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Qian Cheng,1 Yishu Tang,2 Jing Liu,1 FeiYang Liu,1,&ast; Xin Li1,&ast; 1Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Emergency, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: FeiYang Liu; Xin Li, Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China, Tel +86-731-88618814 (88618214) ; Tel +86-731-88618814 (88618214), Email 546917399@qq.com; lixiner1975@163.comObjective: The role of chest computed tomography (CT) in distinguishing the causative pathogens of pulmonary infections in patients with hematological malignancies (HM) is unclear. The aim of our study was to compare and assess the clinical characteristics, radiologic features and potential differential diagnostic value of CT in HM patients and other different immune statuses patients with pulmonary infections.Methods: Patients were divided into immunocompetent (105 cases) and immunocompromised groups (99 cases) according to immune status. Immunocompromised patients included the HM group (63 cases) and the non-HM group (42 cases). The basic clinical data and CT findings were collected and statistically analyzed.Results: Regarding the pathogen distribution, viral, Pneumocystis jirovecii and mixed infections were more common in the immunocompromised group than the immunocompetent (p < 0.01), but viral infections were more common in the HM group than in the non-HM group (p=0.013). Immunocompromised patients had more diverse CT findings and more serious lesions (mostly graded 2– 4) than immunocompetent patients. The most common CT findings in HM patients were consolidation and ground-glass opacities (GGO), which were also found in the non-HM group. The overall diagnostic accuracy of CT was lower in immunocompromised patients than in immunocompetent patients (25.7% vs 50.5%, p< 0.01). CT had better diagnostic efficacy for fungi and Pneumocystis jirovecii in HM patients.Conclusion: CT diagnosis is less efficient in distinguishing the causative pathogens of HM patients. However, CT can help distinguish fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients.Clinical Relevance Statement: Our study might facilitate clinical decision-making in fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients.Keywords: pneumonia, hematological malignancies, computed tomography, diagnostic value

Qian Gui,1,&ast; Jingcai Meng,2,&ast; Mingqiang Shen,1 Hongxuan Feng,1 Xiaofeng Dong,1 Daqiang Xu,3 Wenxin Zhu,2 Qingzhang Cheng,1 Linhui Wang,2 Guanhui Wu,1 Yanli Lu3 1Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China; 2Department of Physiology and Neurobiology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 3Department of Radiology, the Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanli Lu, Department of Radiology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Tel +8618251135654, Email luyanli.2009@163.com Guanhui Wu, Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Email ghwusz26@njmu.edu.cnIntroduction: Previous studies have predominantly explored the relationship of the glymphatic system with motor symptoms in Parkinson’s disease (PD); however, research on non-motor symptoms remains limited. Therefore, this study investigated the association between glymphatic function and non-motor symptoms, including cognitive impairment and sleep disorders, in PD patients.Methods: This study recruited 49 PD patients and 38 healthy controls (HC). Glymphatic function was evaluated using enlarged perivascular spaces (EPVS) in the basal ganglia (BG) region and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Cognition, sleep, anxiety, and depression scales were assessed in all participants. According to the scale scores, PD patients were further divided into several groups to identify the presence of non-motor symptoms. Differences in EPVS numbers and ALPS index between PD subgroups and HC group were compared. Spearman correlation analysis was performed to investigate the association between the PD non-motor symptoms and ALPS index. Additionally, receiver operating characteristic (ROC) curves analysis was conducted for ALPS index to predict cognitive impairment and insomnia in PD patients.Results: PD patients with and without non-motor symptoms all showed more EPVS numbers than the controls, and the EPVS numbers in PD patients with cognitive impairment were also greater than those without. Notably, except for the depression subgroup, PD patients with non-motor symptoms showed significantly lower ALPS index than the controls. The Montreal Cognitive Assessment (MoCA) scores were positively correlated, whereas the Parkinson’s Disease Sleep Scale (PDSS)-2 and REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores were negatively correlated with the ALPS index in PD patients (r=0.3618, P=0.0053; r=− 0.4146, P=0.0015; r=− 0.2655, P=0.0326, respectively). The ALPS index proved to be predictive of cognitive impairment and insomnia in PD patients (AUC=0.7733, P=0.001; AUC=0.7993, P=0.0004, respectively).Conclusion: Glymphatic function is closely associated with cognition and sleep of PD patients.Keywords: glymphatic system, parkinson’s disease, non-motor symptoms, cognition, sleep

Aims: A new methanogenic strain, named GFJ07, was isolated from a pond of mountain forests in Guangxi, China. Cells grown in liquid culture tended to form aggregates with pseudosarcina-like or irregular shape.Methodology and Results: The optimum temperature, pH and NaCl concentration were 35 ℃, 7.0 and 0.5%, respectively. The isolate used methanol, trimethylamine, acetate and H2-CO2 as substrates. Analysis of the 16S rDNA sequences revealed strain GFJ07 showed the highest sequence similarity of 99.9% to Methanosarcina mazei.Conclusion, significance and impact of study: The cells were Gram positive and nonmotile. Most of single cell grew as a sausage-like clinder about 0.5 μm in diameter and 1.0 μm in length.

Qiqi Cheng,1 Xiaolin Zhou,1 Peng Wang,2 Rong Liu,3 Qiang Liu1 1Department of Infectious Disease, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China; 2Department of Clinical Laboratory, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China; 3Department of Ultrasound, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of ChinaCorrespondence: Qiang Liu, Department of Infectious Disease, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China, Tel +86 13720181669, Email liuqiang@ctgu.edu.cnAbstract: We report a rare case of mechanical aortic valve infective endocarditis caused by Neisseria sicca. A 44-year-old man, with a history of aortic valve replacement, presented to the hospital with a 10-day history of fever. Investigations revealed that the blood cultures grew Neisseria sicca. Although the transthoracic echocardiogram (TTE) was negative, a transesophageal echocardiogram showed a 0.5 cm × 0.3 cm piece of vegetation attached to the aortic valve. After eight weeks of therapy, according to the antibiotic susceptibility test, the patient’s blood cultures were negative, and repeat TTE showed no vegetation. This report can offer valuable insights for clinical diagnosis and treatment of Neisseria sicca endocarditis, particularly when selecting sensitive antibiotics.Keywords: infective endocarditis, Neisseria sicca, aortic valve, bacteremia

Hongwei Huang,&ast; Wei Liao,&ast; Kaiyue Zhang, Hao Wang, Qi Cheng, Bin Mei Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Mei; Qi Cheng, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Qiaokou, Wuhan, 430030, People’s Republic of China, Email meibingluke@sina.com; chengqi@hust.edu.cnPurpose: The prognosis of patients with huge hepatocellular carcinoma (huge HCC, diameter ≥ 10 cm) is poor owing to the high early recurrence rate. This study aimed to explore the clinical value of postoperative adjuvant transarterial chemoembolization (PA-TACE) plus programmed cell death-1 (PD-1) inhibitors for huge HCC.Patients and Methods: Data from consecutive huge HCC patients treated with hepatectomy during June 2017 and July 2022 were retrospectively collected. Baseline differences were balanced between huge HCC patients who underwent PA-TACE with (AIT group) or without PD-1 inhibitors (AT group) by propensity-score matching (PSM). We compared recurrence-free survival (RFS), overall survival (OS) and recurrence patterns between the two groups. Independent risk factors for RFS and OS were confirmed by Cox regression analysis, and subgroup analysis was also conducted.Results: A total of 294 patients were enrolled, and 77 pairs of patients in the AIT and AT groups were matched by PSM. The 1-year and 2-year RFS were 49.9% and 35.7% in the AIT group compared to 24.7% and 15.5% in the AT group respectively (p< 0.001). The 1-year and 2-year OS were 83.6% and 66.9% in the AIT group compared to 50.6% and 36.8% in the AT group respectively (p< 0.001). There were no significant differences in recurrence patterns between the two groups. Multivariable analysis demonstrated that combined therapy of PA-TACE plus PD-1 inhibitors was a protective factor related to both RFS and OS.Conclusion: PA-TACE plus PD-1 inhibitors could improve survival outcomes for huge HCC patients.Keywords: hepatocellular carcinoma, postoperative adjuvant therapy, programmed cell death-1 inhibitors, transarterial chemoembolization, early recurrence

Xiuri Wang,1,&ast; Yunxiao Liang,1,&ast; Qiuchen Cheng,1 Wei Nong,1 Liuyang Hu2 1Department of Gastroenterology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of China; 2Department of Laboratory Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liuyang Hu, Department of Laboratory Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Taoyuan Road N 6, Nanning, Guangxi, 530016, People’s Republic of China, Email 1225432679@qq.comAbstract: Nocardiosis is mainly an opportunistic infection that affects immunosuppressed individuals, with the most common manifestation being the pulmonary infection and cerebral abscesses. Abdominal abscesses caused by Nocardia is rare in diabetes patients. Here, we report a rare case of abdominal abscesses caused by Nocardia farcinica (N. farcinica) in a 56-year-old man with poorly controlled type 2 diabetes and prolonged use of corticosteroids for the treatment of secondary adrenal insufficiency. Abdominal CT suggested abdominal abscesses, and the culture of the abscess puncture fluid identified it as N. farcinica by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Treatment with a combination of trimethoprim-sulfamethoxazole (TMP-SMX) and imipenem/cilastatin (IPM/CS), along with surgical drainage and reduction in corticosteroid dosage, achieved successful outcomes in treating disseminated abdominal abscesses. Immunocompromised patients with unexplained fever, abdominal pain, and abdominal abscess should be suspected of Nocardia infection.Keywords: abdominal nocardiosis, Nocardia farcinica, abdominal abscesses, diabetes, corticosteroid

Miao Zhu,1 Juan Zhao,1 Xiaoli Zhu,2 Qi Cheng,2 Shuyou Zhang,2 Lingming Kong2 1Psychiatry Department, The Oriental People’s Hospital of Xuzhou, Xuzhou, 221004, People’s Republic of China; 2Psychological Intervention Center, No.904 Hospital, Changzhou, 213003, People’s Republic of ChinaCorrespondence: Lingming Kong, Psychological Intervention Center, No.904th Hospital, Peace Road 55, Changzhou, Jiangsu, 213003, People’s Republic of China, Tel +86 519 83064556, Fax +8651983064560, Email lingming123@163.comPurpose: Late-onset depression (LOD) with poor treatment response has high incidence and mortality in the China’s aged people, this study aims to explore the correlation between health-promoting lifestyle, meaning in life, interleukin-6 (IL-6) and LOD for providing scientific basis of LOD prevention and rehabilitation.Patients and Methods: A total of 496 LOD patients (study group) and healthy older adults (control group) were enrolled and investigated by using the Health-promoting lifestyle Profile-II, revised (HPLP-IIR), Meaning in Life Questionnaire-Chinese Version (MLQ-C), and Hamilton Depression Scale (HAMD). The interleukin-6 (IL-6) in the circulating blood was detected by utilizing ELISA kit.Results: The results showed that the scores of all factors in HPLP-IIR and MLQ were significantly lower and IL-6 level was higher in the study group than the control group. Scores of most factors in HPLP-IIR and MLQ negatively and IL-6 positively correlated with scores of subscales and total HAMD score. Meaning in life and IL-6 partially mediated the relationship between health-promoting lifestyles and depression severity in the study group, with the mediating effect explains 15.76% and 22.64% of the total effect, respectively.Conclusion: Health-promoting lifestyles, meaning in life, and IL-6 are predictors of LOD, and an unhealthy lifestyle could induce LOD through the mediating effect of meaning in life and IL-6 in older adults.Keywords: late-onset depression, meaning in life, health-promoting lifestyle, older adult

An Li,1 Huxiong Piao,1 Jiamin Zhang,2 Qingtao Cheng,1 Fangyu Piao,1 Chang Cao,1 Yuqi Yan,1 Jingxu Li,1 Bin Jin1 1Stomatology, Affiliated Hospital of Yanbian University, Yanji, People’s Republic of China; 2Department of Periodontal Mucosal Disease, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Jingxu Li; Bin Jin, Email ljx0502@126.com; jinbin198629@sina.comPurpose: To compare the clinical repair effects of leaving the defect empty and using Platelet-Rich Fibrin (PRF) combined with BIO-GENE artificial bone powder in patients with bone defects 6 months after jaw cystectomy.Patients and Methods: From June 2021 to June 2022, 70 patients who were admitted to the Department of Stomatology, Affiliated Hospital of Yanbian University, and were diagnosed with jaw cysts postoperatively were selected. All of the patients were divided into two groups according to random method, among which 35 patients who underwent cystectomy alone were recorded as group A, which served as blank control; 35 patients who underwent cystectomy and PRF combined with BIO-GENE artificial bone meal repaired bone defects during the same period were recorded as group B. 3D Slicer 5.0.3 software was used to reconstruct Cone Beam Computed Tomography (CBCT) after operation. In this study, the preoperative and postoperative CBCT data of the patients were analyzed using 3D Slicer 5.0.3 software in DICOM format to calculate the cleft volume before surgery and the newly formed bone volume after surgery. The osteogenesis rate was measured based on these calculations.The bone formation percentage in the bone defect area was recorded at 6 months, and the clinical curative effects of the two groups were compared.Results: After 6 months of surgery, the patients showed varying degrees of restoration in the jaw cyst area.The osteogenesis rate at 6 months in group A was 76.06± 13.38%, while group B had a rate of 92.87± 5.72%.The CBCT values in group B were higher than those in group A at 6 months post-surgery (P< 0.05), t=− 6.84.Group A and Group B showed a statistically significant difference.Conclusion: Compared with simple cystectomy, PRF combined with BIO-GENE artificial bone powder has a better effect on the speed of bone repair after cystectomy within 6 months and provides more favorable effects for the repair of postoperative dentition defects, and provides support to repair teeth after defects such as dental implants.Keywords: PRF, bone transplantation, jaw cysts, bone regeneration

Bin Wei,&ast; Wen-Wen Fu,&ast; Yu Ji, Qi Cheng, Ben-Liang Shu, Qin-Yi Huang, Xiao-Rong Wu Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Rong Wu, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330000, People’s Republic of China, Email wxr98021@126.comAim: The objective of this study was to examine changes in functional connectivity (FC) in the hippocampus among patients with high myopia (HM) compared to healthy controls (HCs) through the utilization of seed-based functional connectivity (FC) analysis.Methods: Resting-state functional magnetic resonance imaging (fMRI) was conducted on a sample of 82 patients diagnosed with high myopia (HM) and 59 HCs. The two groups were matched based on age, weight and other relevant variables. Using seed-based FC analysis to detect alterations in hippocampal FC patterns in HM patients and HCs. Furthermore, a correlation analysis was performed to examine the associations between the mean functional connectivity (FC) signals in various brain regions of patients with HM and their corresponding clinical manifestations.Results: The FC values in the left temporal pole-temporal gyrus (L-TPOsup), right hippocampus (R-HIP), left medial temporal gyrus (L-MTG) and left hippocampus in HM patients were significantly lower than those of healthy subjects. In the left temporal pole-superior temporal gyrus (L-TPOsup), right orbital part of middle frontal gyrus (RO-MFG), left fusiform gyrus (L-FG), left cerebellum superior (L-Cbe6), left middle temporal gyrus (L-MTG), right thalamus (R-THA), and right hippocampus, FC values were also significantly lower.Conclusion: Brain dysfunction was observed in various regions of the HM patients, suggesting the existence of neurobiological alterations that could lead to impairments in visual cognition, movement, emotional processing, and visual memory.Keywords: high myopia, hippocampus, resting state, brain function, brain region, functional connectivity

Yunhao Zheng,1 Rui Zhu,2 Chuqiao Xiao,3 Qiaoyu Cheng,3 Yifei Long,3 Xueman Zhou,3 Shilong Zhang,4 Jun Wang,3 Xin Xiong1,3 1Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 4Department of Orthodontics, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Shijiazhuang, People’s Republic of ChinaCorrespondence: Xin Xiong, National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China, Tel/Fax +86-28-85503898, Email drxiongxin@scu.edu.cnPurpose: This study aims to explore the association of pressure pain thresholds (PPTs) with age, gender, and pain in patients with temporomandibular disorders (TMD).Patients and Methods: A total of 301 TMD patients (248 female and 53 male) were recruited and classified into the high and low age groups according to their median age of 26 years. Patients’ demographics, pain-related variables, TMD-related variables, and PPTs of both left and right temporomandibular joints (TMJs), masseter, and temporalis were collected.Results: Pain duration and visual analog scale of pain (VAS) showed no significant correlations with PPTs (P> 0.05). Multiple linear regression analysis revealed a significant positive association of PPTs of all six sites with males (β=0.41– 0.72 kg·cm− 2, 95% CI (0.19– 0.38, 0.74– 0.99), P< 0.001), as well as with the high age group [β=0.28– 0.36 kg·cm− 2, 95% CI (0.07– 0.20, 0.47– 0.53), P< 0.020]. Furthermore, PPTs of the left TMJ showed a significant negative association with left pain-related TMD (PT) [β=− 0.21 kg·cm− 2, 95% CI (− 0.38, − 0.04), P=0.026], but PPTs of the remaining sites did not show a significant association with PT (P> 0.05). Stratified analysis showed that PPTs in females were associated with the high age group [β=0.25– 0.37 kg·cm− 2, 95% CI (0.04– 0.20, 0.45– 0.56), P< 0.020] and that PPT of the left TMJ was associated with left PT [β=− 0.21 kg·cm− 2, 95% CI (− 0.39, − 0.03), P=0.043]. The remaining PPTs did not show a significant association with PT (P> 0.05). In males, PPTs did not show significant correlations with age, PT and VAS (P> 0.05).Conclusion: PPTs in the orofacial region are associated with gender and age in TMD patients. Pain duration and intensity show no significant correlations with PPTs in TMD patients. Researchers and dentists should take age and gender into account when using PPTs as auxiliary diagnostic indicators for PT.Keywords: pain sensitivity, temporomandibular disorders, pressure pain threshold, age, gender

We review the motivation, goals, and achievements of the Photonic Integrated Networked Energy efficient datacenter (PINE) project, which is part of the Advanced Research Projects Agency-Energy (ARPA-E) ENergy-efficient Light-wave Integrated Technology Enabling Networks that Enhance Dataprocessing (ENLITENED) program. The PINE program leverages the unique features of photonic technologies to enable alternative mega-datacenters and high-performance computing (HPC) system architectures that deliver more substantial energy efficiency improvements than can be achieved through link energy efficiency alone. In phase 1 of the program, the PINE system architecture demonstrated an average factor of 2.2 ×2.2× improvement in transactions/joule across a diverse set of HPC and datacenter applications. In phase 2, PINE will demonstrate an aggressive 1.0 pJ/bit total link budget with high-bandwidth-density dense wavelength-division multiplexing (DWDM) links to enable additional 2.5 ×2.5× or more efficiency gains through deep resource disaggregation.

Anqi Lin,1,&ast; Jiarong Yao,1,&ast; Quan Cheng,2,3 Zaoqu Liu,4 Peng Luo,1 Jian Zhang1 1Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Luo; Jian Zhang, Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China, Tel +86-18588447321 ; +86-13925091863, Email luopeng@smu.edu.cn; zhangjian@i.smu.edu.cnPurpose: In recent years, tumour immunotherapy has ushered in a new era of oncology treatment. However, the use of immune checkpoint inhibitors (ICIs) in the treatment of CRC remains limited. There is an urgent clinical need for precise biomarkers that can aid in the screening and treatment of CRC subtypes. Therefore, we focused on the NOTCH pathway mutation status and conducted a systematic analysis for its predictive value of ICI therapy efficacy.Methods: We collected mutational and clinical data from cohorts of CRC patients treated with ICIs. The relationship between NOTCH pathway mutations (NOTCH-MT) and CRC immunotherapy prognosis was analysed using univariate and multivariate Cox regression models. CRC cohort data from The Cancer Genome Atlas (TCGA) database were combined to obtain a comprehensive overview of immunogenicity and tumour microenvironment (TME) differences among different NOTCH pathway mutation statuses.Results: We observed greater infiltration of M1 macrophages, CD8+ T cells, neutrophils, and activated natural killer (NK) cells with NOTCH-MT status. Immunogenicity was also significantly higher in patients with NOTCH-MT, as were tumour mutational burden (TMB), neoantigen load (NAL), and the number of mutations in DNA damage repair (DDR) pathways.Conclusion: NOTCH-MT status was strongly associated with the prognosis of CRC patients treated with ICIs and is expected to serve as a novel biomarker and therapeutic target for CRC.Keywords: NOTCH, CRC, ICIs, biomarker, tumour microenvironment

Hao Zhang,1,&ast; Ping Zhou,1,&ast; Yi Jiang,1 Liu Li,1 Fei Ju,2 Quan Cheng,1 You Lang Zhou,2 Yuan Zhou1 1Department of Pain, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, People’s Republic of China; 2Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Zhou; You Lang Zhou, Tel +86 0513 85052222 ; +86 0513 85052488, Email nina_shine@126.com; zhouyoulang@ntu.edu.cnIntroduction: Esketamine, one of the few non-opioid potent analgesics, has demonstrated efficacy in the treatment of various chronic pain, particularly neuropathic pain. However, its potential clinical applications are confined due to its short half-life and severe side effects including delirium, hallucinations, and other psychiatric symptoms. Here, we reported a nanosized drug delivery system for sustained-release esketamine based on polylactic-co-glycolic acid (PLGA) nanoparticles and hyaluronic acid (HA) hydrogel.Results: In this study, esketamine in the delivery system was continuously released in vitro for at least 21 days, and spinal nerve root administration of the delivery system successfully attenuated (spinal nerve ligation) SNL-induced pain hypersensitivity for at least 14 days. Notably, the excitability of neurons in murine dorsal root ganglion (DRG) was inhibited and the activation of astrocytes in the spinal cord was additionally reduced after administration. Finally, there was no obvious pathophysiological change in the nerves at the administration site after treatment at 14 days.Conclusion: These results indicate that the sustained-release esketamine based on the nanoparticle-hydrogel delivery system can safely produce a lasting analgesic effect on SNL mice, and its mechanism might be related to modulating the activation of astrocytes in the spinal cord and inhibiting the excitability of neurons in DRG.Keywords: esketamine, nanoparticles, hyaluronic acid hydrogel, neuropathic pain

Jing Liu,1,&ast; Xianglu Sun,2,&ast; Qianyu Du,3 Jinghao Yao,1,4 Mengfen Dai,1 Qianqian Cheng,1 Han Xu,5 Yawei Li,6 Xiuli Liu,7 Mingliang Zhang,8 Yongchun Zhou,2 Yan Yang1 1Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China; 2Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China; 3Department of Medical Oncology, Suzhou Municipal Hospital, Suzhou, Anhui, 234000, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230000, People’s Republic of China; 5Department of Medical Oncology, The Third People’s Hospital of Bengbu, Bengbu, Anhui, 233000, People’s Republic of China; 6Department of Medical Oncology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233040, People’s Republic of China; 7Department of Oncology, The Fifth People’s Hospital of Fuyang, Fuyang, Anhui, 236000, People’s Republic of China; 8Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Yang, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China, Tel/Fax +86 552 3086178, Email qiannianhupo@163.com Yongchun Zhou, Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China, Tel/Fax +86 552 3086845, Email zhouyongchun_1@hotmail.comPurpose: To explore the efficacy, safety, and potential factors influencing efficacy and outcome of pyrotinib-based therapy in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) in complex clinical practice.Methods: Real-world data for HER2-positive MBC patients treated with pyrotinib-based regimens from 6 hospitals in Northern Anhui, China, from September 2018 to February 2022, were retrospectively collected, and clinicopathological features, efficacy, prognosis, and safety were analyzed. Potential influencing factors including baseline serum vascular endothelial growth factor-A (VEGF-A) for evaluating pyrotinib’s treatment response and outcome were also explored.Results: A total of 169 patients with HER2-positive MBC were enrolled. The objective response rate (ORR), disease control rate (DCR), and median progression-free survival (mPFS) of the overall cohort were 65.1%, 87.6%, and 12.4 months, respectively. Pyrotinib is highly beneficial as different treatment lines and appears to be a feasible strategy both in combination with chemotherapeutic drugs and alone. The mPFS values were 16.5 months, 12.4 months, and 9.3 months in the first, second, and third-or-higher lines of anti-HER2 therapy, respectively (P=0.027). The most common adverse event (AE) was diarrhea (88.2%), and patients with < grade 3 diarrhea achieved a longer mPFS than patients with ≥ grade 3 diarrhea (13.3 months vs 6.9 months, P=0.007). Among the patients with available baseline VEGF-A data, the ORR was 43.5% in patients with a high level of VEGF-A, compared to 81.5% in patients with a low level of VEGF-A (P=0.005). Moreover, patients in the VEGF-A-high group exhibited a shorter mPFS time than those in the VEGF-A-low group (7.8 months vs 19.1 months, P=0.004). Further analysis demonstrated AE of diarrhea and VEGF-A at baseline to be independent prognostic factors for PFS.Conclusion: Pyrotinib-based regimens showed promising efficacy, with manageable tolerance, and AE occurrence of severe diarrhea and baseline level of serum VEGF-A are helpful in predicting the treatment outcome of pyrotinib in HER2-positive MBC.Keywords: breast cancer, HER2, pyrotinib, efficacy, prognostic factor, vascular endothelial growth factor A

Zheng Y, Zhu R, Xiao C, et al. J Pain Res. 2023;16:2205–2216. The authors have advised that they neglected to include a funding statement on page 2215 of the published paper. The funding statement should read as follows. Funding This work was supported by the Technology Innovation Project of Science and Technology Bureau of Chengdu (2022-YF05-01691-SN) and Clinical Research Project of West China Hospital of Stomatology, Sichuan University (LCYJ-2023-YY-2). The authors apologize for this error.

In this paper, a post superacid (SA) treatment was proposed to enhance the performance of InAs FinFETs on SiO2/Si substrates. Typically, the subthreshold swing (SS) has reduced from 217 to 170 mV/decade and the transconductance (gm) has increased from 6.44 to 26.5 μS/μm after SA treatment. It was found that the interfacial In2O3 at the InAs/ZrO2 interface was effectively reduced after SA treatment due to the strong protonating nature of the SA solution. As a result, the interface trap density was reduced leading to a pronounced reduction of sheet resistance after SA treatment. The modeling of transfer characteristics indicates that the carrier mobility is enhanced by 5.87.1 folds after SA treatment due to interfacial traps reduction. The results suggest that SA treatment can be potentially extended to other III-V MOSFETs to enhance the device performances.

Xue Yang,1,&ast; Chuantao Lin,2,&ast; Sisi Chen,3 Yuezhou Huang,3 Qiong Cheng,1 Yusheng Yao3 1Department of Neurology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Anesthesiology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiong Cheng, Email chengqiong13@126.comPurpose: To identify the effectiveness of remimazolam at the end of tonsillectomy and adenoidectomy for preventing emergence delirium in children under sevoflurane anesthesia.Patients and Methods: One hundred and four patients aged 3– 7 years scheduled for tonsillectomy and adenoidectomy under sevoflurane anesthesia were recruited. Patients were randomly assigned to receive either remimazolam 0.2 mg kg– 1 (intervention, n=52) or 0.9% normal saline (control, n=52) at the end of the procedure. The primary outcome was the incidence of emergence delirium, defined as a Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10. Secondary outcomes were peak PAED score, emergence time, postoperative pain intensity, length of postanesthesia care unit (PACU) stay, parental satisfaction, and postoperative behavior changes three days postoperatively.Results: Emergence delirium occurred in 6 of 51 (12%) patients receiving remimazolam versus 22 of 50 (44%) patients receiving saline (risk difference 32% [95% confidence interval, 16% to 49%], relative risk 0.27 [95% confidence interval, 0.12 to 0.60]; P< 0.001). The peak PAED scores (median [interquartile range]) were lower in the remimazolam group than in the saline group (7 [6– 8] versus 9 [8– 11], P< 0.001). Likewise, parental satisfaction was improved in the remimazolam group compared with the saline group (9 [8– 10] versus 8 [7– 8], P< 0.001). There was no difference between groups concerning postoperative pain scores, length of PACU stay, or postoperative behavior changes.Conclusion: In children undergoing tonsillectomy and adenoidectomy, administration of remimazolam 0.2 mg kg– 1 at the end of the surgery, compared with 0.9% saline, resulted in a significantly lower likelihood of emergence delirium after sevoflurane anesthesia.Keywords: remimazolam, general anesthesia, pediatric anesthesia, emergence delirium

Anqi Lin,1,&ast; Jianbo Fang,1,&ast; Quan Cheng,2,3 Zaoqu Liu,4 Peng Luo,1 Jian Zhang1 1Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Luo; Jian Zhang, Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, People’s Republic of China, Tel +86-18588447321 ; +86-13925091863, Email luopeng@smu.edu.cn; zhangjian@i.smu.edu.cnPurpose: The advent of immune checkpoint inhibitors (ICIs) is a revolutionary breakthrough. However, without the selection of a specific target population, the response rate of ICI therapy in lung adenocarcinoma (LUAD) is low, so a clinical challenge has arisen in effectively using biomarkers to determine which patients can benefit from ICI therapy.Methods: In this study, patients were divided according to whether or not nonsynonymous mutations were present in the BCR signaling pathway, and univariate and multivariate Cox regression models were established based on a LUAD cohort treated with ICIs (Miao-LUAD). Then the relationship between the mutation status of the BCR signaling pathway and the prognosis of immunotherapy was examined. Finally, data from The Cancer Genome Atlas (TCGA) LUAD cohort, the Rizvi-LUAD, the Samstein-LUAD, and the Zhujiang Hospital of Southern Medical University LUAD (Local-LUAD) cohort were combined, and the mutation panorama, immunogenicity, tumor microenvironment (TME) and pathway enrichment analysis between the BCR signaling pathway mutant group (BCR signaling MUT) and the BCR signaling pathway wild group (BCR signaling WT) were comprehensively compared.Results: It was found that, compared with the BCR signaling WT, the BCR signaling MUT had a significantly improved progression-free survival (PFS) rate and overall survival (OS) rate, higher immunogenicity (tumor mutational burden, neoantigen load, and DNA damage response signaling mutations), and anti-tumor immune microenvironment.Conclusion: These results revealed that the mutation state of the BCR signaling pathway has potential as a biomarker to predict the efficacy of ICIs in LUAD.Keywords: non-small cell lung cancer, B cell receptor, immune checkpoint inhibitor, biomarker, microenvironment

Xuejie Zheng, Yuanzhi Li, Qiyuan Cheng, Lili Wang Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Lili Wang, Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China, Tel +86 13075578390, Email wllwywz@163.comPurpose: Previous studies have shown that ionized calcium (iCa) is strongly correlated with critical illnesses, including sepsis. However, there are few studies on the association of iCa levels and sepsis in very low birth weight infants (VLBWI). Therefore, the aim of this study was to investigate the role of iCa in assessing the severity of sepsis and in predicting the prognosis of sepsis in VLBWI.Patients and Methods: 249 eligible VLBWI with sepsis were included in the present study and were divided into good and poor prognosis groups according to prognosis. We collected complete laboratory and clinical data. The lowest iCa measured during the first 24h from sepsis onset was recorded, and the Pediatric Risk of Mortality (PRISM III) score was calculated for each newborn.Results: Neonatal mortality was higher in the hypocalcemia group (32.80% vs 12.80%, P < 0.001), and iCa levels were negatively correlated with PRISM III scores (r= − 0.819, P < 0.001). The result of multiple logistic regression analysis showed that iCa was an independent predictor of poor prognosis (odds ratio [OR]= 0.558, 95% confidence interval [CI], 0.406– 0.768, P < 0.001). Furthermore, our data demonstrated that iCa was also an independent predictor for the occurrence of death in VLBWI with sepsis who have a poor prognosis (OR= 0.659, 95% CI, 0.445– 0.977, P =0.038). ROC curve analysis showed that iCa had good discriminatory power in predicting the poor prognosis (AUC=0.739, 95% CI, 0.664– 0.813, P < 0.001) in VLBWI with sepsis.Conclusion: iCa levels correlate with the severity of sepsis and can be an independent predictor of poor prognosis in VLBWI with sepsis.Keywords: ionized calcium, sepsis, very low birth weight infants, poor prognosis

Mei Ma,1,&ast; Yijia Liu,1,&ast; Fanfan Liu,1 Zhu Li,1 Qi Cheng,1 Zhao Liu,2,&ast; Rongrong Yang,1 Chunquan Yu1 1Department of Graduate Schools, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2Department of Information Center, Second Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongrong Yang; Chunquan Yu, Department of Graduate Schools, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China, Email rongrong0423@hotmail.com; ycqtjutcm@foxmail.comAim: This study aimed to elucidate the relationship between the prognostic nutrition index (PNI) of patients with coronary heart disease (CHD) and the New York Heart Association (NYHA) classification and the complex relationship between PNI combined body mass index (BMI) and NYHA classification.Methods: The PNI was applied to 17,413 consecutive patients with CHD. Patients were divided into three groups according to PNI: normal nutrition (PNI ≥ 38), moderate malnutrition (35 < PNI < 38), and severe malnutrition (PNI ≤ 35). A total of 2,052 CHD patients with BMI were selected and stratified by combined subgroups of nutritional status and BMI. Logistic regression analysis was used to evaluate the relationship between the PNI and NYHA classification and to adjust for confounding factors.Results: The prevalence of malnutrition among the 17,413participants with CHD was 4.2%. Moderate and severe malnutrition were significantly related to NYHA class III and V, and the strongest relationship was observed in NYHA class V (odd ratio [OR]: 6.564; 95% confidence interval [CI]: 4.043– 10.658). Malnourished-underweight patients and malnourished-overweight patients were significantly associated with higher NYHA classification, and malnourished-underweight patients (OR: 8.038; 95% CI: 2.091– 30.892) were significantly more than malnourished-overweight patients (OR: 3.580; 95% CI: 1.286– 9.966).Conclusion: There were differences in the NYHA classification of CHD patients with different nutritional statuses. The lower the PNI, the worse the NYHA classification of CHD patients. Malnourished-underweight patients had a worse NYHA classification than malnourished-overweight patients.Graphical Abstract: Keywords: coronary heart disease, prognostic nutrition index, malnourished-underweight, malnourished-overweight, New York Heart Association classification

Linli Lu,1 Cong Xu,1 Yishu Tang,2 Liwen Wang,1 Qian Cheng,1 Xin Chen,1 Jian Zhang,1 Ying Li,1 Han Xiao,1 Xin Li1 1Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Emergency, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Xin Li, Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China, Tel/Fax +86-731-88618241, Email lixiner1975@163.comBackground: Carbapenem-resistant Gram-negative bacteria (CRGNB) bloodstream infection (BSI) pose a significant threat to the prognosis of hematologic malignancies (HM) patients. Understanding the distribution of pathogenic bacteria, changes in carbapenem-resistant trends, risk factors for CRGNB infections, and exploring the early detection measures can help reduce mortality.Methods: We conducted a multicenter retrospective study of Gram-negative bacteria (GNB) BSI in patients with HM in three university-affiliated hospitals in Hunan Province, China, from January 2010 to December 2020. Demographic and clinical data were collected from the hospital electronic medical records system.Results: CRGNB caused 138 (15.3%) of 902 GNB BSI. The detection rate of CRGNB increased from 6.4% in 2010– 2012 to 35.4% in 2019– 2020. The 7-day mortality rate was significantly higher in patients with CRGNB BSI than in patients with carbapenem-susceptible Gram-negative bacteria (CSGNB) BSI [31.9% (44/138) vs 9.7% (74/764), P < 0.001], and the mortality rate in patients with carbapenem-resistant non-fermenting bacteria (CRNFB) bloodstream infections was generally higher than that of carbapenem-resistant Enterobacteriaceae (CRE). Urinary catheter (OR, 2.814; CI=1.395– 5.680; P=0.004) and prior exposure to carbapenem (OR, 4.372; CI=2.881– 6.635; P< 0.001) were independent risk factors for CRGNB BSI. Analysis of co-infections showed that 50%– 85% of patients with CRGNB BSI had pulmonary infections, sputum culture results suggested that sputum culture positivity rate was as high as 57.1%– 66.7% in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) and Stenotrophomonas maltophilia BSI, and the results of antimicrobial susceptibility testing of sputum cultures were consistent with the blood cultures.Conclusion: Carbapenem resistance has dramatically increased in HM patients with GNB BSI in recent years and is associated with a worse outcome, especially for non-fermenting bacteria. In high-risk patients, early screening of the respiratory tract specimens may help to detect CRNFB colonization and protect patients from breakthrough BSI.Keywords: hematological malignancies, carbapenem-resistant, gram-negative bacteria, bloodstream infections, non-fermentative bacteria

Yanan Xu,1,&ast; Ying Jing,2,&ast; Lingfei Hu,2 Qiaoxiang Cheng,1 Huixia Gao,3 Zhi Zhang,3 Huiying Yang,2 Yuee Zhao,2 Dongsheng Zhou,2 Zhe Yin,2 Erhei Dai1,3 1Department of Clinical Laboratory Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 2State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China; 3Department of Laboratory Medicine, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, 050021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Erhei Dai; Zhe Yin, Tel +86-311-85814612 ; +86-10-66948557, Email daieh2008@126.com; jerry9yin@163.comPurpose: To establish a typing scheme for IncFIB replicon and to dissect genomic features of IncFIB-4.1/4.2 single-replicon plasmids.Methods: A total of 146 representative fully sequenced IncFIB-replicon-containing plasmids were selected to construct a phylogenetic tree of repBIncFIB sequences. A collection of nine IncFIB-4.1/4.2 single-replicon plasmids from China were fully sequenced here and compared with the first sequenced IncFIB-4.1/4.2 single-replicon plasmids from GenBank to dissect their genomic diversity.Results: In this study, a repB sequence-based scheme was proposed for grouping IncFIB replicon into seven primary types and further into 70 subtypes. A collection of nine IncFIB-4.1/4.2 single-replicon plasmids were fully sequenced here and compared with the first sequenced IncFIB-4.1/4.2 single-replicon plasmids from GenBank. These 11 plasmids had small backbones and shared only three key backbone markers repB together with its iterons, parABC, and stbD. Each plasmid contained one large accessory region (LAR) inserted into the backbone, and these 11 LARs had significantly distinct profiles of mobile genetic elements (MGEs) and resistance/metabolism gene loci. Antibiotic resistance regions (ARRs; the antibiotic resistance gene-containing genetic elements) were found in seven of these 11 LARs. Besides resistance genes, ARRs carried unit or composite transposons, integrons, and putative resistance units. IncFIB-4.1/4.2 single-replicon plasmids were important vectors of drug resistance genes. This was the first report of three novel MGEs: In1776, Tn 6755, and Tn 6857.Conclusion: Data presented here provided a deeper insight into diversity and evolution of IncFIB replicon and IncFIB-4.1/4.2 single-replicon plasmids.Keywords: IncFIB, IncFIB-4 single-replicon plasmids, large accessory regions, antibiotic resistance regions, In1776, Tn 6755, Tn 6857

Dengue is the fastest spreading mosquito-transmitted disease in the world. In China, Guangzhou City is believed to be the most important epicenter of dengue outbreaks although the transmission patterns are still poorly understood. We developed an autoregressive integrated moving average model incorporating external regressors to examine the association between the monthly number of locally acquired dengue infections and imported cases, mosquito densities, temperature and precipitation in Guangzhou. In multivariate analysis, imported cases and minimum temperature (both at lag 0) were both associated with the number of locally acquired infections (P < 0.05). This multivariate model performed best, featuring the lowest fitting root mean squared error (RMSE) (0.7520), AIC (393.7854) and test RMSE (0.6445), as well as the best effect in model validation for testing outbreak with a sensitivity of 1.0000, a specificity of 0.7368 and a consistency rate of 0.7917. Our findings suggest that imported cases and minimum temperature are two key determinants of dengue local transmission in Guangzhou. The modelling method can be used to predict dengue transmission in non-endemic countries and to inform dengue prevention and control strategies.

At present, the energy consumption in buildings occupies a large proportion of total energy use, and air-conditionings cost a large proportion of energy in the buildings. The liquid desiccant air-conditioning system has a good energy saving potential and the electrodialysis (ED) regeneration is a reliable choice for the liquid desiccant regeneration. In order to establish the energy consumption model and the performance coefficient model of liquid desiccant air-conditioning system based on ED regeneration using LiCl, experimental and theoretical research on the electrical conductivity of LiCl aqueous solution with a lot of concentrations and temperatures was conducted in this paper. The results show that when polynomial degrees of the mass concentration and the temperature of the LiCl aqueous solution are both 3, the electrical conductivity model for the LiCl aqueous solution is most suitable as its simplicity and high accuracy. Moreover, when the concentration is 36% and the temperature is 22 °C, the liquid desiccant cooling system has the maximum COP of about 5. Finally, a case study of a small office room was conducted, and the result shows that the liquid desiccant cooling system based on electrodialysis regeneration has a good energy-saving potential.

Weiwei Lou,1 Qun Cheng,1 Yanqiu Liang,1 Ding Xia2 1Department of Rehabilitation, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Urology Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaCorrespondence: Ding XiaDepartment of Urology, Tongji Hospital, 1095 Jiefang Ave, Wuhan, Hubei, 430030, People’s Republic of ChinaTel +86 18177494319Email dingxia123123@126.comBackground: Cardiovascular diseases (CVDs) have a high incidence rate in population with diabetic patients. Studies on the association between urinary N-acetyl-β-d-glucosaminidase (NAG) levels, the biomarker of renal tubular damage, with cardiovascular (CV) events diabetic patients was still few.Methods: The relationship between urinary NAG levels and CV events was analyzed in a prospective cohort including 357 patients with type 2 diabetes mellitus at a follow-up of 5 years.Results: Twenty-six (7.3%) patients have CV events. Kaplan–Meier analysis suggested that diabetic patients with urine NAG levels ≥ 37.5 IU/L had a higher rate of CV events than those with urine NAG levels < 37.5 IU/L (Log rank test, P = 0.021). Cox analysis revealed that elevated urine NAG levels significantly contributed to increased risk of CV events (HR = 1.43, 95% CI 1.23– 1.93, P < 0.001) after adjusting for clinical confounding factors. Interestingly, we also found that “abnormal renal function” has an effect modification on the association between urine NAG levels and CV events. ROC-AUC analysis suggested that the urine NAG (AUC = 0.81, P < 0.001) had a better predictive value than eGFR (AUC = 0.74, P = 0.012).Conclusion: Elevated urine NAG levels are associated with higher risk of CV events in patients with type 2 diabetes. These results might further suggested that urinary NAG is a value urinary biomarker for early detecting CV events among diabetic patients.Keywords: N-acetyl-β-d-glucosaminidase, type 2 diabetes mellitus, cardiovascular event, diabetic nephropathy

In this study, thermal and calcium oxide (CaO) pretreatment were used as a strategy to improve the performance of the anaerobic digestion of food waste. Meanwhile, the carbon emissions among the two strategies were evaluated. The results showed that both the two strategies could effectively promote the solubilization of organic matter in food waste and improve the hydrolysis rate of anaerobic digestion, which resulted in an increase of the methane yield. The highest methane yield (284.4 mL/g VS) was obtained in the group pretreated with 1.0 g/L CaO, which was increased by 23.8% compared with the control group. After the pretreatment, the anaerobic digestion pathway changed from acetotrophic methanogenesis to the co-dominated methanogenesis process by hydrogentrophic and acetotrophic. Meanwhile, CaO pretreatment had a better performance on the carbon emission which was increased by 23.75% compared with the control group. [ABSTRACT FROM AUTHOR]

Point-of-care (POC) platelet function analysis can enable timely and precise management of bleeding and clotting in emergency rooms, operation rooms and intensive care units. However, POC platelet testing is currently not commonly performed, due to the complexity of sample preparation and limitations of existing technologies. Here, we report the development of an integrated microfluidic multiple electrode aggregometry (μMEA) sensor which uses multi-frequency impedance measurement of an embedded microelectrode array to perform platelet aggregometry directly from whole blood, sensing and measuring platelet activation in a label-free manner and without requiring any additional sample preparation. Additionally, the sensor incorporates blood flow during the assay to account for physiological flow and shear conditions. We show that the impedance signal from the sensor can be used to accurately detect and quantify platelet aggregation in a label-free manner, which was further validated by simultaneous fluorometric measurement and visualization of platelet aggregation. Further, we optimized the sensitivity and repeatability of the sensor using its frequency response and demonstrated that the sensor could be used to characterize drug dose–response in antiplatelet therapy with a frequency-tunable dynamic range. We also demonstrate that the sensor provides high sensitivity to perform platelet aggregometry under thrombocytopenic or low platelet count conditions. The μMEA sensor could thus enable POC platelet function analysis across several clinical applications. [ABSTRACT FROM AUTHOR]

The spatial distributions of single‐frequency and dual‐frequency Electromagnetic ion cyclotron (EMIC) waves in the subauroral ionosphere are investigated under varying geomagnetic activities, using high‐resolution magnetic field data from dual Swarm satellites spanning from 2015 to 2017. Single‐frequency EMIC waves predominantly occur in the dawn sector, whereas dual‐frequency waves exhibit peaks around both dawn and dusk. The occurrence rate of dual‐frequency waves shows a more pronounced increase with increasing geomagnetic activity. As magnetic storms evolve, both types of EMIC waves shift from dusk to dawn. The South Atlantic Anomaly (SAA) emerges as a high‐incidence region for ionospheric EMIC waves. Dual‐frequency EMIC waves display lower frequencies compared to other regions. Additionally, the low‐frequency components of dual‐frequency waves observed at higher latitudes demonstrate greater power density and longer durations than their high‐frequency counterparts. This suggests that higher frequency waves experience more significant damping during propagation. Most dual‐frequency EMIC waves observed in the ionosphere belong to the O‐band and He‐band waves, indicating that magnetospheric bands below the cyclotron frequency of H+ are more likely to propagate into the ionosphere. Key Points: Single‐frequency ionospheric electromagnetic ion cyclotron (EMIC) waves mainly occur in the dawn sector while dual‐frequency EMIC waves peak around dawn and duskThe occurrence rate of dual‐frequency waves increases more significantly with enhanced geomagnetic activity than single‐frequency wavesLow‐frequency components of dual‐frequency waves observed at higher latitudes exhibit greater power density and extended duration [ABSTRACT FROM AUTHOR]

Chunjie Su,1 Qian Cheng,2 Liyun Wang2 1Department of Gastrointestinal Surgery, Jingmen No.1 People’s Hospital, Jingmen, 448000, People’s Republic of China; 2Department of Endocrinology, Yixing People’s Hospital, Yixing, 214200, Jiangsu, People’s Republic of ChinaCorrespondence: Liyun WangDepartment of Endocrinology, Yixing People’s Hospital, No. 75, Tongzhenguan Road, Yicheng Street, Yixing, 214200, Jiangsu, People’s Republic of ChinaEmail wangliyunly@163.comBackground: Roux-en-Y gastric bypass (RYGB) is the most effective treatment for type 2 diabetes mellitus (T2DM). Previous studies have reported that silent information regulator 1 (Sirt1) closely relates to many pathological processes of glucose metabolism and insulin resistance (IR). However, it is unclear whether Sirt1 is involved in the hepatic glucose metabolism of T2DM after RYGB.Methods: T2DM rats were randomly divided into four groups: Control, DM, Diet and RYGB. Normal rats were served as the control group. Hematoxylin and eosin (H&E) staining and Masson staining assays were performed to explore the changes of liver fibrous tissue after RYGB. The effect of RYGB on the protein expression of Sirt1 was detected by the Western blotting assay and immunohistochemical assay. Next, we built the insulin resistance model of human hepatocyte cell lines (FL62891 and HHL5) using the human recombinant insulin. Western blotting assay was applied to determine the expression of Sirt1 and the expression change of IRS1/mTOR2 /PKB pathway-related proteins in FL62891 and HHL5 cells. Additionally, the effects of Sirt1 on the expression of PTP1B and FGF-21 in insulin-resistant FL62891 and HHL5 cells were investigated using Western blotting and immunofluorescence assay.Results: Our results showed that following RYGB improved the pathological changes of liver and increased the expression of Sirt1 in rats with T2DM compared with the diabetic rats. In experiments in vitro, the expression of Sirt1 was downregulated in insulin-resistance FL62891 and HHL5 cells. Moreover, overexpression of Sirt1 significantly increased the expression of FGF-21 whereas decreased the expression of PTP1B in insulin-resistance FL62891 and HHL5 cells. These above changes were alleviated in RYGB and Diet groups. Furthermore, RYGB could improve the glucose metabolism through activating IRS1/mTOR2/PKB pathways by regulating Sirt1 in rats with T2DM.Conclusion: RYGB could significantly improve hepatic glucose metabolism and increase the expression of Sirt1 in T2DM rats, which is related to the IRS1/mTOR2 /PKB pathway.Keywords: Roux-en-Y gastric bypass, RYGB, hepatic glucose metabolism, insulin resistance, Sirt1, IRS1, mTOR2, PKB

Xuemei Li,1,2 Qingfeng Cheng,3 Zhipeng Du,3 Shenyin Zhu,2 Chao Cheng4 1Department of Pharmacy, Chongqing Health Center for Women and Children, Chongqing, People’s Republic of China; 2Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Endocrinology, First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Critical Care Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Hubei, People’s Republic of ChinaCorrespondence: Chao ChengDepartment of Critical Care Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangcheng District, Hubei, 441021, People’s Republic of ChinaTel +86 23 8901 2401Fax +86 23 68811793Email chengchao11c0@163.comShenyin ZhuDepartment of Pharmacy, First Affiliated Hospital of Chongqing Medical University, No. 1, Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel +86 23 8901 2401 Fax +86 23 68811793 Email zhushenyin0486@sina.comObjective: This study aimed to assess the microbiological concordance between swab and soft tissue cultures, and corresponding bone specimen cultures from patients with diabetic foot osteomyelitis (DFO). We aimed to analyze the bone specimens’ antimicrobial susceptibilities, and to improve clinical management of diabetic foot ulcer infections by using proper antibiotics.Methods: The microbial culture results of ulcer swabs, and soft tissue and bone tissue specimens, and the antimicrobial susceptibility tests of bone specimens from patients with DFO were analyzed in a single diabetic foot center.Results: A total of 60 patients with results from three specimens were included. Staphylococcus aureus was the most common bacterium isolated from the three specimens. The microbiological results for the three specimens were identical in 12 cases, the culture results from swabs and bone tissue specimens were identical in 14 cases, and the results from soft tissue and bone tissue were identical in 46 cases. The concordance of the results of pathogens isolated between soft tissue and bone specimen cultures was higher than that between the swab and bone cultures. Gram-positive bacteria were more sensitive to moxifloxacin, linezolid, and vancomycin, while Gram-negative bacteria were more sensitive to piperacillin/tazobactam, cefoperazone/sulbactam, and carbapenems.Conclusion: Soft tissue culture results have more reliable microbiological concordance to identify DFO bacteria than swab culture results and targeted antibiotic therapy for DFO should be based on antimicrobial susceptibility testing in bone tissue specimen cultures.Keywords: diabetic foot osteomyelitis, ulcer swabbing, microbiological concordance, antimicrobial susceptibility test, targeted antibiotic therapy