Search

Li-Wei Zhang,1– 3,&ast; Man-Qing Luo,4,&ast; Ji-Lang Zeng,1– 3,&ast; Zhe-Bin You,2,3,5 Li-Chuan Chen,1– 3 Jun-Han Chen,1– 3 Kai-Yang Lin,1– 3 Yan-Song Guo1– 3 1Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 2Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular Diseases, Fuzhou, People’s Republic of China; 3Fujian Heart Failure Center Alliance, Fuzhou, People’s Republic of China; 4Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Geriatric Medicine, Fujian Key Laboratory of Geriatrics, Fujian Provincial Hospital, Fujian Provincial Center for Geriatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai-Yang Lin; Yan-Song Guo, Tel +86-13559355708 ; +86-059188217410, Email lky7411@sina.com; ysguo1234@126.comPurpose: The estimated glomerular filtration rate (eGFR) based on creatinine is crucial for the risk assessment of contrast-associated acute kidney injury (CA-AKI). In recent, the difference between cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr) has been widely documented. We aimed to explore whether intraindividual differences between eGFRcys and eGFRcr had potential value for CA-AKI risk assessment in patients undergoing elective percutaneous coronary intervention (PCI).Patients and Methods: From January 2012 to December 2018, we retrospectively observed 5049 patients receiving elective PCI. To determine eGFR, serum creatinine and cystatin C levels were measured. CA-AKI was defined as serum creatinine being increased ≥ 50% or 0.3 mg/dL within 48 h after contrast agents exposure. Chronic kidney disease (CKD) was defined as the eGFR < 60 mL/min/1.73 m2.Results: Approximately half of the participants (2479, 49.1%) had a baseline eGFRdiff (eGFRcys-eGFRcr) between − 15 and 15 mL/min/1.73 m2. Restricted cubic splines analysis revealed a nonlinear relationship between eGFRdiff and CA-AKI. Multivariable logistic regression analysis indicated that compared with the reference group (− 15 to 15 mL/min/1.73 m2), the negative-eGFRdiff group (less than − 15 mL/min/1.73 m2) had a higher risk of CA-AKI (OR, 3.44; 95% CI, 2.57– 4.64). Furthermore, patients were divided into four groups based on CKD identified by eGFRcys or eGFRcr. Multivariable logistic analysis revealed that patients with either CKDcys (OR, 2.94; 95% CI, 2.19– 3.95, P < 0.001) or CKDcr (OR, 2.44; 95% CI, 1.19– 4.63, P < 0.001) had an elevated risk of CA-AKI compared to those without CKDcys and CKDcr.Conclusion: There are frequent intraindividual differences between eGFRcys and eGFRcr, and these differences can be used to forecast the risk of CA-AKI.Keywords: estimated glomerular filtration rate, contrast-associated acute kidney injury, cystatin C, percutaneous coronary intervention

Study Objective: The lactate-to-albumin ratio (LAR) has been confirmed to be an effective prognostic marker in sepsis, heart failure, and acute respiratory failure. However, the relationship between LAR and mortality in patients with acute respiratory distress syndrome (ARDS) remains unclear. We aim to evaluate the predictive value of LAR for ARDS patients., Design: A retrospective cohort study., Setting: Medical Information Mart for Intensive Care IV (v2.2) database., Patients: 769 patients with acute respiratory distress syndrome(ARDS)., Interventions: We divided the patients into two subgroups according to the primary study endpoint (28-days all-cause mortality): the 28-day survivors and the 28-day non-survivors., Measures: Multivariate Cox Regression, Receiver Operator Characteristic (ROC) and Kaplan-Meier survival analysis were used to investigate the relationship between LAR and short-time mortality in patients with ARDS., Main Results: The 28-day mortality was 38 % in this study. Multivariable Cox regression analysis showed that LAR was an independent predictive factor for 28-day mortality (HR 1.11, 95 %CI: 1.06-1.16, P < 0.001). The area under curve (AUC) of LAR in the ROC was 70.34 % (95 %CI: 66.53 % - 74.15 %) that provided significantly higher discrimination compared with lactate (AUC = 68.00 %, P = 0.0007) or albumin (AUC = 63.17 %, P = 0.002) alone. LAR was also not inferior to SAPSII with the AUC of 73.44 % (95 %CI: 69.84 % - 77.04 %, P = 0.21). Additionally, Kaplan-Meier survival analysis displayed that ARDS patients with high LAR (> the cut-off value 0.9055) had a significantly higher 28-day overall mortality rate (P < 0.001) and in-hospital mortality rate (P < 0.001). However, patients in high LAR group had shorter length of hospital stay (P < 0.001), which might be caused by higher in-hospital mortality., Conclusions: We confirmed that there was a positive correlation between LAR and 28-day mortality. This could provide anesthesiologists and critical care physicians with a more convenient tool than SAPSII without being superior for detecting ARDS patients with poor prognosis timely., Competing Interests: Declaration of competing interest Luo Meng-Qiang reports financial support was provided by Association between lactate-to-albumin ratio and short-time mortality in patients with acute respiratory distress syndrome. Luo Meng-Qiang reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored., Methods: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures., Results: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation., Conclusion: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Marital status is associated with cardiovascular disease (CVD) incidence and overall mortality, yet limited research on this topic in elderly individuals is available. Our aim was to comprehensively assess the impact of marital status and other family factors on CVD incidence and long-term mortality among elderly people., Methods: Data from the Chinese Longitudinal Healthy Longevity Survey (2002/2005/2008-2018) for participants aged ≥60 years were analysed. A cross-sectional study initially examined the correlation between spouses, offspring, living arrangements, and CVD using logistic regression. Subsequently, a retrospective cohort study investigated the long-term associations of these factors with overall mortality via Kaplan-Meier and Cox regression analyses., Results: The study involved 48 510 subjects (average age: 87 years). The cross-sectional analysis revealed a correlation between living with a spouse and an increased incidence of heart disease (adjusted OR 1.27, 95% CI 1.04-1.55) and cerebrovascular disease/stroke (adjusted OR 1.26, 95% CI 1.11-1.42). According to the retrospective cohort analysis, living with a spouse significantly reduced overall mortality (adjusted HR 0.84, 95% CI 0.80-0.87), irrespective of marital relationship quality. Conversely, living with offspring (adjusted HR 1.12, 95% CI 1.08-1.16), having more children (adjusted Pnonlinearity = 0.427) or cohabitants (adjusted Pnonlinearity < 0.0001) were associated with increased overall mortality., Conclusion: In the elderly population, being married and living with a spouse were not significantly associated with a decrease in CVD incidence but were associated with a reduction in long-term overall mortality. Living with offspring, having more children, or having a larger family size did not replicate the protective effect but indicated greater overall mortality., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Asperphenol A ( 1 ), a new isoprenyl-phenol-type meroterpenoid, was isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y65 together with five known compounds ( 2 - 6) . All structures were assigned using extensive NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-6 were evaluated for their cytotoxic activity against A549 and T24 human cancer cell lines. Among them, compounds 1 and 5 exhibited moderate inhibitory activities against T24 cancer cell lines with the IC 50 values of 26.71 and 43.50 μM, respectively.

Synthetic α-galactosylceramide (αGalCer) and its analogues as powerful agonists for natural killer T (NKT) cell manipulation have received significant attention in immunotherapy and adjuvant development. However, identifying new potent NKT cell agonists, especially those with Th1 selectivity that promote anticancer effects, remains a challenging task. In this work, we introduced a sulfonamide group into the acyl chain of αGalCer to form additional hydrogen bonds to intensify the glycolipid/CD1d interaction. Two compounds GCS-11 and GCS-12 demonstrated remarkable potency while exhibiting different cytokine induction patterns. Compared to αGalCer, the Th1-biased GCS-11 exhibited a 6-fold increase in IFN-γ but not IL-4, while the Th1/2-balanced GCS-12 elicited 7- and 5-fold increase in IFN-γ and IL-4, respectively, in vivo . These findings place them among the most potent NKT cell agonists, with superior antitumor effects. Therefore, hydrogen-bond-involved derivatization could be a powerful strategy to develop potent and polarized NKT cell agonists for various immunotherapies.

Background: Elevated intraocular pressure (IOP) and optic nerve edema occurring during prone surgeries may cause ocular and optic nerve ischaemia injury. We hypothesized that a liberal fluid protocol might further increase IOP and optic nerve sheath diameter (ONSD) than a restrictive fluid protocol for patients in the prone position., Methods: A single-centre, prospective and randomized trial was conducted. Patients were randomly allocated into 2 groups: the liberal fluid infusion group, in which repeated bolus doses of Ringer's lactate solution were given to maintain pulse pressure variation (PPV) within 6~9%, and the restrictive fluid infusion group, where PPV was maintained within 13-16%. IOP and ONSD were measured in both eyes at 10min after the anaesthesia induction in the supine position, 10min after the prone position placement, and 1h and 2h since the prone position was placed, at the conclusion of surgery, and returned to the supine position., Results: A total of 97 patients were recruited and completed the study. IOP increased significantly from 12±3mmHg in the supine position to 31±5 mmHg (p<0.001) at the end of surgery in the liberal fluid infusion group and from 12±2 to 28±4 mmHg (p<0.001) in the restrictive fluid infusion group. There was a statistically significant difference in the change of IOP over time between the two groups (p=0.019). ONSD increased significantly from 5.3±0.3mm in the supine position to 5.5±0.3mm (p<0.001) at the end of surgery in both groups (both p<0.001). There was no statistically significant difference in the change of ONSD over time between the two groups (p>0.05)., Conclusions: Compared to the restrictive fluid protocol, the liberal fluid protocol increased IOP but not ONSD in patients undergoing prone spine surgery., Trial Registration: The study was registered in ClinicalTrials.gov ( https://clinicaltrials.gov ) prior to patient enrollment, ID: NCT03890510, on March 26, 2019. The principal investigator was Xiao-Yu Yang., (© 2023. The Author(s).)

Previous studies have demonstrated that non-invasive liver fibrosis scores (LFSs) are associated with kidney function deterioration. This study aimed to assess the predictive performance of LFSs in contrast-associated acute kidney injury (CA-AKI) in coronary artery disease (CAD) patients undergoing elective percutaneous coronary intervention (PCI). This retrospective study involved 5627 patients. The frequency of CA-AKI was 6.3% (n = 353). In a multivariate logistic analysis after adjustment, non-invasive LFSs, including fibrosis-5 score (FIB-5), fibrosis-4 score (FIB-4), aspartate aminotransferase to alanine aminotransferase ratio (AAR), and aspartate aminotransferase to platelet ratio index were independent risk factors for CA-AKI (all P < .05), whereas the Forns score was not ( P > .05). The highest predictive performance was observed for FIB-5 (area under the curve [AUC] = .644) compared to other LFSs. A restricted cubic spline analysis confirmed approximately linear relationships between LFSs and risks of CA-AKI. Furthermore, adding FIB-5 (AUC = .747; net reclassification improvement [NRI] = .441, P < .001; integrated discrimination improvement [IDI] = .008, P < .001) or AAR (AUC = .747; NRI = .419, P < .001; IDI = .006, P = .010) to an established clinical risk model could significantly improve the prediction of CA-AKI. The LFSs were significantly associated with CA-AKI, possibly serving as predictive tools for early identification of CAD patients undergoing elective PCI that are at high risk of CA-AKI.

The model for end-stage liver disease (MELD) score, which can reflect liver and renal function, is associated with poor prognosis. However, the prognostic performance of the modified MELD score in patients undergoing elective percutaneous coronary intervention (PCI) has not been fully evaluated and compared. This study retrospectively enrolled 5324 patients. During a median follow-up of 2.85 years, 412 patients died. Time-dependent receiver operating characteristic curves at 3 years indicated that the MELD including albumin (MELD-Albumin) score had the highest prognostic performance (AUC = .721) than the MELD score (AUC = .630), the MELD excluding the international normalized ratio (MELD-XI) score (AUC = .606), and the MELD including sodium (MELD-Na) score (AUC = .656) (all P < .001). The MELD-Albumin score, the MELD score, and the MELD-Na score were independent predictors of long-term mortality; however, the MELD-XI score was not when treated as a categorical variable ( P = .254). Adding the MELD-Albumin score to the model of clinical risk factors could improve the prognostic performance. For the subgroup analysis, the association between the MELD-Albumin score and long-term mortality was more pronounced in patients ≤75 years (interaction P value = .005). The MELD-Albumin score showed the strongest prognostic performance than the other versions of the MELD score in patients undergoing elective PCI.

Background Shrunken pore syndrome (SPS) as a novel phenotype of renal dysfunction is characterized by a difference in renal filtration between cystatin C and creatinine. The manifestation of SPS was defined as a cystatin C-based estimated glomerular filtration rate (eGFR) <60% of the creatinine-based eGFR. SPS has been shown to be associated with the progression and adverse prognosis of various cardiovascular and renal diseases. However, the predictive value of SPS for contrast-associated acute kidney injury (CA-AKI) and long-term outcomes in patients undergoing percutaneous coronary intervention remains unclear. Methods and Results We retrospectively observed 5050 consenting patients from January 2012 to December 2018. Serum cystatin C and creatinine were measured and applied to corresponding 2012 and 2021 Chronic Kidney Disease Epidemiology Collaboration equations, respectively, to calculate the eGFR. Chronic kidney disease (CKD) was defined as a creatinine-based eGFR <60 mL/min per 1.73 m 2 without dialysis. CA-AKI was defined as an increase in serum creatinine ≥50% or 0.3 mg/dL within 48 hours after contrast medium exposure. Overall, 649 (12.85%) patients had SPS, and 324 (6.42%) patients developed CA-AKI. Multivariate logistic regression analysis indicated that SPS was significantly associated with CA-AKI after adjusting for potential confounding factors (odds ratio [OR], 4.17 [95% CI, 3.17-5.46]; P <0.001). Receiver operating characteristic analysis indicated that the cystatin C-based eGFR:creatinine-based eGFR ratio had a better performance and stronger predictive power for CA-AKI than creatinine-based eGFR (area under the curve: 0.707 versus 0.562; P <0.001). Multivariate logistic analysis revealed that compared with those without CKD and SPS simultaneously, patients with CKD and non-SPS (OR, 1.70 [95% CI, 1.11-2.55]; P =0.012), non-CKD and SPS (OR, 4.02 [95% CI, 2.98-5.39]; P <0.001), and CKD and SPS (OR, 8.62 [95% CI, 4.67-15.7]; P <0.001) had an increased risk of CA-AKI. Patients with both SPS and CKD presented the highest risk of long-term mortality compared with those without both (hazard ratio, 2.30 [95% CI, 1.38-3.86]; P =0.002). Conclusions SPS is a new and more powerful phenotype of renal dysfunction for predicting CA-AKI than CKD and will bring new insights for an accurate clinical assessment of the risk of CA-AKI.

Background: Sarcopenia is an age-related decline in skeletal muscle mass, which depends on an assessment of muscle strength and muscle mass. The diagnostic definition of sarcopenia varies by region., Aim: To determine the optimal diagnostic criteria for sarcopenia in a plateau population. Cut off values for the components of diagnostic algorithms for sarcopenia in plateau populations should consider altitude., Methods: One hundred and fifty subjects aged > 60 years attending a tertiary comprehensive hospital in the city of Xining (elevation: 2260 m) between October and December 2018 were enrolled. Handgrip strength, muscle mass, and physical performance were measured. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria, Beijing criteria, and Lasha criteria., Results: Across diagnostic criteria, there were significant differences in the prevalence of sarcopenia in the overall population and stratified by gender. The prevalence of sarcopenia measured by the AWGS 2019 or Lasha criteria was significantly higher in female compared to male subjects. In males, the prevalence of sarcopenia measured by the Beijing criteria was significantly higher in subjects who identified as Han compared to Minority. In females, there were no significant differences in the prevalence of sarcopenia by ethnicity according to any criteria., Conclusion: The Lasha criteria provided a lower prevalence of sarcopenia (males, 8.7%; females, 22.41%; overall, 14%) and were able to differentiate between males and females. The Lasha criteria are likely most appropriate for detection of sarcopenia in this plateau population. We recommend the Lasha criteria for detection of sarcopenia in Xining., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The efficacy of acupuncture alone in the treatment of irritable bowel syndrome (IBS) is controversial, but the benefit of acupuncture added to usual care has rarely been studied. We aimed to examine the benefit of acupuncture added to usual care through network meta-analysis (NMA)., Methods: PubMed, Embase, and the Cochrane Register of Controlled Trials (CENTRAL) were searched from their inception to 1 July 2021, without any language restriction. Randomized controlled trials (RCTs) testing the effect of acupuncture alone or acupuncture combined with usual care for IBS were included. The primary outcome was improvement of global IBS symptoms. Standard NMA was performed to compare differential combinations of acupuncture (including manual acupuncture (MA) and electroacupuncture (EA)), and component network meta-analysis (CNMA) was subsequently performed to determine whether acupuncture provided additional benefits to usual care. The effect size of an intervention was measured using relative ratio (RR)., Results: We included 25 RCTs (n = 3041 participants) after screening 582 retrieved articles. Five RCTs were classified as low risk of bias. The results of standard NMA showed that MA combined with usual care ranked the most effective (sham acupuncture as common comparator; RR = 1.96 (95% confidence interval (CI) 1.23 to 3.12)). The results of CNMA showed that MA was the most effective component (RR = 1.38 (95% CI, 1.12 to 1.70)) when added to usual care., Conclusion: Acupuncture provided additional benefits to usual care, and it might be considered as adjunctive therapy for patients who respond inadequately to usual care.

Background: Alzheimer's disease (AD) influences the social and economic quality of life of older adult patients and their families., Aim: To explore the efficacy of cognitive training in clinical nursing for patients with early AD residing in the plateau area., Methods: This pilot study was conducted in patients with early AD treated in the Geriatric Department of the Qinghai Provincial People's Hospital between August 2019 and March 2021. The patients were divided into a cognitive training group and a conventional nursing group using the random number table method. Patients in the conventional nursing group received conventional nursing, whereas the patients in the cognitive training group received the new nursing intervention. The mini-mental state examination (MMSE) and activities of daily living (ADL) scales were used to compare the cognitive ability and daily activities, respectively, between the two groups before and after the intervention., Results: Sixty patients were enrolled in this study, with 30 patients in the cognitive training group and conventional nursing group, respectively. The MMSE and ADL scores were significantly higher in the cognitive training group than in the conventional nursing group after the intervention (MMSE: 25.11 ± 2.02 vs 22.26 ± 1. 23, P = 0.032; ADL: 68.72 ± 4.86 vs 60.16 ± 2.27, P = 0.018)., Conclusion: The application of cognitive training in clinical nursing for patients with early AD could improve both their cognitive ability and ADL. This method could be applied in clinical practice to manage cognitive dysfunction in patients with early AD., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Pre-procedure liver insufficiency has been demonstrated as a poor prognostic factor after percutaneous coronary intervention (PCI). Recent research discovered that the aspartate aminotransferase-to-alanine aminotransferase ratio (De-Ritis ratio) reflects the severity of liver insufficiency and was associated with adverse outcomes. We aim to evaluate the predictive value of the De-Ritis ratio for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective PCI., Methods: We retrospectively enrolled 5780 consenting patients undergoing elective PCI between January 2012 and December 2018. CA-AKI was defined as an increase in serum creatinine ≥0.3 mg/dl or ≥50% within 48 h after the administration of contrast media., Results: The incidence of CA-AKI was 6.3% (n = 363). The De-Ritis ratio >1.30 was identified as the best cut-off value for CA-AKI prediction. The De-Ritis ratio showed an area under the curve (AUC) of 0.636 [95% confidence interval (CI): 0.605-0.667] in predicting CA-AKI, which was significantly greater than alanine aminotransferase (p<0.001) and aspartate aminotransferase (p = 0.012) alone. Furthermore, compared to currently recognized liver function assessment tools, the predictive value of the De-Ritis ratio on CA-AKI was similar to the MELD score (AUC: 0.636 vs 0.626, p = 0.631) and higher than the MELD-XI score (AUC: 0.636 vs 0.561, p<0.001). Multivariate logistic analysis showed that the De-Ritis ratio >1.30 was independently associated with CA-AKI (odds ratio=1.551, 95% CI: 1.185-2.030, p = 0.001). The addition of the De-Ritis ratio to the fully adjusted logistic regression model has significant incremental effects on the risk prediction for CA-AKI with a continuous net reclassification improvement of 0.395 (p<0.001) and an integrated discrimination improvement of 0.005 (p = 0.018). Additionally, the De-Ritis ratio >1.30 was significantly associated with long-term mortality (hazard ratio=1.285, 95% CI: 1.007-1.641, p = 0.044)., Conclusions: The De-Ritis ratio was an independent risk factor for CA-AKI and long-term mortality in patients undergoing elective PCI., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Pre-procedure liver dysfunction was associated with acute kidney injury after percutaneous coronary intervention (PCI). The aim of this study is to assess and compare the predictive value of different liver function scoring systems for contrast-associated acute kidney injury (CA-AKI) in patients undergoing elective PCI., Methods and results: A total of 5,569 patients were retrospectively enrolled. The model for end-stage liver disease (MELD) including albumin (MELD-Albumin) score (AUC=0.661) had the strongest predictive value in comparison to the MELD score (AUC=0.627), the MELD excluding the international normalized ratio (MELD-XI) score (AUC=0.560), and the MELD including sodium (MELD-Na) score (AUC=0.652). In the fully adjusted logistic regression model, the MELD-Albumin score and the MELD-Na score were independently associated with CA-AKI regardless of whether they were treated as continuous or categorical variables; however, this was not the case for the MELD score and the MELD-XI score. Furthermore, the addition of the MELD-Albumin score significantly improved the reclassification beyond the fully adjusted logistic regression model. The study further explored the association between different versions of the MELD score and CA-AKI using restricted cubic splines and found a linear relationship between the MELD-Albumin score and the risk of CA-AKI., Conclusions: The MELD-Albumin score had the highest predictive value for CA-AKI in patients undergoing elective PCI. The addition of the MELD-Albumin score to the existing risk prediction model significantly improved the reclassification for CA-AKI.

Background: Neutrophil and albumin are well-known biomarkers of inflammation, which are highly related to contrast-associated acute kidney injury (CA-AKI). We aim to explore the predictive value of neutrophil percentage-to-albumin ratio (NPAR) for CA-AKI and long-term mortality in patients without chronic kidney disease (CKD) undergoing elective percutaneous coronary intervention (PCI)., Methods: We retrospectively observed 5083 consenting patients from January 2012 to December 2018. CA-AKI was defined as an increase in serum creatinine ≥50% or 0.3 mg/dL within 48 h after contrast medium exposure., Results: The incidence of CA-AKI was 5.6% (n=286). The optimal cut-off value of NPAR for predicting CA-AKI was 15.7 with 66.8% sensitivity and 61.9% specificity [C statistic=0.679; 95% confidence interval (CI), 0.666-0.691]. NPAR displayed higher area under the curve values in comparison to neutrophil percentage (p < 0.001) and neutrophil-to-albumin ratio (NAR) (p < 0.001), but not albumin (p = 0.063). However, NPAR significantly improved the prediction of CA-AKI assessed by the continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) compared to neutrophil percentage (NRI=0.353, 95% CI: 0.234-0.472, p < 0.001; IDI=0.017, 95% CI: 0.010-0.024, p < 0.001) and albumin (NRI=0.141, 95% CI: 0.022-0.260, p = 0.020; IDI=0.009, 95% CI: 0.003-0.015, p = 0.003) alone. After adjusting for potential confounding factors, multivariate analysis showed that NPAR >15.7 was a strong independent predictor of CA-AKI (odds ratio =1.90, 95% CI: 1.38-2.63, p < 0.001). Additionally, NPAR >15.7 was significantly associated with long-term mortality during a median of 2.9 years of follow-up (hazard ratio =1.68, 95% CI: 1.32-2.13; p < 0.001)., Conclusions: NPAR was an independent predictor of CA-AKI and long-term mortality in patients without CKD undergoing elective PCI., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Background and Purpose: To assess the safety and effectiveness of oral methylprednisolone (oMP) in comparison with intramuscular adrenocorticotropic hormone (imACTH) and oral prednisolone (oP) therapies in children with infantile spasms (IS). Methods: In this prospective, open-label, non-blinded, uncontrolled observational study, children (aged 2-24 months) with newly diagnosed IS presenting with hypsarrhythmia or its variants on electroencephalogram (EEG) were included. It was followed by imACTH, oP, or oMP (32-48 mg/day for 2 weeks followed by tapering) treatments. Electroclinical remission/spasm control, relapse, and adverse effects were evaluated in the short-term (days 14 and 42) and intermediary-term (3, 6, and 12 months) intervals. Results: A total of 320 pediatric patients were enrolled: 108, 107, and 105 in the imACTH, oMP, and oP groups, respectively. The proportion of children achieving electroclinical remission on days 14 and 42 was similar among the three groups (day 14: 53.70 vs. 60.75 vs. 51.43%, p = 0.362; day 42: 57.55 vs. 63.46 vs. 55.34%, p = 0.470). The time to response was significantly faster in the oMP group (6.5 [3.00, 10.00] days vs. 8.00 [5.00, 11.00] days for imACTH and 8.00 [5.00, 13.00] days for oP, p = 0.025). Spasm control at 3, 6, and 12 months was also similar in the three groups ( P = 0.775, 0.667, and 0.779). The relapse rate in the imACTH group (24.10%) was lower than oMP (30.77%) and oP groups (33.33%), and the time taken for relapse in the imACTH group (79.00 [56.50, 152.00] days) was longer than oMP (62.50 [38.00, 121.75] days) and oP groups (71.50 [40.00, 99.75] days), but the differences were not statistically significant ( p = 0.539 and 0.530, respectively). The occurrence of adverse effects was similar among the three groups. Conclusions: The short and intermediary-term efficacy and recurrence rates of oMP are not inferior to those of imACTH and oP for the treatment of IS. Significantly, the time to achieve electroclinical remission with oMP was quicker than that with imACTH and oP. Considering its convenience, affordability, and the absence of irreversible side effects, oMP can serve as a form of first-line treatment for newly diagnosed IS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Yuan, Luo, Deng, Huang, Wu, Hu, Yao and Liu.)

MicroRNA-506 (miR-506), a miRNA, has been proven to act as a tumor suppressor gene in nonsmall-cell lung cancer (NSCLC); Tubby-like protein 3 (TULP3) is a potential target gene of miR-506. This study investigates whether miR-506 can prevent NSCLC progression by mediating TULP3. In vivo and in vitro experiments were performed to explore the function and potential regulatory relationship of miR-506 and TULP3 in NSCLC. Our results revealed that miR-506 is high expression in NSCLC cell lines, and the overexpression of miR-506 could inhibit cell viability and enhance cell apoptosis in H1299 and A549 cells. Pro-apoptotic related protein (cytochrome C, Bax, and cleaved caspase-9) expression increased while anti-apoptotic related protein (BCL-2 and BCL-XL) expression decreased after miR-506 was overexpression. Meanwhile, the overexpression of miR-506 could notably downregulate TULP3. Additionally, silence of TULP3 inhibited cell viability and promoted cell apoptosis. At the same time, pro-apoptotic related protein expression was promoted while anti-apoptotic related protein expression was inhibited. Furthermore, TULP3 overexpression could markedly reverse the inhibitory effect of miR-506 on the proliferation and induction of mitochondrial apoptosis in H1299 and A549 cells. In vivo tumor formation experiments also exhibited consistent results indicating that the functions of TULP3 might be correlated with the promotion of tumorigenesis. In conclusion, we firstly found that miR-506 can be involved in the processes of NSCLC and exert a suppressive effect on tumorigenesis by regulating TULP3 expression.

Background: The notch signal pathway is important in the development of both tumor-associated macrophages (TAMs) and stomach cancer, but how Notch signaling affects TAMs in stomach cancer is barely understood., Methods: The expressions of Notch1, Notch2, Notch3, Notch4, hes family bHLH transcription factor 1 (Hes1), and delta-like canonical Notch ligand 3 (DLL3) were detected by Western blot and the expressions of interleukin (IL)-10, IL-12, and IL1-β were detected using enzyme-linked immunosorbent assay after the co-culture of macrophages and stomach-cancer cells. The proliferation and migration of cancer cells were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and scratch assay, respectively, and the cell cycle was detected using Annexin V/propidium iodide assay. The protein interactions with DLL3 were detected using co-immunoprecipitation and mass spectrometry., Results: The co-culture of macrophages and stomach-cancer cells MKN45 and BGC823 could enhance cell proliferation accompanied by the activation of Notch1/Notch2 signaling and upregulation of DLL3. Notch signaling gamma-secretase inhibitor (DAPT) blocked this process. The overexpression of DLL3 in stomach-cancer cells could promote the proliferation of cancer cells, enhance the activation of Notch1/Notch2 signaling, induce the expression of IL-33, lead to the degradation of galectin-3-binding protein (LG3BP) and heat shock cognate 71 kDa protein (HSPA8), and result in elevated IL-1β, IL-12, and IL-10 secretion by macrophages. Higher expression of DLL3 or IL-33 could lead to a lower survival rate based on University of California, Santa Cruz Xena Functional Genomics Explorer and The Cancer Genome Atlas data set., Conclusions: This is evidence that DLL3 regulates macrophages in stomach cancer, suggesting that DLL3 may be a novel and potential target for stomach-cancer therapy., (© The Author(s) 2021. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Background: Acute necrotizing encephalopathy of childhood (ANE) is a rare but rapidly progressing encephalopathy. Importantly, the exact pathogenesis and evidence-based treatment is scarce. Thus, we aimed to identify the clinical, imaging, and therapeutic characteristics that associated with prognosis of pediatric ANE patients. Methods: A retrospective study was conducted on pediatric patients with ANE who were admitted to Wuhan Children's Hospital between January 2014 and September 2019. All cases met the diagnostic criteria for ANE proposed by Mizuguchi in 1997. The clinical information and follow-up data were collected. The prognostic factors were analyzed by trend chi-square test and Goodman-Kruskal gamma test. Results: A total of 41 ANE patients ranging in age from 8.9 to 142 months were included in this study. Seven cases (17%) died, and the other 34 survivors had different degrees of neurological sequelae. Factors tested to be significantly correlated with the severity of neurological sequelae were the intervals from prodromal infection to acute encephalopathy (G = -0.553), conscious disturbance ( r = 0.58), endotracheal intubation ( r = 0.423), elevation of alanine aminotransferase ( r = 0.345), aspartate aminotransferase ( r = 0.393), and cerebrospinal fluid protein ( r = 0.490). In addition, dynamic magnetic resonance imaging (MRI) evaluation on follow-up revealed that the total numbers of brain lesion location (χ 2 = 6.29, P < 0.05), hemorrhage ( r = 0.580), cavitation ( r = 0.410), and atrophy ( r = 0.602) status were significantly correlated with the severity of neurological sequelae, while early steroid therapy ( r = -0.127 and 0.212, respectively) and intravenous immunoglobulin (IVIG) ( r = 0.111 and -0.023, respectively) within 24 h or within 72 h after onset showed no association. Conclusions: Intervals from prodromal infection to acute encephalopathy (≤1 day), total numbers of brain lesion location (≥3), the recovery duration of hemorrhage and atrophy (>3 months), and the presence of cavitation predict severe neurological sequelae in pediatric patients with ANE. Early treatments, including steroid therapy and IVIG, had no correlation with better outcomes. Further studies are needed to establish a consensus guideline for the management of ANE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Zhang, Yao, Luo, Ma, Lei, Yuan, Wu, Hu, Cai and Liu.)

Objective: To explore the clinical effect of operative reduction and internal fixation in treating atypical unstable Hangman fracture in elderly osteoporotic patients., Methods: The clinical data of 9 elderly osteoporotic patients with atypical unstable Hangman fracture treated from December 2012 to December 2017 were retrospectively analyzed. There were 5 males and 4 females with an average age of 72.7 years (range 65 to 79) old. The fracture line was located on bilateral inferior articular surface or lamina with anterior dislocation of axis in 3 cases (similar to Levine-Edwards type II); one side of the fracture line was located on the lower articular surface and opposite side involved on the upper articular surface and the body of axis with atlantoaxial lateral mass dislocation in 4 cases; the fracture line was located at the pedicle of the axis, transverse foramen and posterior inferior wall of the vertebral body, accompanying by anterior and posterior longitudinal ligaments and C₂-C₃ intervertebral disc injury resulted in C₂-C₃ intervertebral instability in 2 cases. According to ASIA grade of spinal cord injury, 2 cases were grade D and 7 cases were grade E. Preoperative JOA scores were 9 to 11 points with an average of 9.8 points. All patients underwent routinely skull traction for reduction. Three patients with anterior dislocation of axis were treated with stage I anterior-posterior internal fixation and 6 patients with simple posterior pedicle screw fixation. Postoperative JOA score, ASIA system and the imaging data were used to evaluate clinical effects., Results: All patients were followed up from 12 to 20 months with an average of 18 months. The neck pain disappeared after operation and cervical spine movement was well in all patients. The improvement rate of JOA at 3 months after operation was 75% to 87.5%. Two cases of ASIA grade D fully recovered to grade E. All fractures healed at 6 to 12 months after operation. Except one case occurred superior laryngeal nerve injury and had a complete recovery after 3 months, the other patients had no complications like spinal cord and vertebral artery injury, plate screw loosening and wound infection., Conclusions: According to the type of atypical unstable Hangman fracture in elderly osteoporotic patients, choosing a reasonable and personalized surgical plan can achieve immediate cervical stability and well reduction, which is beneficial for early ambulation and quick rehabilitation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Fibroblast-like synoviocytes (FLSs) contribute to synovial hyperplasia in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist (GDC-0449) and small interfering RNA (siRNA) targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls (P < 0.05). Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G 1 phase cells compared to controls (P < 0.05). Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells (P < 0.05). Protein expression of cyclin D1 was also downregulated after Smo gene knockdown (P < 0.05). The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.

Objective: The aim of this study was to investigate the expression of smoothened protein (Smo), a sonic hedgehog (Shh) signalling component, in synovium of RA and its role in the survival and apoptosis of endothelial cells., Methods: The expression of Smo pxrotein in RA synovial tissue was examined by immunohistochemistry. Real-time PCR and western blotting techniques were employed to measure the expression of Shh signalling components in EA.hy926 endothelial cells exposed to TNF-α in the presence or absence of cyclopamine (a Smo-specific antagonist). Lastly, the effect of cyclopamine and Smo small interfering RNA on apoptosis induced by TNF-α and actinomycin D (ActD) was determined., Results: We found that Smo was highly expressed in synovial tissues of RA, especially in endothelial cells, compared with the trauma group. TNF-α significantly increased the expression of Shh signalling components in EA.hy926 endothelial cells, while cyclopamine decreased the expression of Shh signalling components. EA.hy926 endothelial cells treated with various concentrations of cyclopamine (2-8 μmol/l) showed a significant decrease in cell viability and cell survival rate, and an increase in the rate of cell apoptosis compared with endothelial cells treated with TNF-α and ActD (P < 0.05). EA.hy926 endothelial cells transfected with Smo-siRNA also showed a lower cell survival rate and higher apoptotic rate, compared with cells in the control group (P < 0.05)., Conclusion: The Shh signalling pathway plays a role in regulating endothelial cell apoptosis in a Smo-dependent manner., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.

Objective: To evaluate the efficacy and adverse effects of weekly irinotecan combined with capecitabine as a second-line chemotherapy for treatment of advanced gastric cancer., Methods: Twenty-one patients with advanced gastric cancer who had failed first-line therapy received irinotecan on days 1 and 8 plus capecitabine on days 1-14 for a 21-day cycle. Each patient was treated for at least two cycles and evaluated 4 weeks later for the responses., Results: Of the 21 patients, none showed complete remission (CR), 5 (23.8%) showed partial remission (PR), 6 (28.6%) showed stable disease (SD) and 10 (47.6%) showed progressive disease (PD). The overall response rate was 23.8%, and 11 patients (52.4%) benefited (CR+PR+SD) from the clinical therapy, with a mean time to tumor progression of 3.61±0.97 months. The main adverse effects of this regimen included myelosuppression, nausea, vomiting and diarrhea., Conclusion: The regimen of weekly irinotecan plus capecitabine has a definite effect for treatment of advanced gastric cancer with tolerable toxicity.

The feasibility of inducing rheumatic myocarditis lesions in Lewis rats by immunization with formalin-killed group A Streptococcus was evaluated. The rats were divided into three groups. Group A was immunized by injecting formalin-killed group A Streptococcus suspended in complete Freund's adjuvant (CFA) into the hind-foot pads and repeat immunization was given 1 week later by subcutaneous injection into the belly. The rats were then sacrificed 3 weeks after the initial immunization. In group B, the rats received the same initial immunization as group A, but the repeat immunization was carried out at 1, 2 and 3 weeks after the initial immunization and the rats were sacrificed 6 weeks after the initial immunization. Group C was a control group with the rats injected with saline/CFA and sacrificed on the same schedule as group A. Heart pathology sections showed that myocarditis lesions, focal inflammatory cell infiltration in interstitial near small vessels and valvulitis were induced in Lewis rats following immunization with formalin-killed group A Streptococcus.