简介：AbstractObjective:Subjective tinnitus is characterized by the perception of sound in the absence of any external auditory stimuli. This perceived sound may be related to altered intrinsic neural activity generated along the central auditory pathway. This retrospective study was designed to investigate regional homogeneity and functional connectivity in the resting-state brain activity of patients with tinnitus.Methods:We recruited tinnitus patients with normal hearing or mild hearing loss (n = 17) and age-matched healthy controls (n = 20), and examined regional homogeneity and functional connectivity in resting-state brain activity using resting-state functional magnetic resonance imaging data. The present study protocol was approved by the Institutional Review Board on Experimental Ethics at Sun Yat-sen University, China (approval No. SYSEC-KY-KS-2019-083).Results:Compared with normal controls, patients with tinnitus had significantly decreased regional homogeneity in the anterior lobe of the cerebellum and increased homogeneity in the inferior frontal gyrus (P < 0.05 corrected at a cluster-level). In addition, tinnitus patients showed enhanced functional connectivity between the inferior frontal gyrus and the ventral striatum and midbrain, as well as increased connectivity between the cerebellum and ventromedial prefrontal cortex (P < 0.05 corrected at a cluster-level). We also found decreased connectivity between the cerebellum and the anterior insula compared with controls (P < 0.05 corrected at a cluster-level).Conclusion:Abnormal connectivity in non-auditory brain structures, particularly those related to emotion processing, may be associated with tinnitus persistence.

简介：AbstractBackground:Fibroblast-like synoviocytes (FLSs), resident mesenchymal cells of synovial joints, play an important role in the pathogenesis of rheumatoid arthritis (RA). Dickkopf-1 (DKK-1) has been proposed to be a master regulator of bone remodeling in inflammatory arthritis. Here, potential impairation on the activity of FLSs derived from RA to small interfering RNAs (siRNAs) targeting DKK-1 was investigated.Methods:siRNAs targeting DKK-1 were transfected into FLSs of patients with RA. Interleukin (IL)-1β, IL-6, IL-8, matrix metalloproteinase (MMP) 2, MMP3, MMP9, transforming growth factor (TGF)-β1, TGF-β2 and monocyte chemoattractant protein (MCP)-1 levels in the cell culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Invasion assay and 3H incorporation assay were utilized to investigate the effects of siRNAs targeting DKK-1 on FLSs invasion and cell proliferation, respectively. Western blotting was performed to analyze the expression of nuclear factor (NF)-κB, interleukin-1 receptor-associated kinase (IRAK)1, extracellular regulated protein kinases (ERK)1, Jun N-terminal kinase (JNK) and β-catenin in FLSs.Results:DKK-1 targeting siRNAs inhibited the expression of DKK-1 in FLSs (P < 0.01). siRNAs induced a significant reduction of the levels of IL-6, IL-8, MMP2, MMP3 and MMP9 in FLSs compared to the control group (P < 0.05). DKK-1 targeting siRNAs inhibited the proliferation and invasion of FLSs (P < 0.05). Important molecules of pro-inflammatory signaling in FLSs, including IRAK1 and ERK1, were decreased by the inhibition of DKK-1 in FLSs. In contrast, β-catenin, a pivotal downstream molecule of the Wnt signaling pathway was increased.Conclusions:By inhibiting DKK-1, we were able to inhibit the proliferation, invasion and pro-inflammatory cytokine secretion of FLSs derived from RA, which was mediated by the ERK or the IRAK-1 signaling pathway. These data indicate the application of DKK-1 silencing could be a potential therapeutic approach to RA.

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简介：AbstractBackground:Rheumatoid arthritis (RA), a systemic autoimmune disease characterized by synovial inflammation, can cause cartilage and bone damage as well as disability. The aim of this study was to explore whether serum glucose-6-phosphate isomerase (GPI) is correlated with disease activity and the value of GPI in the evaluation of infliximab treatment in patients with RA.Methods:Sixty-two patients with RA who had an inadequate response to methotrexate (MTX) were enrolled in Peking University People’s Hospital from July 1, 2016 to July 31, 2018. Infliximab (3 mg/kg, intravenous at weeks 0, 2, and 6 and then every 8 weeks) was administered to patients with stable background MTX therapy. Serum samples were obtained at baseline and week 18. Serum GPI levels were determined using enzyme-linked immunosorbent assay. The associations between serum GPI levels and clinical features were analyzed.Results:Serum GPI was positively correlated with Disease Activity Score in 28 joints (DAS28), swollen joint count, tender joint count and C-reactive protein level (P < 0.001, P < 0.001, P < 0.001, and P = 0.033, respectively). The change of DAS28 in GPI-positive patients was greater than that in GPI-negative patients (P < 0.001). Compared with those for patients receiving MTX monotherapy at baseline, the GPI levels were significantly declined when MTX was combined with infliximab (P < 0.001).Conclusion:Serum GPI is related to disease activity and clinical response to infliximab treatment.

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简介：AbstractBackground:As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus.Methods:In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R0) from the RP model to assess the transmissibility of the SARS-CoV-2.Results:The value of R0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58.Conclusions:Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.

简介：摘要After severe COVID-19 disease, many patients will experience a variety of problems with normal functioning and will require rehabilitation services to overcome these problems. The principles of and evidence on rehabilitation will allow an effective response. These include a simple screening process; use of a multidisciplinary expert team; four evidence-based classes of intervention (exercise, practice, psychosocial support, and education particularly about self-management); and a range of tailored interventions for other problems. The large number of COVID-19 patients needing rehabilitation coupled with the backlog remaining from the crisis will challenge existing services. The principles underpinning vital service reconfigurations needed are discussed.

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简介：AbstractPurpose:Various organizations and institutions are involved in road traffic injury (RTI) and crash registration such as police, forensic medicine organization, hospitals and emergency medical services. But there is a substantial uncertainty in interpreting the data, duplicated data collection and missing data in relation to RTI in most systems. This study aims to identify data sources for RTI surveillance in Iran and to explore traffic safety data source domains, data elements and detailed information by each data source.Methods:This is a qualitative study which was conducted in 2017 in Iran. Data were collected employing semi-structured interviews with informants in road safety organizations in relation to traffic safety including Police, Ministry of Health and Medical Education as well as Forensic Medicine Organization and other authorities-in-charge. For completing the preliminary extraction information, the minimum data set was used and compared in each system.Results:Eight different organizations relevant to road traffic safety were identified. The main domain of data provided by each one consists of Emergency Medical System form, Police KAM114 form, Ministry of Transport and Road Administration, Red Crescent Organization/Disaster Management Information System, Ministry of Health and Medical Education, Forensic Medicine Organization, Insurance Company and Ministry of Justice. Each system has its own database, based upon its scope and mainly at crash and post-crash status and little on pre-crash circumstance.Conclusion:All current registry systems are not surveillance systems for RTI prevention. Huge data have been collected in various registry systems in Iran, but most of the collected variables are duplicated in each system. On the other hand, some variables like alcohol and substance abuse, child seat belt, helmet use in relation to RTI prevention are missed in all systems. Accordingly, it is a critical need to integrate and establish a comprehensive surveillance system, with focus on the goal of each system and collection of minimum data in each organization, which currently is underway.

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简介：摘要OBJECTIVEThe COVID-19 pandemic is rapidly evolving and has led to increased numbers of hospitalizations worldwide. Hospitalized patients with COVID-19 experience a variety of symptoms, including fever, muscle pain, tiredness, cough, and difficulty breathing. Elderly people and those with underlying health conditions are considered to be more at risk of developing severe symptoms and have a higher risk of physical deconditioning during their hospital stay. Physical therapists have an important role in supporting hospitalized patients with COVID-19 but also need to be aware of challenges when treating these patients. In line with international initiatives, this article aims to provide guidance and detailed recommendations for hospital-based physical therapists managing patients hospitalized with COVID-19 through a national approach in the Netherlands.METHODSA pragmatic approach was used. A working group conducted a purposive scan of the literature and drafted initial recommendations based on the knowledge of symptoms in patients with COVID-19, and current practice for physical therapist management for patients hospitalized with lung disease and patients admitted to the intensive care unit (ICU). An expert group of hospital-based physical therapists in the Netherlands provided feedback on the recommendations, which were finalized when consensus was reached among the members of the working group.RESULTSThe recommendations include safety recommendations, treatment recommendations, discharge recommendations, and staffing recommendations. Treatment recommendations address 2 phases of hospitalization: when patients are critically ill and admitted to the ICU, and when patients are severely ill and admitted to the COVID ward. Physical therapist management for patients hospitalized with COVID-19 comprises elements of respiratory support and active mobilization. Respiratory support includes breathing control, thoracic expansion exercises, airway clearance techniques, and respiratory muscle strength training. Recommendations toward active mobilization include bed mobility activities, active range-of-motion exercises, active (-assisted) limb exercises, activities-of-daily-living training, transfer training, cycle ergometer, pre-gait exercises, and ambulation.

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简介：AbstractBackground:Gliomas are the most common primary malignant brain tumors and have a poor prognosis. Early detection of gliomas is crucial to improve patient outcomes. Urine accumulates systematic body changes and thus serves as an excellent early biomarker source.Methods:At the biomarker discovery phase, we performed a self-controlled proteomics analysis by comparing urine samples collected from five glioma patients at the time of tumor diagnosis and after surgical removal of the tumor. At the biomarker validation phase, we further validated some promising proteins using parallel reaction monitoring (PRM)-based targeted proteomics in another cohort, including glioma, meningioma, and moyamoya disease patients as well as healthy controls.Results:Using label-free proteome quantitation (LFQ), we identified twenty-seven urinary proteins that were significantly changed after tumor resection, many of which have been previously associated with gliomas. The functions of these proteins were significantly enriched in the autophagy and angiogenesis, which are associated with glioma development. After targeted proteomics validation, we identified a biomarker panel (AACT, TSP4, MDHM, CALR, LEG1, and AHSG) with an area under the curve (AUC) value of 0.958 for the detection of gliomas. Interestingly, AACT, LEG1, and AHSG are also potential cerebrospinal fluid or blood biomarkers of gliomas.Conclusions:Using LFQ and PRM proteome quantification, we identified candidate urinary protein biomarkers with the potential to detect gliomas. This study will also provide clues for future biomarker studies involving brain diseases.

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简介：AbstractBackground:A steady progress on schistosomiasis control in the Peoples’ Republic of China (P.R. China) was achieved and broadened into the twelve-year medium and long term national plan (MLNP) which marled the implementation of an integrated control strategy across all endemic areas in P.R. China in 2004. To understand the endemic trends of schistosomiasis to assess the effectiveness of an integrated strategy, we conducted an analysis of schistosomiasis surveillance data spanned from 2005 to 2015.Methods:The schistosomiasis sentinel surveillance data from sentinel sites were collected and analyzed from 2005 to 2015. In these sentinel sites, residents aged 6 years or above were screened annually by indirect hemagglutination assay (IHA), while only antibody positives were followed by stool examination either Kato-katz method (KK) and/or hatching technique (HT). Domestic animals raised in sentinel sites were examined by HT for confirming the infection of schistosomes. Snail investigation was conducted each year through systematic sampling method combined with environmental sampling method. The snails collected from field were tested by microscopic dissection method. The infection rates of schistosomes in residents, domestic animals and snails, as well as the indicators reflecting the snails’ distribution were calculated and analyzed. ANOVA analysis was used to examine the changes of the number of eggs per gram feces in population and Chi-square test was used to examine any change in proportions among groups.Results:A total of 148 902 residents from sentinel sites attended this study and 631 676 blood samples were examined by IHA test during the 11 covered years. The annual average antibody positive rates presented a significant decrease trends, from 17.48% (95% CI: 17.20–17.75%) in 2005 to 5.93% (95% CI: 5.71–6.15%) (χ2= 8890.47, P < 0.001) in 2015. During 2005–2015, the average infection rate of schistosomes in residents declined from 2.07% (95% CI: 1.96–2.17%) to 0.13% (95% CI: 0.09–0.16%), accompanied by significant decrease of infection intensity in population. In 2015, the stool positives were only found in farmers, fishermen and boatmen with infection rate of 0.16% (95% CI: 0.11–0.20%), 0.17% (95% CI: 0–0.50%) respectively. The infection rate of schistosomes in domestic animals dropped from 9.42% (538/5711, 95% CI: 8.66–10.18%) to 0.08% (2/2360, 95% CI: 0–0.20%) from 2005 to 2015. Infections were found in eight species of domestic animals at the beginning of surveillance while only two cattle were infected in 2015. Totally 98 ha of new snail habitats were found, while 94.90% (93/98) distributed in lake and marshland regions. The percentage of frames with snails decreased from 16.96% (56 884/33 5391, 95% CI: 16.83–17.09%) in 2005 to 4.28% (18 121/423 755, 95% CI: 4.22–4.34%) in 2014, with a slightly increase in 2015. Meanwhile, the infection rate of schistosomes in snails was decreased from 0.26% (663/256 531, 95% CI: 0.24–0.28%) to zero during 2005–2015.Conclusions:The infection rate of schistosomes declined significantly, providing evidence that the goal of the MLNP was achieved. Elimination of schistosomiasis as a public health problem defined as WHO was also reached in P.R. China nationwide. Surveillance-response system should be improved and strengthened to realize the final goal of schistosomiasis elimination.