Search

Abstract Background Debates persist on the optimal surgical approach for treating Periprosthetic joint infection (PJI) following total hip arthroplasty (THA). This meta-analysis aimed to compare the reinfection rate of one-stage revision versus two-stage revision for PJI after THA. Methods A comprehensive search was performed in four databases (PubMed, Embase, Web of Science, and Cochrane Library) to locate articles that assessed the reinfection rate of one-stage revision compared to two-stage revision. Meta-analyses of reinfection rate were performed. Results A total of 14 articles including of 1429 patients were chosen for inclusion in this meta-analysis, with 561 patients in the one-stage group and 868 patients in the two-stage group. The meta-analysis of the 14 trials revealed that there was no statistically significant disparity in the reinfection rate between the two groups(OR = 1.34, 95% CI 0.92 ~ 1.93, P = 0.12, I2 = 0). A subgroup analysis was conducted based on the presence of a well-defined algorithm for decision making in either a one-stage or two-stage revision. There was no statistically significant difference in reinfection rate between one-stage and two-stage revision if there was a decision algorithm(OR = 0.83, 95% CI 0.44 ~ 1.54, P = 0.55, I2 = 0). If not, the reinfection rate of one-stage revision was significantly higher than that of two-stage revision(OR = 1.79, 95% CI 1.11 ~ 2.88, P = 0.02, I2 = 0). Postoperative hip function score was significantly better in the one-stage revision group than that of the two-stage revision group(SMD = 0.54, 95% CI 0.31 ~ 0.78, P

Abstract Clean fracturing fluid exhibits desirable characteristics, such as low residue, easy flowback, minimal reservoir damage, and favorable rheology, making it highly adaptable. However, challenges remain in terms of high cost, large consumption, and poor stability. Hence, this study focuses on incorporating SiO2 nanoparticles into clean fracturing fluid to develop a novel nano‐modified system. Experimental tests were conducted to analyze the impact of mass fractions of hexadecyltrimethylammonium chloride (CTAC), sodium salicylate (Nasal), and SiO2 nanoparticles on the viscosity of the solution. The results indicate a significant increase in viscosity with higher mass fractions of SiO2. A nano‐modified clean fracturing fluid composition of 1.5 wt% CTAC, 0.4 wt% Nasal, and 0.1 wt% SiO2 was selected as it meets the technical specifications for fracturing fluid while exhibiting excellent elastic modulus (2.279 Pa) and viscous modulus (0.818 Pa), thereby displaying superior viscoelastic properties. Furthermore, the system maintains a viscosity above 20 mPa.s under temperature (70°C) and shear stress (170 s−1), indicating robust temperature and shear resistance to meet the demands of downhole fracturing and proppant transport. Based on rheological experimental data, a Carreau rheological model was established for the nano‐modified clean fracturing fluid. Considering particle interaction, wall blockage, and fluid filtration, a settlement model was modified with a correction coefficient, leading to the construction of a mathematical model for correcting proppant particle settling in fractures. The error between measured settlement velocity and calculated values remained within 10%. Finally, the migration law of proppant is studied, and the settlement law of proppant in fracturing fluid and fracture is clarified.

Summary: Background: Given the distinctive physiological characteristics of pregnant women, non-pharmacological therapies are increasingly being used to improve depressive and anxiety symptoms. Our objective was to explore and compare the impact of various non-pharmacological interventions in improving depressive and anxiety symptoms, and to identify the most effective strategies for pregnant women with depressive and/or anxiety symptoms. Methods: We conducted a systematic search of PubMed, Embase, the Cochrane Library, and Web of Science for randomized controlled trials (RCTs) that compared non-pharmacological interventions to usual care, from the inception of each database up to October 5, 2024. We included pregnant women with singleton pregnancies who, at baseline, exhibited early signs of depressive and/or anxiety symptoms but did not meet clinical diagnostic criteria or exceed the threshold for clinically significant symptoms. We excluded pregnant women diagnosed with schizophrenia, bipolar disorder, or severe acute psychiatric conditions, those with a history of substance abuse, and those undergoing in vitro fertilisation. We performed both pairwise meta-analyses and random-effects network meta-analyses (NMAs), calculating standardised mean differences (SMDs) with 95% credible intervals (CrI). We used the surface under the cumulative ranking probability curve (SUCRA) to estimate treatment ranking probabilities. The outcomes were assessed in two groups of participants: a high-risk pregnancy group, including pregnant women with depressive and/or anxiety symptoms and high-risk pregnancies (defined as having a history of miscarriage, pregnancy complications such as gestational hypertension, gestational diabetes mellitus, or preeclampsia, and advanced maternal age (i.e., over 35 years old); and a healthy group, including participants who exhibited depressive and/or anxiety symptoms only during pregnancy and did not have other high-risk pregnancy conditions or underlying health issues. This study is registered with PROSPERO, CRD42024523053. Findings: We included 101 studies (92 RCTs and 9 quasi-RCTs) involving a total of 15,330 participants across 11 interventions (mindfulness, education, counseling, cognitive behavioral therapy, muscle acupoint therapy, relaxation, mind-body exercise, psychotherapy, foetal movement counting, physical exercise, and music). Among the studies included in this analysis, 73 studies exhibited a low risk of bias, 9 studies had an unclear risk of bias, and 19 studies demonstrated a high risk of bias. The results indicate that, for both high-risk pregnancy population and healthy populations, mindfulness therapy was found to be an effective non-pharmacological treatment for significantly improving depressive and anxiety symptoms in pregnant women compared with control groups. For pregnant women with depressive symptoms, mindfulness therapy (SUCRA = 80%; SMD = −0.86, 95% CrI = −1.2, −0.52; Nn = 598), cognitive behavioral therapy (CBT) (SUCRA = 65%; SMD = −0.69, 95% CrI = −1.0, −0.39; Nn = 712), and education therapy (SUCRA = 48%; SMD = −0.54, 95% CrI = −0.86, −0.23; Nn = 2285) all significantly improve depressive symptoms. In the subgroup analysis of healthy populations, muscle acupoint therapy (SUCRA = 77.17%; SMD = −0.89, 95% CrI = −1.55, −0.23; N = 99) and mind-body exercise (SUCRA = 47.54%; SMD = −0.53, 95% CrI = −0.88, −0.19; N = 352) also significantly reduce depressive symptoms. Subgroup analysis shows that, in addition to mindfulness therapy, mind-body exercises (SUCRA = 67.43%; SMD = −0.97, 95% CrI = −1.61, −0.33; N = 382) and cognitive-behavioral therapy (SUCRA = 52.60%; SMD = −0.74, 95% CrI = −1.38, −0.09; N = 480) may also be effective in alleviating anxiety symptoms among healthy pregnant women. Interpretation: Our findings indicate that mindfulness therapy significantly reduces the risk of depressive and anxiety symptoms in both high-risk pregnancy population and healthy populations. Therefore, when selecting non-pharmacologic therapies for managing depressive and anxiety symptoms during pregnancy, it is recommended that this therapy be considered. We cannot overlook the limitations of this study. For example, some interventions, such as muscle acupoint therapy for depressive symptoms and relaxation therapy for anxiety symptoms, have limited literature support. Additionally, the diversity of conditions within the high-risk pregnancy population and the high heterogeneity observed in certain interventions are also issues that require attention. These factors may affect the accuracy of the data results. Although we have employed reliable methods to address these issues, the findings of this study should still be interpreted with caution. Funding: None.

Treatment methods in traditional Chinese medicine (TCM) are foundational to their theoretical, methodological, formulaic, and pharmacological systems, significantly contributing to syndrome differentiation and therapy. The principle of “promoting urination to regulate bowel movements” is a common therapeutic approach in TCM. The core concept is “promoting the dispersion and drainage of water dampness, regulating urination to relieve diarrhea,” yet its scientific underpinning remains unclear. Modern medical treatment for watery diarrhea primarily focuses on electrolyte replenishment, as diuretics may lead to dehydration and other side effects. Some reports suggest that this TCM approach lacks scientific validity. Microecology, an area associated with the origins of TCM, is closely related to the development, diagnosis, and treatment of diarrhea. The renal-intestinal axis offers a molecular biological basis for examining associated pathological mechanisms, advancing therapeutic targets such as “treating the intestine to address kidney issues” and highlighting the interactions within the “renal-intestinal microbiota-liquid metabolism” framework, thus providing an endogenous mechanism to support “treating the intestine through the kidney.” An increasing number of studies have shown that the intestinal microbiota and its metabolites, as unique mediators, are involved in the physiological and pathological changes of the body. Therefore, this study explores the relationship between fluid metabolism and diarrhea from the perspective of the intestinal microbiota and its metabolites, aiming to elucidate the biological mechanisms underlying the “promoting urination to regulate bowel movements” therapeutic approach and to clarify the scientific basis for treating diarrhea via the renal-intestinal axis. This research provides new insights for the study of TCM microbiology.

Negative air ions (NAIs) play an important role in human well-being, serving as key indicators of air cleanliness and contributing to both psychological and physiological health. This study aims to investigate the factors influencing NAI concentration in urban and suburban forest parks, enhancing our understanding of the correlation between NAIs and environmental factors. Songjiacheng Urban Forest Park and Runyang Wetland Suburban Forest Park in Yangzhou City were selected as the subjects of this research, and continuous measurements of NAI concentration were conducted over a three-year period. Additionally, seven meteorological factors were monitored. A random forest model was employed to analyze and compare the data from the two forest parks, identifying the environmental factors with significant impacts on NAI concentration. The results indicate that in Songjiacheng Urban Forest Park, NAIs exhibited significant sensitivity to temperature, followed by atmospheric pressure. Conversely, in Runyang Wetland Suburban Forest Park, PM2.5 (particulate matter 2.5) exerted the greatest impact on NAIs, followed by humidity. We conducted a thorough analysis of data to explore the intricate connections between negative air ions and a variety of environmental factors within two urban forest parks. Our findings have significantly broadened our perspective on the characteristics of Negative Air Ions (NAIs) and their management implications within these urban green spaces. This enhanced understanding is pivotal for developing more effective strategies for environmental stewardship and the preservation of these vital urban ecosystems.

Abstract Aims The long‐term cost‐effectiveness of MitraClip in heart failure patients with secondary mitral regurgitation is still unclear. This study aimed to evaluate the long‐term cost‐effectiveness of MitraClip added to guideline‐directed medical therapy vs. guideline‐directed medical therapy alone in heart failure patients with secondary mitral regurgitation from the perspective of the healthcare systems of mainland China, the United Kingdom, Germany, and the United States. Methods and results A two‐stage (decision + Markov) model was built. Health utilities were defined by the New York Heart Association class, heart failure re‐hospitalization, and death and were calculated based on the 5 year follow‐up results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation trial. Direct healthcare costs were derived from the nationally representative data. Future utilities and costs were discounted at country‐specific rates. The primary outcome was the lifetime incremental cost‐effectiveness ratio. The mean age of the base case in our model was 72.2 years. Over a lifetime horizon, treatment with MitraClip was associated with 829 fewer heart failure re‐hospitalizations per 1000 treated patients. The MitraClip treatment was associated with incremental quality‐adjusted life‐year gains of 0.71, 0.76, 0.78, and 0.78, as well as incremental cost‐effectiveness ratios of ¥468 462, £28 910, €26 045, and $71 199 per quality‐adjusted life‐year for a lifetime horizon in mainland China, the United Kingdom, Germany, and the United States, respectively. In probabilistic sensitivity analysis, 0.2%, 59.4%, 99.6%, and 84.7% of patients were cost‐effective in mainland China, the United Kingdom, Germany, and the United States at the country‐specific willingness‐to‐pay thresholds. Conclusions MitraClip + guideline‐directed medical therapy was cost‐effective in heart failure patients with secondary mitral regurgitation in the United Kingdom, Germany, and the United States, but not in mainland China from the perspective of the national healthcare system.

Abstract Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT (Cas12a-based One-for-all High-speed Isothermal Test), a one-pot CRISPR-based assay for indel detection. Leveraging an engineered AsCas12a protein variant with high mismatch tolerance and broad PAM scope, CoHIT can use a single crRNA to detect multiple NPM1 gene c.863_864 4-bp insertions in acute myeloid leukemia (AML). After optimizing multiple parameters, CoHIT achieves a detection limit of 0.01% and rapid results within 30 minutes, without wild-type cross-reactivity. It successfully identifies NPM1 mutations in 30 out of 108 AML patients and demonstrates potential in monitoring minimal residual disease (MRD) through continuous sample analysis from three patients. The CoHIT method is also competent for detecting indels of KIT, BRAF, and EGFR genes. Integration with lateral flow test strips and microfluidic chips highlights CoHIT’s adaptability and multiplexing capability, promising significant advancements in clinical cancer diagnostics.

Heterozygous mutations in the FOXG1 gene manifest as FOXG1 syndrome, a severe neurodevelopmental disorder characterized by structural brain anomalies, including agenesis of the corpus callosum, hippocampal reduction, and myelination delays. Despite the well-defined genetic basis of FOXG1 syndrome, therapeutic interventions targeting the underlying cause of the disorder are nonexistent. In this study, we explore the therapeutic potential of adeno-associated virus 9 (AAV9)-mediated delivery of the FOXG1 gene. Remarkably, intracerebroventricular injection of AAV9-FOXG1 to Foxg1 heterozygous mouse model at the postnatal stage rescues a wide range of brain pathologies. This includes the amelioration of corpus callosum deficiencies, the restoration of dentate gyrus morphology in the hippocampus, the normalization of oligodendrocyte lineage cell numbers, and the rectification of myelination anomalies. Our findings highlight the efficacy of AAV9-based gene therapy as a viable treatment strategy for FOXG1 syndrome and potentially other neurodevelopmental disorders with similar brain malformations, asserting its therapeutic relevance in postnatal stages.

Abstract Background The triglyceride-glucose (TyG) index and blood pressure (BP) are correlated and serve as risk factors for cardiovascular disease (CVD). The potential impact of BP status on the association between the TyG index and CVD risk remains uncertain. This study aims to investigate the relationships between the TyG index and incident CVD in Chinese middle-aged and elderly adults, considering variations in BP status among participants. Methods 6558 participants (mean age: 58.3 (± 8.7) years; 46.0% were men) without prevalent CVD were recruited from the China Health and Retirement Longitudinal Study. Participants were divided into three groups according to their systolic blood pressure (SBP) levels (

Abstract Shox2 plays a vital role in the morphogenesis and physiological function of the sinoatrial node (SAN), the primary cardiac pacemaker, manifested by the formation of a hypoplastic SAN and failed differentiation of pacemaker cells in Shox2 mutants. Shox2 and Nkx2-5 are co-expressed in the developing SAN and regulate the fate of the pacemaker cells through a Shox2-Nkx2-5 antagonistic mechanism. Here we show that simultaneous inactivation of Nkx2-5 in the SAN of Shox2 mutants (dKO) rescued the pacemaking cell fate but not the hypoplastic defects, indicating uncoupling of SAN cell fate determination and morphogenesis. Single-cell RNA-seq revealed that the presumptive SAN cells of Shox2 -/- mutants failed to activate pacemaking program but remained in a progenitor state preceding working myocardium, while both wildtype and dKO SAN cells displayed normal pacemaking cell fate with similar cellular state. Shox2 thus acts as a safeguard but not a determinant to ensure the pacemaking cell fate through the Shox2-Nkx2-5 antagonistic mechanism, which is segregated from its morphogenetic regulatory function in SAN development.

Abstract Background The prognosis of patients with light‐chain amyloidosis (AL) has improved markedly in the past decade in China; whether the current staging systems are suitable to predict the overall survival (OS) of the patients remains undetermined. Methods Based on 980 biopsy‐proved AL patients with 5‐year follow‐up from China Registration Network for Light‐chain Amyloidosis, we evaluated the efficacy of existing staging systems and developed a new stratification model. This involved analyzing parameters such as N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) thresholds and estimated glomerular filtration rate (eGFR). Results We found that 30% patients were classified as stage I, 25% as stage II, 26% as stage III, and 19% as stage IV disease using the Mayo 2012 staging system, with varying median OS values. However, the observed median OS values were notably higher than previously reported. By incorporating NT‐proBNP thresholds and eGFR values, we developed a four‐stage score system. With this new model, 41.6% patients were reclassified to stage I, 34.3% to stage II, 17.8% to stage III, and 6.3% to stage IV disease, with adjusted median OS values. Conclusion The new stratification model exhibited improved consistency compared to traditional staging systems. It effectively identified patients with the best and worst prognoses, even among those receiving comprehensive treatment. Specifically, NT‐proBNP levels exceeding 9000 pg/mL combined with an eGFR less than 60 mL/min/1.73 m2 proved superior in prognosticating patient outcomes. Overall, the median OS of AL amyloidosis patients in China has significantly improved, underscoring the need for tailored prognostic models in clinical practice.

IntroductionThis meta-analysis seeks to evaluate the efficacy and safety of endoscopic breast-conserving surgery (E-BCS) compared to conventional breast cancer surgery (C-BCS) in patients diagnosed with early-stage breast cancer.Materials and methodsFour databases (Medline, Embase, Web of Science and CENTRAL) were searched published from establishment of database to January 30,2024, for articles studying E-BCS compared to C-BCS in patients diagnosed with early-stage breast cancer. Meta-analyses of procedure time, blood loss, length of incision, drainage duration, total postoperative drainage volume, average duration of hospital stay, positive rate of margin, complication rate, recurrence rate, metastasis rate and cosmetic scoring were performed.ResultsTotally 11 studies were included for meta-analysis. Compared with C-BCS, E-BCS exhibited significantly reduced incision length (WMD = -6.44, 95%CI: -10.78 to -2.11, P=0.004, I2 = 99.0%) and superior cosmetic scoring (WMD = 2.69, 95%CI: 1.46 to 3.93, P=0.001, I2 = 93.2%), but had significantly longer operation time (WMD = 34.22, 95%CI: 20.89~47.55, P=0.000, I2 = 90.7%) and blood loss (WMD = 3.65, 95%CI: -3.12 to 10.43, P=0.291, I2 = 86.8%). There was no significant difference in terms of recurrence rate, metastasis rate, positive rate of tumor resection margins, drainage duration, drainage volume, complication rate and hospital days.ConclusionsOur research findings indicate that E-BCS is a viable and secure method for treating breast cancer in its early stages. E-BCS provides distinct advantages in terms of the length of the incision and the aesthetic result, without demonstrating an elevated recurrence rate or metastasis rate.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024535164, identifier CRD42024535164.

Abstract An intrinsic link between metabolism and function in immune cells, and in particular macrophages, has been well established recently. However, the molecular mechanisms controlling the metabolic switch in these sentinel cells for their integral roles in host defense, inflammation, homeostasis, and pathogenesis remain largely unknown. Here, we identify the master transcription factor NF-κB RelA as a vital cell-intrinsic checkpoint restricting aerobic glycolysis to favor mitochondrial oxidative phosphorylation (OXPHOS) and “M2” activation (alternative anti-inflammatory and pro-tumorigenic activation, in contrast to classical pro-inflammatory and anti-tumor M1 activation) of macrophages under oncogenic stress. RelA specific knockdown or genetic deletion in macrophages causes metabolism to shift away from OXPHOS toward glycolysis, resulting in drastically decreased oxygen consumption but significantly increased lactate and ATP production. The metabolic change in RelA deficient cells is associated with the decrease in the expressions of the OXPHOS gene SCO2 as well as the M2 marker and function genes arginase-1 and VEGF. These data suggest that RelA induces SCO2 expression to enhance OXPHOS and restrict glycolysis in macrophages for their pro-tumorigenic activation.

Abstract Background The prognostic value of triglyceride-glucose (TyG) index in general type 2 diabetes mellitus (T2DM) patients is still unclear. Therefore, we aimed to determine the associations between TyG and all-cause/cause-specific death in a T2DM cohort and explore whether such associations would be modified by age. Methods A total of 3,376 patients with T2DM from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were selected and divided into the younger group (

Adipose-derived stem cells (ADSCs) have emerged as a promising resource for craniofacial bone regeneration due to their high abundance and easy accessibility, significant osteogenic potential, versatile applications, and potential for personalized medicine, which underscore their importance in this field. This article reviews the current progress of preclinical studies that describe the careful selection of specific ADSC subpopulations, key signaling pathways involved, and usage of various strategies to enhance the osteogenic potential of ADSCs. Additionally, clinical case reports regarding the application of ADSCs in the repair of calvarial defects, cranio-maxillofacial defects, and alveolar bone defects are also discussed.

Abstract Gender differences in heart failure (HF), ranging from epidemiological and pathophysiological factors to therapeutic response and prognosis, have been well documented in Western countries, especially in Europe and North America. The above gender differences in HF found in Westerners are rarely investigated in Asians. In this review, we explore the worrying knowledge gap on the gender differences in HF that existed in Asia in contrast with Western populations based on the following four aspects: epidemiology, risk factors, therapy, and prognosis. Finally, we conclude that investigations of gender differences in HF in Asia lag behind those in Europe and North America. Future work is required to establish and better use the high‐level, population‐based cohorts and develop our own high‐quality, convincing clinical trials to deliver robust gender‐specific conclusions in Asia.

Objectives There was no evidence regarding the relationship between septic shock and tracheal injury scores. Investigate whether septic shock was independently associated with tracheal injury scores in intensive care unit (ICU) patients with invasive ventilation.Design Prospective observational cohort study.Setting Our study was conducted in a Class III hospital in Hebei province, China.Participants Patients over 18 years of age admitted to the ICU between 31 May 2020 and 3 May 2022 with a tracheal tube and expected to be on the tube for more than 24 hours.Primary and secondary outcome measures Tracheal injuries were evaluated by examining hyperaemia, ischaemia, ulcers and tracheal perforation by fiberoptic bronchoscope. Depending on the number of lesions, the lesions were further classified as moderate, severe or confluent.Results Among the 97 selected participants, the average age was 56.6±16.5 years, with approximately 64.9% being men. The results of adjusted linear regression showed that septic shock was associated with tracheal injury scores (β: 2.99; 95% CI 0.70 to 5.29). Subgroup analysis revealed a stronger association with a duration of intubation ≥8 days (p=0.013).Conclusion Patients with septic shock exhibit significantly higher tracheal injury scores compared with those without septic shock, suggesting that septic shock may serve as an independent risk factor for tracheal injury.Trial registration number ChiCTR2000037842, registered 03 September 2020. Retrospectively registered, https://www.chictr.org.cn/edit.aspx?pid=57011&htm=4.

Abstract Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function, and is associated with a high risk of death. Many pathological changes happen in the process of AKI, including crucial alterations to oxidative stress levels. Numerous efforts have thus been made to develop effective medicines to scavenge excess reactive oxygen species (ROS). However, researchers have encountered several significant challenges, including unspecific biodistribution, high biotoxicity, and in vivo instability. To address these problems, engineered nanoparticles have been developed to target oxidative stress and treat AKI. This review thoroughly discusses the methods that empower nanodrugs to specifically target the glomerular filtration barrier and presents the latest achievements in engineering novel ROS‐scavenging nanodrugs in clustered sections. The analysis of each study's breakthroughs and imperfections visualizes the progress made in developing effective nanodrugs with specific biodistribution and oxidative stress‐targeting capabilities. This review fills the blank of a comprehensive outline over current progress in applying nanotechnology to treat AKI, providing potential insights for further research.

Abstract Background N-terminal B-type natriuretic peptide (NT-proBNP) discriminates mortality risk in diabetes mellitus (DM) and in heart failure (HF) populations. Whether DM status modifies the association between NT-proBNP and all-cause mortality risk in ischemic HF is unknown. Methods This was a single-center, prospective cohort study conducted with 2287 ischemic HF patients. Subjects were divided into with DM group and without DM group. Multivariate Cox proportional-hazards models were conducted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). The product of DM status and NT-proBNP were used to assess the interaction. Propensity score matching analysis was used to verify the robustness of the results. Results Of 2287 ischemic HF participants, 1172 (51.2%) had DM. After a median follow-up of 3.19 years (7287 person-years), 479 (20.9%) of the participants died. After adjusting for the covariates, continuous NT-proBNP was more prominently associated with risk of mortality in HF patients with DM (HR: 1.65, 95% CI: 1.43–1.91) than those without (HR: 1.28, 95% CI: 1.09–1.50). A significant interaction of DM status and NT-proBNP was observed (P-interaction = 0.016). The relationships were consistent when NT-proBNP was considered as a categorical variable and in the propensity matching analysis. Conclusions DM status modified the association between NT-proBNP and all-cause mortality in ischemic HF patients, suggesting that NT-proBNP was more prominently associated with risk of mortality in patients with DM than those without. Future studies to clarify the mechanisms underlying these observations are needed.

Background Whether the association between pulse pressure (PP) and mortality varies with systolic blood pressure (SBP) in ischaemic heart failure (HF) with left ventricular systolic dysfunction (LVSD) is unknown.Objective To evaluate the association between PP and all-cause mortality in ischaemic HF patients with SBP status at admission.Patients and methods This prospective cohort study included 1581 ischaemic HF patients with LVSD. A total of 23.3% (n = 368) and 22.2% (n = 351) of the participants had SBP 140 mmHg, respectively, with more than 80% of participants being male. Restricted cubic spline was performed to determine whether a nonlinear relationship existed between PP and all-cause mortality risk. A multivariable Cox proportional hazards model was used to assess the association between PP and all-cause mortality.Results After a median of follow-up of 3.0 years, 257 events (16.4%) were observed in the cohort. There was a J-shaped relationship between PP and all-cause mortality (P value for nonlinearity = 0.020), with a risk nadir of approximately 46–49 mmHg. All-cause mortality risk varied with SBP status. Higher PP was associated with worse prognosis when the SBP was ≥110 mmHg, whereas the relationship did not reach statistical significance when the SBP was

The adoption of the UN 2030 Agenda and the Sustainable Development Goals is a landmark in international sustainability politics. For example, Europe has set ambitious targets to achieve 100 climate-neutral and smart cities by 2030. However, numerous case studies from different countries have found that accelerating the transition to net-zero carbon emissions is easily hampered by the lack of a coherent systems framework, and that implementation gaps remain at the community level. These barriers are often due to a lack of an adequate end-user (i.e., household) input and early planning participation. This work therefore aims to improve on conventional planning methods that do not reflect innovative technologies with uncertainty and may not be applicable due to the lack of community empowerment, which is a dynamic learning and intervention opportunity for end-users at different planning stages (i.e., outreach, survey, planning, implementation, management, and maintenance). Using the lessons learned from participatory action research, whereby the author was involved as a project director throughout the planning and design process, we identified a six-step cycle principle. The steps are (1) collective action commitments, (2) local values and resource identification, (3) carbon footprint inventory, (4) optimized integration of environment, economy, and energy action plans, (5) Flexible strategic energy system plans, and (6) digital performance monitoring. Ultimately, the outcomes provide application support for policymakers and planners and stimulate community engagement to contribute to the achievement of zero net carbon emissions.

BackgroundEctopic thyroid gland (ETG) is an uncommon clinical condition, presenting various challenges and limitations in its regulate diagnosis and treatment currently. This study aims to enhance our understanding of ETG and improve the strategies for its diagnosis and treatment.MethodsThe retrospective single-center study was conducted, encompassing clinical data from ETG patients screened at our institution between 2013 and 2022. Patients were categorized based on the location of the disease, and follow-ups were performed on each.ResultsThis study included a total of 47 patients who were confirmed to hav confirmed to have ETG. Among them, we found 29 cases of accessory thyroid and 18 cases of aberrant thyroid. Furthermore, 42 cases exhibited the single ETG, while 5 cases displayed the double ETG. The distribution of the ETG was as follows: 20 were lingual, 10 were submandibular, 10 were lateral cervical, 4 were thoracic mediastinal, 1 was esophageal, and 7 were ovarian. Of these cases, 22 patients underwent surgery, 18 received thyroid hormone replacement therapy, and 7 were placed under observation. All patients were followed up for 59.4 (12-117) months. No significant abnormalities were detected at the conclusion of the follow-up period.ConclusionETG is frequently observed in the head and neck, particularly in lingual. Accessory thyroid glands are commonly reported, with most cases being single ETG. Notably, these glands usually do not manifest specific clinical symptoms. Therefore, the appropriate and comprehensive examinations during the initial diagnosis are crucial to avoid misdiagnosis. Treatment should be individualized, and long-term follow-up is essential for managing ETG effectively.

Negative air ions (NAIs) are an important indicator of air cleanliness in an area, and play a vital role in promoting the psychological and physiological functions of the human body. However, there are few studies regarding the relationship between NAI concentration and various environmental factors in urban forests. Therefore, we established an observation point in the Zhuyu Bay Scenic Area in Yangzhou City and continuously measured concentration changes in NAIs for three years. At the same time, we also monitored 14 meteorological factors. A random forest model was used to determine the important environmental factors that affected changes in negative air ion concentrations from a non-comprehensive perspective, determine the prediction accuracy of the model, and screen out environmental factors that have a significant impact on negative air ions. The results showed that the environmental factor that NAIs were the most sensitive to in the Zhuyu Bay urban forest was humidity, followed by PM2.5, then wind direction, methane gas, and finally, temperature. Humidity was the most critical factor primarily because it directly affects the formation of NAIs in the environment and vegetation. We used big data to analyze the relationship between NAIs and environmental factors in forest parks. The results help deepen our understanding of NAIs characteristics and their application in urban forests.

Abstract A nomogram for assessing the risk of IgA vasculitis nephritis (originally termed Henoch–Schönlein purpura nephritis, HSPN) in IgA vasculitis (originally termed Henoch–Schönlein purpura, HSP) pediatric patients can effectively improve early diagnosis and prognosis of IgA vasculitis nephritis. However, currently, no nomogram is available. 246 IgA vasculitis and 142 IgA vasculitis nephritis Asian pediatric patients confirmed by renal biopsy were enrolled. Univariate and multivariate logistic regressions were performed to identify the independent risk factors and construct a series of predictive models. The receiver operating characteristic curve, calibration plot, decision curve analysis, net reclassification index and integrated discrimination index were used to screen the best model. Stratification analysis was applied to optimize model’s clinical utility. An external validation set was introduced to verify the predictive efficiency. The final predictive model was converted to nomogram for visual use. We identified age, duration of rash (Dor), D-dimer and IgG as independent risk factors and constructed four models as follows: AIDD (Age + IgG + Dor + D-dimer), AIDi (Age + IgG + D-dimer), AIDo (Age + IgG + Dor) and ADD (Age + Dor + D-dimer), which achieved the receiver operator characteristic curve (AUROC) of 0.931, 0.920, 0.856 and 0.907, respectively. Finally, AIDi model with an AUROC of 0.956 and 0.897 in internal and external validating sets was proposed as a novel predictive model. In stratification analysis by gender and histological grade, the AUROC of AIDi was 0.949 in female, 0.926 in male, 0.933 in mild histological grades and 0.939 in severe histological grades, respectively. AIDi nomogram is an effective and visual tool for assessing the risk of nephritis in IgA vasculitis Asian pediatric patients, regardless of IgA vasculitis nephritis histological grades and gender.

Abstract This study aimed to review the clinical significance of BRAFV600E mutations in pediatric papillary thyroid carcinoma (PTC). From 2018 to 2021, 392 pediatric thyroid operations were performed in the first affiliated Hospital of Zhengzhou University. Of these, 169 patients underwent their first operation in our hospital and were histopathologically diagnosed as papillary thyroid carcinoma. BRAFV600E gene mutation detection was performed in these 169 pediatric patients to investigate the correlation between BRAF gene mutations and clinicopathological features. Ninety-seven of our 169 patients had a BRAFV600E mutation, with a mutation rate of 57.4%. The incidence of BRAFV600E was higher in boys than in girls, and in the 13–18-year age group as compared with the 6–12-year age group (P

Digitalization has emerged as a new trend in healthcare, with great potential and creating many unique opportunities, as well as many challenges. Cardiovascular disease is one of the major causes of disease-related morbidity and mortality worldwide, and the threat to life posed by acute heart failure is evident. In addition to traditional collegiate therapies, this article reviews the current status and subdisciplinary impact of digital healthcare at the level of combined Chinese and Western medical therapies. It also further discusses the prospects for the development of this approach, with the objective of developing an active role for digitalization in the combination of Western and Chinese medicine for the management of acute heart failure in order to support maintenance of cardiovascular health in the population.

Abstract Epigenetic abnormalities play a crucial role in many tumors, including glioma. RNA methylation occurs as an epigenetic modification similar to DNA methylation and histone modification. m6A methylation is the most common and most intensively studied RNA methylation, which can be found throughout the RNA life cycle and exert biological functions by affecting RNA metabolism. The m6A modification is primarily associated with three types of protease, which are encoded by the writer, eraser and reader genes, respectively. It has been shown that the m6A methylation has close connections with the occurrence and development of many tumors, including glioma. In this study, the concept and the research progress of m6A methylation are reviewed, especially the role of m6A methylation in glioma. Moreover, we will discuss how glioma is paving the way to the development of new therapeutic options based on the inhibition of m6A deposition.

Abstract Background Lipoprotein(a) is genetically determined and increasingly recognized as a major risk factor for arteriosclerotic cardiovascular disease. We examined whether plasma lipoprotein(a) concentrations were associated with intraplaque neovascularization (IPN) grade in patients with carotid stenosis and in terms of increasing plaque susceptibility to haemorrhage and rupture. Methods We included 85 patients diagnosed with carotid stenosis as confirmed using carotid ultrasound who were treated at Guangdong General Hospital. Baseline data, including demographics, comorbid conditions and carotid ultrasonography, were recorded. The IPN grade was determined using contrast-enhanced ultrasound through the movement of the microbubbles. Univariate and multivariate binary logistic regression analyses were used to evaluate the association between lipoprotein(a) and IPN grade, with stepwise adjustment for covariates including age, sex, comorbid conditions and statin therapy (model 1), total cholesterol, triglyceride, low-density lipoprotein cholesterol calculated by Friedwald's formula, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B (model 2), maximum plaque thickness and total carotid maximum plaque thickness, degree of carotid stenosis and internal carotid artery (ICA) occlusion (model 3). Results Lipoprotein(a) was a significant predictor of higher IPN grade in binary logistic regression before adjusting for other risk factors (odds ratio [OR] 1.238, 95% confidence interval [CI] (1.020, 1.503), P = 0.031). After adjusting for other risk factors, lipoprotein(a) still remained statistically significant in predicting IPN grade in all model. (Model 1: OR 1.333, 95% CI 1.074, 1.655, P = 0.009; Model 2: OR 1.321, 95% CI 1.059, 1.648, P = 0.014; Model 3: OR 1.305, 95% CI 1.045, 1.628, P = 0.019). Lp(a) ≥ 300 mg/L is also significantly related to IPN compare to

Abstract Aims The aims of the current study were to evaluate the association between anaemia and all‐cause mortality according to chronic kidney disease (CKD) status and to explore at what level of haemoglobin concentration would the all‐cause mortality risk increase prominently among CKD and non‐CKD patients, respectively. Methods and results This is a prospective cohort study, and 1559 patients with ischaemic heart failure (IHF) were included (mean age of 63.5 ± 11.0 years, 85.8% men) from December 2015 to June 2019. Patients were divided into the CKD (n = 481) and non‐CKD (n = 1078) groups based on the estimated glomerular filtration rate of 60 mL/min/1.73 m2. In the CKD group, the incidence rate of all‐cause mortality in anaemic and non‐anaemic patients was 15.4 per 100 person‐years and 10.8 per 100 person‐years, respectively, with an incidence rate ratio of 1.42 (95% confidence interval: 1.00–2.02; P‐value = 0.05). In the non‐CKD group, the incidence rate of all‐cause mortality in anaemic and non‐anaemic patients was 9.8 per 100 person‐years and 5.5 per 100 person‐years, respectively, with an incidence rate ratio of 1.78 (95% confidence interval: 1.20–2.59; P‐value = 0.005). After a median follow‐up of 2.1 years, the cumulative incidence rate of all‐cause mortality in anaemic and non‐anaemic patients was 41.5% and 44.1% (P‐value = 0.05) in the CKD group, and 30.9% and 18.1% (P‐value

Abstract Background Inherited dilated cardiomyopathy (DCM) contributes to approximately 25% of idiopathic DCM cases, and the proportion is even higher in familial DCM patients. Most studies have focused on familial DCM, whereas the genetic profile of sporadic DCM in Chinese patients remains unknown. Methods Between June 2018 and September 2019, 24 patients diagnosed with idiopathic DCM without a family history were included in the present study. All patients underwent genetic screening for 80 DCM-related genes using targeted next-generation sequencing. Results By in silico analysis, 10 of 99 detected variants were considered pathogenic or likely-pathogenic, including seven TTN truncating variants (TTNtv), one in-frame deletion in TNNT2, one missense mutation in RBM20, and one frameshift deletion variant in FLNC. Of these variants, eight are reported for the first time. Conclusions Using targeted next-generation sequencing, potential genetic causes of idiopathic DCM were identified. Sarcomere mutations remained the most common genetic cause of inherited DCM in this cohort of sporadic Chinese DCM.

BackgroundUncontrolled hypertension rate was still high across China. This study develops and validates an index to help quantify the combination of socio-behavioral aspects to screen high-risk patients in uncontrolled hypertension in Chinese primary care.MethodsA cross-sectional study included 1,039 of patients with hypertension in the Chinese community. We assessed independent risk factors of uncontrolled blood pressure (defined as having a blood pressure ≥140/90 mmHg, even with antihypertensive therapy) and develop a risk prediction model.ResultsAmong the 1,039 patients (53.9% male, the average age was 61 ± 13 years), 452 (43.5%) were uncontrolled hypertensive. Multivariable analysis showed that worker (odds ratio, OR: 1.98, 95% CI: 1.46–2.69), no health insurance (OR: 3.47, 95% CI: 2.08–5.80), non-marital status (OR: 2.01, 95% CI: 1.35–3.27), and other socio-behavioral aspects were independent risk factors of uncontrolled hypertension, which were included the final prediction model (C-static: 0.781). With internal validation by the bootstrap method, the risk score showed good discriminating ability and predicting ability for the incidence of uncontrolled hypertension (C-static: 0.771).ConclusionsThis study showed that nearly half of the patients suffered from uncontrolled hypertension in the Chinese community. We established a prediction model with good predictability to help quantify the combination of socio-behavioral aspects and screen high-risk patients with uncontrolled hypertension.

Iron is an essential trace element for the human body, and its deficiency or excess can induce a variety of biological processes. Plenty of evidences have shown that iron metabolism is closely related to the occurrence and development of tumors. In addition, iron plays an important role in cell death, which is very important for the development of potential strategies for tumor treatment. Here, we reviewed the latest research about iron metabolism disorders in various types of tumors, the functions and properties of iron in ferroptosis and ferritinophagy, and new opportunities for iron-based on treatment methods for tumors, providing more information regarding the prevention and treatment of tumors.

Abstract Aims The aim of this study was to investigate the impact of digoxin use on the outcomes of patients with heart failure with reduced ejection fraction (HFrEF) and its possible interaction with atrial fibrillation or use of currently guideline‐recommended treatments in the real world in China. Methods and results Patients hospitalized with HFrEF from 45 hospitals participating in the China National Heart Failure Registration Study (CN‐HF) were enrolled to assess the all‐cause mortality, HF mortality, all‐cause re‐hospitalization, and HF re‐hospitalization associated with digoxin use. Eight hundred eighty‐two eligible HFrEF patients in the CN‐HF registry were included: 372 patients with digoxin and 510 patients without digoxin. Among them, 794 (90.0%) patients were followed up for the endpoint events, with a median follow‐up of 28.6 months. Kaplan–Meier survival analysis showed that the all‐cause mortality (P < 0.001) and all‐cause re‐hospitalization (P = 0.020) were significantly higher in digoxin group than non‐digoxin group, while HF mortality (P = 0.232) and HF re‐hospitalization (P = 0.098) were similar between the two groups. The adjusted Cox proportional‐hazards regression analysis demonstrated that digoxin use remained as an independent risk factor for increased all‐cause mortality [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.27–2.44; P = 0.001] and all‐cause re‐hospitalization (HR 1.27; 95% CI 1.03–1.57; P = 0.029) in HFrEF patients and the predictive value of digoxin for all‐cause mortality irrespective of rhythm or in combination with other guideline‐recommended therapies. Conclusions Digoxin use is independently associated with increased risk of all‐cause mortality and all‐cause re‐hospitalization in HFrEF patients.

PDLIM2 is repressed epigenetically in lung cancers, which are frequently resistant to anti-PD-1/PD-L1 and chemotherapy. Here, the authors describe the mechanism through which epigenetic restoration of PDLIM2 synergises with anti-PD-1 and chemotherapy in lung cancers.

Lipoprotein (a) [Lp(a)] is a genetically determined risk factor of coronary artery disease (CAD). Previous genome-wide association studies (GWASs), which were mostly carried out in Caucasians, have identified many Lp(a)-associated SNPs. Here, we performed a GWAS on Lp(a) levels and further explored the relationships between Lp(a)-associated SNPs and CAD severity in 1,403 Han Chinese subjects. We observed that elevated Lp(a) levels were significantly associated with the increased synergy between percutaneous coronary intervention with TAXUS and cardiac surgery (SYNTAX) score and the counts of heavily calcified lesions and long-range lesions (LRLs; P < 0.05), which are defined as lesions spanning >20 mm. Moreover, we identified four independent SNPs, namely, rs7770628, rs73596816, and rs6926458 in LPA, and rs144217738 in SLC22A2, that were significantly associated with Lp(a) levels. We also found that rs7770628 was associated with high SYNTAX scores [odds ratio (OR) (95% CI): 1.37 (1.05–1.80), P = 0.0213, false discovery rate (FDR) = 0.0852], and that rs7770628 and rs73596816 were associated with high risk of harboring LRLs [OR (95% CI): 1.53 (1.17–2.01), P = 0.0018, FDR = 0.0072 and 1.72 (1.19–2.49), P = 0.0040, FDR = 0.0080, respectively]. Our study was a large-scale GWAS to identify Lp(a)-associated variants in the Han Chinese population. Our findings highlight the importance and potential of Lp(a) intervention and expand our understanding of CAD prevention and treatment.

Abstract Background Exploring the role of vasoactive intestinal peptide (VIP) in the lateral geniculate body (LGBd) in visual development and studying the therapeutic effect of VIP on amblyopic kittens. Methods Three-week-old domestic cats were divided into a control group (n = 10) and a monocular deprivation group (n = 20), with an eye mask covering the right eye of those in the deprived group. After pattern visual evoked potential (PVEP) recording confirmed the formation of monocular amblyopia, the left LGBd was isolated from 5 kittens in each group. The remaining control kittens continued to be raised, and the remaining deprivation group was divided into a VIP intervention group (n = 5), Sefsol (caprylic acid monoglyceride, VIP solution) intervention group (n = 5) and amblyopia non-intervention group (n = 5) after removal of the eye mask. Three weeks later, PVEPs, VIP immunohistochemistry and VIP mRNA expression in the left LGBd were compared across groups. Results At 6 weeks of age, there were significant differences in P100 wave latency and amplitude and VIP immunohistochemistry and in situ hybridization between the control group and the deprivation group (P 0.05), as well as the number (P

One of the most fundamental and challenging questions in the field of cancer is how immunity is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identified the tumor suppressor PDZ-LIM domain–containing protein 2 (PDLIM2) as a checkpoint of alveolar macrophages (AMs) important for lung tumor suppression. During lung tumorigenesis, PDLIM2 expression in AMs is downregulated by ROS-activated transcription repressor BTB and CNC homology 1 (BACH1). PDLIM2 downregulation leads to constitutive activation of the transcription factor STAT3, driving AM protumorigenic polarization/activation and differentiation from monocytes attracted from the circulation to suppress cytotoxic T lymphocytes and promote lung cancer. PDLIM2 downregulation also decreases AM phagocytosis. These findings establish ROS/BACH1/PDLIM2/STAT3 as a signaling pathway driving AMs for lung tumor promotion.

m6A, the main form of mRNA modification, participates in regulating multiple normal and pathological biological events, especially in tumorigenesis. However, there is little known about the association of m6A-related genes with prognosis of clear cell renal cell cancer (ccRCC). Therefore, the prognostic value of m6A-related genes was investigated using Kaplan–Meier curves of overall survival (OS) with the log-rank test and Cox regression analysis. The differential expression of YTHDF2 mRNA in ccRCC and tumor-adjacent normal tissues and associated with clinicopathological characteristics was also analyzed. The alteration of cancer signaling pathways was screened by Gene Set Enrichment Analysis (GSEA). Univariate analysis showed that 15 m6A-related genes (including YTHDF2) were closely related to prognosis. Multivariate analysis further confirmed that YTHDF2 could serve as an independent prognostic factor for the OS of ccRCC patients (P < 0.001). Low-level expression of YTHDF2 had poor prognosis in ccRCC patients with lower tumor–node–metastasis (TNM) stage, age > 61, non-distant metastasis, non-lymph node metastasis, female gender, and higher histological grade (P < 0.05). Moreover, YTHDF2 expression in ccRCC tissues (N = 529) is significantly lower than that of tumor-adjacent normal tissues (N = 72, P = 0.0086). Furthermore, GSEA demonstrated that AKT/mTOR/GSK3 pathway, EIF4 pathway, CHREBP2 pathway, MET pathway, NFAT pathway, FAS pathway, EDG1 pathway, and CTCF pathway are altered in tumors with high YTHDF2 expression. Taken together, our results demonstrated that YTHDF2 (an m6A-related gene) could serve as a potential prognostic biomarker of ccRCC, and targeting epigenetic modification may be a novel therapeutic strategy for the treatment of ccRCC.

Purpose: Our goal was to analyze postoperative bleeding in patients undergoing total thyroidectomy and to explore the possible risk factors.Materials and Methods: Patients undergoing total thyroidectomy were retrospectively enrolled, and the main study outcomes were postoperative bleeding and 30-day mortality. Univariate and multivariate analyses were used to determine the independent risk factors for postoperative bleeding.Results: A total of 31,706 patients were enrolled for analysis during January 2010 and December 2018 from the Affiliated First Hospital of Zhengzhou University. Benign and malignant disease was reported in 4,521 and 27,185 patients, respectively. Postoperative bleeding occurred in 48 patients with benign disease and in 263 patients with malignant disease. There was one bleeding site in 243 patients. The branch of the superior thyroid artery was the most common arterial bleeding site, occurring in 124 patients, and the anterior jugular vein was the most common venous bleeding site, occurring in 85 patients. Multivariable analysis confirmed that hypertension, diabetes, BMI, and disease pathology were independent factors affecting postoperative bleeding in patients with benign disease and that hypertension, diabetes, BMI, operation time, tumor stage, and tracheotomy were independent factors affecting postoperative bleeding in patients with malignant disease. In patients with postoperative bleeding, there were 5 deaths; in patients without postoperative bleeding, there were 42 deaths, and the difference was significant (p < 0.001).Conclusions: Compared with malignant disease patients, benign disease patients have a similar postoperative bleeding rate. A previous history of chemotherapy or radiotherapy has no significant effect on postoperative bleeding.

Background: Although a large number of studies on heart failure with reduced ejection fraction (HFrEF) have found that anemia and renal dysfunction (RD) independently predicted poor outcomes, there are still few reports on patients with heart failure with preserved ejection fraction (HFpEF). Methods: Clinical data of HFpEF patients registered in the China National Heart Failure Registration Study (CN-HF) were evaluated and the clinical features of patients with or without anemia/RD were compared to explore the impact of anemia and RD on all-cause mortality and all-cause re-hospitalization. Results: 1604 patients with HFpEF were enrolled, the prevalence of anemia was 51.0%. Although anemia was associated with increased risk of all-cause mortality and all-cause re-hospitalization in univariate COX regression (p

This study aimed to investigate whether atorvastatin reduce the contrast-induced nephropathy inflammatory response and apoptosis of renal tubular epithelial cells and the relationship with MAPK signaling pathway. We utilized the iopamidol-induced contrast-induced nephropathy (CIN) rat model which was induced by a single dose of iopamidol (2.9 g iodine/kg) and a cell model in which human embryonic proximal tubular (HK2) cells were treated with iopamidol. The rats were divided into five groups: (1) control rats (CR); (2) atorvastatin (CA); (3) iopamidol (CM); (4) iopamidol and atorvastatin (20 mg/kg d) (CMA2); (5) iopamidol and atorvastatin (40 mg/kg d) (CMA4). On days 1, 2 and 6 after iopamidol injection, the urea nitrogen and cystatin C increased in CM compared with CR but decreased in CMA compared with CM. Inflammatory parameters and the percentage of apoptotic cells were increased in CM compared with CR and CA, but they were decreased in CMA compared with CM. We also found that atorvastatin ameliorated the renal tubular necrosis, apoptosis, and the deterioration of renal function in a dose dependent manner (P

Activation of the inflammatory transcription factor NF-κB in tumor-associated macrophages (TAMs) is assumed to contribute to tumor promotion. However, whether and how NF-κB drives the antitumor macrophages to become pro-tumorigenic have not been determined in any cancer type yet. Similarly, how TAMs repress CD8+ cytotoxic T lymphocytes (CTLs) remains largely unknown, although their importance in regulatory T (Treg) cell regulation and tumor promotion has been well appreciated. Here, using an endogenous lung cancer model we uncover a direct crosstalk between TAMs and CTLs. TAMs suppress CTLs through the T-cell inhibitory molecule B7x (B7-H4/B7S1) in a cell-cell contact manner, whereas CTLs kill TAMs in a tumor antigen-specific manner. Remarkably, TAMs secrete the known T-cell suppressive cytokine interleukin-10 (IL-10) to activate, but not to repress, CTLs. Notably, one major role of cell-intrinsic NF-κB RelA is to drive TAMs to suppress CTLs for tumor promotion. It induces B7x expression in TAMs directly, and restricts IL-10 expression indirectly by repressing expression of the NF-κB cofactor Bcl3 and subsequent Bcl3/NF-κB1-mediated transcription of IL-10. It also renders TAMs resistant to CTLs by up-regulating anti-apoptotic genes. These studies help understand how immunity is shaped in lung tumorigenesis, and suggest a RelA-targeted immunotherapy for this deadliest cancer.

BackgroundDue to the high prevalence in pregnant women and potential association with pregnancy complications or perinatal outcomes, sleep-disordered breathing (SDB) has become an increasing concern.MethodsPubmed and Embase were retrieved from inception until 2017 to conduct a meta-analysis to explore the association of SDB and several outcomes during gestation. A stratified analysis differentiated by the type of SDB [snoring alone/obstructive sleep apnea (OSA)] was also performed. Pooled odds ratios were produced for binary outcomes. Weighted mean differences were also produced for continuous outcomes. Sensitivity analysis was performed to identify the impact of individual studies on summary results and estimation of publication bias was performed by funnel plot.Results35 studies with a total of 56,751,837 subjects were included. SDB during pregnancy was associated with a significantly increased risk of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and preeclampsia (PEC), but not significantly associated with fetal maternal outcomes, namely APGAR score and birth weight. Moreover, OSA was linked with an increasing risk of GDM, PIH, PEC and preterm birth while snoring appeared to increase the risk of GDM, PIH, and PEC.ConclusionThe finding provided potential evidence for association between SDB and adverse perinatal outcomes. SDB increased the risk of some pregnancy complications while its influence to fetal outcomes was not clear.

Abstract: The adsorption/desorption effects impact the petro-physical properties of matrix pores during gas depressurizing production, such as effective pore radius, effective porosity, apparent permeability, which will further impact the gas flow regime. In this paper, the dynamic models of effective pore radius and apparent permeability under the action of gas adsorption/desorption are derived. The mathematical model of shale gas flow is established considering the effects of adsorbed gas on apparent properties and gas flow regime. After that, the model is solved and validated using a finite volume method and experimental and field data. Finally, the variations of apparent parameters of matrix pores and gas flow regimes during gas production, and the influences of adsorption on gas production are demonstrated. The results show that the effective pore radius, porosity and apparent permeability increase during gas production; the gas flow regime in stimulated reservoir volume (SRV) changes from slip flow to transition flow; if the impacts of adsorbed gas on gas production is overlooked, both original gas in place (OGIP) and gas production will be significantly overestimated. The cumulative gas production changes slightly as the adsorption layer thickness increases, but the gas recovery factor decreases. Key words: shale gas, adsorption, desorption, matrix pore, apparent properties, flow regime, flow model

P-glycoprotein (P-gp)-induced drug resistance is a major road block for successful cancer chemotherapy. Through phenotypic screening, the compound 2-(2-chlorophenylimino)-5-(4-dimethylaminobenzylidene)thiazolidin-4-one (CDBT) was discovered to have potent antitumor activity in P-gp over-expressing drug-resistant non-small-cell lung cancer (NSCLC) H460TaxR cells. Here, we report mechanistic investigations of the P-gp–evading anti-tumor activity of CDBT. CDBT is evidently not a P-gp substrate and escapes the P-gp efflux pump. As a novel microtubule and heat shock protein 90 (HSP90) dual targeting inhibitor, CDBT causes the destabilization of microtubules and degradation of HSP90 client proteins CRAF-1 and ERBB2, resulting in cell cycle arrest at the G2/M phase and apoptosis. Furthermore, CDBT effectively inhibits tumor growth by 60.4% relative to the vehicle control after intraperitoneal administration at 30 mg/kg for 11 days and shows no toxicity in normal tissues in the NSCLC H460TaxR xenograft mouse model. Our data suggest a novel drug discovery strategy to combat P-gp over-expressing drug-resistant NSCLC cancer cells with a single therapeutic agent.[Supplementary materials: available only at http://dx.doi.org/10.1254/jphs.14050FP] Keywords:: HSP90, microtubule, multidrug resistance, non-small-cell lung cancer, P-glycoprotein

OBJECTIVES: Hyperuricemia is a risk factor for contrast-induced acute kidney injury in patients with chronic kidney disease. This study evaluated the value of hyperuricemia for predicting the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine who were undergoing percutaneous coronary interventions. METHODS AND RESULTS: A total of 788 patients with relatively normal baseline serum creatinine (7 mg/ dL in males and >6 mg/dL in females. The incidence of contrast-induced acute kidney injury was significantly higher in the hyperuricemic group than in the normouricemic group (8.1% vs. 1.4%, p75 years, emergent percutaneous coronary intervention, diuretic usage and the need for an intra-aortic balloon pump. CONCLUSION: Hyperuricemia was significantly associated with the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine after percutaneous coronary interventions. This observation will help to generate hypotheses for further prospective trials examining the effect of uric acid-lowering therapies for preventing contrast-induced acute kidney injury.

Repeated administrations of anti-cancer drugs to patients often induce drug resistance. P-glycoprotein (Pgp) facilitates an efficient drug efflux, preventing cellular accumulation of drugs and causing multi-drug resistance (MDR). In this study, we developed a gold-paclitaxel nanoconjugate system to overcome MDR. Gold nanoparticles (GNPs) were conjugated with β-cyclodextrin enclosing paclitaxel (PTX) molecules and PEG molecules. GNP conjugates were effectively endocytosed by both drug-sensitive human lung cancer H460 cells and Pgp-overexpressed drug-resistant H460PTX cells. Compared with PTX, PGNPs did not induce the Pgp overexpression in drug-sensitive H460 cells after long-term treatment and also avoided being pumped out of cells by overexpressed Pgp molecules in H460PTX with a 17-fold lower EC50 compared to PTX. Fluorescent microscopy and flow cytometry further confirmed that fluorescent labeled PGNPs (f-PGNPs) maintained a high cellular PTX level in both H460 and H460PTX cells. These results demonstrated that nano-drug conjugates were able to avoid the development of drug resistance in sensitive cells and evade Pgp-mediated drug resistance and to maintain a high cytotoxicity in drug-resistant cancer cells. These findings exemplify a powerful nanotechnological approach to the long-lasting issue of chemotherapy-induced drug resistance.

BACKGROUND:Over the past several decades, the endoscopic endonasal transsphenoidal approach (EETA) has gradually become a preferred option of pituitary adenomas surgery because of its minimal invasiveness and high efficiency. However, some EETA operations were performed through one nostril (mononostril), while other EETA operations were performed through both nostrils (binostril). Therefore, we conducted this study to compare the pros and cons of these two methods in an attempted to confirm which method is more effective. METHODS:We executed a systematic literature search of PubMed, the Cochrane Library, and the Web of Science and Medline (1992-2015). The language is limited to English and all studies should meet the inclusion criteria. Comparisons were made for postoperative outcomes, complications, and other relevant parameters between the mononostril and the binostril group. Statistical analyses of categorical variables were undertaken by the use of Stata 12.0 and SPASS 19.0. RESULTS:Thirty studies, involving 4805 patients, were included. The two groups had similar results in GTR rate (included GTR rate of macroadenomas), hormonal remission rate, improvement in visual function, postoperative CSF leak, permanent diabetes insipidus, meningitis, and sinusitis. The binostril group had less temporary diabetes insipidus (2.9% vs. 5.3%, p = 0.022), less anterior pituitary insufficiency (2.3% vs. 6.4%, p = 0.000) and few hospitalization days (3.2 days vs. 4.4 days, p

The present investigation was carried out to elucidate a possible molecular mechanism related to the protective effect of quercetin administration against oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in mitochondrial biogenesis. Recently, quercetin has been proved to have a protective effect against mitochondria damage after traumatic brain injury (TBI). However, its precise role and underlying mechanisms in traumatic brain injury are not yet fully understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism of these effects in a weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administrated 30 min after TBI. In this experiment, ICR mice were divided into four groups: A sham group, TBI group, TBI + vehicle group, and TBI + quercetin group. Brain samples were collected 24 h later for analysis. Quercetin treatment resulted in an upregulation of Nrf2 expression and cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were restored by quercetin treatment. Quercetin markedly promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus. These observations suggest that quercetin improves mitochondrial function in TBI models, possibly by activating the Nrf2 pathway.