Disseminated central nervous system tuberculoma in a patient with scrub typhus: A case report.

Central nervous system (CNS) tuberculosis mainly manifests as tuberculous meningitis and intracranial tuberculosis; intramedullary tuberculosis is uncommon. Scrub typhus is an acute naturally occurring infectious disease caused by Orientia tsutsugamushi. CNS tuberculoma following typhus is rare. The present study described a 60-year-old man with high fever, muscle soreness, yellowish skin and sclera and hepatosplenomegaly. At first, the patient was diagnosed with scrub typhus, after treatment with doxycycline he recovered completely. However, half a month after discharge, the patient experienced headache, night sweats and anorexia. Tuberculosis-specific enzyme-linked immunospot assay showed positive Mycobacterium tuberculosis antibody in cerebrospinal fluid (CSF). Metagenomic next-generation sequencing detected the presence of Mycobacterium tuberculosis in CSF. Magnetic resonance imaging of the brain and spinal cord showed multiple rings enhancing lesions in the cerebral hemispheres, cerebellum, brainstem and spinal cords. After the diagnosis of CNS tuberculoma, the patient was started on conventional anti-tuberculosis therapy resulting in a good prognosis.

Utilizing ChatGPT as a scientific reasoning engine to differentiate conflicting evidence and summarize challenges in controversial clinical questions.

OBJECTIVE: Synthesizing and evaluating inconsistent medical evidence is essential in evidence-based medicine. This study aimed to employ ChatGPT as a sophisticated scientific reasoning engine to identify conflicting clinical evidence and summarize unresolved questions to inform further research. MATERIALS AND METHODS: We evaluated ChatGPT's effectiveness in identifying conflicting evidence and investigated its principles of logical reasoning. An automated framework was developed to generate a PubMed dataset focused on controversial clinical topics. ChatGPT analyzed this dataset to identify consensus and controversy, and to formulate unsolved research questions. Expert evaluations were conducted 1) on the consensus and controversy for factual consistency, comprehensiveness, and potential harm and, 2) on the research questions for relevance, innovation, clarity, and specificity. RESULTS: The gpt-4-1106-preview model achieved a 90% recall rate in detecting inconsistent claim pairs within a ternary assertions setup. Notably, without explicit reasoning prompts, ChatGPT provided sound reasoning for the assertions between claims and hypotheses, based on an analysis grounded in relevance, specificity, and certainty. ChatGPT's conclusions of consensus and controversies in clinical literature were comprehensive and factually consistent. The research questions proposed by ChatGPT received high expert ratings. DISCUSSION: Our experiment implies that, in evaluating the relationship between evidence and claims, ChatGPT considered more detailed information beyond a straightforward assessment of sentimental orientation. This ability to process intricate information and conduct scientific reasoning regarding sentiment is noteworthy, particularly as this pattern emerged without explicit guidance or directives in prompts, highlighting ChatGPT's inherent logical reasoning capabilities. CONCLUSION: This study demonstrated ChatGPT's capacity to evaluate and interpret scientific claims. Such proficiency can be generalized to broader clinical research literature. ChatGPT effectively aids in facilitating clinical studies by proposing unresolved challenges based on analysis of existing studies. However, caution is advised as ChatGPT's outputs are inferences drawn from the input literature and could be harmful to clinical practice.

Trends and socioeconomic inequality of the burden of congenital abnormalities of the kidney and urinary tract among children and adolescents.

BACKGROUND: Although congenital abnormalities of the kidney and urinary tract (CAKUT) is the leading cause of childhood onset chronic kidney disease (CKD) and kidney failure, comprehensive information on the disease burden among children and adolescents globally is lacking. We aim to report the trends and socioeconomic inequality of CAKUT burden for people aged 0-24 years from 1990 to 2019·. METHODS: We reported the prevalence, mortality and disability-adjusted life-years (DALYs) for CAKUT based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, quantified the association of disease burden and socio-demographic index (SDI), calculated the slope index of inequality (SII) the relative index of inequality (RII) and concentration index. RESULTS: In 2019, the global prevalence, mortality, and DALYs of CAKUT among individuals aged 0-24 years were 167.11 (95%Confident Interval 166.97, 167.25), 0.30 (0.29, 0.30), and 32.22 (32.16, 32.29) per 100 000 population. The greatest prevalence, mortality and DALYs were recorded in the 0-4 year age group. The greatest mortality and DALYs were recorded in low SDI countries and territories. During 1990 to 2019, the prevalence, mortality and DALYs decreased globally, while in low and low-middle countries and territories the reduction was much less slower. India, Nigeria and Pakistan had the highest DALYs. Saudi Arabia and China exhibited a markedly decrease of CAKUT burden. Globally for every 0.1 increase in SDI, there was a 20.53% reduction in mortality, a 16.31% decrease in DALYs, but a 0.38% rise in prevalence. CONCLUSIONS: Inequality for disease burden of varying SDI was increasing globally. Thus, specific preventive and health service measures are needed to reduce the global burden from CAKUT.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Higher disease burden and lower utilization in mongolian with breast cancer: a 9-year retrospective cohort study of 18.19 million adults in China.

BACKGROUND: Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. We aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female breast cancer patients in China. MATERIALS AND METHODS: Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012-2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. RESULTS: A total of 34,878 female patients (mean [SD] age, 52.34 [10.93] years) were included among 18.19 million Chinese, and 4,315 [12.03%] participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39-44.98) per 100,000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of breast cancer annually per capita was significantly lower for Mongolian than Han in FBC ($1,948.43 [590.11-4 776.42] vs. $2,227.35 [686.65-5,929.59], P<0.001). Mongolian females showed higher all-cause mortality (30.92, [95% CI: 28.15-33.89] vs. 27.78, [95% CI: 26.77-28.83] per 1,000, P=0.036) and breast cancer-specific mortality (18.78, [95% CI: 16.64-21.13] vs. 15.22, [95% CI: 14.47-16.00] per 1,000, P=0.002) than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality (HR, 1.21, [95% CI, 1.09-1.34]; P<0.001) and breast cancer-specific mortality (HR, 1.31, [95% CI, 1.14-1.49]; P<0.001). CONCLUSION: The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.

Competitive and synergic evolution of the water-food-ecology system: A case study of the Beijing-Tianjin-Hebei region, China.

A vital approach to attaining sustainable development lies in the in-depth examination of both competition and synergy between these subsystems from a water-food-ecology (WFE) system perspective, while previous or existing studies have limitations in to quantitative characterize and evaluation the cooperative and competitive relationships between different systems. In this study, an evaluation indicator system is constructed from the two dimensions of resources and efficiency, and the WFE synergic development capacity (WFE-SDC) is proposed by integrating the order degree of the coupled system, enables a multidimensional and comprehensive quantitative assessment of the sustainable development of the WFE system. Then a synergic evolution model is constructed to explore the competitive and synergic evolution of the WFE system in the Beijing-Tianjin-Hebei region. The following key insights were obtained: (1) The WFE-SDC (range of 0-1) shows a fluctuating increase, indicating a shift from mild dysfunctional recession to intermediate synergic development (0.24 to 0.72). (2) Principal factors impeding WFE-SDC encompass diversion water, ecology water consumption, grain demand, reclaimed water consumption, and outbound water, both come from resource dimension, with a combined impediment degree of over 46 %, and the improvement of efficiency dimension may improve the WFE-SDC. (3) The water subsystem acts as a driving force for synergic development, fostering cooperation within the food and ecology subsystems, although they mainly operate in a competitive state. (4) Within the WFE system, Beijing, Tianjin, and Hebei exhibited mutual cooperation and significantly contributed to one another's development. Beijing has played a pivotal role in the progress of both Tianjin and Hebei. This study offers valuable insights for the formulation of policies and the application of technical approaches for the sustainable development of the WFE system in relevant regions.

Higher fibrinogen and neutrophil-to-lymphocyte ratio are associated with the early poor response to intravenous thrombolysis in acute ischemic stroke.

Background: Inflammation and platelet activation play pivotal roles in acute ischemic stroke (AIS) pathogenesis. Early response to thrombolysis is a vital indicator for the long-term prognosis of AIS. However, the correlation between fibrinogen or the neutrophil-to-lymphocyte ratio (NLR) and the early response to intravenous thrombolysis in patients with AIS remains unclear. Methods: AIS patients undergoing intravenous thrombolysis were enrolled between January 2018 and May 2023. Blood cell counts were sampled before thrombolysis. A good response was defined as a National Institutes of Health Stroke Scale (NIHSS) score decreased ≥4 or complete recovery 24 h after thrombolysis treatment. A poor response was defined as any increase in the NIHSS score or a decrease in the NIHSS score <4 at the 24 h after thrombolysis treatment compared with that at admission. Logistic regression analysis was performed to explore the relationship of the fibrinogen level and NLR with a poor thrombolysis response. Receiver operating characteristic (ROC) analysis was used to assess the ability of the fibrinogen level and NLR to discriminate poor responders. Results: Among 700 recruited patients, 268 (38.29%) were diagnosed with a good response, and 432 (61.71%) were diagnosed with a poor response to intravenous thrombolysis. A binary logistic regression model indicated that an elevated fibrinogen level (odds ratio [OR], 1.693; 95% confidence interval [CI] 1.325-2.122, P < 0.001) and NLR (OR, 1.253; 95% CI, 1.210-2.005, P = 0.001) were independent factors for a poor response. The area under the curve (AUC) values for the fibrinogen level, NLR and fibrinogen level combined with the NLR for a poor response were 0.708, 0.605, and 0.728, respectively. Conclusions: Our research indicates that the levels of fibrinogen and NLR at admission can be used as a prognostic factor to predict early poor response to intravenous thrombolysis.

FEM analysis of a new three-way drainage and pressure reduction system for road tunnels.

For water-rich areas, tunnel elevation arches under high water pressure often cause elevation arch cracking and leakage, bulging and other failures. When the drainage system is not designed properly, these failures occur more frequently, and conventional road tunnel drainage cannot effectively reduce the water pressure at the elevation arch. Therefore, this paper proposes a new concept of "three-way drainage". The three-way drainage system is based on a conventional drainage system with a new drainage inlet at the elevation arch. On this basis, a series of numerical simulation studies are conducted to verify the pressure-reducing performance of the three-way drainage system on the lining. After demonstration and analysis, the three-way drainage concept can not only effectively reduce the water pressure at the elevation arch of the tunnel but also have a significant effect on the overall drainage effect of the tunnel. The factors affecting the performance of the three-way drainage system are assessed by varying the model parameters. It is found that the hydraulic conduction coefficient of the surrounding rock and initial support, the number of reverse diversion holes in the elevation arch, the change in head height, and the change in secondary lining parameters all have a significant effect on the water pressure outside the tunnel.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04563936.

MicroRNA-511-3p regulates Aß1-40 induced decreased cell viability and serves as a candidate biomarker in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease with high incidence in the elderly population. MicroRNAs have been reported to abnormally expressed in patients with AD. In this study, we investigated the role of inflammation-related miR-511-3p in AD patients and AD cell models. METHOD: The level of miR-511-3p was quantified by Real-Time PCR. The diagnostic value was evaluated by receiver operating characteristic curve (ROC) analysis. The correlation between miR-511-3p expression levels and ini-mental state examination (MMSE) scores, Montreal Cognitive Assessment (MoCA) scores and inflammatory factors was analyzed. The concentrations of IL-1ß, IL-6 and TNF-α were measured by Enzyme-Linked Immunosorbent Assay (ELISA) in AD cell model and serum from AD patients. RESULT: Serum miR-511-3p expression was decreased in AD patients and correlated with MMSE score, MoCA score and inflammatory response. MiR-511-3p mimics significantly reversed the effects of Aß 1-40 on inflammation in AD cells. ROC curve results showed that miR-511-3p had high diagnostic accuracy in distinguishing normal controls from AD patients. CONCLUSION: Our results show that miR-511-3p is down-regulated in AD patients and has high diagnostic value. MiR-511-3p may participate in the development of AD by regulating the levels of neuroinflammatory factors in AD cells. MiR-511-3p may provide a new perspective for the prevention and pathogenesis of AD.

The spectrum and changes of biopsy-proven kidney diseases in Chinese children.

AIM: The study aimed to investigate the spectrum of biopsy-proven kidney disease in Chinese children. METHODS: Records of children 0-17 years old who underwent native kidney biopsy from June 1st, 2013 to December 31st, 2018 in the national inpatients' database of China were analyzed. Biopsy-proven kidney diseases of different sex, age groups, and diagnosis, and the changing patterns of kidney disease compared with the previous study were analyzed. RESULTS: A total of 21,311 patients from 232 hospitals with a median age of 11.34 years were included. Immunoglobulin A vasculitis with nephritis (IgAVN) was the most common pathological finding [29.17%, 95% confidence interval (confidence interval, CI) = 28.56-29.78], followed by IgA nephropathy (IgAN) (22.70%, 95% CI = 22.14-23.27). IgAN was the most common finding in patients with hematuria (60.75%, 95% CI = 58.83-62.65], proteinuria (33.43%, 95% CI = 30.54-36.42), and hematuria plus proteinuria (62.77%, 95% CI = 56.19-69.02). Minimal change disease was the most common finding (40.69%, 95% CI = 39.41-41.98) in nephrotic syndrome. The proportion of IgAVN in patients with biopsy-proven glomerular disease increased year by year during 2013-2018 (p for trend < 0.001) and was higher than that of 2004-2014 [29.41% (95% CI = 29.10-29.72) in 2013-2018 vs. 13.35% (95% CI = 12.97-13.73) 2004-2014, p < 0.001]. The proportion of hepatitis B virus associated nephritis during 2013-2018 was lower than that of  2004-2014 [0.44% (95% CI = 0.36-0.54) in 2013-2018 vs. 0.87% (95% CI = 0.67-1.10) in 2004-2014, p < 0.001]. CONCLUSIONS: IgAVN and IgAN were the most common types of pathological findings in children who underwent kidney biopsies from 2013 to 2018. The pathological spectrum of kidney biopsy changed over time.

A copula-based security risk evaluation and probability calculation for water-energy-food nexus.

Water-energy-food (WEF) are essential for human survival and development and they interact complexly. The research on Water-energy-food-coupling security risk (WEF-CSR) is crucial to promoting multi resource collaborative management. In this study, a comprehensive index system was constructed using three dimensions: reliability (Ra), coordination (C), and resilience (Rs). We selected the middle and upper reaches of the Yellow River Basin in China to study WEF-CSR conflicts, coupled with the Copula method of risk probability calculation. The results showed that: 1) from 2005 to 2021, the WEF-CSR index in the study area showed a progressively increasing trend, with a mean value of 0.49 in a critical safety state and lower values in the upper reaches of Ningxia and Gansu provinces. 2) The Ra-indexes in the criterion layer is not clearly affected by resource endowment conditions between annual periods; C-indexes are growing rapidly, with their annual growth rate four times as fast as the Ra-indexes, and Rs-indexes growing at about 2.7 times faster. 3) "Energy consumption per capita, carbon emissions, and water-related indicators" are the six main limiting factors, with a combined impediment degree of over 35 %, water resources are major constraint. 4) The Ra-C, C-Rs, and Ra-C-Rs indexes are well fitted by Clayton copula, and the C-Rs indexes are well fitted by Frank copula. The three-dimensional joint distribution risk probability, Ra-C-Rs (Ra ≤ 0.4, C ≤ 0.4, Rs ≤ 0.4) is 0.29. When the Ra or C indexes increases, the probability of unsafe Rs rises to 40 %-50 %, meaning future development must emphasize synergy, especially in Rs. In future, the five provinces in the middle and upper reaches of the Yellow River should focus on reducing energy pressure, improving water shortage conditions, and enhancing the overall resilience to avoid single-factor adverse conditions affecting WEF's coordinated and sustainable development.

A Model of Panic Buying and Workforce under COVID-19.

Allowing there to be an undersupply of medical resources and infection amid the social workforce, this paper proposes a theory to show how panic buying is induced and how bad the workforce status could be. By developing a novel general equilibrium model, we find that for any retail price that is higher than the buyer's reserve value, the buying competition will be induced and the medical resources supply will further be tightened. Moreover, if the transmission rate of COVID-19 surpasses the theoretical threshold that is proposed by this paper, the whole workforce in our simulated economy will inevitably be infected.

Benefits of non-work interactions with your supervisor: Exploring the bottom-up effect of employee boundary blurring behavior on abusive supervision.

Abusive supervision has long been found to have remarkably negative impacts on individual and organizational outcomes. Accordingly, prior studies have explored many organizational and supervisory predictors of abusive supervision and offered several interventions to reduce it. However, extant research lacks the bottom-up perspective to explore how employees can act to reduce abusive supervision, which is an important factor that enriches abusive supervision literature and helps employees protect themselves from being abused. Drawing on self-disclosure theory, we develop a model of whether and how employee boundary blurring behavior may protect them from being abused by their supervisors. Specifically, we conducted two studies to test the theoretical model, including a scenario-based experimental study and a multi-source, multi-wave field study. The results reveal a negative indirect effect of employee boundary blurring behavior on abusive supervision via supervisor liking toward the employee. By uncovering employee boundary blurring behavior as an antecedent of abusive supervision, we enrich the abusive supervision literature with a bottom-up behavioral strategy for employees to proactively protect themselves from being abused. We hope our findings will encourage future studies to identify boundary conditions and other solutions for employees to minimize the risk of being abused.

Association of insurance status with chronic kidney disease stage at diagnosis in children.

BACKGROUND: Whether medical insurance impacts the timely diagnosis in chronic kidney disease (CKD) children is unknown. We aim to examine the extent to which insurance is associated with access to timely diagnosis and different stages of CKD among a large population of children in China. METHODS: A retrospective, cross-sectional study based on China's national hospitalized record database was carried out. Children aged 0-17 years diagnosed as CKD stages 1-5 between June 1, 2013, and December 31, 2018, were included. A diagnosis of advanced CKD stage (CKD stage 4 or 5) was the primary outcome. Multivariable logistic regression model adjusted for age, sex, cross-regional hospitalization, year of diagnosis, and cause of CKD was used to assess the association between insurance status and the stage of CKD when diagnosed. RESULTS: A total of 10,256 children (median [interquartile range, IQR] age, 12.4 [7.9, 15.4] years) were included. There were 4716 (46.0%) uninsured children in the included population. The insurance coverage was highest in children 13-17 years old (60.9%). The hospitalized charge was highest in stage 5 uninsured children (median [IQR], ¥13,000.89 [7640.63, 24,585.00]). More uninsured children are diagnosed in CKD stage 4 or 5 (48.1%) than insured children (47.5%). Uninsured children had higher odds (odds ratio [OR] 1.20, [95% CI, 1.08-1.32]) of receiving a diagnosis of CKD stage 4 or 5 compared with insured children. CONCLUSIONS: Lack of medical insurance was associated with a more advanced stage of CKD when diagnosed in hospitalized children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Zebularine protects against blood-brain-barrier (BBB) disruption through increasing the expression of zona occludens-1 (ZO-1) and vascular endothelial (VE)-cadherin.

Blood-brain-barrier (BBB) disruption is an important pathological characteristic of ischemic stroke (IS) and mainly results from dysfunction of brain vascular endothelial cells and tight junctions. Zebularine is a novel inhibitor of DNA methyltransferase (DNMT). Here, we assessed its effects on BBB disruption in IS. Firstly, we reported that Zebularine maintained BBB integrity in middle cerebral artery occlusion (MCAO) mice by increasing the expressions of zona occludens-1 (ZO-1) and vascular endothelial (VE)-cadherin. Importantly, we found that Zebularine reduced the production of pro-inflammatory cytokines, attenuated brain edema, and improved neurological deficits. In in vitro experiments, the bEnd.3 brain endothelial cells were exposed to oxygen and glucose deprivation/reoxygenation (OGD/R), and the protective effects of Zebularine were assessed. Our findings demonstrated that Zebularine prevented OGD/R-induced cytotoxicity by reducing the release of lactate dehydrogenase (LDH). Additionally, Zebularine protected bEnd.3 cells against OGD/R-induced hyper-permeability and reduction of trans-endothelial electrical resistance (TEER). Notably, we found that treatment with Zebularine activated the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway by increasing the phosphorylation of adenosine monophosphate-activated protein kinase α (AMPKα). Blockage of AMPKα using its specific inhibitor compound C abolished the beneficial effects of Zebularine in mitigating endothelial hyper-permeability by reducing the expressions of ZO-1 and VE-cadherin. These findings suggest that the protective effects of Zebularine against OGD/R-induced endothelial hyper-permeability are mediated by the activation of AMPKα. In conclusion, our study sheds light on the potential application of Zebularine in the treatment of IS.

Knockdown of circHECTD1 inhibits oxygen-glucose deprivation and reperfusion induced endothelial-mesenchymal transition.

Ischemic stroke (IS) has become a cerebrovascular disease which seriously threatens the elderly people. It has been reported that circRNAs participate in multiple diseases, including IS. However, the role of circHECTD1 in IS remains largely unknown. To mimic IS in vitro, human cerebral microvascular endothelial cells (HCMECs) were treated with oxygen glucose deprivation/reperfusion (OGD/R). Meanwhile, MCAO mouse model was established to detect the expression of circHECTD1 in IS. qRT-PCR and western blot were used to test gene and protein expressions, respectively. CCK-8 assay was used to investigate the cell viability. Moreover, cell migration and tube formation were assessed by transwell and tube formation assays. In addition, RIP and luciferase assay were performed to explore the association among circHECTD1, miR-335 and NOTCH2. CircHECTD1 was significantly upregulated in IS. OGD/R significantly induced EndoMT in HCMECs, while knockdown of circHECTD1 notably reversed this phenomenon. In addition, silencing of circHECTD1 remarkably reversed OGD/R-induced promotion of HCMEC tube formation and migration. Meanwhile, circHECTD1 upregulated the level of NOTCH2 through binding with miR-335. Furthermore, miR-335 inhibited the process of EndoMT in IS via targeting NOTCH2. In summary, circHECTD1 knockdown significantly alleviated EndoMT process in HCMECs via mediation of miR-335/NOTCH2 axis. Thus, circHECTD1 might act as a potential target against IS.

Risk Factors for Progression of Chronic Kidney Disease With Glomerular Etiology in Hospitalized Children.

Aim: To Identify association between risk factors to Chronic kidney disease (CKD) stage 5 in children with glomerular diseases in children in China. Methods: The Hospital Quality Monitoring System database was used to extract data for the study cohort. The primary outcome included progression to CKD stage 5 or dialysis. Cox regression was used to assess potential risk factors. Patients with lower stages (CKD stage 1 and 2) and higher stages (CKD stage 3 and 4) at baseline were analyzed separately. Results: Of 819 patients (4,089 hospitalization records), 172 (21.0%) patients reached the primary outcome during a median followed-up of 11.4 months. In the lower stages group, factors associated with the primary outcome included older age [Hazard Ratio (HR), 1.21; 95% confidence interval (CI), 1.10-1.34] and out-of-pocket payment (HR, 4.14; 95% CI, 1.57-10.95). In the higher stages group, factors associated with the primary outcome included CKD stage 4 (HR, 2.31; 95% CI, 1.48-3.62) and hypertension (HR, 1.99; 95% CI, 1.29-3.07). The medical migration rate was 38.2% in this study population. Conclusion: There are different risk factors for progression to the primary outcome in different stages in CKD with glomerular etiology. Further prospective studies are needed to assess these risk factors. The high medical migration rate reflected the regional disparities in the accessibility of pediatric kidney care between regions.

A Study on Relationship of Hounsfield Units Value on Non-contrast Computer Tomography and Recanalization of Intravenous Thrombolysis.

OBJECTIVE: The objective of this study is to determine whether the administration of intravenous alteplase would be beneficial or futile to patients with acute ischemic stroke caused by large vessel occlusion (LVO) before endovascular treatment (EVT) and determine the relationship between Hounsfield units (HU) in non-contrast computed tomography (NCCT) and recanalization by alteplase. METHODS: We performed a retrospective analysis of patients with acute ischemic stroke caused by LVO who received intravenous thrombolysis (IVT) or followed by EVT at our center during November 2016 and October 2020. The clinical characteristics and imaging features of patients who achieved recanalization after IVT, and those who did not, were compared. RESULTS: Forty-three eligible patients were enrolled; 12 achieved recanalization by IVT. Baseline clinical characteristics did not differ between patients of the recanalization and non-recanalization groups. HU in the NCCT were estimated and statistically significant maximum and mean values of the ipsilateral middle cerebral artery (MCA) were found between the groups (P< 0.05). The results hint that patients in the non-recanalization group have a higher rHU and δHU value of the ipsilateral MCA compared with recanalization group (P< 0.05). With regards to the receiver operator characteristic (ROC) curve, we demonstrated that a high HU value of the ipsilateral MCA could be a predictor for non-recanalization by IVT. CONCLUSION: Patients suffering LVO stroke are less likely to obtain recanalization by IVT with a high HU value of the ipsilateral MCA. It is feasible to screen patients with LVO using HU for direct EVT.

Energy-water security challenge: Impact of energy production on water sustainable developments in Northwest China in 2017 and 2030.

Energy consumption has gradually become an important factor affecting the sustainable use of regional water resources, especially in areas with abundant energy but scarce water. In this research, the water consumption for energy production in arid Northwest China (NWC) in 2017 and 2030 was evaluated, and the virtual water (VW) transfer embodied in the energy trade was also calculated based on a large amount of data collected from multiple sources. The results showed that the energy-related water consumption in NWC in 2017 was 2.6 billion m3, accounting for approximately 3.4% of the total regional water consumption and 61.8% of the total regional industrial water consumption. This value is projected to reach 8.6 billion m3 in 2030 under a normal water consumption scenario (BAU scenario), and 5.4 and 3.6 billion m3 under a regular water-saving scenario (RWS scenario) and enhanced water-saving scenario (EWS scenario), respectively. In 2017, except for Qinghai and Gansu, the other province in the study area was a VW exporter and the total VW output volume was 710.3 million m3, accounting for 26.9% of the total water consumption for energy production, this ratio will reach approximately 60% in 2030 due to the expansion of energy industry. In addition, based on our research, the available water in four provinces cannot meet the future energy requirements under EWS scenario owing to the water shortage, however, different energy development strategies need to be selected faced with the different types of water shortage condition. This study also proposed some countermeasures to ensure the coordinated development of regional water and energy.