To investigate the effect and mechanism of exosomes derived from human amniotic mesenchymal stem cells (hAMSC-Exos) promoting angiogenesis. HAMSC-Exos were isolated using ultracentrifugation and characterized by transmission electron microscopy, NTA, and Western blot. The uptake of hAMSC-Exos by hUVECs was analyzed using PKH-26 labeling, and the effect of hAMSC-Exos on angiogenesis was analyzed in human umbilical vein endothelial cells hUVECs by cell viability assay, Transwell migration assay, Matrigel tube formation assay, and Matrigel plug assays in nude mice. Bioinformatics methods were used to analyze miRNA high-throughput sequencing data of hAMSC-Exos, and RT-qPCR was used to validate the novel miRNAs. HAMSC-Exos with high and low N-194 expression were obtained by transfection, respectively. Target genes were predicted using TargetScan, and the mRNA and protein levels of potential target genes were analyzed by RT-qPCR and Western blot after N-194 mimics transfection. Interaction between miRNAs and target genes was detected using the dual-luciferase reporter assay. Target genes were overexpressed in hUVECs by transfection. The roles of target genes in the influence of N-194 on cell function were determined by analyzing angiogenesis. The extracted hAMSC-Exos showed saucer-shaped under transmission electron microscopy, and the NTA results showed the particle size of 115.6 ± 38.6 nm. The positive expression of CD9, CD63, and CD81 were verified using Western blot. The treatment of hUVECs with hAMSC-Exos significantly increased cell proliferation, migration, and angiogenesis. HAMSC-Exos contained the novel miRNAs N-194, N-314, N-19, N-393, and N-481, and the expression of N-194 was higher. The Exos derived from hAMSCs which were transfected with FAM-N-194 mimics were able to deliver FAM-N-194 mimics to hUVECs. The hAMSC-Exos with high N-194 significantly promoted angiogenesis in hUVECs. N-194 mimics transfection significantly reduced mRNA and protein levels of potential target gene ING5, and N-194 mimics significantly reduced the luciferase activities expressed by wild-type reporter gene vectors for ING5. The ING5 overexpression significantly reduced the angiogenic capacity of hUVECs. ING5 overexpression suppressed the expression of HSP27 and PLCG2. HAMSC-Exos promotes angiogenesis in hUVECs by delivering novel miRNA N-194 which targets ING5.

Purpose: In the context of Chinese clinical texts, this paper aims to propose a deep learning algorithm based on Bidirectional Encoder Representation from Transformers (BERT) to identify privacy information and to verify the feasibility of our method for privacy protection in the Chinese clinical context. Methods: We collected and double-annotated 33,017 discharge summaries from 151 medical institutions on a municipal regional health information platform, developed a BERT-based Bidirectional Long Short-Term Memory Model (BiLSTM) and Conditional Random Field (CRF) model, and tested the performance of privacy identification on the dataset. To explore the performance of different substructures of the neural network, we created five additional baseline models and evaluated the impact of different models on performance. Results: Based on the annotated data, the BERT model pre-trained with the medical corpus showed a significant performance improvement to the BiLSTM-CRF model with a micro-recall of 0.979 and an F1 value of 0.976, which indicates that the model has promising performance in identifying private information in Chinese clinical texts. Conclusions: The BERT-based BiLSTM-CRF model excels in identifying privacy information in Chinese clinical texts, and the application of this model is very effective in protecting patient privacy and facilitating data sharing.

OBJECTIVES:Preoperative diagnosis of oral ameloblastoma (AME) and odontogenic keratocyst (OKC) has been a challenge in dentistry. This study uses radiomics approaches and machine learning (ML) algorithms to characterize cone-beam CT (CBCT) image features for the preoperative differential diagnosis of AME and OKC and compares ML algorithms to expert radiologists to validate performance. METHODS:We retrospectively collected the data of 326 patients with AME and OKC, where all diagnoses were confirmed by histopathologic tests. A total of 348 features were selected to train six ML models for differential diagnosis by a 5-fold cross-validation. We then compared the performance of ML-based diagnoses to those of radiologists. RESULTS:Among the six ML models, XGBoost was effective in distinguishing AME and OKC in CBCT images, with its classification performance outperforming the other models. The mean precision, recall, accuracy, F1-score, and area under the curve (AUC) were 0.900, 0.807, 0.843, 0.841, and 0.872, respectively. Compared to the diagnostics by radiologists, ML-based radiomic diagnostics performed better. CONCLUSIONS:Radiomic-based ML algorithms allow CBCT images of AME and OKC to be distinguished accurately, facilitating the preoperative differential diagnosis of AME and OKC. ADVANCES IN KNOWLEDGE:ML and radiomic approaches with high-resolution CBCT images provide new insights into the differential diagnosis of AME and OKC.

Targeted temperature management (TTM) has been partially applied in patients with restoration of spontaneous circulation (ROSC) after cardiac arrest (CA). In the 2020 American Heart Association (AHA) cardiopulmonary resuscitation (CPR) guidelines, TTM is used as advanced life support after ROSC for the treatment of patients with CPR. TTM has a protective effect on cardiac function after CA, but the specific mechanism of its protective effect on cardiac function remains unclear. In this paper, the basic experimental progress, clinical trial progress and development prospect of TTM on the protective mechanism of cardiac function after CA are reviewed.

Purpose: China developed an innovative episode-based payment scheme for outpatient care, namely "Ambulatory Patient Groups (APGs) + capitation" payment, to constrain inflation in outpatient expenditures. This study aimed to assess the effects of this payment method on volume and expenditures in Chinese public hospitals. Methods: A quasi-experimental study was conducted with 7 municipal and 12 county hospitals from Jinhua as the intervention group and 15 municipal and 24 county hospitals from three neighbouring cities as the control group. The payment reform was introduced to municipal and county hospitals in the intervention group in January 2020 and January 2021, respectively. Monthly data on volumes and outpatient expenditures were collected from each hospital from January 2019 to December 2021. Controlled interrupted time -series analyses were performed to determine the effects of the funding reforms. Results: Outpatient visits in municipal hospitals decreased by 1417.54 (p=0.048) per month on average compared with control ones after the reform was implemented, whilst that in county hospitals increased by 1058.04 (p=0.041) per month on average. The trend of drug expenditures (67=-1.41, p=0.019) in municipal hospitals dropped, which was accompanied by an immediate reduction in consumable expenditures (66 =-6.89, p=0.044). The funding reform also led to the significant declines in drug (66=-10.96, p=0.009) and consumable (66=-4.78, p=0.041) expenditures in county hospitals. Municipal hospitals experienced the drop in the trend of total outpatient expenditures (67=-3.99, p=0.018) over the same period. Conclusion: The strength of the "AGPs + capitation" payment for outpatient care lies in its ability to control the excessive growth of medical expenses through correcting inappropriate incentives. However, minimising potential cost-shifting and risk-shifting to uninsured service items should be given attention.

PURPOSE: Identifying patients at risk for severe complications (i.e., respiratory failure, shock, or multiorgan dysfunction) following COVID-19 infection represents a critical challenge.Emerging evidence suggests that the microbiota in various body sites, including the oropharynx, upper airways, and gut, play a critical role in the development and progression of these complications.We hypothesize that understanding the shift in microbial populations in the oropharynx, upper airways, and gut of patients with severe coronavirus infection has the potential to identify pathways involved in the development of more severe complications of viral infection and predict disease severity.METHODS: Stool, oral, and nasal samples collected from COVID-19 patients admitted at the University of Maryland Medical Center between January 2021-June 2021 were characterized using whole community shotgun metagenomic sequencing on Illumina HiSeq NovaSeq 4000 6000 platform.Clinical factors including ICU status, survival, and use of ventilator were correlated with microbiome characteristics.MetaPhlAn was used to profile the composition and structure of the microbiome of the samples at high taxonomic resolution.The PhyloSeq R package was employed to evaluate community alpha diversity, and LEfSe DESeq2 was used to determine biomarkers significantly different by clinical features. RESULTS:The stool samples of patients with severe cases, admitted to the ICU, had significantly more Parasutterella, Odoribacter, Staphylococcus, and Sellimonas, all of which have been previously implicated in dysbiotic conditions.The oral microbiome of patients who required mechanical ventilation demonstrated increased abundance of Staphylococcus and Enterococcus, both of which generally attach to skin and mucous membranes but also can be aerosolized.Patients with COVID pneumonia requiring supplemental oxygen demonstrated significantly lower community biodiversity in both the GI tract and oral cavity.CONCLUSIONS: Patients admitted with severe COVID infection had lower microbiome diversity and significantly altered microbial community composition and structure.Our data indicates COVID-19 infection imposes a systemic influence on the body and changes in the gut and oral microbiome may represent an indicator of disease severity.CLINICAL IMPLICATIONS: Our study has the potential to identify biomarkers of disease progression and severity, that also promote local immune activation and contribute to the high rates of death in COVID patients.These results allow us to plan tests of microbiota-based actionable targets for diagnostic applications and guide new treatments for patients with severe disease.

Background: Post-stroke depression (PSD) is the most common psychological consequence of stroke. Increased inflammatory markers resulting from ischemic stroke may played an important role in the pathogenesis of depressive symptomology. The present study was conducted to further elucidate the relationship between stroke severity, systemic low-grade inflammation and chronic phase post-stroke depressive symptomology (CP-PSDS). Methods: A total of 897 stroke patients were consecutively recruited in this multicenter prospective cohort study and followed up for 1 year. The analytical sample consisted of 436 patients with ischemic stroke (23.4% female, median age = 57 years) from this cohort. Serum concentrations of inflammatory markers were measured in all 436 patients with ischemic stroke, from fasting morning venous blood samples on admission. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) on admission and post-stroke depressive symptomology (PSDS) was evaluated by 17-item Hamilton Rating Scale for Depression (HRSD). Results: In the fully adjusted models, we observed that 1) NIHSS (Model 2: beta = 0.200, 95%CI, 0.057 similar to 0.332), fibrinogen (Model 2: beta = 0.828, 95%CI, 0.269 similar to 1.435), white blood cell counts (WBC, model 2: beta = 0.354, 95% CI, 0.122 similar to 0.577) and neutrophil counts (Model 2: beta = 0.401, 95%CI, 0.126 similar to 0.655) can independently predict the CP-PSDS after ischemic stroke onset; 2) fibrinogen (Indirect effect = 0.027, 95%CI, 0.007 similar to 0.063, 13.4% mediated), WBC (Indirect effect = 0.024, 95%CI, 0.005 similar to 0.058, 11.8% mediated) and neutrophil counts (Indirect effect = 0.030, 95%CI, 0.006 similar to 0.069, 14.8% mediated) could partially mediate the association between stroke severity and CP-PSDS, and 3) stroke severity might cause CP-PSDS partly through the chain-mediating role of both fibrinogen and neutrophil counts (chain mediated effect = 0.003, 95%CI, 0.000 similar to 0.011, p = 0.025, 1.6% mediated). Conclusions: Findings revealed that fibrinogen, WBC and neutrophil counts may be independent predictors of CP-PSDS and partial mediators of the relationship between stroke severity and CP-PSDS among patients with ischemic stroke. In addition, the chain mediating effect of fibrinogen and neutrophil counts might play an important role in the occurrence of CP-PSDS. However, no inflammatory markers were associated with CP-PSDS in females.

Background: For large hemispheric infarction (LHI), malignant cerebral edema (MCE) is a life-threatening complication with a mortality rate approaching 80%. Establishing a convenient prediction model of MCE after LHI is vital for the rapid identification of high-risk patients as well as for a better understanding of the potential mechanism underlying MCE. Methods: 142 consecutive patients with LHI within 24h of onset from January 1, 2016 to August 31, 2019 were retrospectively collected. MCE was defined as patient death or received decompressive hemicraniectomy (DHC) with obvious mass effect (≥ 5mm midline shift or Basal cistern effacement). Binary logistic regression was performed to identify independent predictors of MCE. Independent prognostic factors were incorporated to build a dynamic nomogram for MCE prediction. Results: After adjustment for confounders, four independent factors were identified, including previously known atrial fibrillation (KAF), midline shift (MLS), National Institutes of Health Stroke Scale (NIHSS) and anterior cerebral artery (ACA) territory involvement. To facilitate the use of nomogram for clinicians, we use “Dynnom” package to build dynamic MANA (acronym for MLS, ACA territory involvement, NIHSS and KAF) nomogram on web page (http://www.MANA-nom.com) to calculate the exact probability of developing MCE. The c-statistic of MANA nomogram was up to 0.887 ± 0.041 and AUC-ROC value in this cohort was 0.887 (95%CI, 0.828~0.934). Conclusions: Independent predictors of MCE included KAF, MLS, NIHSS, and ACA territory involvement. The dynamic MANA nomogram is a convenient, practical and effective clinical decision-making tool for predicting MCE after LHI in Chinese patients.

During the coronavirus disease 2019 (COVID-19) pandemic, numerous existing chemicals have been screened for antiviral potential against the emerging coronavirus severe acute respiratory syndrome coronavirus 2. Chloroquine and hydroxychloroquine, after exhibiting potent in vitro efficacy, have gained tremendous attention. Both therapeutics are derivatives of natural alkaloid quinine and were first synthesized to treat malaria. Thereafter, the pharmaceutical applications of the agents have expanded to many new areas. In this article, the medicinal history and pharmacological activities of chloroquine and hydroxychloroquine are summarized. Antimalarial, anti-inflammatory, antitumor, antiviral properties, and therapeutic potential in the emerging viral infection COVID-19 are discussed. Pharmacokinetics, adverse effects, and toxicities are reviewed.

ABSTRACTBackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19), but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19.MethodsA total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized.ResultsA total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT.ConclusionsPatients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.

BACKGROUND Since the early 1970s, health care provision has experienced rapid growth in the investment and adoption of health information technologies (HITs). However, the development and deployment of HITs has often been conducted in silos, at different organizational levels, within different regions, and in various health care settings; this has resulted in their infrastructures often being difficult to manage or integrate. Health information standards (ie, the set norms and requirements that underpin the deployment of HITs in health care settings) are expected to address these issues, yet their adoption remains to be frustratingly low among health care information technology vendors. OBJECTIVE This study aimed to synthesize a comprehensive framework of factors that affect the adoption and deployment of health information standards by health care organizations. METHODS First, electronic databases, including Web of Science, Scopus, and PubMed, were searched for relevant articles, with the results being exported to the EndNote reference management software. Second, study selection was conducted according to pre-established inclusion and exclusion criteria. Finally, a synthesized best fit framework was created, which integrated a thematic analysis of the included articles. RESULTS In total, 35 records were incorporated into the synthesized framework, with 4 dimensions being identified: technology, organization, environment, and interorganizational relationships. The technology dimension included relative advantage, complexity, compatibility, trialability, observability, switching cost, standards uncertainty, and shared business process attributes. The organization dimension included organizational scale, organizational culture, staff resistance to change, staff training, top management support, and organizational readiness. The environment dimension included external pressure, external support, network externality, installed base, and information communication. Finally, the interorganizational relationships dimension included partner trust, partner dependence, relationship commitment, and partner power. CONCLUSIONS The synthesized framework presented in this paper extends the current understanding of the factors that influence the adoption of health information standards in health care organizations. It provides policy and decision makers with a greater awareness of factors that hinder or facilitate their adoption, enabling better judgement and development of adoption intervention strategies. Furthermore, suggestions for future research are provided.

Objective:To study the manifestations of digestive system of hospitalized patients with coronavirus disease 2019 (COVID-19) in Wuhan, China, and to provide a reference for disease control and treatment.Methods:The data of hospitalized patients with COVID-19 in the Sino-French Branch of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 27 to February 14, 2020 were retrospectively analyzed, which included general information, positive rate of nucleic acid test, severity of disease, incubation period, initial symptoms and manifestations of digestive system. The general information, positive rate of nucleic acid detection, and manifestations of digestive system were compared between critical patients who required non-invasive or invasive assisted ventilation (critical group) and non-critical patients without assisted ventilation (non-critical group). Continuous corrected Chi-square test and independent sample median Chi-square test were used for statistical analysis.Results:Among the 305 patients, there were 146 males (47.9%) and 159 females (52.1%), and the median age was 57 years old. Nucleic acid assay of nasopharyngeal swabs or pharyngeal swabs were positive in 84.1% (228/271) patients including 46 patients (15.1%) of critical group and 259 patients (84.9%) of non-critical group. The incubation period was one to fifteen days, and the median period was six days. The initial symptoms were mainly fever (81.1%, 163/201), cough (39.3%, 79/201), fatigue (54.7%, 110/201), and loss of appetite (50.2%, 101/201). In one to ten days after the disease onset, 79.1% (159/201) of patients developed gastrointestinal symptoms including nausea (29.4%, 59/201), vomiting (15.9%, 32/201), or abdominal pain (6.0%, 12/201). 49.5% (146/295) of patients had diarrhea, with a median time of 3.3 days, (3.3±1.6) times per day, and a duration of (4.1±2.5) days. After excluding possible drug-related diarrhea, the incidence of diarrhea was still 22.2%. Only 6.9% (4/58) of patients had positive fecal leukocytes or fecal occult blood test. Alanine aminotrans ferase (ALT), aspartate aminotransferase (AST), or total bilirubin (TBil) increased in 39.1% (119/304) of patients on admission. Patients with ALT or AST ≥ 80 U/L only accounted for 7.9% (24/304) and 6.3% (19/304), respectively. About 2.0% (6/304) of patients also had increased TBil level, and the average level was (37.4±21.1) μmol/L. The median age of critical group was older than that of non-critical group (65 years vs. 56 years), the proportion of patients with abnormal liver function and slightly increased AST (40-<80 U/L) on admission of critical group were both higher than those of non-critical group (67.4% (31/46) vs. 34.1% (88/258) and 47.8% (22/46) vs. 21.7% (56/228)), and the differences were statistically significant ( χ2=5.885, 18.154 and 15.723; all P <0.05). There were no significant differences in the proportion of males (58.7% (27/46) vs. 45.9% (119/259)), the positive rate of nucleic acid test (94.6% (35/37) vs. 82.5% (193/234)), the percentage of patients with gastrointestinal symptoms (85.0% (17/20) vs. 78.5% (142/181)), the incidence of diarrhea (44.7% (17/38) vs. 50.2% (129/257)) and the proportion of patients with abnormal TBil level on admission (6.5% (3/46) vs. 1.2% (3/258)) (all P>0.05). Conclusions:The manifestation of digestive system of hospitalized COVID-19 patients in Wuhan is significant, the proportion of patients with diarrhea and abnormal aminotransferase level is high. And on admission the proportion of patients with abnormal liver function of critical group is higher than that of non-critical group, which will provide reference for the prevention and treatment of COVID-19.

Background: An emerging outbreak of COVID-19 has rapidly caused global pandemic. Few studies were reported on the incidence and role of influenza virus co-infection on COVID-19. Methods: 273 hospitalized patients with COVID-19 and tests of influenza A/B virus were enrolled from February to March 2020 in Wuhan, China. Data on baseline characteristics, clinical manifestations and outcomes, laboratory findings were collected and analysed. Findings: The incidence of influenza virus co-infection in patients with COVID-19 was 55·3% (151/273), with 48·5% (133/273) of influenza A and 6·6% (18/273) of influenza B, respectively. Influenza virus co-infection was significantly more common in non-critical group (60·5%, 115/190) than critical group (43·4%, 36/83; p=0·01). The fatality of COVID-19 in influenza group was 9·9% (15/151), while it was 23·8% (29/122) in non-influenza group (p=0·01). Accordingly, the incidence of critical type was higher in influenza group (p=0·01). Cox regression analysis revealed that co-infection with influenza virus had significant reduction of fatality than non-influenza group (OR 0·470, p<0·05). Other fatality indicators included age (p=0·02), sex (OR 3·626, p=0·00), and low lymphocytes (OR 2·368, p=0·04). Interpretation: There is a high incidence of influenza virus co-infection in patients with COVID-19 in Wuhan, China. It seems like co-infection with influenza virus acts as a protective factor for COVID-19. The relationship between SARS-nCoV-2 and influenza virus co-infection warrants further studies. Funding Statement: This study was supported by National Natural Science Foundation of China Grant (No. 81800493). Declaration of Interests: All authors have no conflicts of interest to declare. Ethics Approval Statement: The procedure was approved by the Institutional Ethics Board of Tongji Medical College. The follow-up was up to March 22, 2020.

Currently, there is no approved therapy for coronavirus disease 2019 (COVID-19). The World Health Organization (WHO) therefore endorses supportive care only. However, frontline clinicians and researchers have been experimenting with several virus-based and host-based therapeutics since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China. China's National Health Commission has issued the first COVID-19 treatment guidelines with therapy suggestions, which has inspired clinical studies worldwide. This review evaluates the major therapeutics. Key evidence from in vitro research, animal models and clinical research in emerging coronaviruses is examined. The antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, should be initiated before the peak of viral replication for an optimal outcome. Ribavirin may be beneficial as an add-on therapy but is ineffective as monotherapy. Corticosteroid use should be limited to specific co-morbidities. Intravenous immunoglobulin (IVIg) is not recommended owing to lack of data in COVID-19. The traditional Chinese medicine Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear owing to conflicting outcomes in coronavirus studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2, but studies on their clinical efficacy and whether the benefits outweigh the risk of dysrhythmias remain inconclusive. For patients who develop cytokine release syndrome, interleukin-6 inhibitors may be beneficial.