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Shixuan Liu,&ast; Lin Liu,&ast; Xinyue Lu, Tingfeng Yao Department of Rehabilitation, School of Sport Health, Nanjing Sport Institute, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Liu, Department of Rehabilitation, School of Sport Health, Nanjing Sport Institute, Nanjing, People’s Republic of China, Email liulinst1989@126.comPurpose: Myofascial trigger points (MTrPs) are the main cause of myofascial pain syndrome (MPS), and patients with MPS also have symptoms of sympathetic abnormalities. Consequently, this study aimed to investigate the potential relationship between MTrPs and sympathetic nerves.Materials and Methods: Twenty-four seven-week-old male rats were randomly divided into four groups (six rats every group). Groups I and II were kept in normal condition (n=12), and groups III and IV underwent MTrPs modelling (n=12). After successful MTrPs modelling, differences in sympathetic outcomes between the MTrPs groups (III and IV) and non-MTrPs groups (I and II) were observed. Sympathetic blockade was then applied to groups III and I (n=12). Data were collected on peak inversion spontaneous potentials (PISPs) and the H-reflex-evoked electromyography during spontaneous discharge at the MTrPs before and after sympathetic blockade.Results: Systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate were significantly higher in the MTrPs group than in the non-MTrPs group (P< 0.05). Compared with group I, group III had the PISPs potential lower wave amplitude, shorter duration and amplitude-to-duration ratio, and lower H latency and latency difference H-M (P< 0.05). Compared with group IV, group III had the PISPs potential lower wave amplitude, duration, amplitude-to-duration ratio, M-wave latency, H maximum wave amplitude, and maximal wave amplitude ratio H/M (P< 0.05). The changes before and after sympathetic blockade in the MTrPs group were significant, and the amplitude, duration, and amplitude-to-duration ratio of the PISPs potentials were lower after the blockade (P< 0.05).Conclusion: MTrPs and sympathetic nerves interact with each other forming a specific relationship. MTrPs sensitize sympathetic nerves, and sympathetic nerve abnormalities affect local muscle myoelectric hyperactivity, leading to MTrPs. This finding is instructive for the clinical management of sympathetic disorders.Keywords: myofascial trigger point, sympathetic blockade, electromyography, H-reflex, myofascial pain syndrome

Wenjuan Yang,1,2 Bing Han,1 Bei Zheng,1 Ying Li,1 Tiefei Yao,3 Mei Han,3 Gonghua Li,1 Meiling Zhang1 1Department of Pharmacy, Tongde Hospital of ZheJiang Province, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Geriatric Medicine, Tongde Hospital of ZheJiang Province, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Gonghua Li; Meiling Zhang, Department of Pharmacy, Tongde Hospital of ZheJiang Province, Hangzhou, Zhejiang, People’s Republic of China, Tel +86-0571-89972239, Email ligonghua88@163.com; zml9998@sina.comAbstract: Coronavirus disease 2019 (COVID-19) emergence in late 2019, and wide spread quickly in the world. In China, the COVID-19 epidemic situation entered a low level now. With the arrival of flu season, the number of patients with respiratory symptoms is increasing. We reported three cases of patients who co-infected with SARS-CoV-2 and influenza A virus (IAV), and they were all treated with nirmatrelvir-ritonavir (NMV/r) and baloxavir marboxil. Due to the overlapping clinical features between the two diseases, it is important to identified them and gave the antiviral therapy timely.Keywords: COVID-19, influenza, co-infection, baloxavir marboxil, nirmatrelvir-ritonavir

Subseasonal-to-seasonal (S2S) prediction, especially the prediction of extreme hydroclimate events such as droughts and floods, is not only scientifically challenging, but also has substantial societal impacts. Motivated by preliminary studies, the Global Energy and Water Exchanges (GEWEX)/Global Atmospheric System Study (GASS) has launched a new initiative called "Impact of Initialized Land Surface Temperature and Snowpack on Subseasonal to Seasonal Prediction"(LS4P) as the first international grass-roots effort to introduce spring land surface temperature (LST)/subsurface temperature (SUBT) anomalies over high mountain areas as a crucial factor that can lead to significant improvement in precipitation prediction through the remote effects of land-atmosphere interactions. LS4P focuses on process understanding and predictability, and hence it is different from, and complements, other international projects that focus on the operational S2S prediction. More than 40 groups worldwide have participated in this effort, including 21 Earth system models, 9 regional climate models, and 7 data groups. This paper provides an overview of the history and objectives of LS4P, provides the first-phase experimental protocol (LS4P-I) which focuses on the remote effect of the Tibetan Plateau, discusses the LST/SUBT initialization, and presents the preliminary results. Multi-model ensemble experiments and analyses of observational data have revealed that the hydroclimatic effect of the spring LST on the Tibetan Plateau is not limited to the Yangtze River basin but may have a significant large-scale impact on summer precipitation beyond East Asia and its S2S prediction. Preliminary studies and analysis have also shown that LS4P models are unable to preserve the initialized LST anomalies in producing the observed anomalies largely for two main reasons: (i) inadequacies in the land models arising from total soil depths which are too shallow and the use of simplified parameterizations, which both tend to limit the soil memory; (ii) reanalysis data, which are used for initial conditions, have large discrepancies from the observed mean state and anomalies of LST over the Tibetan Plateau. Innovative approaches have been developed to largely overcome these problems.

AbstractThe Third Pole (TP) is experiencing rapid warming and is currently in its warmest period in the past 2,000 years. This paper reviews the latest development in multidisciplinary TP research associated with this warming. The rapid warming facilitates intense and broad glacier melt over most of the TP, although some glaciers in the northwest are advancing. By heating the atmosphere and reducing snow/ice albedo, aerosols also contribute to the glaciers melting. Glacier melt is accompanied by lake expansion and intensification of the water cycle over the TP. Precipitation has increased over the eastern and northwestern TP. Meanwhile, the TP is greening and most regions are experiencing advancing phenological trends, although over the southwest there is a spring phenological delay mainly in response to the recent decline in spring precipitation. Atmospheric and terrestrial thermal and dynamical processes over the TP affect the Asian monsoon at different scales. Recent evidence indicates substantial roles that mesoscale convective systems play in the TP’s precipitation as well as an association between soil moisture anomalies in the TP and the Indian monsoon. Moreover, an increase in geohazard events has been associated with recent environmental changes, some of which have had catastrophic consequences caused by glacial lake outbursts and landslides. Active debris flows are growing in both frequency of occurrences and spatial scale. Meanwhile, new types of disasters, such as the twin ice avalanches in Ali in 2016, are now appearing in the region. Adaptation and mitigation measures should be taken to help societies’ preparation for future environmental challenges. Some key issues for future TP studies are also discussed.

Yan Su,1 Yikun Guo,2 Zhuoyou Chen,2 Min Zhang,2 Jianfang Liu,2 Qian Wang,2 Tian Yao2 1Department of Radiology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Neurology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Yikun Guo, Department of Neurology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, 68# Middle Gehu Road, Changzhou, 213164, Jiangsu Province, People’s Republic of China, Tel +86-519-81087079, Fax +86-519-81087711, Email guoyikun000@163.comPurpose: This study was to explore the role of pre-existing small vessel disease (SVD) on the 3-month outcomes of acute cardioembolic stroke (CES) patients.Patients and Methods: Data of 189 consecutive acute CES patients at a single center were retrospectively enrolled. SVD imaging markers of lacunes, white matter hyperintensities (WMH) and enlarged perivascular spaces (EPVS) were evaluated and their total burden score (0– 3 points) was calculated. Patients were divided into the good functional outcome group (modified Rankin scale, mRS ≤ 2) and the poor functional outcome group (mRS ≥ 3) at 3 months after stroke onset. The effect of each single SVD marker and its total burden score on the outcome was identified using binary logistic regression.Results: Overall, 100 (52.9%), 52 (27.1%), 28 (14.8%) and 9 (4.8%) patients had 0, 1, 2 and 3 SVD imaging markers. Patients with a total SVD burden score of 2 and 3 were significantly older and had higher baseline National Institutes of Health Stroke Scale (NIHSS) score than those with a score of 0 and 1 (P< 0.01). Forty-seven (24.9%) patients had a poor outcome. Patients in the poor outcome group had significantly higher baseline NIHSS score, increased incidence of stroke associated pneumonia, and heavier burden of lacunes, WMH and EPVS, and thus had elevated total SVD burden score than those in good outcome group (P< 0.05). After adjusting for potential confounders, the WMH (odds ratio [OR] = 2.6777, 95% confidence interval [CI] = 1.052– 6.812, P = 0.039) and the total SVD burden score (OR = 1.717, 95% CI = 1.072– 2.749, P = 0.024) were, respectively, independent risk factors for a poor outcome.Conclusion: The pre-existing SVD may be associated with the 3-month prognosis of CES.Keywords: cardioembolic stroke, small vessel disease, imaging marker, total burden score, prognosis

Urban traffic problems are one of the major challenges in the development of smart cities. To effectively alleviate traffic congestion and improve urban traffic management, a distributed big data analytics platform based on the MapReduce computing framework is investigated to process urban traffic data containing millions of traffic flow, speed and timestamp records. The study proposes an improved Long Short-Term Memory (LSTM) neural network algorithm and describes the network structure, training process and parameter tuning in detail. The effectiveness of the improved algorithm was verified through comparative analysis with the traditional ARIMA, linear regression and support vector regression algorithms. The results showed that the improved LSTM algorithm achieved an accuracy of 97.62% in traffic flow prediction, which was significantly better than other algorithms. The results demonstrate that the method can provide reliable technical support and decision-making basis for traffic management in smart cities. [ABSTRACT FROM AUTHOR]

In this paper, we present the progress made in developing multimodal and multispectral light microscopy for label-free malaria diagnosis. Our previously developed light emitting diode (LED) illumination system was replaced by laser diodes as light sources in order to narrow the spectral bands and improve the effectiveness of the contrast function for infected blood cell detection. The acquisition system is now equipped with an algorithm for automatic field scanning and best in-focus determination. We demonstrate the potential of this platform to provide multiple investigation modalities like transmission, reflection, scattering, fluorescence, excitation, emission and polarisation. The application of this platform on malaria-infected samples has shown the effectiveness of such a system in label-free and all-optical malaria detection by allowing the possibility of using a different type of imaging set-up for the samples analysed. Also, fewer illumination sources are used to characterise malaria-infected red blood cells compared to our previous works on malaria detection using LEDs illumination sources.

Deting Xue,1,* Erman Chen,1,* Huiming Zhong,2,* Wei Zhang,1 Shengdong Wang,1 Muhammad Umar Joomun,1 Tianyi Yao,3 Yanbin Tan,1 ShiSheng Lin,3 Qiang Zheng,1 Zhijun Pan1 1Department of Orthopaedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 3Department of Information Science and Electronic Engineering and State Key Laboratory of Modern Optical Instrumentation, Zhejiang University, Hangzhou 310027, People’s Republic of China *These authors contributed equally to this work Background: The osteo-immunomodulatory properties of biomaterials play an important role in the outcomes of bone regeneration. Graphene oxide (GO) has been widely applied in many research fields due to its unique properties. However, the immunomodulatory properties of GO as a biomaterial for bone tissue engineering are still unclear. Materials and methods: In this study, we evaluated the Inflammatory response of RAW264.7 cells influenced by GO. Then the osteogenic differentiation of BMSCs, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) by stimulation with GO/RAW 264.7-conditioned culture medium were accessed. We also further investi­gated the possible mechanisms underlying the osteo- and angio-immunomodulatory effects of GO. Results: Our results showed that GO stimulates the secretion of oncostatin M, tumor necrosis factor alpha and other factors through the nuclear factor-κB pathway. GO/RAW264.7-conditioned medium promoted the osteogenic differentiation of BMSCs, stimulated upregulation of the HUVECs of vascular-related receptors, and promoted their tube formation in vitro. Conclusion: In conclusion, our research shows that GO, as a biomaterial, can induce the formation of a beneficial osteo-immunomodulatory environment and is a promising biomaterial for bone tissue engineering. Keywords: graphene oxide, osteo-immunomodulatory, bone marrow mesenchymal stem cells, osteogenesis, angiogenesis, RAW264.7 cells, HUVECs

Naomi Uemura,1 Yoshikazu Kinoshita,2 Ken Haruma,3 Takashi Yao,4 Ryoji Kushima,5 Tatsuhiro Kanoo6 1Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Chiba, Japan; 2Department of Gastroenterology and Hepatology, Faculty of Medicine, Shimane University, Shimane, Japan; 3Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan; 4Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan; 5Department of Clinical Laboratory Medicine, Shiga University of Medical Science Hospital, Shiga, Japan; 6Takeda Pharmaceutical Co., Ltd, Osaka, Japan Abstract: Erosive esophagitis (EE) occurs when the epithelial mucosa is damaged due to gastric acid reflux, and the incidence of this disease is increasing in Japan due to changes in diet and lifestyle. The condition can be treated using proton pump inhibitors (PPIs) that act by irreversibly blocking the H+,K+-ATPase responsible for acid secretion. Vonoprazan is a K+ competitive channel inhibitor, which reversibly and potently inhibits gastric acid secretion. However, long-term data on vonoprazan use are limited. The aim of the VISION trial is to investigate the long-term efficacy and safety of vonoprazan in comparison with the PPI lansoprazole. This randomized, multicenter, 5-year, open-label study has a planned recruitment of 195 participants (2:1 allocation vonoprazan:lansoprazole) from 33 sites in Japan. The study comprises an 8-week “healing” phase (vonoprazan 20 mg or lansoprazole 30 mg p.o.) and a 260-week “maintenance” phase (vonoprazan 10 mg or lansoprazole 15 mg). Safety populations in both phases are defined as participants who receive at least one dose of the study or control drug in the healing and maintenance phases, respectively. The full analysis set in both phases is defined as participants who are randomized and receive at least one dose of the study or control drug in the healing and maintenance phases, respectively. The primary endpoint of the study is the histopathological evaluation of gastric mucosa for the presence of neoplastic alteration of gastric mucosal epithelial cells. Secondary efficacy endpoints include endoscopic EE recurrence rate and EE healing rate, and secondary safety endpoints include incidence of adverse events (coded using MedDRA terminology) and endoscopic evaluation of malignant changes in the gastric mucosa. Patient recruitment started in March 2016 and is now complete. The estimated study completion date is February 2022. Keywords: erosive esophagitis, gastric mucosa, lansoprazole, long-term safety, vonoprazan, K+ competitive channel inhibitor, neoplasia

Previous research has shown that multi-principal element alloys (MPEAs) using chromium, molybdenum, niobium, tantalum, titanium, vanadium, and zirconium can form stable body-centered-cubic (BCC) structures across a large temperature region (25°C to 1000°C). This is the same crystal structure as γ-uranium (U), which has shown desirable thermal and irradiation behavior in previous alloy fuel research. It is hypothesized then that the MPEA alloying approach can be used to produce a stable BCC uranium-bearing alloy and to retain its stability throughout anticipated operating regimes of power-producing reactors. Candidate elements were assessed using Monte Carlo N-Particle (MCNP) analysis to determine uranium densities necessary to make the alloy an economically viable fuel compared to conventional fuel forms. Following neutronic considerations, materials property databases and empirical predictors were used to determine the compositions with a high potential to form a BCC solid solution alloy. The final four alloys were MoNbTaU2, MoNbTiU2, NbTaTiU2, and NbTaVU2, which were cast using arc melting of raw elemental foils and chunks. Characterization of the fabricated alloys included scanning electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and transmission electron microscopy. The results showed a two-phase system with a U-rich matrix phase surrounding the refractory precipitates. The U phase was found to contain varying concentrations of the alloying elements and was a BCC γ-U phase. These results warrant further research to identify ideal compositions for use as an advanced alloy fuel. [ABSTRACT FROM AUTHOR]

Chronic infectious laryngitis is a clinical mimic of laryngeal carcinoma which can be due to bacterial or fungal aetiology. Both conditions present with non-specific symptoms with leucoplakia on examination. The role of biopsy of laryngeal lesions in the absence of risk factors of laryngeal carcinoma is debatable as it responds to antifungal therapy. This study aimed to review the predisposing factors and role of biopsy in chronic infectious laryngitis. A retrospective review of all cases of chronic infectious laryngitis presented to our centre between 2018 and 2021 were conducted. Clinical features, risk factors, antifungal therapy and its response were reviewed. All cases of chronic infectious laryngitis avoided the need of biopsy while had successful empirical antifungal therapy except for one refractory case. Biopsy of the refractory case was negative for malignancy and the cultureproven Staphylococcus aureus laryngitis was successfully treated with antibiotics. Empirical antifungal therapy in cases of chronic infectious fungal laryngitis with close serial follow-up had good outcome. Biopsy should be reserved for refractory cases to exclude malignancy and guide further antimicrobial therapy. [ABSTRACT FROM AUTHOR]