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Wenbin Guo,1,&ast; Lin Sun,1,&ast; Huijun Yue,1,&ast; Xueqin Guo,1 Lin Chen,1 Jinhong Zhang,1 Zhuqi Chen,1 Yiming Wang,1 Jiao Wang,2 Wenbin Lei1 1Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Wang, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, People’s Republic of China, Email wangj836@mail.sysu.edu.cn Wenbin Lei, Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, People’s Republic of China, Email leiwb@mail.sysu.edu.cnPurpose: Clinical studies focusing on the association between the gut microbiota and obstructive sleep apnea (OSA) are limited. This study aimed to explore the relationship between intermittent hypoxia and the composition of gut microbiota in adults by analyzing the differences in the characteristics and functional distribution of gut microbiota between patients with different severities of OSA and healthy individuals.Patients and Methods: A cohort of 113 individuals from the First Affiliated Hospital of Sun Yat-sen University underwent overnight polysomnography from July 2019 to August 2021. The individuals included 16 healthy controls and 97 patients with OSA, categorized by the apnea-hypopnea index into mild, moderate, and severe groups. Fecal samples were analyzed using high-throughput sequencing of the 16S rRNA V3–V4 region to assess gut microbiota composition and function. Correlation analysis was used to evaluate the association between clinical indicators and microbiota markers.Results: In patients with OSA, the gut microbiota diversity and the abundance of specific microbes that produce short-chain fatty acids decreased (P< 0.05). The phyla Verrucomicrobia and Candidatus Saccharibacteria, genera Gemmiger and Faecalibacterium, and the species Gemmiger formicilis exhibited decreasing abundance with increasing OSA severity. Correlation analysis revealed a robust association between the proportion of total sleep time, characterized by nighttime blood oxygen saturation below 90%, and the alterations in the gut microbiota, demonstrating that elevated levels of desaturation are correlated with pronounced microbiota dysbiosis (P< 0.05).Conclusion: Compared to the control group, the intermittent hypoxia exhibited by patients with OSA may be related to alterations in the composition and structure of the gut microbiota. Our results demonstrate the importance of monitoring hypoxia indicators in future clinical practice.Keywords: obstructive sleep apnea, gut microbiota, 16S rRNA, intermittent hypoxia

Huizhen Yue,1– 3 Xiaolong Xu,1– 3 Bing Peng,1– 3 Xuanyu Wang,1 Shengnan Zhang,1 Jinhao Tian,4 Shuo Wang,1 Maifen Song,1 Qingquan Liu1– 3 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Chinese Medicine, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, People’s Republic of China; 4Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Qingquan Liu, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Gallery Backstreet, Dongcheng District, Beijing, People’s Republic of China, Email liuqingquan_2003@126.comPurpose: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of Candida-related infection. However, its antifungal mechanisms against the emerging fungal pathogen Candida auris remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against C. auris.Methods: The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against C. auris, including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a Galleria mellonella infection model.Results: First, 20 major compounds in CHGX-DME were detected and characterized. The MIC50% and MIC90% of CHGX-DME against C. auris isolates ranged from 50– 200 mg/L and 100– 400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of C. auris cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in C. auris. Importantly, it significantly improved the survival rate and reduced the fungal burden in G. mellonella infection models, suggesting a remarkable treatment effect against C. auris infection.Conclusion: CHGX-DME exhibited potent antifungal activity against C. auris and significantly ameliorated this fungal infection in the G. mellonella model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen C. auris.Keywords: Candida auris, multidrug resistance, CaoHuangGuiXiang formula, aggregative form, biofilm formation, antifungal efficiency

Wenpei Wu,1,2,&ast; Zhi Geng,3– 5,&ast; Aimei Wu,2,&ast; Xinyi Chen,6,7 Xiaoying Meng,2 Qianyun Zhang,2 Zheng Tan,2 Hong Yue,2 Juncang Wu1,2 1Department of Neurology, Hefei Second People’s Hospital Affiliated to Bengbu Medical University, Hefei, Anhui, 230011, People’s Republic of China; 2Department of Neurology, Hefei Second People’s Hospital, Hefei, Anhui, 230011, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, People’s Republic of China; 5Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, 230000, People’s Republic of China; 6Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China; 7The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juncang Wu; Hong Yue, Intersection of Guangde Road and Leshui Road, Hefei, Anhui, 230011, People’s Republic of China, Tel/Fax +86 551 13956076148 ; +86 551 18949855780, Email wujuncang126@126.com; yuehong01@foxmail.comBackground and Purpose: The role of serum uric acid (UA) level in patients suffering from stroke remains controversial. Our aim was to investigate the effect of UA level on clinical outcomes in patients with intracerebral hemorrhage (ICH).Methods: In the retrospective cohort study, we analyzed data from 250 patients with intracerebral hemorrhage (85 women and 165 men) to investigate the difference in UA levels between patients with a good prognosis and those with a poor prognosis. Additionally, we analyzed the impact of UA levels on the risk of short-time prognosis of ICH patients.Results: Patients with a good prognosis presented with significantly lower levels of UA (348.71 ± 84.97 μmol/L) than those with poor prognosis (393.06 ± 148.46 μmol/L). Furthermore, multivariate logistic regression model demonstrated that a high UA level was a likely risk factor for worse prognosis among patients suffering in ICH (odds ratio [95% confidence interval], 1.006 [1.0012, 1.0108]; P = 0.015). Additionally, UA has a threshold effect value of 363.9 μmol/L and was presented in levels that were in a nonlinear relationship with incidence rate of short-time prognosis outcome of ICH patients.Conclusion: Our findings indicate that higher UA levels can increase the risk of poor clinical prognosis in patients with ICH and high UA levels are not conductive to the clinical prognosis of patients with ICH. These findings provide a new perspective on the treatment and prevention of ICH.Keywords: intracerebral hemorrhage, uric acid, oxidative stress, follow-up, nonlinear relationship, prognosis

Zhongjie Liang,1,2 Huilin Yue,1 Congcong Xu,1 Qian Wang,3 Shengwei Jin2,3 1Department of Neonatology, The Second Affiliated Hospital, Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China; 2Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China; 3Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of ChinaCorrespondence: Qian Wang; Shengwei Jin, Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang Province, 325027, People’s Republic of China, Tel +86 577-88002806, Fax +86 577-88832693, Email wqian84@163.com; jinshengwei69@163.comBackground: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants with limited treatments and poor prognosis. Damaged endothelial glycocalyx leads to vascular permeability, lung edema and inflammation. However, whether hyperoxia increases neonatal pulmonary microvascular permeability by degrading the endothelial glycocalyx remains unknown.Methods: Newborn mice were maintained in 60– 70% O2 for 7 days. Protectin DX (PDX), an endogenous lipid mediator, was injected intraperitoneally on postnatal d 0, 2, 4 and 6. Lung samples and bronchoalveolar lavage fluid were taken at the end of the study. Primary human umbilical vein endothelial cells (HUVECs) were cultured in 80%O2.Results: Hyperoxia exposure for 7 days led to neonatal mice alveolar simplification with less radial alveolar count (RAC), mean linear intercept (MLI) and mean alveolar diameter (MAD) compared to the control group. Hyperoxia exposure increased lung vascular permeability with more fluid and proteins and inflammatory factors, including TNF-α and IL-1β, in bronchoalveolar lavage fluid while reducing the heparan sulfate (HS), the most abundant component of the endothelial glycocalyx, in the pulmonary endothelial cells. PDX relieve these changes. PDX attenuated hyperoxia-induced high expression of heparanase (HPA), the endoglycosidase that shed endothelial glycocalyx, p‐P65, P65, and low expression of SIRT1. BOC‐2 and EX527 abolished the affection of PDX both in vivo and intro.Conclusion: In summary, our findings indicate that PDX treatment relieves hyperoxia‐induced alveolar simplification, vascular leakage and lung inflammation by attenuating pulmonary endothelial glycocalyx injury via the SIRT1/NF‐κB/ HPA pathway.Keywords: bronchopulmonary dysplasia, endothelial glycocalyx, inflammation, protectin DX

Yuan Zhang,1,&ast; Hongli Yue,1,&ast; Yirui Qin,1 Jiajing Wang,1 Chenyang Zhao,1 Miao Cheng,1 Bo Han,2 Ruquan Han,1 Weihua Cui1,&ast; 1Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruquan Han; Weihua Cui, Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, No. 119, Nan Si Huan Xi Lu, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +8613701285393 ; Tel +8613701285393, Fax +861059976658, Email ruquan.han@ccmu.edu.cn; weihuacui@ccmu.edu.cnPurpose: Patients undergoing intraspinal tumor resection usually experience severe postoperative pain. Inadequate postoperative analgesia usually leads to severe postsurgical pain, which could cause patients to suffer from many other related complications. Recently, an increasing number of studies have found that gabapentin can relieve hyperalgesia, postoperative pain, and postoperative inflammation. However, there have been no reports on the use of gabapentin combined with sufentanil preoperatively for acute pain following intraspinal tumor resection.Study Design and Methods: This is a protocol for a randomized, placebo-controlled, and double-blinded trial. One-hundred and sixty-eight participants with chronic pain related to the intraspinal tumor will be randomized into the gabapentin and placebo groups in a 1:1 ratio. In the gabapentin group, patients will be given 300 mg gabapentin orally 36 h, 24 h, and 12 h before surgery; the placebo group will receive a placebo orally at the same time points preoperatively. To estimate the efficacy and safety endpoints, all the researchers and patients will be blinded until the completion of this study. The primary outcome will be the consumption of sufentanil within 48 h postoperatively. The secondary outcomes include the visual analog scale pain score and Von Frey mechanical pain threshold 36 h and 24 h before and 24 h and 48 h after surgery, the incidence of postoperative nausea, vomiting, and drowsiness, the length of hospital stay and medical expenses.Discussion: This trial is to evaluate the efficacy and safety of gabapentin combined with sufentanil for postoperative analgesia in patients who complain of pain before intraspinal tumor resection. The findings will provide a new strategy for multimode perioperative analgesia management in these patients.Keywords: gabapentin, intraspinal tumor resection, multimode perioperative analgesia, opiates

Hongli Yue,1,&ast; Man Zhou,2,&ast; Yingzi Chong,1 Miao Cheng,1 Hui Qiao,3 Yu Lu,1 Weihua Cui1 1Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Anesthesiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 3Department of Neurophysiology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Lu; Weihua CuiDepartment of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, No. 119, Nan Si Huan Xi Lu, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +8613661067447; +8613651315600, Fax +861059976658, Email luyutiantan@163.com; weihuacui@ccmu.edu.cnPurpose: At present, it is believed that intravenous (IV) infusion of lidocaine can inhibit hyperalgesia, relieve postoperative acute and chronic pain, and accelerate the rehabilitation of patients. However, studies of its effects on necessary electrophysiological monitoring during neurosurgery are few, and the results are controversial. This study assumes that the propofol-remifentanil based anaesthesia combined with lidocaine in patients undergoing intraspinal tumour resection will not have adverse effects on motor-evoked potentials (MEPs) or somatosensory-evoked potentials (SEPs).Study Design and Methods: This is a prospective, randomized, placebo-controlled double-blind trial. A total of 96 patients undergoing intraspinal tumour resection will be randomly allocated to lidocaine and placebo group. The lidocaine group will receive IV lidocaine during anaesthesia, while the placebo group will receive the same dose of normal saline with the same infusion rate and infusion time, and the anaesthesia procedures of the two groups will be the same. All patients will be monitored the MEPs and SEPs of all four limbs during operation. The primary outcome will be the MEP amplitudes of both upper limbs at the end of operation. The secondary outcome measures will be the other electrophysiological parameters at the end of operation, the incidence of alert events for all four limbs, and the incidence of false positive events.Discussion: The purpose of this study is to evaluate the effects of IV infusion of lidocaine on SEPs and MEPs during intraspinal tumour resection to determine whether electrophysiological monitoring can accurately reflect the integrity of nerve functions while infusing lidocaine and to explore the possibility of lidocaine use during intraspinal tumour resection as an anaesthesia option.Keywords: motor-evoked potentials, somatosensory-evoked potentials, intraspinal tumour resection, lidocaine

Jiao Zhao,&ast; Li Liu,&ast; Shanshan Lv, Chun Wang, Hua Yue, Zhenlin Zhang Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Disease, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenlin Zhang; Hua YueShanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Disease, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Yishan Road 600, Shanghai, 200233, People’s Republic of ChinaTel +86 21 64369181Fax +86 21 64701361Email zhangzl@sjtu.edu.cn; yueyinglonghua@163.comPurpose: Alendronate is a widely used anti-osteoporotic drug. PFN1 gene is a newly identified early-onset Paget’s disease pathogenic gene. The purpose of this study is to study whether the genetic variations in this gene affect the clinical efficacy of alendronate in postmenopausal Chinese women with low bone mass.Patients and Methods: Seven single nucleotide polymorphisms in PFN1 gene were genotyped. A total of 500 postmenopausal women with osteoporosis or osteopenia were included. All participants were treated with weekly alendronate 70 mg for 12 months. A total of 466 subjects completed the follow-up. Bone mineral density (BMD) of lumbar spine, femoral neck and total hip were measured at baseline and after treatment.Results: After 12 months of treatment, the BMD of lumbar spine, femoral neck and total hip all increased significantly (all P < 0.001), with an average increase of 4.72 ± 5.31%, 2.08 ± 4.45%, and 2.42 ± 3.46%, respectively. At baseline, there were no significant differences in BMD at lumbar spine, femoral neck and total hip between different genotype groups (P > 0.05). We failed to identify any significant association between the genotypes or haplotypes of PFN1 and the BMD response to alendronate therapy.Conclusion: Genetic polymorphisms of PFN1 may not be a major contributor to the therapeutic response to alendronate treatment in Chinese women with low bone mass.Keywords: alendronate, bone mineral density, osteoporosis, PFN1 gene, single-nucleotide polymorphism

Minwei Zhang,1,2,&ast; Shuxuan Shao,1,2,&ast; Haitao Yue,1,2 Xin Wang,3 Wenrui Zhang,1,2 Fei Chen,1,2 Li Zheng,1,2 Jun Xing,1,2 Yanan Qin1,2 1College of Life Science & Technology, Xinjiang University, Urumqi, 830046, People’s Republic of China; 2Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, Urumqi, 830046, People’s Republic of China; 3The First Hospital of Jilin University, Changchun, 130061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanan Qin Email qingyalan12345@sina.comAbstract: In recent years, Au-based nanomaterials are widely used in nanomedicine and biosensors due to their excellent physical and chemical properties. However, these applications require Au NPs to have excellent stability in different environments, such as extreme pH, high temperature, high concentration ions, and various biomatrix. To meet the requirement of multiple applications, many synthetic substances and natural products are used to prepare highly stable Au NPs. Because of this, we aim at offering an update comprehensive summary of preparation high stability Au NPs. In addition, we discuss its application in nanomedicine. The contents of this review are based on a balanced combination of our studies and selected research studies done by worldwide academic groups. First, we address some critical methods for preparing highly stable Au NPs using polymers, including heterocyclic substances, polyethylene glycols, amines, and thiol, then pay attention to natural product progress Au NPs. Then, we sum up the stability of various Au NPs in different stored times, ions solution, pH, temperature, and biomatrix. Finally, the application of Au NPs in nanomedicine, such as drug delivery, bioimaging, photothermal therapy (PTT), clinical diagnosis, nanozyme, and radiotherapy (RT), was addressed concentratedly.Keywords: high stability Au NPs, polymer, natural product, resistance, nanomedicine

Huijun Yue,1,* Yu Lin,1,* Yitao Wu,2,* Yongquan Wang,1 Yun Li,1 Xueqin Guo,1 Ying Huang,3 Weiping Wen,1 Gansen Zhao,2 Xiongwen Pang,2 Wenbin Lei1 1Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2School of Computer Science, South China Normal University, Guangzhou, 510631, People’s Republic of China; 3Guangdong Province Traditional Chinese Medical Hospital, Guangzhou, 510000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenbin LeiOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong, 510080, People’s Republic of ChinaTel +86-13922113299Email leiwb@mail.sysu.edu.cnXiongwen PangSchool of Computer Science, South China Normal University, 55 West Zhongshan Avenue, Guangzhou, Guangdong, 510631, People’s Republic of ChinaTel +86-18620638848Email augepang@scnu.edu.cnPurpose: This study evaluated a novel approach for diagnosis and classification of obstructive sleep apnea (OSA), called Obstructive Sleep Apnea Smart System (OSASS), using residual networks and single-channel nasal pressure airflow signals.Methods: Data were collected from the sleep center of the First Affiliated Hospital, Sun Yat-sen University, and the Integrative Department of Guangdong Province Traditional Chinese Medical Hospital. We developed a new model called the multi-resolution residual network (Mr-ResNet) based on a residual network to detect nasal pressure airflow signals recorded by polysomnography (PSG) automatically. The performance of the model was assessed by its sensitivity, specificity, accuracy, and F1-score. We built OSASS based on Mr-ResNet to estimate the apnea‒hypopnea index (AHI) and to classify the severity of OSA, and compared the agreement between OSASS output and the registered polysomnographic technologist (RPSGT) score, assessed by two technologists.Results: In the primary test set, the sensitivity, specificity, accuracy, and F1-score of Mr-ResNet were 90.8%, 90.5%, 91.2%, and 90.5%, respectively. In the independent test set, the Spearman correlation for AHI between OSASS and the RPSGT score determined by two technologists was 0.94 (p < 0.001) and 0.96 (p < 0.001), respectively. Cohen’s Kappa scores for classification between OSASS and the two technologists’ scores were 0.81 and 0.84, respectively.Conclusion: Our results indicated that OSASS can automatically diagnose and classify OSA using signals from a single-channel nasal pressure airflow, which is consistent with polysomnographic technologists’ findings. Thus, OSASS holds promise for clinical application.Keywords: deep learning, nasal airflow, obstructive sleep apnea, residual network

Shanshan Li,1,* Zhaoqin Wang,2,* Huangan Wu,3,* Hongyu Yue,1 Ping Yin,1 Wei Zhang,4 Lixing Lao,5 Yiqun Mi,1 Shifen Xu1 1Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, People’s Republic of China; 2Department of Aeronautics and Astronautics, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai 200433, People’s Republic of China; 3Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, People’s Republic of China; 4Department of Biostatistics, School of Public Health, Fudan University, Shanghai 200032, People’s Republic of China; 5Virginia University of Integrative Medicine, Fairfax, VA 22031, USA*These authors contributed equally to this workCorrespondence: Shifen Xu; Yiqun MiShanghai Municipal Hospital of Traditional Chinese Medicine, 274 Middle Zhijiang Road, Shanghai 200071, People’s Republic of ChinaTel +86 13761931393; Tel +8618930177567Email xu_teacher2006@126.com; miyiqun@126.comObjective: To evaluate the short- and long-term effects of acupuncture on perimenopausal insomnia (PMI) and quality of life.Patients and Methods: We designed a semi-standardized, patient-blinded, randomized placebo-controlled trial. A total of 84 patients were recruited, all of whom met the criteria for diagnosis of PMI. Either acupuncture therapy or a noninvasive placebo acupuncture therapy designed to treat insomnia was implemented 18 times over the course of 8 weeks (3 times per week for 4 weeks, twice per week for 2 weeks, once per week for 2 weeks). The primary outcome was the change in Pittsburgh Sleep Quality Index (PSQI) scores from baseline to the end of treatment, week 8. Secondary outcomes included climacteric symptoms and quality of life measured by the Menopause Quality of Life (Men-QoL), Insomnia Severity Index (ISI), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), sleep parameters recorded in the actigraphy and adverse events. The PSQI and Men-QoL were assessed at weeks 0, 4, 8, 12 and 20. Other assessments were performed at week 0 and week 8.Results: The participants were randomly assigned to either acupuncture (n=42) or sham acupuncture (n=42) groups. The mean difference from baseline of PSQI score at the end of treatment between real acupuncture and sham acupuncture group was − 2.38 (95% CI, − 3.46 to − 1.30; P< 0.001). The acupuncture group was associated with significantly lower scores than the sham acupuncture group at week 12 and during the 20-week follow-up visits (all P < 0.001). Acupuncture was also associated with significantly higher quality of life in vasomotor and other physical dimensions (all P < 0.001). At the end of treatment, researchers found a significantly higher total sleep time (TST), sleep efficiency (SE) and lower number of average awakenings (AA) (P =0.007 0.023 and 0.011, respectively) in the acupuncture group than in the sham acupuncture group. No severe adverse events were reported.Conclusion: The findings suggest that acupuncture may be a safe and effective treatment for PMI and improving quality of sleep in patients with menopause and could have a long-lasting effect.Trial Registration: Chinese Clinical Trial Registry (ChiCTR); Trial ID: ChiCTR1800018645. URL: http://www.chictr.org.cn/showproj.aspx?proj=31482.Keywords: acupuncture, perimenopausal insomnia, randomized controlled trial

Hongli Yue,* Man Zhou,* Yu Lu, Liang Chen, Weihua Cui Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weihua CuiDepartment of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, No. 119, Nan Si Huan Xi Lu, Fengtai District, Beijing 100070, People’s Republic of ChinaTel +8613651315600Fax +861059976658Email weihuacui@ccmu.edu.cnPurpose: Patients undergoing intraspinal tumor resection usually experience severe acute pain, delaying postoperative rehabilitation, and increasing incidence of chronic pain. Recently, an increasing number of studies have found that low-dose intravenous lidocaine infusion during and/or after surgery can reduce opioid usage and the incidence of related side effects, inhibit hyperalgesia and promote recovery. Thus far, no studies have evaluated the analgesic effect and safety of perioperative intravenous lidocaine infusion for intraspinal tumor resection, especially the long-term analgesic effects of patient-controlled analgesia (PCA) with lidocaine during the first postoperative 48 hours. This study tests the hypothesis that intra- and postoperative systemic lidocaine infusion for patients undergoing intraspinal tumor resection can relieve postoperative acute or chronic pain and reduce the opioid dosage and incidence of related side effects without other problems.Study Design and Methods: This is a prospective, randomized, placebo-controlled, and double-blinded study. In total, 180 participants scheduled for intraspinal tumor resection will be randomly divided into lidocaine and placebo groups. The lidocaine group will be administered lidocaine intravenously during anesthesia and postoperative pain management during the first 48 postoperative hours; the placebo group will be administered normal saline at the same volume, infusion rate, and timing. The primary outcome will be the postoperative visual analog scale (VAS) score. Secondary outcomes will be postoperative cumulative sufentanil consumption, indicators of postoperative recovery, and the incidence of perioperative adverse events.Discussion: This study investigates the effect of continuous intravenous lidocaine infusion on postoperative sufentanil consumption and VAS scores. The findings will provide a new strategy of anesthesia and analgesia management for intraspinal tumor resection.Keywords: postoperative pain, intraspinal tumor resection, lidocaine, opiates

Kexing Lyu,1,* Yang Xu,1,* Huijun Yue,1 Yun Li,1 Jing Zhao,2 Lin Chen,1 Jianhui Wu,3 Xiaolin Zhu,1 Liping Chai,1 Chunwei Li,1 Weiping Wen,1 Wenbin Lei1 1Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Otolaryngology, The Third Hospital of Heibei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Otolaryngology, Meizhou People’s Hospital, Meizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiping Wen; Wenbin LeiDepartment of Otolaryngology, The First Affiliated Hospital of Sun Yet-Sen University, Yuexiu, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20 8733 3733Fax +86 20 8733 3108Email wenwp@mail.sysu.edu.cn; leiwb@mail.sysu.edu.cnPurpose: Long noncoding RNAs (lncRNAs) have been identified as an important class of noncoding RNAs that are deeply involved in multiple biological processes in tumorigenesis. This study is to investigate the critical roles and biological function of lncRNA growth arrest-specific 5 (GAS5) in tumorigenesis of laryngeal squamous cell carcinoma (LSCC).Patients and methods: A total of 59 samples of LSCC and paired adjacent tissue, as well as corresponding clinicopathological information were collected. GAS5 expression in both LSCC tissues and human SUN1076 and SNU899 cell lines were analyzed by Real-time quantitative RT-PCR method. Ectopic expression of GAS5 by vector transfection in LSCC cell lines and followed by in vitro experiments was to investigate the critical roles and function of GAS5 in LSCC. Cell Counting Kit 8 (CCK8) assay and PE/7AAD Annexin V Apoptosis analysis was to evaluate cell proliferation ability and cell apoptosis. Co-transfection of GAS5 and miR-21 was to explore the interaction between GAS5 and miR-21 in LSCC. BAX and CDK6 protein level were analyzed by western blot method.Results: This study demonstrated that GAS5 was significantly downregulated in LSCC tissue and human LSCC cell lines. GAS5 levels were correlated with the clinicopathological features of LSCC patients. In addition, the ectopic expression of GAS5 significantly inhibited cell proliferation and promoted apoptosis. Co-expression analyses indicated that GAS5 is negatively correlated with miR-21 in LSCC tissues. Overexpression of miR-21 eliminated GAS5-mediated cell apoptosis and proliferation suppression. Furthermore, GAS5, which upregulated BAX mRNA expression and downregulated CDK6 mRNA expression, was reversed by ectopic expression of miR-21.Conclusion: GAS5 suppresses LSCC progression through the negative regulation of miR-21 and its targets involved in cell proliferation and apoptosis, indicating that GAS5 may serve as a biomarker and potential target for LSCC therapy.Keywords: long noncoding RNA, GAS5, LSCC, miR-21, proliferation, apoptosis

Yang Yang,1,2 Guangyuan Zhang,2 Chuangang Li,3 Sihan Wang,2 Manning Zhu,2 Jinan Wang,2 Hangtian Yue,2 Xiaodong Ma,2 Yuhong Zhen,2 Xiaohong Shu1,21College of Integrative Medicine, Dalian Medical University, Dalian 116044, People’s Republic of China; 2College of Pharmacy, Dalian Medical University, Dalian 116044, People’s Republic of China; 3Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People’s Republic of ChinaPurpose: Resveratrol (RV), a promising anti-cancer candidate, is limited in application for its poor bioavailability. However, the better bioavailability has been found in some RV derivatives. So in this paper, we explore the structure–activity relationship and the metabolic profiles of RV and its analogs (polydatin [PD], oxyresveratrol [ORV], acetylresveratrol [ARV]) in human bladder cancer T24 cells, and then evaluate their active forms and key chemical functional groups which may determine the fate of tumor cells.Methods: Drug sensitivity is evaluated by MTT assay, HE staining and flow cytometry analysis after T24 cells treated with RV, PD, ORV and ARV, respectively. Then the drug metabolites, in alive and dead T24 cells, also in T24 cell supernatant and lysates, are qualitatively and quantitatively analyzed by high-performance liquid chromatography, liquid chromatography coupled with tandem mass spectrum and high-resolution mass spectrometry technologies, respectively.Results: RV, ORV and ARV inhibit bladder cancer cells growth in a dose- and time-dependent manner, and exert the anti-tumor potency to T24 cells in order of ORV>ARV>RV>PD. Meanwhile, similar metabolic profiles of the above compounds are found not only in cell supernatant and lysate, but also in dead and alive T24 cells after drug treatment, and the main metabolites of RV, ORV and PD are their prototypes, but ARV is mainly metabolized to RV.Conclusion: The inhibitory potencies to T24 cells in the order of ORV>ARV>RV>PD are related to the structure and metabolism of RV and its analogs. Meanwhile, the number and position of free phenolic hydroxyl groups play a prominent role in antitumor activities. Therefore, protecting phenolic hydroxyl groups, and inhibiting drug metabolism to keep phenolic hydroxyl groups free would be the promising strategies to ensure the bioactivity of RV and its analogs, and thus to improve RV’s bioactivity and promote RV clinical translation.Keywords: bladder cancer, resveratrol, oxyresveratrol, acetylresveratrol, polydatin, structure–activity relationship

Yuan Li,1 Pan Huang,2 Hongju Peng,1 Hongcheng Yue,1 Min Wu,1 Shanshan Liu,1 Rongsheng Qin,1 Juan Fan,1 Yunwei Han11The Oncology Department, Affiliated Hospital of Southwest Medical University, Lu Zhou, Si Chuan 646000, People’s Republic of China; 2Neurology Department, Deyang People’s Hospital, Deyang, Sichuan 618000, People’s Republic of ChinaBackground: Endostatin therapy is known to efficiently inhibit angiogenesis and growth of endothelial cells. Nonetheless, the antitumor mechanisms of endostatin combined with chemotherapy remain to be elucidated.Methods: In our study, a Lewis lung carcinoma transplant mouse model was established and treated with the recombinant human [rh]-endostatin, Endostar, combined with gemcitabine at different sequences. 18F-FDG PET/CT imaging was performed to monitor tumor growth, and hypoxia was examined using an oxygen microelectrode. Vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA) levels were detected via immunohistochemistry analysis and cell cycle distributions were analyzed by flow cytometry.Results: Endostar decreased VEGF expression, improved hypoxia, and influenced cell cycle distributions. Simultaneous treatment of Endostar and gemcitabine displayed significantly tumor inhibition, possessed the lowest uptake of FDG, improved oxygen partial pressure, decreased expression of VEGF, and increased pericyte coverage. Cell cycle analysis demonstrated that cells accumulated in the S phase following gemcitabine treatment and G0/G1 arrest occurred following Endostar treatment. An increase of cells in G0/G1 phase was observed following treatment with Endostar and gemcitabine.Conclusions: Our study suggests that the combination therapy of Endostar with gemcitabine simutaneously may optimally enhance their individual antitumor effects.Keywords: recombinant human endostatin, gemcitabine, antiangiogenic, combination therapy

During the “Day of the Dead” celebration in México, altars are installed to commemorate the dead in different places, such as schools’ libraries. To preserve this cultural tradition, students visit them to know about the meaning of the altars’ elements. In a similar way to museums, children can perceive altars as boring places where they should see objects passively or listen to historical accounts of the past. To address these challenges, we propose using augmented reality to make this cultural tradition a more engaging learning experience. We implemented an augmented reality (AR) prototype which recognizes the altar’s elements/objects to present narrative information through video, text, and images. We evaluated it through a within-subjects experiment to test two conditions: (A) A teacher explaining the altar (the usual method), and (B) Using the AR application. For collecting data, we used the User Engagement Scale (UES), a questionnaire to assess children’s perception about the learning experience, and observations. From twenty-nine students, only nine perceived that condition A was more engaging than B (augmenting reality). A Wilcoxon Signed-ranks test indicated a significant difference between both conditions (W = 124.5; Z = −2.012; p < 0.05). Our results helped us identify new design features in order for AR support learning experiences about this tradition, such as including narratives through multimedia.

ABSTRACTMotile cells migrate directionally in the electric field in a process known as galvanotaxis. Galvanotaxis is important in wound healing, development, cell division, and nerve growth. Different cell types migrate in opposite directions in electric fields, to either cathode, or anode, and the same cell can switch the directionality depending on chemical conditions. We previously reported that individual fish keratocyte cells sense electric fields and migrate to the cathode, while inhibition of PI3K reverses single cells to the anode. Many physiological processes rely on collective, not individual, cell migration, so here we report on directional migration of cohesive cell groups in electric fields. Uninhibited cell groups of any size move to the cathode, with speed decreasing and directionality increasing with the group size. Surprisingly, large groups of PI3K-inhibited cells move to the cathode, in the direction opposite to that of individual cells, which move to the anode, while such small groups are not persistently directional. In the large groups, cells’ velocities are distributed unevenly: the fastest cells are at the front of the uninhibited groups, but at the middle and rear of the PI3K-inhibited groups. Our results are most consistent with the hypothesis, supported by the computational model, that cells inside and at the edge of the groups interpret directional signals differently. Namely, cells in the group interior are directed to the cathode independently of their chemical state. Meanwhile, edge cells behave like the individual cells: they are directed to the cathode/anode in uninhibited/PI3K-inhibited groups, respectively. As a result, all cells drive uninhibited groups to the cathode, but a mechanical tug-of-war between the inner and edge cells directs large PI3K-inhibited groups with cell majority in the interior to the cathode, while rendering small groups non-directional.Significance statementMotile cells migrate directionally in electric fields. This behavior – galvanotaxis – is important in many physiological phenomena. Individual fish keratocytes migrate to the cathode, while inhibition of PI3K reverses single cells to the anode. Uninhibited cell groups move to the cathode. Surprisingly, large groups of PI3K-inhibited cells also move to the cathode, in the direction opposite to that of individual cells. The fastest cells are at the front of the uninhibited groups, but at the middle and rear of the PI3K-inhibited groups. We posit that inner and edge cells interpret directional signals differently, and that a tug-of-war between the edge and inner cells directs the cell groups. These results shed light on general principles of collective cell migration.

The Macau Science Satellites (MSS‐1) mission, consisting of twin low earth orbit satellites (Satellite A and B), is the first low‐inclination and high‐precision geomagnetic surveying satellite project in China. Among the multiple scientific payloads equipped with the scientific satellites, MSS‐1 carries a GNSS radio occultation (RO) receiver on Satellite A, and aims to observe the Earth's ionosphere and monitor the space weather especially in the South Atlantic Anomaly (SAA) area. This paper focuses on the ionospheric data of MSS‐1 obtained during the first 3 months after its launch, and assesses the RO products as well as initial scintillation measurements. Results show that MSS‐1 RO data have very good agreement with contemporary COSMIC‐2 and ionosonde observations. The scintillation amplitude indices S4 are comparable with that of COSMIC‐2 and well reflect the occurrence rates and distributions of equatorial plasma bubble and sporadic E (Es) in June solstice season. Special attentions are paid to the SAA longitude sector and inspire explorations on the seasonal variations and local‐time dependences of ionospheric irregularities. Key Points: The MSS‐1 ionospheric radio occultation products are comparable with COSMIC‐2 and ionosondesScintillation characteristics in the June solstice season are well reflected based on MSS‐1 high‐rate measurements [ABSTRACT FROM AUTHOR]