cnBackground: Eosinophilic esophagitis (EoE) is a complex allergic condition frequently accompanied by various atopic comorbidities in children, which significantly affects their life qualities. Therefore, this study aimed to evaluate pivotal molecular markers that may facilitate the diagnosis of EoE in pediatric patients.Methods: Three available EoE-associated gene expression datasets in children: GSE184182, GSE 197702, GSE55794, along with GSE173895 were downloaded from the GEO database. Differentially expressed genes (DEGs) identified by “limma” were intersected with key module genes identified by weighted gene co-expression network analysis (WGCNA), and the shared genes went through functional enrichment analysis. The protein–protein interaction (PPI) network and the machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest (RF), and XGBoost were used to reveal candidate diagnostic markers for EoE. The receiver operating characteristic (ROC) curve showed the efficacy of differential diagnosis of this marker, along with online databases predicting its molecular regulatory network. Finally, we performed gene set enrichment analysis (GSEA) and assessed immune cell infiltration of EoE/control samples by using the CIBERSORT algorithm. The correlations between the key diagnostic biomarker and immune cells were also investigated.Results: The intersection of 936 DEGs and 1446 key module genes in EoE generated 567 genes, which were primarily enriched in immune regulation. Following the construction of the PPI network and filtration by machine learning, CXCR2 served as a potential diagnostic biomarker of pediatric EoE with a perfect diagnostic efficacy (AUC = ~1.00) in regional tissue/peripheral whole blood samples. Multiple infiltrated immune cells were observed to participate in disrupting the homeostasis of esophageal epithelium to varying degrees.Conclusion: The immune-correlated CXCR2 gene was proved to be a promising diagnostic indicator for EoE, and dysregulated regulatory T cells (Tregs)/neutrophils might play a crucial role in the pathogenesis of EoE in children.Keywords: Eosinophilic esophagitis, pediatrics, bioinformatic analysis, machine-learning, potential diagnostic/therapeutic biomarker

Abstract The complex neuromuscular network that controls body movements is the target of severe diseases that result in paralysis and death. Here, we report the development of a robust and efficient self-organizing neuromuscular junction (soNMJ) model from human pluripotent stem cells that can be maintained long-term in simple adherent conditions. The timely application of specific patterning signals instructs the simultaneous development and differentiation of position-specific brachial spinal neurons, skeletal muscles, and terminal Schwann cells. High-content imaging reveals self-organized bundles of aligned muscle fibers surrounded by innervating motor neurons that form functional neuromuscular junctions. Optogenetic activation and pharmacological interventions show that the spinal neurons actively instruct the synchronous skeletal muscle contraction. The generation of a soNMJ model from spinal muscular atrophy patient-specific iPSCs reveals that the number of NMJs and muscle contraction is severely affected, resembling the patient’s pathology. In the future, the soNMJ model could be used for high-throughput studies in disease modeling and drug development. Thus, this model will allow us to address unmet needs in the neuromuscular disease field.

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

Yaxin Guo,1 Haiyan Ji,1 Junfeng Liu,1 Yong Wang,1 Jinming Liu,1 Hong Sun,1 Yuanhui Fei,1 Chunhui Wang,1 Tieliang Ma,2 Chao Han1,3 1Department of Anesthesiology, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China; 2Central Laboratory, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China; 3Yixing Clinical College, Medical College of Yangzhou University, Yixing, Jiangsu, 214200, People’s Republic of ChinaCorrespondence: Chao Han, Department of Anesthesiology, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China, Tel +86 13961568178, Fax +86 051087921010, Email staff940@yxph.comPurpose: This study aimed to develop and validate a post-operative delirium (POD) nomogram in a population of elderly patients undergoing elective orthopedic surgery.Patients and Methods: A predictive model was developed based on a training dataset of 474 elderly patients undergoing elective orthopedic surgery from March 2021 to May 2022. POD was identified using the Confusion Assessment Methods (CAM). The least absolute shrinkage and selection operator (LASSO) method was used to screen risk factors, and prediction models were created by combining the outcomes with logistic regression analysis. We employ bootstrap validation for internal validation to examine the model’s repeatability. The results were validated using a prospective study on 153 patients operated on from January 2022 to May 2022 at another institution.Results: The predictors in the POD nomogram included age, the Mini-Mental State Examination(MMSE), sleep disorder, neurological disorders, preoperative serum creatinine (Pre-SCR), and ASA classification. The c-index of the model was 0.928 (95% confidence interval 0.898 ~ 0.957) and the bootstrap validation still achieved a high c-index of 0.912. The c-index of the external validation was 0.921. The calibration curve for the diagnostic probability showed good agreement between prediction by nomogram and actual observation.Conclusion: By combining preoperative and intraoperative clinical risk factors, we created a POD risk nomogram to predict the probability of POD in elderly patients who undergo elective orthopedic surgery. It could be a tool for guiding individualized interventions.Keywords: post-operative delirium, elderly, elective orthopedic surgery, predictive models, nomogram

Abstract Background SAMHD1 is a deoxynucleotide triphosphohydrolase that restricts replication of HIV-1 in differentiated leucocytes. HIV-1 is not restricted in cycling cells and it has been proposed that this is due to phosphorylation of SAMHD1 at T592 in these cells inactivating the enzymatic activity. To distinguish between theories for how SAMHD1 restricts HIV-1 in differentiated but not cycling cells, we analysed the effects of substitutions at T592 on restriction and dNTP levels in both cycling and differentiated cells as well as tetramer stability and enzymatic activity in vitro. Results We first showed that HIV-1 restriction was not due to SAMHD1 nuclease activity. We then characterised a panel of SAMHD1 T592 mutants and divided them into three classes. We found that a subset of mutants lost their ability to restrict HIV-1 in differentiated cells which generally corresponded with a decrease in triphosphohydrolase activity and/or tetramer stability in vitro. Interestingly, no T592 mutants were able to restrict WT HIV-1 in cycling cells, despite not being regulated by phosphorylation and retaining their ability to hydrolyse dNTPs. Lowering dNTP levels by addition of hydroxyurea did not give rise to restriction. Compellingly however, HIV-1 RT mutants with reduced affinity for dNTPs were significantly restricted by wild-type and T592 mutant SAMHD1 in both cycling U937 cells and Jurkat T-cells. Restriction correlated with reverse transcription levels. Conclusions Altogether, we found that the amino acid at residue 592 has a strong effect on tetramer formation and, although this is not a simple “on/off” switch, this does correlate with the ability of SAMHD1 to restrict HIV-1 replication in differentiated cells. However, preventing phosphorylation of SAMHD1 and/or lowering dNTP levels by adding hydroxyurea was not enough to restore restriction in cycling cells. Nonetheless, lowering the affinity of HIV-1 RT for dNTPs, showed that restriction is mediated by dNTP levels and we were able to observe for the first time that SAMHD1 is active and capable of inhibiting HIV-1 replication in cycling cells, if the affinity of RT for dNTPs is reduced. This suggests that the very high affinity of HIV-1 RT for dNTPs prevents HIV-1 restriction by SAMHD1 in cycling cells.

Pengzhu Huang,1,2,&ast; Xin Guo,1,2,&ast; Mengke Duan,1,2 Huanrong Li,1,2 Cha Han,1,2 Fengxia Xue1,2 1Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengxia Xue; Cha Han, Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China; Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China, Tel +86-22-60363769, Fax +86-22-27813550, Email xuefengxia@tmu.edu.cn; tjhancha@tmu.edu.cnAbstract: Listeria monocytogenes is the conditional pathogenic bacteria, and pregnant women are at higher risk of infection due to depressed immunity. Infection with Listeria monocytogenes in twin pregnancy is rare but devastating, which puts forwards a great challenge for clinical management. Here, a 24-year-old woman was diagnosed with twin pregnancy, intrauterine death of one fetus and fever at 29+4 week of gestation. Two days later, she developed into pericardial effusion, pneumonedema and potential septic shock. The emergent cesarean delivery was performed after anti-shock treatment. One alive and another dead fetus were delivered. Then, she developed postpartum hemorrhage after the surgery. Urgent exploratory laparotomy was conducted at the sites of cesarean section and B-Lynch suture to stop bleeding. The culture of blood and maternal side of both placentas indicated Listeria monocytogenes. Following anti-infection therapy with ampicillin-sulbactam, she recovered well and discharged with negative result of blood bacterial culture and normal inflammatory indicators. The patient was hospitalized for a total of 18 days including 2 days in the intensive care unit (ICU), and the anti-infection treatment was conducted throughout the course. Symptoms of the Listeria monocytogenes infection in pregnancy are non-specific, which should be paid more attention in case of unexplained fever and fetal distress. The blood culture is effective for accurate diagnosis. Listeria monocytogenes infection is associated with poor pregnancy outcomes. Close monitoring of fetal condition, early intervention with antibiotics, timely termination of pregnancy and comprehensive management of complications are essential for better prognosis.Keywords: Listeria monocytogenes, twin pregnancy, outcomes

Ping Diao, Chenglong Han, Xiaoxue Li, Yi Yang, Xian Jiang Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Xian Jiang, Email jennyxianj@163.comAbstract: Port wine stain (PWS) is a congenital and progressive capillary malformation characterized by structural abnormalities of intradermal capillaries and postcapillary venules. The visible manifestation is often considered a disfigurement and the accompanying social stigma often causes serious emotional and physical impact. Hematoporphyrin monomethyl ether (HMME) is a newly authorized photosensitizer for treating PWS in China. Hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) has successfully treated thousands of Chinese patients with PWS since 2017, and HMME-PDT may be one of the most promising strategies for the treatment of PWS. However, there are few reviews published about the clinical use of HMME-PDT. So in this article, we want to briefly review the mechanism, efficacy evaluation, effectiveness and influencing factors, and the common postoperative reactions and treatment suggestions of HMME-PDT in the treatment of PWS.Keywords: port wine stain, photodynamic therapy, photosensitizer, HMME, PDT

Chunjie Han,1,&ast; Lingli Zhang,2,&ast; Jihong Liu,2 Ping Zhang3 1Department of Rehabilitation Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 2Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 3Department of Nursing, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, 100144, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Liu, Department of Neurology, Beijing Luhe Hospital, Capital Medical University, No. 82 of Xin Hua South Road, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86 10-69543901-1041, Fax +86 10 69531069, Email l_jihong0@163.com Ping Zhang, Department of Nursing, Beijing Rehabilitation Hospital, Capital Medical University, No. 15 of Xixiazhuang South Road, Shijingshan District, Beijing, 100144, People’s Republic of China, Tel +86 10 5689 1513, Fax +86 10 5698 1555, Email doczp@163.comObjective: As an important hospital task, the quality and efficiency of nursing practice directly affect the medical quality and sustainable development of the hospital. Increasing attention is now paid by managers to nursing teamwork. From the level of the nursing team, this study explored the relationship between team roles, using teamwork as the intermediate variable, and team performance to provide a theoretical foundation for the human resource management of nursing managers.Methods: Taking 29 general inpatient areas of a tertiary general hospital in Beijing as research objects, a questionnaire survey was used to collect basic information on nursing staff, teamwork, team roles and team performance. The collected data were analysed. A pathway analysis based on a multiple regression analysis was used to interpret the effect of each team role on teamperformance.Results: ①The mean and maximum value of emotional type (Teamworker and Finisher) were the largest in the role combination of nursing team. In the team role combination, the average value of emotional type was 12.58 ± 1.48, with significant difference (P< 0.001). ② The average level of emotion, thinking and decision of team role combination is positively correlated with work performance; The average level and maximum value of emotion have a positive correlation with team cooperation; The average level of willingness was negatively correlated with team cooperation, job performance and satisfaction (P< 0.05). ③ Teamwork plays a certain intermediary role in the mean value of emotion to improve level of team satisfaction and performance.Conclusion: This study identified the important roles of different types of nursing staff in work performance and used a pathway analysis to create a path showing each role. Increasing the emotional-type nursing staff in a team can not only improve the mean level of team emotion but also effectively improve both teamwork and work performance.Keywords: nursing staff, teamwork, team role, team performance, intermediary role

Lingli Zhang,1,&ast; YaoYa Shu,2,&ast; Chunjie Han,3,&ast; Jihong Liu1 1Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Nursing, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Department of Rehabilitation Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Liu, Department of Neurology, Beijing Luhe Hospital, Capital Medical University, No. 82 of Xin Hua South Road, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86 10-69543901-1041, Fax +86 10 69531069, Email l_jihong0@163.comObjective: To explore the relationship between family functioning and health beliefs in patients with stroke.Methods: A total of 253 patients with stroke were selected from Beijing Luhe Hospital, Capital Medical University from May 2021 to November 2021. All patients were of Chinese nationality, and 240 valid questionnaires were obtained. The Family Assessment Device and Champion’s Health Belief Model Scale were used to collect patients’ family functioning and health beliefs information, and correlation analysis was used to analyse it.Results: The total score for family functioning in patients with stroke was 130.5 (22). The highest mean score was 2.46 for behaviour control, and the lowest score was 2.00 for total function. The items were ranked from high to low in this order: behaviour control, emotional response, role, communication, emotional intervention, problem solving and total function. The total score of the patients’ health beliefs was 116 (33), The items were ranked from high to low in this order: were self-efficacy, health motivation, perceived benefit, susceptibility, severity and perceived impairment. The scores for family functioning were negatively correlated with the total scores for health beliefs (P < 0.05).Discussion: Stroke can reduce the self-care ability of the patients and aggravate the burden of family care. This can lead to abnormal function roles for patients and their families, emotional reactions in patients with stroke and weaker levels of family functioning.Conclusion: The health beliefs scores of patients with stroke were at the middle level, and family functioning was at the general level. There was a negative correlation between the family functioning score and the total score for health beliefs in patients with stroke.Keywords: health belief, family function, stroke

Chenlu Lan,1,2,&ast; Xinlei Huang,1,2,&ast; Xiwen Liao,1,2 Xin Zhou,1,2 Kai Peng,1,2 Yongguang Wei,1,2 Chuangye Han,1,2 Tao Peng,1,2 Jianyao Wang,3 Guangzhi Zhu1,2 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, 530021, People’s Republic of China; 3Department of General Surgery, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangzhi Zhu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China, Tel +86-771-5356528, Fax +86-771-5350031, Email zhuguangzhi0792@hotmail.com Jianyao Wang, Department of General Surgery, Shenzhen Children’s Hospital, Lianhua District, Shenzhen, 518026, Guangdong Province, People’s Republic of China, Email yaozi66@126.comObjective: The mechanisms of pseudouridine synthase (PUS) are not definite in hepatocellular carcinoma (HCC), the objective of this study is to investigate the effect of PUS genes in HCC.Materials and Methods: Differentially expressed and prognostic gene of PUS enzymes was identified based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. For the identified gene, pseudouridine synthase 1 (PUS1), was used for further research. The clinicopathological feature of PUS1 was analyzed by Student’s t-test. Prognostic significance was explored by Kaplan-Meier (KM) analysis and Cox proportional hazards regression model. Receiver operating characteristic (ROC) curve was applied to appraise diagnostic and prognostic value. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) were implemented to explore mechanism of PUS1. A Guangxi cohort was applied to verify differential expression. In vitro cell experiments were implemented to investigate the influence for proliferation, reactive oxygen species (ROS) level, migration, and invasion of HCC cells after a knockdown of PUS1.Results: PUS1 was significantly overexpressed in HCC tissues, and patients with high PUS1 were related to unpromising clinicopathological features. Survival analysis revealed high PUS1 expression was associated with a poor overall survival (OS) and 1 year-recurrence free survival (RFS), was an independent risk factor. Meanwhile, ROC curve showed that PUS1 had a diagnostic and prognostic significance to HCC. Functional enrichment analysis implied that PUS1 may be involved in metabolic pathways, mitochondrial function, non-alcoholic fatty liver disease (NAFLD), and some important carcinogenic pathways. Cell assays revealed that knockdown of PUS1 significantly constrained the migration, proliferation, invasion and improved the ROS level of HCC cells.Conclusion: PUS1 may be a prognostic biomarker and a underlying treatment target for HCC.Keywords: PUS1, pseudouridine synthase, poor prognosis, gene knockout, HCC

Chao Han,1,2 Haiyan Ji,1 Yaxin Guo,1 Yuanhui Fei,1 Chunhui Wang,1 Yanbo Yuan,1 Zhihui Ruan,1 Tieliang Ma1,2 1Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China; 2Yixing Clinical College, Medical College of Yangzhou University, Yixing, Jiangsu, 214200, People’s Republic of ChinaCorrespondence: Chao Han, Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China, Tel +86 13961568178, Fax +86 051087921010, Email staff940@yxph.comBackground: Perioperative neurocognitive disorders (PND), including delayed neurocognitive recovery (dNCR) and postoperative cognitive dysfunction (POCD), are common postoperative complications in elderly patients and adversely affect their prognosis. The study was designed to explore the effects of esketamine on postoperative cognitive function in elderly patients who underwent gastrointestinal surgery under general anesthesia and its potential mechanism.Methods: Eighty-four patients aged 65 and above undergoing gastrointestinal surgery were randomly divided into 2 groups: the esketamine group (group S) and the control group (group C). Group S received intravenous sub-anesthetic doses of esketamine (0.15 mg/kg) 5 minutes before the initiation of surgery, while group C received the same volume of saline. A battery of neuropsychological tests was used to assess cognitive function before surgery, 7 days, and 3 months after surgery. The primary outcome was the incidence of dNCR at 7 days postoperatively and POCD at 3 months postoperatively in both groups. The secondary outcome measures included changes in the levels of serum interleukin-6 (IL-6) and calcium-binding protein β (S100β) before and 1 day after surgery.Results: The incidence of dNCR in group S was lower than that of group C (18.15% vs 38.24% P=0.033). Contrarily, there was no difference in both groups regarding POCD 3 months postoperatively (6.06% vs 14.37% P=0.247). Plasma IL-6 and S100β levels were significantly elevated in both groups on postoperative day 1 (p< 0.05), but esketamine pretreatment reduced these levels to some extent compared with group C (p< 0.05).Conclusion: Sub-anesthetic doses of esketamine might reduce the incidence of dNCR and improve early postoperative cognitive function in elderly patients undergoing gastrointestinal surgery, which might be related to the anti-neuroinflammation effects of esketamine.Keywords: esketamine, perioperative neurocognitive disorders, gastrointestinal surgery, elderly, neuroinflammatory

Yining Wu,1,&ast; Shenjian Ou,1,&ast; Xiwen Liao,1,2 Chuangye Han,1,2 Chengkun Yang,1,2 Wei Qin,1 Yufeng Tan,1 Quan Lao,1 Tao Peng,1,2 Xinping Ye1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinping Ye; Tao Peng, Tel +86-771-5356528, Fax +86-771-5350031, Email yexinping@gxmu.edu.cn; pengtaogmu@163.comAbstract: Situs inversus totalis (SIT) is a rare congenital condition in which abdominal and thoracic organs are transposed from normal positions. Two-stage hepatectomy (TSH) combined with translational therapy for hepatocellular carcinoma (HCC) with SIT has been rarely reported. We report a 41-year-old man with giant hepatocellular carcinoma (71 mm × 55 mm × 51 mm) whose future residual liver (FLR) and standard liver volume (SLV) ratio at first diagnosis was 37.4%. Preoperative volume assessment of portal vein ligation (PVL) revealed inadequate hypertrophy of FLR. After a multidisciplinary group discussion (MDT), the patient decided to follow conversion therapy. Three months later, ratio of the FLR/SLV increased from 37.4% to 71% after operation, which met the surgical requirements. Second hepatectomy, right lobectomy was successful. There was no recurrence after six months of follow-up. In our case, conversion therapy appears to be effective in maintaining residual liver hyperplasia, reducing tumor load, and preventing tumor progression in patients with large HCC during TSH.Keywords: situs inversus totalis, two-stage hepatectomy, hepatocellular carcinoma, future residual liver, multidisciplinary group discussion

Qian Wang,1,&ast; Bin Zhang,1,&ast; Bing Li,1 Shengnan Yang,1 Zhifang Wang,2 Chao Han,3 Jie Wu,4 Rui Tian1 1The Second Division of General Geriatrics, Department of Geriatrics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Division of Endocrinology, Department of Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Division of Ultrasound, Department of Medical Imaging, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Wang; Rui Tian, The Second Division of General Geriatrics, Department of Geriatrics, the First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +8615838328873, Fax +8637166295183, Email qiansmile320@163.com; tianruiyfy@sina.comPurpose: To investigate the relationship between benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and renal function in elderly men aged 80 years and older.Patients and Methods: We selected 389 elderly men aged 80– 97 years with BPH/LUTS hospitalized at The Second Division of General Geriatrics, The First Affiliated Hospital of Zhengzhou University, between July 2018 and July 2020. In the cross-sectional study, patients were divided into the treatment (233 patients) and non-treatment (156 patients) groups based on whether they received treatment for BPH/LUTS. In the prospective self-case-control study, we included 129 of the non-treatment group patients who received oral BPH/LUTS medication and completed the 6-month outpatient follow-up. We compared prostate indicators and renal function in the cross-sectional study and baseline and after-treatment data in the prospective self-case-control study. Multiple linear regression analysis was performed for risk factors affecting renal function before and after BPH/LUTS treatment.Results: In the cross-sectional study, renal function was significantly better in the treatment group than in the non-treatment group. In the subgroup analysis of the prospective self-case-control study, renal function significantly improved after treatment among patients with hypertension and those with chronic kidney disease (CKD) 3a, but not in the entire cohort. Multivariable linear regression analysis showed that hypertension (β=2.06, 95% CI 0.40 to 3.71) and CKD 3a (β=17.16, 95% CI 15.53 to 18.79) were independent risk factors for creatinine differences before and after treatment, whereas hypertension (β=− 2.27, 95% CI − 3.65 to − 0.89), CKD 3a (β=− 11.93, 95% CI − 13.29 to − 10.58), and baseline prostate volume (β=− 0.11, 95% CI − 0.20 to − 0.02) were independent risk factors for estimated glomerular filtration rate differences before and after treatment.Conclusion: Treatment for moderate and severe BPH/LUTS can improve renal function in elderly patients with hypertension or CKD 3a.Keywords: benign prostatic hyperplasia, lower urinary tract symptoms, renal function, elderly men, drug therapy

Chao Han,1,2 Peiqi Shao,1 Huili Li,1 Rong Shi,1 Yun Wang1 1Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Anesthesiology, Beijing Longfu Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yun Wang, Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China, Email wangyun129@ccmu.edu.cnBackground and Purpose: Although unilateral intermediate cervical plexus block (ICPB) can be used for perioperative analgesia in neck surgery, its effect on diaphragm function remains controversial. This prospective study aimed to examine whether unilateral ICPB with different concentrations of ropivacaine resulted in the diaphragmatic dysfunction in unilateral thyroidectomy.Methods: A total of 54 patients scheduled to undergo unilateral thyroidectomy under general anesthesia were randomly allocated to receive either 10 mL of 0.3% (Group L) or 0.5% (Group H) ropivacaine for ICPB. General anesthesia was then administered for surgery. The diaphragm thickness and diaphragmatic excursion were measured at three different times: before the ICPB, at 40 min and 4 h after the block. The primary outcome was the incidence of diaphragmatic dysfunction of the block side at 40 min and 4 h after ICPB. Secondary outcomes included the maximum pain score within 24 h after the surgery, rescue analgesics within 24 h after the surgery, and time to first ambulation.Results: The incidence of diaphragmatic dysfunction on the block side of Group H was higher than that of Group L at 40 min after block (58% vs 29%, P = 0.01). However, the incidence of diaphragmatic dysfunction was comparable between Group H and Group L (65% vs 46%) at 4 h after block placement. Within 24 h after the operation, the maximum VAS pain score of Group H was significantly lower than Group L (P = 0.04), and fewer patients in Group H required rescue analgesics (P < 0.01).Conclusion: The ICPB with different concentrations of ropivacaine can induce the ipsilateral diaphragmatic dysfunction. The high concentration of ropivacaine results in higher incidence of diaphragmatic dysfunction at 40 min, but comparable incidence at 4 h after block compared with lower concentration of ropivacaine.Chinese Clinical Trial Registry: ChiCTR2000029348.Keywords: intermediate cervical plexus block, regional block, diaphragmatic dysfunction, ultrasound

Renhui Huang,1,2,&ast; Qi Shi,1,&ast; Shutian Zhang,1,2 Hong Lin,1,2 Chengzhi Han,1,2 Xinyi Qian,1 Yijun Huang,1 Xiaorong Ren,1 Jiayuan Sun,3 Nana Feng,4 Chunmei Xia,1 Meng Shi5 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Respiratory Endoscopy, Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China; 4Department of Respiratory and Critical Medicine, Shanghai Eighth People’s Hospital Affiliated to Jiangsu University, Shanghai, People’s Republic of China; 5Department of Thoracic and Cardiovascular Surgery, Huashan Hospital, Affiliated with Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meng Shi, Department of Thoracic and Cardiovascular Surgery, Huashan Hospital, Affiliated with Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, People’s Republic of China, Tel +86 15921527577, Email huashan_heart@sina.cn Chunmei Xia, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 13917406439, Email cmxia@fudan.edu.cnPurpose: Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis of lung ischemia/reperfusion (I/R) injury. Cyclic GMP-AMP synthase (cGAS) is a cytosol dsDNA sensor, coupling with downstream stimulator of interferon genes (STING) located in the ER, which involves innate immune responses. The aim of our present study was to investigate the effects of cGAS on lung I/R injury via regulating ERS.Methods: We used Sprague-Dawley rats to make the lung I/R model by performing left hilum occlusion-reperfusion surgery. cGAS-specific inhibitor RU.521, STING agonist SR-717, and 4-phenylbutyric acid (4-PBA), the ERS inhibitor, were intraperitoneally administered in rats. Double immunofluorescent staining was applied to detect the colocalization of cGAS or BiP, an ERS protein, with alveolar epithelial type II cells (AECIIs) marker. We used transmission electron microscopy to examine the ultrastructure of ER and mitochondria. Apoptosis and oxidative stress in the lungs were assessed, respectively. The profiles of pulmonary edema and lung tissue injury were evaluated. And the pulmonary ventilation function was measured using a spirometer system.Results: In lung I/R rats, the cGAS-STING pathway was upregulated, which implied they were activated. After cGAS-STING pathway was inhibited or activated in lung I/R rats, the ERS was alleviated after cGAS was inhibited, while when STING was activated after lung I/R, ERS was aggravated in the AECIIs, these results suggested that cGAS-STING pathway might trigger ERS responses. Furthermore, activation of cGAS-STING pathway induced increased apoptosis, inflammation, and oxidative stress via regulating ERS and therefore resulted in pulmonary edema and pathological injury in the lungs of I/R rats. Inhibition of cGAS-STING pathway attenuated ERS, therefore attenuated lung injury and promoted pulmonary ventilation function in I/R rats.Conclusion: Inhibition of the cGAS-STING pathway attenuates lung ischemia/reperfusion injury via alleviating endoplasmic reticulum stress in alveolar epithelial type II cells of rats.Graphical Abstract: Keywords: cGAS-STING, endoplasmic reticulum stress, alveolar epithelial type II cells, lung ischemia/reperfusion injury

Chunjie Han,1,&ast; Lingli Zhang,2,&ast; Jihong Liu2 1Department of Rehabilitation Medicine, Beijing Luhe Hospital of China Capital Medical University, Beijing, 101149, People’s Republic of China; 2Department of Neurology, Beijing Luhe Hospital of China Capital Medical University, Beijing, 101149, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Liu, Department of Neurology, Beijing Luhe Hospital of China Capital Medical University, Beijing, 101149, People’s Republic of China, Tel +86 10 69543901-1041, Fax +86 10 69531069, Email l_jihong0@163.comObjective: A scale for evaluating the protective motivation of patients who had suffered a stroke was developed to preliminarily verify the reliability of the scale and provide scientific measurement tools for clinical professionals.Methods: A descriptive research design method was adopted. First, an initial draft of the questionnaire was formed by conducting a literature review supplemented by semi-structured interviews and modified using the Delphi method. A total of 287 patients who had suffered a stroke were selected for the formal survey using the convenience sampling method. Further item screening was performed using an item analysis and an exploratory factor analysis, and reliability testing was also performed.Results: The scale consisted of 34 entries in the following 6 dimensions: severity, susceptibility, internal and external rewards, response efficacy, response cost and self-efficacy. The overall Cronbach’s alpha coefficient was 0.935, with correlation coefficients between dimensions and total scale scores ranging from 0.604 to 0.805 (P < 0.05) and correlation coefficients between dimensions ranging from 0.154 to 0.537 (P < 0.05).Conclusion: The protective motivation scale prepared in this study was tested and had good reliability, so this scale can be used as a scientific tool to evaluate the implementation of secondary prevention strategies for protective motivation of patients who have suffered a stroke.Keywords: stroke, protection motivation, health belief

Abstract Objective The US risdiplam expanded access program (EAP; NCT04256265) was opened to provide individuals with Type 1 or 2 spinal muscular atrophy (SMA) who had no satisfactory treatment options access to risdiplam prior to commercial availability. The program was designed to collect safety data during risdiplam treatment. Methods Patients were enrolled from 23 non‐preselected sites across 17 states and treated with risdiplam orally once daily. Eligible patients had a 5q autosomal recessive Type 1 or 2 SMA diagnosis, were aged ≥2 months at enrollment, and were ineligible for available and approved SMA treatments or could not continue treatment due to a medical condition, lack/loss of efficacy, or the COVID‐19 pandemic. Results Overall, 155 patients with Type 1 (n = 73; 47.1%) or 2 SMA (n = 82; 52.9%) were enrolled and 149 patients (96.1%) completed the EAP (defined as obtaining access to commercial risdiplam, if desired). The median treatment duration was 4.8 months (range, 0.3–9.2 months). The median patient age was 11 years (range, 0–50 years), and most patients (n = 121; 78%) were previously treated with a disease‐modifying therapy. The most frequently reported adverse events were diarrhea (n = 10; 6.5%), pyrexia (n = 7; 4.5%), and upper respiratory tract infection (n = 5; 3.2%). The most frequently reported serious adverse event was pneumonia (n = 3; 1.9%). No deaths were reported. Interpretation In the EAP, the safety profile of risdiplam was similar to what was reported in pivotal risdiplam clinical trials. These safety data provide further support for the use of risdiplam in the treatment of adult and pediatric patients with SMA.

Lu Yu,1 Haiyan Ji,2 Minmin Zhou,1 Yaxin Guo,2 Junfeng Liu,2 Daoyun Lei,3 Chao Han,1 Tieliang Ma1 1Department of Anesthesiology, Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China; 2Medical College of Jiangsu University, Zhenjiang, Jiangsu, 212013, People’s Republic of China; 3Department of Anesthesiology, Zhongda Hospital Southeast University, Nanjing, Jiangsu, 210029, People’s Republic of ChinaCorrespondence: Chao Han, Email staff940@yxph.comBackground: Several studies have shown that ATP-binding cassette transporter A7 (ABCA7) gene variation is associated with cognitive impairment. This study was aimed to investigate the relationship between ABCA7 rs3764650 polymorphism and perioperative neurocognitive disorder (pNCD).Methods: A total of 132 elderly patients aged 65 and over who underwent elective non-cardiac surgery were enrolled in the study, while 28 healthy volunteers matching age and sex were recruited as the control group. A battery of neuropsychological tests was conducted 1 day before, 7 days, and 3 months after surgeries. Delayed neurocognitive recovery (dNCR) and postoperative mild or major neurocognitive disorder (POCD) were determined using the Z value method. The venous blood sample of the surgical patients was taken before the operation. Genotyping of rs3764650 was performed using polymerase chain reaction amplification and restriction fragment length polymorphism analysis.Results: The incidences of dNCR and POCD were 29.7% and 16.8% at 7 days and 3 months after surgery, respectively. The G allele frequency and GG frequency of dNCR patients were significantly higher than that of non-dNCR patients (43.3% vs 28.2%, P=0.035; 23.3% vs 4.2%, P=0.013, respectively) at 7 days following surgery. No significant differences in ABCA7 alleles between POCD and non-POCD patients were observed 3 months postoperatively.Conclusion: ABCA7 rs3764650 gene polymorphism is associated with dNCR and GG genotype might be a predisposing factor for postoperative cognitive impairment in Chinese Han elderly populations.Keywords: ATP-binding cassette transporter, rs3764650, polymorphism, postoperative neurocognitive disorders

Huasheng Huang,&ast; Xiwen Liao,&ast; Guangzhi Zhu, Chuangye Han, Xiangkun Wang, Chengkun Yang, Xin Zhou, Tianyi Liang, Ketuan Huang, Tao Peng Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Peng; Xiwen Liao, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Road 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China, Tel +86-771-5356528, Fax +86-771-5350031, Email pengtaogmu@163.com; LXWen1991@hotmail.comBackground: The aim of our study was to evaluate the potential of expression and single nucleotide polymorphism of Acyl-CoA binding domain containing 4 (ACBD4) gene as prognosis biomarkers in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after hepatectomy.Methods: HBV-related HCC patients from the First Affiliated Hospital of Guangxi Medical University and GSE14520 were included in the current study, as well as The Cancer Genome Atlas (TCGA) HCC verification cohort. Prognostic analysis and multiple functional enrichment analysis methods were used to evaluate the prognostic value and potential biological functions of the ACBD4 gene in HBV-related HCC.Results: We found that ACBD4 gene is highly expressed in normal liver tissues and markedly down-regulated in HBV-related HCC tissues. ACBD4 gene was significantly related to overall survival (OS) of HCC in TCGA and GSE14520 cohorts, and patients with low ACBD4 expression were markedly related to poor OS. Rs4986172 was observed as an OS biomarker after hepatectomy in the Guangxi HBV-related HCC cohort. The OS of rs4986172 GG genotype was worse than that of HCC patients with A allele (AA and AG genotypes). Multifunctional enrichment analysis suggested that ACBD4 gene is closely related to the metabolic, peroxisome proliferator-activated receptor and cytochrome P450 pathway. Through connectivity map, we also identified eight compounds that may be used as targeted therapeutic agents for ACBD4 gene in HBV-related HCC; these compounds were scopoletin, alfaxalone, bephenium hydroxynaphthoate, apramycin, 4,5-dianilinophthalimide, DL-thiorphan, aminohippuric acid and quinidine. Immune microenvironment analysis revealed that there were significant differences in immune scores of HBV-related HCC tumor tissues with different ACBD4 expression levels.Conclusion: Our study reveals that ACBD4 expression and rs4986172 can be serve as biomarkers of OS in HBV-related HCC patients after hepatectomy.Keywords: rs4986172, ACBD4, HBV-related HCC, overall survival, hepatectomy

Jingmin Zhang,1,2 Guangzhao Qi,1,2 Chao Han,1,2 Yubing Zhou,1,2 Yongjie Yang,1 Xinru Wang,1,2 Suna Liu,3 Xiaojian Zhang1,2 1Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Henan Key Laboratory for Precision Clinical Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Newborn Screening Center, Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Guangzhao Qi; Xiaojian Zhang Tel +86-37166295269Email qiguangzhao1223@sina.com; zhangxiaojian15@126.comPurpose: Pharmacogenetic testing is recognized as the major method for the individualized pharmacotherapy in clinical pharmacy practice, but information about the clinical implementation of pharmacogenetic testing in China is limited. The present study aimed to determine the situation of clinical implementation for pharmacogenetic testing in central China.Methods: The study is conducted in the department of clinical pharmacy in The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. We collected and analyzed pharmacogenetic testing results from November 1, 2013 to November 2, 2018 in our hospital, which were checked in the electronic medical record system. The main outcome measures were the number and type of pharmacogenetic testing across five years.Results: A total of 47,265 (56.9% male, mean age = 51.5 years) pharmacogenetic testing results were obtained with an average annual rate of growth of 63.0% across five years. A 50.2% (23,748/47,265) of all the pharmacogenetic testing results were for the determination of cytochrome P450 2C19 (CYP2C19) &ast;2, &ast;3 genotypes, and 41.7% were for the methylene tetrahydrofolate reductase (MTHFR) C677T genotype. The number of departments performing the pharmacogenetic testing was 35, 63, 55, 52, 52 and 39 for 2013– 2018, respectively, and the main top five departments were cardiology, psychiatry, ICU, cardiac surgery and intervention.Conclusion: Clinical implementation of pharmacogenetic testing in China is growing rapidly, but the types and implementing departments of pharmacogenetic testing were limited. Our present study reported the real-world implementation modality of pharmacogenomic tests in China. It will help us to understand the testing of pharmacogenetics in China in order to promote the rational development of pharmacogenetics.Keywords: clinical implementation, pharmacogenomics, pharmacogenetics, China, preemptive

Shutian Zhang,1,&ast; Li Hu,2,&ast; Chengzhi Han,1 Renhui Huang,1 Kokwin Ooi,1 Xinyi Qian,1 Xiaorong Ren,1 Dechang Chu,3 Haili Zhang,3 Dongshu Du,4 Chunmei Xia1 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200240, People’s Republic of China; 3College of Agriculture and Bioengineering, Heze University, Heze, 274000, People’s Republic of China; 4School of Life Science, Shanghai University, Shanghai, 200444, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunmei XiaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of ChinaTel +86 21 54237612-805Email cmxia@fudan.edu.cnDongshu DuSchool of Life Science, Shanghai University, Shanghai, 200444, People’s Republic of ChinaEmail sdhzdds@163.comPurpose: Oxidative/nitrosative stress, neuroinflammation and their intimate interactions mediate sympathetic overactivation in hypertension. An immoderate inflammatory response is characterized not only by elevated proinflammatory cytokines (PICs) but by increases in mitochondrial dysfunction, reactive oxygen species (ROS), and nitric oxide (NO). Recent data pinpoint that both the phospholipid and lipid droplets (LDs) are potent modulators of microglia physiology.Methods: Stress rats underwent compound stressors for 15 days with PLIN2-siRNA or scrambled-siRNA (SC-siRNA) administrated into the rostral ventrolateral medulla (RVLM). Lipids were analyzed by mass spectroscopy-based quantitative lipidomics. The phenotypes and proliferation of microglia, LDs, in the RVLM of rats were detected; blood pressure (BP) and myocardial injury in rats were evaluated. The anti-oxidative/nitrosative stress effect of phosphatidylethanolamine (PE) was explored in cultured primary microglia.Results: Lipidomics analysis showed that 75 individual lipids in RVLM were significantly dysregulated by stress [PE was the most one], demonstrating that lipid composition changed with stress. In vitro, prorenin stress induced the accumulation of LDs, increased PICs, which could be blocked by siRNA-PLIN2 in microglia. PLIN2 knockdown upregulated the PE synthesis in microglia. Anti-oxidative/nitrosative stress effect of PE delivery was confirmed by the decrease of ROS and decrease in 3-NT and MDA in prorenin-treated microglia. PLIN2 knockdown in the RVLM blocked the number of iNOS+ and PCNA+ microglia, decreased BP, alleviated cardiac fibrosis and hypertrophy in stressed rats.Conclusion: PLIN2 mediates microglial polarization/proliferation via downregulating PE in the RVLM of stressed rats. Delivery of PE is a promising strategy for combating neuroinflammation and oxidative/nitrosative stress in stress-induced hypertension.Keywords: lipid droplets, PLIN2, phosphatidylethanolamine, lipidomics, microglial expansion, neuroinflammation, stress, RVLM, oxidative/nitrosative stress