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Yucheng Hu,1 Rong Zhang,2 Junjie Li,1 Huan Wang,3 Meiya Wang,3 Qiuyi Ren,1 Yueqi Fang,1 Li Tian1 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Chengdu university of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Li Tian, Hospital of Chengdu university of Traditional Chinese Medicine, No. 41, 12 Qiaolu, Qingyang District, Chengdu, Sichuan, People’s Republic of China, Email 18980880129@qq.comhaAbstract: Allergic rhinitis is a chronic non-infectious inflammation of the nasal mucosa mediated by specific IgE. Recently, the human microbiome has drawn broad interest as a potential new target for treating this condition. This paper succinctly summarizes the main findings of 17 eligible studies published by February 2024, involving 1044 allergic rhinitis patients and 954 healthy controls from 5 countries. These studies examine differences in the human microbiome across important mucosal interfaces, including the nasal and intestinal areas, between patients and controls. Overall, findings suggest variations in the gut microbiota between allergic rhinitis patients and healthy individuals, although the specific bacterial taxa that significantly changed were not always consistent across studies. Due to the limited scope of existing research and patient coverage, the relationship between the nasal microbiome and allergic rhinitis remains inconclusive. The article discusses the potential immune-regulating role of the gut microbiome in allergic rhinitis. Further well-designed clinical trials with large-scale recruitment of allergic rhinitis patients are encouraged.Keywords: allergic rhinitis, microbiota dysbiosis, nasal microbiome, short-chain fatty acids, immunomodulation

Stefan Stübinger,1 Stefanie Altenried,2 Qun Ren2 1Department of Oral and Cranio-Maxillofacial Surgery, Research Group MIOSTE University Hospital Basel, Basel, 4032, Switzerland; 2Laboratory for Biointerfaces, Empa - Swiss Federal Laboratories for Materials Science and Technology, St. Gallen, 9014, SwitzerlandCorrespondence: Stefan Stübinger, Department of Oral and Cranio-Maxillofacial Surgery, Research Group MIOSTE University Hospital Basel, Spitalstrasse 21, Basel, 4032, Switzerland, Tel +41 61 265 70 70, Email stefan.stuebinger@unibas.chAbstract: Professional tooth whitening in the dental office is a popular cosmetic procedure and is performed under carefully monitored conditions. This allows the controlled application of a relatively high concentration of bleaching ingredients based on hydrogen peroxide or peroxide derivatives which produce reactive oxygen species, and consequently induce enamel erosion, alteration of the microhardness of the teeth, irritation of the gums, pain or post bleach sensitivity. This short communication describes the successful and reliable application of a new professional tooth whitening technique using a novel phthalimido peroxycaproic acid complex while avoiding reactive oxygen species.Keywords: in-office bleaching, SEM, composite gel, hydrogen peroxide, esthetics

Yang Bo, Xiaojing Zhong, Yanping Xiang, Qingjun Ren, Pingsheng Hao Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Pingsheng Hao, Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, 39 Shi-Er-Qiao Road, Jinniu District, Chengdu, Sichuan, 610072, People’s Republic of China, Tel +86138 8196 5024, Fax +86-28-87732407, Email hpswl@126.comAbstract: We report a fatal case of disseminated herpes zoster in a patient with multiple myeloma, illustrating the severe risks immunocompromised individuals face from viral infections. By combining a detailed case report with an extensive literature review, the paper seeks to shed light on the underlying susceptibility factors for varicella-zoster virus infection in multiple myeloma patients. We further evaluate effective prophylactic protocols for herpes zoster, aiming to equip clinicians with improved therapeutic strategies. The case underscores the critical need for vigilant clinical assessments and tailored patient management to mitigate infection risks and enhance patient outcomes.Keywords: multiple myeloma, disseminated herpes zoster, antiviral prophylaxis, immunodeficiency

Yunyu Xiao, Shaofeng Zhang, Qiusheng Ren Department of Anesthesiology, Hangzhou Ninth People’s Hospital, Hangzhou, Zhejiang, 311225, People’s Republic of ChinaCorrespondence: Qiusheng Ren, Department of Anesthesiology, Hangzhou Ninth People’s Hospital, No. 298, Yilong Road, Hangzhou, Zhejiang, 311225, People’s Republic of China, Tel +86 15372085337, Email renqiusheng1971@yahoo.comPurpose of Review: Postoperative analgesia is currently a significant topic in anesthesiology. Currently, the predominant approach for achieving multimodal analgesia involves the utilization of pharmacotherapy and regional anesthesia procedures. The primary objectives of this approach are to mitigate postoperative pain, enhance patient satisfaction, and diminish overall opioid usage. Nevertheless, there is a scarcity of research on the use of remote ischemia preconditioning aimed at mitigating postoperative pain.Recent Findings: Transient stoppage of blood flow to an organ has been found to elicit remote ischemia preconditioning (RIPC), which serves as a potent intrinsic mechanism for protecting numerous organs. In addition to its established role in protecting against reperfusion injury, RIPC has recently been identified as having potential benefits in the context of postoperative analgesia.Summary: In addition to traditional perioperative analgesia, RIPC provides perioperative analgesia and organ protection.Keywords: postoperative pain, remote ischemic preconditioning, inflammation, opioids

Shu Niu,1,* Qingjuan Ren,1,* Shuchun Chen,2 Xiaoyu Pan,2,3 Lin Yue,4 Xing Chen,2 Zelin Li,2 Ruoxi Zhen3 1Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu Niu, Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, People’s Republic of China, Email niushucccc@163.comPurpose: Among chronic liver diseases, non-alcoholic fatty liver disease (NAFLD) is one of the commonest. Although empagliflozin has several therapeutic uses in treating cardiovascular and renal disorders, its impacts and mechanisms on NAFLD are poorly understood. This research aimed to examine the metabolic regulatory mechanism through which empagliflozin protects against NAFLD.Methods: Equal grouping of twenty-seven male C57BL/6J mice into those fed a normal diet (NCD), those fed a high-fat diet (HFD), and those fed an HFD with empagliflozin (Empa) was approached. HE, oil red O staining, and Masson staining were utilized for evaluating the pathological damage to the liver and the mice’s liver and body weights. Lipids, blood glucose, and inflammation index were compared across the three groups. Liquid chromatography/mass spectrometry (LC-MS) has been employed for identifying liver metabolomics.Results: The findings suggested that empagliflozin mitigated the inflammatory and oxidative stress response associated with the buildup of lipids caused by HFD. Differentially expressed metabolites (DEMs) were identified by metabonomics analysis as present in both the HFD/NCD and Empa/HFD groups. These DEMs were primarily found in lipids and organic acids like lysophosphatidylcholine (lysoPC), lecithin (PC), triglyceride (TG), palmitic acid, and L-isoleucine. Among the enriched pathways that were shown to be important were those involved in the metabolism of histidine, arachidonic acid, the control of lipolysis in adipocytes, and insulin resistance. There was a strong correlation between inflammation and oxidative stress in most of the metabolites. The inflammation and oxidative stress unbalance were ameliorated by empagliflozin.Conclusion: NAFLD mice model showed considerable improvement in metabolic abnormalities and liver protection after treatment with empagliflozin. The process may include the overexpression of L-isoleucine and the downregulation of lysoPC, PC, TG, and palmitic acid to reduce liver harm caused by lipotoxicity.Keywords: NAFLD, empagliflozin, metabolomics, differentially expressed metabolites, obesity

Yiting Wang,1,&ast; Yikun Zhou,1,&ast; Yonghong Zhang,1 Qiuting Ren,2 Yan Wang,1 Heng Su1 1Department of Endocrinology and Metabolism, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 2Echocardiogram Laboratory, Department of Cardiology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Wang; Heng Su, Email ayisa_wang@aliyun.com; su_hen@hotmail.comAim: Diabetic cardiomyopathy is a subset of heart disease that is directly associated with diabetes, and left ventricular diastolic dysfunction is the earliest sign. We aimed to investigate the association between sex differences and left ventricular diastolic function in patients with type 2 diabetes.Methods: This was a cross-sectional study included patients with type 2 diabetes who visit the National Metabolic Management Center (MMC) at the First People’s Hospital of Yunnan from 2018 to 2021. Patients with hypertension, history of heart disease or ejection fraction < 50% were excluded from the study. Logistic regression was used to analyze their associations.Results: A total of 1778 patients were included in the study. The study included 1205 (70%) males and 573 (30%) females. Compared with males, females had higher total cholesterol and LDL cholesterol levels but lower diastolic pressure, body mass index (BMI), visceral fat area, HbA1c, blood urea nitrogen (BUN), serum creatinine and triglyceride. Females had a relatively higher ejection fraction than males (68.17 ± 6.055 vs 67.5 ± 6.096, P < 0.05). More female patients than male patients in the age group of 45– 60 years old had left ventricular diastolic dysfunction (female vs male, 54.5% vs 46.9%, P < 0.05). We also found that females were independently associated with left ventricular diastolic dysfunction, after adjusting for important clinical factors.Conclusion: Left ventricular diastolic function might be worse in female patients with type 2 diabetes. Further study is needed to verify the underlying mechanism.Keywords: type 2 diabetes, sex differences, left ventricular diastolic dysfunction

Xing Chen,1 Shuchun Chen,2,3 Qingjuan Ren,3 Shu Niu,3 Xiaoyu Pan,3 Lin Yue,3 Zelin Li,3 Ruiyi Zhu,3 Zhuoya Jia,3 Xiaoyi Chen,3 Ruoxi Zhen,3 Jiangli Ban3 1Department of Nephrology, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China; 3Department of Internal Medicine, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel/Fax +86 311 85988406, Email chenshuchunwork88@163.comPurpose: Semaglutide, a new long-acting glucagon-like peptide-1 analogue, has shown benefits for renal diseases, but its direct role on kidney metabolism under obesity remains unclear. The study aims to elucidate the protective effect and metabolic modulation mechanism of semaglutide on obesity-related kidney injury.Methods: Male C57BL/6J mice were divided into control and obesity groups. Mice in the obesity group had a high-fat diet and were treated with or without semaglutide (30nmol/kg/day). The study assayed blood biochemistry and then evaluated renal pathological injury through Periodic Acid-Schiff staining and electron microscopy. Metabolomics was utilized to analyze obesity-related metabolites in kidney samples.Results: Semaglutide significantly improved glucose homeostasis, insulin resistance, and kidney injury in obese mice. We successfully identified 377 altered metabolites (P< 0.05). It was suggested that semaglutide directly improved oxidative stress and inflammation-related metabolites such as nicotinamide adenine dinucleotide (NAD+) and adenosine in the kidney of obese mice, which have not been documented in obesity-related kidney injury. Relevant enriched pathways were included phospholipids and lysophospholipids metabolism, purine metabolism, NAD+ metabolism, and insulin resistance-related metabolism. They could serve as potential targets for intervention of obesity-related kidney injury.Conclusion: Our study revealed the metabolomics-based renoprotective mechanism of semaglutide in obese mice for the first time. The innovation lied in the identified metabolites such as NAD+ and adenosine targeted by semaglutide, which have not been documented in obesity-related kidney injury. Semaglutide may be a promising therapy for obesity-related kidney diseases.Keywords: semaglutide, glucagon-like peptide-1, metabolomics, obesity, kidney

Qingjuan Ren,1,2 Shuchun Chen,1,3 Xing Chen,1 Shu Niu,4 Lin Yue,5 Xiaoyu Pan,1 Zelin Li,1 Xiaoyi Chen1 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Geriatrics, Shijiazhuang People’s Hospital, Shijiazhuang, 050000, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050000, People’s Republic of China; 4Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, 050000, People’s Republic of China; 5Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, No. 348, Heping West Road, Shijiazhuang, 050000, People’s Republic of China, Tel +86-13833166283, Email chenshuchunwork88@163.comPurpose: This study aimed to investigate the effect of Semaglutide on skeletal muscle and its metabolomics.Methods: A total of 18 male C57BL/6 mice were randomly divided into normal control (NC) group, high-fat diet (HFD) group and HFD+Semaglutide group, and were given standard diet, HFD diet, HFD diet plus Semaglutide, respectively. The body weight, gastrocnemius weight, serum lipid, blood glucose and inflammatory index levels of mice in each group were observed and compared, and the morphological and structural changes of gastrocnemius were also analyzed. Meanwhile, gastrocnemius metabolite changes were analyzed by untargeted metabolomics.Results: After Semaglutide treatment, the food intake and body weight of mice were evidently decreased, while the relative gastrocnemius weight ratio were conversely increased. Meanwhile, the levels of TG, CHO, LDL, HDL, TNF-α, IL-6, IL-1β and HOMA-IR were all observed to decrease remarkably after Semaglutide intervention. Histological analysis showed that Semaglutide significantly improved the pathological changes of gastrocnemius, manifested as increased type I/type II muscle fiber ratio, total muscle fiber area, muscle fiber density, sarcomere length, mitochondrial number and mitochondrial area. Furthermore, metabolic changes of gastrocnemius after Semaglutide intervention were analyzed, and 141 kinds of differential metabolites were screened out, mainly embodied in lipids and organic acids, and enriched in 9 metabolic pathways including a variety of amino acids.Conclusion: Semaglutide can significantly reduce the body weight and the accumulation of intramuscular fat, promote muscle protein synthesis, increase the relative proportion of skeletal muscle, and improve muscle function of obese mice, possibly by altering the metabolism of muscle lipids and organic acids.Keywords: sarcopenic obesity, sarcopenia, glucagon-like peptide-1 receptor agonists, Semaglutide, metabonomics

Qian Ren,1 Caixia Yi,2 Jun Pan,1 Xin Sun,2 Xiao Huang2,3 1Key Laboratory for Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People’s Republic of China; 2School of Sports and Health Science, Tongren University, Tongren, People’s Republic of China; 3School of Physical Education, Guangxi University of Science and Technology, Guangxi, People’s Republic of ChinaCorrespondence: Jun Pan; Xiao Huang, Tel/Fax +86023-65102507, Email panj@cqu.edu.cn; humphrey8531@hotmail.comPurpose: Photodynamic therapy (PDT) is a non-invasive therapeutic modality that is used for several types of cancer and involves three essential elements (light, photosensitizer (PS), and oxygen). However, clinical PS is limited by the low yield of reactive oxygen species (ROS) and a long retention time. Therefore, developing a low-cost PS that can significantly increase ROS yield in a short time is of utmost importance.Methods: In this study, brusatol (Bru) was loaded on the surface of ultraviolet A (UVA)-responsive zinc oxide (ZnO)-coated magnetic nanoparticles (Fe3O4@ZnO-Bru). The PS was well characterized by transmission electron microscopy (TEM), Fourier Transform infrared spectroscopy (FTIR), a superconducting quantum interference device, and dynamic light scattering (DLS). 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Hoechst staining were used to determine the inhibitory effect of Fe3O4@ZnO-Bru on squamous cell carcinoma cells (SCC) with or without UVA radiation. Intracellular ROS levels and expression of the Nrf2 signaling pathway were also determined.Results: FTIR showed that Bru was successfully loaded on Fe3O4@ZnO. Fe3O4@ZnO-Bru was superparamagnetic, and the zeta potential was 8.86 ± 0.77 mV. The Bru release behavior was controlled by UVA. Fe3O4@ZnO-Bru with UVA irradiation induced an increase of 48% ROS productivity compared to Fe3O4@ZnO-Bru without UVA irradiation, resulting in a strong inhibitory effect on SCC. Furthermore, Fe3O4@ZnO-Bru nanocomposites (Fe3O4@ZnO-Bru NCs) had nearly no toxic effect on healthy cells without UVA radiation. The released Bru could significantly inhibit the Nrf2 signaling pathway to reduce the activity of scavenging excess ROS in SCC.Conclusion: In this study, Fe3O4@ZnO-Bru was successfully synthesized. PDT was combined with photochemotherapy, which exhibited a higher inhibitory effect on SCC. It can be inferred that Fe3O4@ZnO-Bru holds great potential for skin SCC therapy.Keywords: UVA-triggered chemotherapy, photodynamic therapy, reactive oxygen species, magnetic targeting

Xing Chen,1 Shuchun Chen,1,2 Zelin Li,1 Xiaoyu Pan,1 Yujiao Jia,1 Zhijuan Hu,3 Kai Niu,3 Bing Liu,3 Qingjuan Ren1 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Department of Nephrology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel/Fax +86 311 85988406, Email chenshuchunwork88@163.comObjective: To investigate the association between body mass index (BMI) and clinicopathologic parameters in patients with idiopathic membranous nephropathy (IMN).Methods: This study was retrospective and included patients with biopsy-proven IMN from 2018 to 2021 in Hebei General Hospital. Patients were categorized into two groups based on BMI. Clinical and histopathologic data were analyzed at the time of renal biopsy. Pathological data included immunofluorescence staining, glomerulosclerosis (GS, 0– 2), mesangial cell proliferation (MCP, 0– 1), tubular atrophy (TA, 0– 1), interstitial fibrosis (IF, 0– 1), vascular wall thickness (VWT, 0– 1) and a combination score (GMTIV) graded from 0 to 5.Results: Our study revealed that the obese group had a higher prevalence of hypertension and diabetes than the overweight/normal weight group (P=0.001, P=0.002). Systolic blood pressure (P=0.005), diastolic blood pressure (P< 0.001), haemoglobin (P=0.006), triglycerides (P< 0.001), serum uric acid (P=0.05), 24 h urine proteinuria concentration (UP) (P=0.012), MCP (P=0.042), IF (P=0.033), and GMITV (P=0.033) score were higher in obese group compared to the other group, while the high-density lipoprotein-cholesterol (P=0.034) and immunoglobulin A deposition score (P=0.005) were lower. Factors significantly associated with UP were the ratio of lymphocyte count to white blood cell count, serum pre-albumin, immunoglobulin G, microscopic hematuria, anti-phospholipase A2 receptor (anti-PLA2R), C3 deposit on multivariable analysis (adjusted R2=0.343). Binary logistic regression analysis illustrated that MCP was correlated to BMI (OR=2.528, P=0.036). Ordinal logistic regression analysis demonstrated that GMTIV was associated with BMI (OR=1.114, P=0.010) and C3 deposit (OR=1.655, P=0.001).Conclusion: High BMI was associated with MCP and GMTIV score in IMN patients. Obesity may play an essential role in mesangial lesions of IMN. This study emphasized the relation between BMI and histological parameters under the universal usage of anti-PLA2R antibodies for diagnosis and prognosis in IMN.Keywords: obesity, body mass index, idiopathic membranous nephropathy

Xinbang Liu,1,2,&ast; Qiuyue Ren,3,&ast; Yangkui Zhai,1,2,&ast; Yihan Kong,1,2 Dong Chen,4 Bai Chang1,2 1NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, People’s Republic of China; 2Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, 300134, People’s Republic of China; 3Department of Nephropathy, Wang Jing Hospital of China Academy of Chinese Medical Sciences, Beijing, 100102, People’s Republic of China; 4Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bai Chang, Email changbai1972@126.comObjective: The aim of this study is to analyze the microbiological characteristics of diabetic foot ulcer (DFU) and drug resistance of multidrug-resistant organisms (MDROs) and to reveal the potential risk factors for MDROs. This provides a basis for early empiric antibiotic treatment.Methods: This study included 348 patients with diabetic foot ulcer in Chu Hsien-I Memorial Hospital & Metabolic Disease Hospital of Tianjin Medical University between May 2020 and November 2021. A total of 475 strains of bacteria were cultured, among which 240 strains were multidrug-resistant bacteria, accounting for 51%. Binary logistic regression was used to analyze risk factors. First, univariate analysis was used to calculate the p value of variables, and then multivariate analysis was conducted for variables with p < 0.1 to analyze independent risk factors. Risk factors with p < 0.05 in multivariable analysis were considered as independent risk factors. The strength of the association was represented by odds ratio and 95% confidence interval.Results: Univariable logistic regression analysis demonstrated that previous hospitalization, previous antibiotic therapy, ulcer size > 4cm2, surgical therapy, D-dimer, and CRP were associated with MDRO infection in patients with DFU. Multivariate logistic regression analysis demonstrated that previous hospitalization (OR = 1.91; 95% CI = 1.11– 3.28; p = 0.02), ulcer size > 4cm2 (OR = 1.68; 95% CI = 1.03– 2.76; p = 0.04), surgical therapy (OR = 2.14; 95% CI = 1.03– 4.47; p = 0.04), and CRP (OR = 1.01; 95% CI = 1.00– 1.01; p = 0.03) were independent risk factors for MDROs infection in diabetic foot patients. Drug resistance analysis may indicate that the proportion and drug resistance rate of Acinetobacter baumannii in Tianjin, China, have changed.Conclusion: Previous hospitalization, ulcer size > 4cm2, surgical therapy and CRP were independent risk factors for MDROs infection in diabetic foot patients. Identifying these risk factors can help us identify the high-risk patients of diabetic foot with MDRO infection early. More attention to high-risk patients and more aggressive isolation precautions may reduce the incidence of MDRO infection in diabetic foot patients.Keywords: diabetic foot ulcer, multidrug-resistant organisms, infection, risk factors, logistic regression analysis

Zhufeng Zhang,1 Dongmei Guo,2 Qi Ren3 1Emergency Department of Sandun District of Zhejiang Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Radiology Department of Sandun District of Zhejiang Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3Qi Ren Intensive Care Unit of Sandun District of Zhejiang Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Qi RenIntensive Care Unit of Sandun District of Zhejiang Hospital, 1229th Gudun Road, Xihu District, Hangzhou, Zhejiang, 310030, People’s Republic of ChinaTel +86-18600754832Email xiewenzhangrenqi@163.comAbstract: Cases of acute tonsillitis, a common disease in the emergency department, are mostly mild and those complicated by severe pneumonia and acute respiratory distress syndrome are rarely reported.Keywords: acute tonsillitis, severe pneumonia, acute respiratory distress syndrome, extracorporeal membrane oxygenation, case report

Ying Zhang, Ruiqiu Zhao, Zhenzhen Zhang, Quanbo Liu, Aihua Zhang, Qiaoli Ren, Siyuan Li, Xiaoru Long, Hongmei Xu Department of Infection, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, The Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Xiaoru Long; Hongmei Xu Tel +86 2368370396; +86 2368370385Email 2387207074@qq.com; xuhongm0095@hospital.cqmu.edu.cnObjective: Pediatric tuberculosis (TB) is one of the top ten causes of death in children. Our study was to analyze influencing factors of multidrug-resistant tuberculosis (MDR-TB) and validation of whole-genome sequencing (WGS) used in children with drug-resistant TB (DR-TB).Methods: All Mycobacterium tuberculosis (Mtb) strains were isolated from patients aged below 18 years old of Children’s Hospital of Chongqing Medical University, China. A total of 208 Mtb isolates were tested for eight anti-TB drugs with phenotypic drug susceptibility test (DST) and for genetic prediction of the susceptible profile with WGS. The patients corresponding to each strain were grouped according to drug resistance and genotype. Influencing factors of MDR-TB and DR-TB were analyzed.Results: According to the phenotypic DST and WGS, 82.2% of Mtb strains were susceptible to all eight drugs, and 6.3% were MDR-TB. Using the phenotypic DSTs as the gold standard, the kappa value of WGS to predict isoniazid, rifampin, ethambutol, rifapentine, prothionamide, levofloxacin, moxifloxacin and amikacin was 0.84, 0.89, 0.59, 0.86, 0.89, 0.82, 0.88 and 1.00, respectively. There was significant difference in the distribution of severe TB, diagnosis, treatment and outcome between MDR and drug-susceptible group (P< 0.05). The distribution of severe TB and treatment between DR and drug-susceptible group was statistically different (P< 0.05). The results of binary logistic regression showed that Calmette–Guérin bacillus (BCG) vaccine is the protective factor for MDR-TB (OR=0.19), and MDR-TB is the risk factor for PTB and EPTB (OR=17.98).Conclusion: The BCG vaccine is a protective factor for MDR-TB, and MDR-TB might not be confined to pulmonary infection, spreading to extrapulmonary organs in children. MDR-TB had more severe cases and a lower recovery rate than drug-susceptible TB. WGS could provide an accurate prediction of drug susceptibility test results for anti-TB drugs, which are needed for the diagnosis and precise treatment of TB in children.Keywords: tuberculosis, whole-genome sequencing, children, consistency test, multidrug-resistant tuberculosis, clinical feature

Wenli Feng, Jing Yang, Yan Ma, Zhiqin Xi, Ying Ji, Qiao Ren, Huan Ning, Shaoyan Wang The Department of Dermatovenereology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, People’s Republic of ChinaCorrespondence: Wenli Feng; Jing YangThe Department of Dermatovenereology, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan, Shanxi, 030001, People’s Republic of ChinaTel +86-0351-3365410Email wenlifeng2010@163.com; yangjing7962@126.comPurpose: This study aimed to investigate the effects of aspirin (acetyl salicylic acid [ASA]) combined with fluconazole (FCA), itraconazole (ITR), or voriconazole (VRC) on Candida albicans under planktonic and biofilm conditions.Methods: A total of 39 clinical C. albicans strains were used to perform the in vitro drug sensitivity assay under different conditions using the M27-A4 broth microdilution method. The minimal inhibitory concentrations (MICs) and fractional inhibitory concentration index (FICI) values were calculated. C. albicans ZY23 was chosen for the further analyses.Results: Under planktonic conditions, the half maximal MIC (MIC50) values of FCA, ITR, and VRC were 64– 0.5 μg/mL, 32– 0.0625 μg/mL, and 16– 0.125 μg/mL, respectively, when applied, whereas in combination with ASA, the values decreased to 32– 0.25 μg/mL, 8– 0.0313 μg/mL, and 8– 0.0313 μg/mL, respectively. Under biofilm conditions, FCA, ITR, or VRC alone showed MIC50 values of 128– 8 μg/mL, 32– 4 μg/mL, and 32– 0.5 μg/mL, whereas in combination with ASA the values were decreased to 32– 0.5 μg/mL, 16– 0.5 μg/mL, and 8– 0.0625 μg/mL, respectively. Analysis of the FICI showed that the sensitization rate of ASA to FCA, ITR, and FCA under planktonic conditions was 43.59%, whereas the sensitization rates of ASP to FCA, ITR, and FCA under biofilm conditions were 46.15%, 46.15%, and 48.72%, respectively. Additionally, the time-growth and time-kill curves of C. albicans ZY23 further verified the synergistic effects of ASA on azole drugs.Conclusion: ASA may act as an enhancer of the inhibitory effects of azole drugs on the growth of clinical C. albicans under planktonic and biofilm conditions.Keywords: acetylsalicylic acid, synergistic effects, invasive fungus, virulence

Qingqi Ren,1,* Shunjun Fu,2,* Dongping Wang,3– 5 Weiqiang Ju,3– 5 Xiaoshun He3– 5 1Department of Hepatobiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoshun He; Weiqiang JuOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, No. 58, ZhongShan Road II, Yuexiu, Guangzhou, 510080 Guangdong, People’s Republic of ChinaEmail gdtrc@163.com; weiqiangju@163.comBackground: Leucine aminopeptidases (LAPs) have been reported to be involved in tumor cell proliferation, invasion and angiogenesis. However, the relationship between serum leucine aminopeptidases and prognosis of hepatocellular carcinoma (HCC) patients who underwent liver transplantation (LT) was not yet reported. We aimed to evaluate the prognostic value of preoperative serum leucine aminopeptidases in these patients.Methods: Clinical data of 106 HCC patients who underwent LT were retrospectively analyzed. The sex ratio, age, HBV infection, Child–Pugh stage, preoperative tumor therapy, AFP, the largest tumor size, tumor number, Edmondson grading, macro- and micro-vascular invasion of patients with different serum LAP level and compositions of patients who met the criteria of Milan, UCSF or Hangzhou were compared using the chi-square test. The Kaplan–Meier method was performed in survival analysis and the log rank test was used in survival comparison.Results: Serum LAPs were correlated with alpha-fetoprotein (AFP), the largest tumor size, tumor number and macro-vascular invasion. Patients with serum LAPs > 87 U/L showed significantly poorer disease-free survival (DFS) and overall survival (OS) than those with serum LAPs ≤ 87 U/L. Univariate analysis indicated that serum LAPs, AFP, the largest tumor size, tumor number, and macro- and micro-vascular invasion were all associated with DFS and OS. Multivariate analysis showed that serum LAPs, macro-vascular invasion and the largest tumor size were independently correlated with DFS and OS. Serum LAPs could also distinguish prognosis between patients with different status of AFP, the largest tumor size, tumor number, and macro- and micro-vascular invasion, as well as patients within and beyond selection criteria, such as Milan, University of California, San Francisco and Hangzhou criteria.Conclusion: Elevated preoperative serum LAPs were associated with advanced tumor stage and aggressive biological behavior, and thus a poor outcome, which could be a prognostic marker for HCC patients who underwent LT.Keywords: leucine aminopeptidases, hepatocellular carcinoma, liver transplantation, disease-free survival, overall survival

Ye Zhang,1,* Bin He,1 Jinqiu Zhao,2,* Muzi Zhang,1 Qinsong Ren,1 Wei Zhang,1 Shuai Xu,1 Zhengxue Quan,1 Yunsheng Ou1 1Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin He Email binheing@163.comBackground: Serious pain commonly occurs after posterior spinal surgery. This study aims to evaluate the effect of preemptive and multimodal analgesia using celebrex, pregabalin and ropivacaine on pain control after this surgery.Methods: Ninety-three patients undergoing posterior spinal surgery were enrolled in this prospective, randomized, double-blind, placebo-controlled clinical trial. All patients were treated with patient- controlled analgesia (PCA, intravenous tramadol hydrochloride and flurbiprofen) as required. They were randomized to combination analgesia intervention (oral celebrex, pregabalin and subcutaneous infiltration of ropivacaine), ropivacaine intervention (only subcutaneous infiltration of ropivacaine), and control intervention (placebo). We compared postoperative visual analog scale (VAS) scores and PCA dose among the three groups.Results: The VAS scores were significantly lower in the combination analgesia group than in the control group at 0 h, 2 h, 12 h, 24 h, 3 d, 5 d, 7 d and 14 d after posterior spinal surgery, while combination analgesia was also superior to ropivacaine in terms of VAS scores at 24 h and 14 d postoperatively. The combination analgesia group was also associated with significantly reduced PCA consumption compared with the control group, but there was no statistical difference in PCA consumption between the ropivacaine group and control group.Conclusion: Combination analgesia using celebrex, pregabalin and ropivacaine is effective and safe to alleviate pain after posterior spinal surgery.Clinical Trial Registration: Chinese Clinical Trial Registry No. ChiCTR2000031236.Keywords: preemptive analgesia, multimodal analgesia, pain control, posterior spinal surgery, randomized trial

A paradigm shift in the traditional sequential design approaches is critically essential to create application-specific hierarchical and multifunctional materials with superior long-term performance for next-generation energy technologies involving extreme environments. In the current work, we aim to leverage the flexibility and geometric/compositional complexity offered by additive manufacturing to demonstrate this new approach by codesigning a compositionally graded Ni-based alloy for molten salts\sCO2 heat exchangers to enable mitigation of environmental degradation of surfaces exposed to molten halide salts, while simultaneously suppressing the consequent deterioration in mechanical stability. Thermokinetic modeling describing the underlying physics of thermally- and environmentally induced spatiotemporal compositional and microstructural evolution will be employed to predict the parameter space of material deposition processes and precisely identify the required composition gradient. Preliminary corrosion and mechanical testing of the dual material demonstrated the potential of the material to replace existing solid solution strengthened materials for this application. [ABSTRACT FROM AUTHOR]

Hui Li,1– 3 Yanlong Liu,4– 6 Lifei Xing,7 Xiaoyu Yang,8 Jinzhong Xu,9 Qiushi Ren,1 Kuan-Pin Su,4,10,11 Yanye Lu,1 Fan Wang2,3,12 1Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, People’s Republic of China; 2Xinjiang Key Laboratory of Neurological Disorder Research, The Second Affiliated Hospital, Xinjiang Medical University, Urumqi 830063, People’s Republic of China; 3Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot 010110, People’s Republic of China; 4Zhuji Institute of Biomedicine, School of Pharmaceutical Sciences, Wenzhou Medical University, Shaoxing 311800, People’s Republic of China; 5School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 6The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou 325035, People’s Republic of China; 7Department of Neurology, Inner Mongolia North Heavy Industries Group Corp. Ltd Hospital, Baotou 014030, People’s Republic of China; 8Beijing Jishuitan Hospital, Beijing 100035, People’s Republic of China; 9The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling 317500, People’s Republic of China; 10An-Nan Hospital, China Medical University, Tainan, Taiwan; 11College of Medicine, China Medical University, Taichung, Taiwan; 12Beijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, People’s Republic of ChinaCorrespondence: Fan WangBeijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, People’s Republic of ChinaTel +86 10 62715511 ext. 6429Fax +86 10 62716285Email fanwang@bjmu.edu.cnBackground: Cigarette smoking has shown to be associated with sleep disturbance, especially prolonged sleep onset latency (SOL). Cigarette smoking stimulates the release of dopamine (DA) and serotonin (5-HT), which might promote awakening and inhibit rapid eye movement sleep. Dopamine transporter (DAT) and serotonin transporter play a key role in the reuptake of DA and 5-HT from the synaptic cleft into presynaptic neurons. However, the relationship among cigarette smoking, sleep disturbance and neurotransmitters has never been investigated in human cerebrospinal fluid (CSF).Methods: A total of 159 Chinese male subjects (81 active smokers and 78 non-smokers) who would undergo lumbar puncture before the surgery of anterior cruciate ligament reconstruction were recruited and 5mL-CSF samples were collected incidentally. CSF levels of DA, DAT, 5-HT, and serotonin transporter were measured using radioimmunoassay and ELISA. Sociodemographic data and the Pittsburgh Sleep Quality Index (PSQI) scale were collected before surgery.Results: PSQI global scores, SOL, and CSF DA levels were significantly higher in active smokers compared to non-smokers (2.00 [1.00– 4.75] scores vs 4.00 [3.00– 6.00] scores, p = 0.001; 10.00 [5.00– 15.00] minutes vs 15.00 [10.00– 30.00] minutes, p = 0.002; 87.20 [82.31– 96.06]ng/mL vs 107.45 [92.78– 114.38] ng/mL, p < 0.001), while CSF DAT levels were significantly lower in active smokers (0.35 [0.31– 0.39] ng/mL vs 0.29 [0.26– 0.34] ng/mL, p < 0.001).Conclusion: Cigarette smoking was indeed associated with sleep disturbance, shown by prolonged SOL, higher DA levels and lower DAT levels in CSF of active smokers.Keywords: sleep, cigarette smoking, dopamine, cerebrospinal fluid

Recent EAST/DIII-D joint experiments on the high poloidal beta tokamak regime in DIII-D have demonstrated fully noninductive operation with an internal transport barrier (ITB) at large minor radius, at normalized fusion performance increased by 30% relative to earlier work (Politzer et al 2005 Nucl. Fusion 45 417). The advancement was enabled by improved understanding of the 'relaxation oscillations', previously attributed to repetitive ITB collapses, and of the fast ion behavior in this regime. It was found that the 'relaxation oscillations' are coupled core-edge modes amenable to wall-stabilization, and that fast ion losses which previously dictated a large plasma-wall separation to avoid wall over-heating, can be reduced to classical levels with sufficient plasma density. By using optimized waveforms of the plasma-wall separation and plasma density, fully noninductive plasmas have been sustained for long durations with excellent energy confinement quality, bootstrap fraction ≥80%, βN ≤ 4, βP ≥ 3, and βT ≥ 2%. These results bolster the applicability of the high poloidal beta tokamak regime toward the realization of a steady-state fusion reactor.

Lijun Huang,1 Qiusheng Ren,1 Shenghui Yu,1 Ya Shao,1 Yijun Chen,2 Xin Huang1 1Department of Anesthesiology, Ningbo Yinzhou People’s Hospital, The Affiliated People’s Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Lijun HuangDepartment of Anesthesiology, Ningbo Yinzhou People’s Hospital, The Affiliated People’s Hospital of Ningbo University, No. 251, East Baizhang Road, Ningbo, Zhejiang Province 315040, People’s Republic of ChinaEmail huanglijunyz@163.comObjective: The goal of the study was to investigate the efficacy of lipid supplement to epinephrine-based therapy in resuscitation of asphyxia-induced cardiac arrest in aged rats.Methods: The study included two parts: in experiment A, rats underwent asphyxial cardiac arrest and cardiopulmonary resuscitation, randomized to receive epinephrine and normal saline (control group, n=22), epinephrine and intralipid 20% (long-chain triglycerides (LCT) group, n=22) or epinephrine and lipovenoes 20% (LCT/medium-chain triglcerides (MCT) group, n=22). Return of spontaneous circulation, recurrence of asystole after resuscitation, hemodynamic metrics, arterial blood gas values, neurological assessment score and indexes of pulmonary transudation were recorded. In experiment B, rats using the same model and resuscitation protocol were randomly divided into 21 groups: Control 0, Control 20, Control 40, Control 60, Control 80, Control 100, Control 120, LCT 0, LCT 20, LCT 40, LCT 60, LCT 80, LCT 100, LCT 120, LCT/MCT 0, LCT/MCT 20, LCT/MCT 40, LCT/MCT 60, LCT/MCT 80, LCT/MCT 100 and LCT 120 (n=10, the subscripts represent respective endpoint of observation in minutes). Myocardial bioenergetics were determined.Results: In experiment A, the LCT and LCT/MCT groups had a shorter time to return of spontaneous circulation (ROSC) (P=0.001and P< 0.001, respectively) and higher survival rate (P=0.033 and P=0.014, respectively) compared with the Control group. The LCT/MCT group had higher MAP (P< 0.001 and P=0.001, respectively), HR (P< 0.001 and P=0.004, respectively) and RPP (P< 0.001 and P< 0.001, respectively) compared with the Control and LCT groups, respectively. In experiment B, the LCT/MCT group had a higher energy charge compared with the control group at 20 (P< 0.001) and 40 (P< 0.001) minutes. The LCT group had higher energy charge compared with the Control group at 40 (P< 0.001) and 60 (P< 0.001) minutes.Conclusion: The supplement of lipid emulsion to epinephrine improves resuscitation outcomes of asphyxia-induced cardiac arrest than epinephrine alone in our in vivo model of aged rat. LCT/MCT emulsion may be superior to LCT emulsion in epinephrine-based resuscitation.Keywords: asphyxia, cardiac arrest, epinephrine, lipid emulsion, cardiopulmonary resuscitation

Li Li, Hua Yu, Qian Ren Department of Ophthalmology, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Qian RenDepartment of Ophthalmology, The First Hospital of Shijiazhuang, No. 36 Fanxi Road, Shijiazhuang, Hebei, People’s Republic of ChinaEmail liliyk@aliyun.comIntroduction: MicroRNA-218-5p (miR-218-5p) was involved in the progression of multiple tumors as a tumor suppressor miRNA. Its specific role on human retinoblastoma (RB) cells remains unknown.Methods: We constructed the miR-218-5p overexpression and knockdown cells to detect their role on RB cell line WERI-Rb-1, and we analyzed its binding sites on TargetScan. CCK8 and clonogenic assays were performed to detect cell viability. Flow cytometry was used for the detection of cell apoptosis.Results: Our results showed that the miR-218-5p inhibitor enhanced cell viability and blocked the apoptosis in RB cells. The AKT/mTOR signaling pathway was also inhibited by the miR-218-5p inhibitor. MiR-218-5p mimics lead to diametrically opposite results. Nucleus accumbens-associated 1 (NAC1) encoded by the NACC1 gene is involved in the regulation of many biological functions, including gene transcription, protein degradation of ubiquitin pathway, cell viability, and apoptosis. In this research, dataset analysis suggested that NACC1 might be a downstream target of miR-218-5p. Then, qPCR and Western blot analysis proved that miR-218-5p inhibited the expression of NACC1 in RB cells. NACC1 could promote cell viability and inhibit the apoptosis by activating the AKT/mTOR signaling pathway. MiR-218-5p mimics blocked the enhancement of cell growth induced by NACC1 overexpression as well as the activation of the AKT/mTOR signaling pathway in RB cells.Discussion: MiR-218-5p inhibited cell growth by targeting NACC1 and suppressing the AKT/mTOR signaling pathway. MiR-218-5p/NACC1/AKT/mTOR might be a new target axis for the clinical treatment strategy.Keywords: retinoblastoma, miR-218-5p, NACC1, apoptosis, signaling pathway