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Aerobic glycolysis has pleiotropic roles in the pathogenesis of hepatocellular carcinoma (HCC). Emerging studies revealed key promoters of aerobic glycolysis, however, little is known about its negative regulators in HCC. In this study, an integrative analysis identifies a repertoire of differentially expressed genes (DNASE1L3, SLC22A1, ACE2, CES3, CCL14, GYS2, ADH4, and CFHR3) that are inversely associated with the glycolytic phenotype in HCC. ACE2, a member of the rennin-angiotensin system, is revealed to be downregulated in HCC and predicts a poor prognosis. ACE2 overexpression significantly inhibits the glycolytic flux as evidenced by reduced glucose uptake, lactate release, extracellular acidification rate, and the expression of glycolytic genes. Opposite results are noticed in loss-of-function studies. Mechanistically, ACE2 metabolizes Ang II to Ang-(1-7), which activates Mas receptor and leads to the phosphorylation of Src homology 2-containing inositol phosphatase 2 (SHP-2). SHP2 activation further blocks reactive oxygen species (ROS)-HIF1α signaling. Addition of Ang-(1-7) or the antioxidant N-acetylcysteine compromises in vivo additive tumor growth and aerobic glycolysis induced by ACE2 knockdown. Moreover, growth advantages afforded by ACE2 knockdown are largely glycolysis-dependent. In clinical settings, a close link between ACE2 expression and HIF1α or the phosphorated level of SHP2 is found. Overexpression of ACE2 significantly retards tumor growth in patient-derived xenograft model. Collectively, our findings suggest that ACE2 is a negative glycolytic regulator, and targeting the ACE2/Ang-(1-7)/Mas receptor/ROS/HIF1α axis may be a promising therapeutic strategy for HCC treatment.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , Reactive Oxygen Species , Angiotensin-Converting Enzyme 2 , Cell Line, TumorABSTRACT
INTRODUCTION: This study investigates the effects of the COVID-19 pandemic on medical education, research opportunities, and mental health in orthopaedic surgical training programs. METHODS: A survey was sent to the 177 Electronic Residency Application Service-participating orthopaedic surgery training programs. The survey contained 26 questions covering demographics, examinations, research, academic activities, work settings, mental health, and educational communication. Participants were asked to assess their difficulty in performing activities relative to COVID-19. RESULTS: One hundred twenty-two responses were used for data analysis. Difficulties were experienced in collaborating with others (49%), learning through online web platforms (49%), maintaining the attention span of others through online web platforms (75%), and in gaining knowledge as a presenter or participating through online web platforms (56%). Eighty percent reported that managing time to study was the same or easier. There was no reported change in difficulty for performing activities in the clinic, emergency department, or operating room. Most respondents reported greater difficulty in socializing with others (74%), participating in social activities with coresidents (82%), and seeing their family (66%). Coronavirus disease 2019 has had a significant effect on the socialization of orthopaedic surgery trainees. DISCUSSION: Clinical exposure and engagement were marginally affected for most respondents, whereas academic and research activities were more greatly affected by the transition from in-person to online web platforms. These conclusions merit investigation of support systems for trainees and evaluating best practices moving forward.
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COVID-19 , Orthopedic Procedures , Orthopedics , Humans , United States/epidemiology , COVID-19/epidemiology , Orthopedics/education , SARS-CoV-2 , Pandemics , Orthopedic Procedures/educationABSTRACT
Objective: To measure sales of antibiotics without a prescription in pharmacies in China in 2017 and 2021, before and during the coronavirus disease 2019 (COVID-19) pandemic, and determine the factors associated with such sales. Methods: We conducted cross-sectional surveys using the simulated patient method in retail pharmacies in 13 provinces in eastern, central and western China in 2017 and 2021. At the pharmacies, the simulated patients (trained medical students) reported that they had mild respiratory tract symptoms and asked for treatment, using a three-stage process: (i) request some treatment; (ii) request antibiotics; (iii) request specific antibiotics. We used multivariable logistic regression analysis to determine factors associated with sale of antibiotics without a prescription. Findings: Of the pharmacies visited in 2017, 83.6% (925/1106) sold antibiotics without a prescription; this figure was 78.3% (853/1090) in 2021 (P-value: 0.002). After excluding pharmacies prohibited from selling antibiotics because of COVID-19, this difference was not significant (83.6% versus 80.9%; 853/1054; P-value: 0.11). Factors significantly associated with selling antibiotics without a prescription in both 2017 and 2019 were: location in central and western China compared with eastern China; being in a township or village compared with in a city; and presence of a counter where antibiotics were dispensed. Conclusion: Although laws became stricter between 2017 and 2021, antibiotic sales without a prescription were still common in pharmacies across China. Existing regulations need to be more strictly enforced, and pharmacy staff and the public should be made more aware of the risks of antibiotic misuse and dangers of antimicrobial resistance.
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Anti-Bacterial Agents , Pharmacies , Humans , Anti-Bacterial Agents/therapeutic use , China , COVID-19/epidemiology , Cross-Sectional Studies , Prescriptions , CommerceABSTRACT
The Coronavirus Disease 2019 (COVID-19) pandemic has become a leading societal concern. eHealth literacy is important in the prevention and control of this pandemic. The purpose of this study is to identify eHealth literacy of Chinese residents about the COVID-19 pandemic and factors influencing eHealth literacy. A total of 15 694 individuals clicked on the link to the questionnaire, and 15 000 agreed to participate and completed the questionnaire for a response rate of 95.58%. Descriptive statistics, χ2 test, and logistic regression analysis were conducted to analyze participants' level of eHealth literacy about COVID-19 and its influencing factors. The results showed 52.2% of participants had relatively lower eHealth literacy regarding COVID-19 (eHealth literacy score ≤ 48). The scores of the information judgment dimension (3.09 ± 0.71) and information utilization dimension (3.18 ± 0.67) of the eHealth literacy scale were relatively lower. The logistics regression showed that sex, age, education level, level of uncertainty, having people around the respondent diagnosed with COVID-19, relationship with family, and relationship with others were associated to eHealth literacy (χ2 = 969.135, P < .001). The public's eHealth literacy about COVID-19 needs to be improved, especially the ability to judge and utilize online information. Close collaboration among global health agencies, governments, healthcare institutions, and media is needed to provide reliable online information to the public. Interventions to improve eHealth literacy should take into account and accentuate the importance of sex, age, educational background, level of uncertainty, exposure to disease, and social support.
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AIM: Timely recruitment of eligible participants is essential for the success of clinical trials, with insufficient accrual being the leading cause for premature termination of both oncology and non-oncology trials. METHODS: In this paper we further elaborate on the challenges for patient participation in oncology trials from physician, patient, healthcare system, and some trial-related perspectives. RESULTS: We present strategies such as use of digital healthcare technologies, real-world data and real-world evidence, decentralized clinical trials, pragmatic trial designs, and supportive services to increase patient participation. CONCLUSIONS: Multifaceted measures are necessary to increase patient participation, especially for those who are under-represented in cancer trials.
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Antibiotic stewardship has been prioritized by governments and health care organizations in recent years as antibiotic resistance is markedly increasing. A tertiary hospital in Guangzhou, China was chosen as a study example to undertake an implementation and effectiveness evaluation of China's antibiotic stewardship to improve and promote antimicrobial stewardship nationwide. The general surgery department of the study hospital was utilized to examine surgical site infection, and samples from across the hospital were used to identify bloodstream infection. Data was analyzed using descriptive analysis, the Mann-Kendall trend test, logit model and panel data model, and t-tests. In terms of prophylactic and therapeutic antibiotic rational use, respectively, we evaluated implementation conditions, the correlation between implementation and corresponding disease progress, and the cost-effectiveness of China's antibiotic stewardship. For perioperative prophylactic antibiotic use, antibiotic stewardship was found to have been well-implemented, cost-effective, and reduced the incidence of surgical site infection. However, concerning therapeutic use and antibiotic-resistant bacterial infection prophylaxis, the complexity of influencing factors and the contradiction between stewardship implementation and clinical demand needs to be further evaluated.
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The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (Mpro), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.
Subject(s)
COVID-19 , Humans , Antiviral Agents/pharmacology , SARS-CoV-2 , Quercetin/pharmacology , Anti-Inflammatory Agents/pharmacology , Molecular Docking SimulationABSTRACT
BACKGROUND: Dysmenorrhea has a significant negative impact on teenagers' quality of life, and its prevalence is increasing annually. Although studies have explored the factors affecting dysmenorrhea, it remains unclear how these factors interact with one another. This study aimed to explore the mediating role of binge eating and sleep quality between depression and dysmenorrhea. METHODS: This cross-sectional study recruited adolescent girls from the Health Status Survey of adolescents in Jinan, Shandong Province, and used multistage stratified cluster random sampling. Data was collected using an electronic questionnaire between March 9, 2022, and June 20, 2022. The Numerical Rating Scale and Cox Menstrual Symptom Scale were used to assess dysmenorrhea and the Patient Health Questionnaire-9 to assess depression. The mediation model was tested by Mplus 8.0, and the mediating effect was analyzed using the Product of Coefficients approach and the Bootstrap method. RESULTS: Among the total of 7818 adolescent girls included in this study, the prevalence of dysmenorrhea is 60.5%. A significant positive association was found between dysmenorrhea and depression. Binge eating and sleep quality seemingly mediate this association. The mediating effect of sleep quality (21.31%) was greater than that of binge eating (6.18%). CONCLUSIONS: The findings of this study point in the right direction for preventing and treating dysmenorrhea in adolescents. For adolescent dysmenorrhea, mental health should be considered and proactive steps taken for educating adolescents on healthy lifestyles to reduce negative consequences of dysmenorrhea. Longitudinal studies on the causal link and influence mechanisms between depression and dysmenorrhea should be conducted in the future.
Subject(s)
Binge-Eating Disorder , Dysmenorrhea , Female , Adolescent , Humans , Dysmenorrhea/epidemiology , Depression/epidemiology , Sleep Quality , Binge-Eating Disorder/complications , Binge-Eating Disorder/epidemiology , Quality of Life , Cross-Sectional Studies , Surveys and QuestionnairesABSTRACT
The second COVID-19 outbreak in Beijing was controlled by non-pharmaceutical interventions, which avoided a second pandemic. Until mass vaccination achieves herd immunity, cities are at risk of similar outbreaks. It is vital to quantify and simulate Beijing's non-pharmaceutical interventions to find effective intervention policies for the second outbreak. Few models have achieved accurate intra-city spatio-temporal epidemic spread simulation, and most modeling studies focused on the initial pandemic. We built a dynamic module of infected case movement within the city, and established an urban spatially epidemic simulation model (USESM), using mobile phone signaling data to create scenarios to assess the impact of interventions. We found that: (1) USESM simulated the transmission process of the epidemic within Beijing; (2) USESM showed the epidemic curve and presented the spatial distribution of epidemic spread on a map; and (3) to balance resources, interventions, and economic development, nucleic acid testing intensity could be increased and restrictions on human mobility in non-epidemic areas eased.
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INTRODUCTION: Stress hyperglycemia is a common symptom in critically ill patients, and is not only a marker indicating the severity of illness but is also related to worsening outcomes. Managing stress hyperglycemia without increasing the likelihood of hypoglycemia is one of the most pressing challenges to be urgently addressed in clinics. The Plan-Do-Check-Act (PDCA) cycle management has been put forward in various surgical management scenarios, and has proven to be effective in the diagnosis and treatment of different diseases. It possesses dynamic characteristics and can be updated according to the results of glycemic control and feedback. This study focused on the use of PDCA to manage glucose levels in critically ill patients. METHODS: Based on the glucose level of 1003 critically ill patients admitted to the emergency intensive care unit (EICU) from 1 October 2019 to 31 December 2020, we collected and matched the prevalence of hyperglycemia, hypoglycemia, and glucose variability on a quarterly basis. According to the PDCA management method, we analyzed the possible causes, supervised the implementation of measures, summarized the feedback on improvements, and then proposed new improvement measures for implementation in the next quarter. RESULTS: Three measures were proposed and applied to enhance the management of hyperglycemia: (I) Updating and formulating three editions of the insulin infusion protocol and increasing the initial and maintenance doses of insulin on a case-by-case basis; (II) reducing the use of parenteral nutrition and ensuring that enteral nutrition is consumed at a uniform and slow rate; and (III) forming a training method during the COVID-19 pandemic and improving implementation of the insulin infusion protocol. Following PDCA management, the prevalence of hyperglycemia fell from 43.18% to 32.61%, the incidence of hypoglycemia was below 1.00%, and there was no significant fluctuation in blood glucose variability. CONCLUSION: The PDCA method is helpful in developing a superior insulin infusion protocol for critically ill patients and lowering the prevalence of hyperglycemia in critically ill patients.
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Catalytic antibodies made it feasible to develop new catalysts, which had previously been the subject of research. Scientists have discovered natural antibodies that can hydrolyze substrates such as nucleic acids, proteins, and polysaccharides during decades of research, as well as several ways of producing antibodies with specialized characteristics and catalytic functions. These antibodies are widely used in chemistry, biology, and medicine. Catalytic antibodies can continue to play a role and even fully prevent the emergence of autoimmune disorders, especially in the field of infection and immunity, where the process of its occurrence and development often takes a long time. In this work, the development, design and evolution methodologies, and the expression systems and applications of catalytic antibodies, are discussed. Trial registration: not applicable.
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The COVID-19 pandemic has posed enormous challenges for existing diagnostic tools to detect and monitor pathogens. Therefore, there is a need to develop point-of-care (POC) devices to perform fast, accurate, and accessible diagnostic methods to detect infections and monitor immune responses. Devices most amenable to miniaturization and suitable for POC applications are biosensors based on electrochemical detection. We have developed an impedimetric immunosensor based on an interdigitated microelectrode array (IMA) to detect and monitor SARS-CoV-2 antibodies in human serum. Conjugation chemistry was applied to functionalize and covalently immobilize the spike protein (S-protein) of SARS-CoV-2 on the surface of the IMA to serve as the recognition layer and specifically bind anti-spike antibodies. Antibodies bound to the S-proteins in the recognition layer result in an increase in capacitance and a consequent change in the impedance of the system. The impedimetric immunosensor is label-free and uses non-Faradaic impedance with low nonperturbing AC voltage for detection. The sensitivity of a capacitive immunosensor can be enhanced by simply tuning the ionic strength of the sample solution. The device exhibits an LOD of 0.4 BAU/ml, as determined from the standard curve using WHO IS for anti-SARS-CoV-2 immunoglobulins; this LOD is similar to the corresponding LODs reported for all validated and established commercial assays, which range from 0.41 to 4.81 BAU/ml. The proof-of-concept biosensor has been demonstrated to detect anti-spike antibodies in sera from patients infected with COVID-19 within 1 h. Photolithographically microfabricated interdigitated microelectrode array sensor chips & label-free impedimetric detection of COVID-19 antibody.
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AIMS: To investigate the effect of a transition programme including cognitive-behaviour-based preceptorship intervention on ICU new graduate nurses' (NGNs)' professional identity and their intention to remain employed. DESIGN: One-arm pre- and post-test design followed the TREND Statement. METHODS: NGNs' professional identity and intention to remain employed were measured at baseline (T1), postintervention (1 month, T2) and 6-month follow-up (T3). RESULTS: Fifty-three NGNs completed the programme, and their professional identity score significantly increased postintervention [from 111.5 (SD = 16.72) at T1 to 114.2 (SD = 9.12) at T2, p < 0.05], but decreased at T3 [105.8 (SD = 9.44) compared with T1 and T2, p < 0.05]. There was no significant difference in ICU NGNs' intention of remain employed outcomes at three time points (p > 0.05). The transition programme was effective to improve ICU NGNs' professional identity immediately after the intervention, but the increment did not maintain at the 6-month follow-up.
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Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.
Subject(s)
COVID-19 , Cytokines , Endoribonucleases , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Child , Humans , COVID-19/immunology , Cytokines/genetics , Cytokines/immunology , Endoribonucleases/genetics , Endoribonucleases/metabolism , RNA, Double-Stranded , SARS-CoV-2/genetics , Systemic Inflammatory Response Syndrome/geneticsABSTRACT
The COVID-19 pandemic has underscored the urgency to focus on the essential value of public health systems (PHSs) in fostering health equity across the US health care delivery system. PHS integration and care coordination can be successfully achieved through health information technology systems. The objective of the study was to examine the association between PHS partnerships (PHSPs), telehealth postdischarge, and racial and ethnic disparities in health care. The analysis used 2017 Centers for Medicare and Medicaid Services Medicare 100% inpatient claims data, the Medicare Beneficiary Summary File, the American Hospital Association Annual Survey, and the American Community Survey. Results showed that compared with those treated in hospitals with neither PHSP nor telehealth postdischarge services, beneficiaries treated in hospitals with PHSP encountered significantly lower Medicare payment and inpatient and readmission rates. Black patients experienced significantly lower cost, inpatient visits, and readmission rates when treated in hospitals with PHSP and telehealth postdischarge services (coefficient = -0.051, P < 0.001; incidence rate ratio [IRR] = 0.982, P = 0.007; IRR = 0.891, P = 0.003). The results of the study demonstrated the importance of combining PHSP and telehealth postdischarge services to improve the efficiency of the health care delivery system and health equity. It is urgent to ensure that PHSs have adequate funding and telehealth infrastructure to support population health.