Enantioselective formal total synthesis of dihydrospirotryprostatin B.

Spirotryprostatins are representative members of medicinally interesting bioactive molecules of the spirooxindole natural products. In this communication, we present a novel enantioselective total synthesis of the spirooxindole alkaloid dihydrospirotryprostatin B. The synthesis takes advantage of copper-catalyzed tandem reaction of o-iodoanilide chiral sulfinamide derivatives with alkynone to rapidly construct the key quaternary carbon stereocenter of the natural product dihydrospirotryprostatin B.

Risk factors for one-year mortality following discharge in patients with acute aortic dissection: development and validation of a predictive model in a cross-sectional study.

PURPOSE: This study was aimed to identify the risk factors that influence the mortality risk in patients with acute aortic dissection (AAD) within one year after discharge, and aimed to construct a predictive model for assessing mortality risk. METHODS: The study involved 320 adult patients obtained from the Medical Information Mart for Intensive Care (MIMIC) database. Logistic regression analysis was conducted to identify potential risk factors associated with mortality in AAD patients within one year after discharge and to develop a predictive model. The performance of the predictive model was assessed using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). To further validate the findings, patient data from the First Affiliated Hospital of Guangxi Medical University (157 patients) were analyzed. RESULTS: Univariate and multivariate logistic regression analyses revealed that gender, length of hospital stay, highest blood urea nitrogen (BUN_max), use of adrenaline, and use of amiodarone were significant risk factors for mortality within one year after discharge (p < 0.05). The constructed model exhibited a consistency index (C-index) and an area under the ROC curve of 0.738. The calibration curve and DCA demonstrated that these indicators had a good degree of agreement and utility. The external validation results of the model also indicated good predictability (AUC = 0.700, p < 0.05). CONCLUSION: The personalized scoring prediction model constructed by gender, length of hospital stays, BUN_max levels, as well as the use of adrenaline and amiodarone, can effectively identify AAD patients with high mortality risk within one year after discharge.

Efficacy and safety of drug-coated balloon for de novo lesions of large coronary arteries: Systematic review and meta-analysis of randomized controlled trials.

Background: Drug-coated balloon (DCB) is a novel approach to avoiding stent-related complications and has proven effective for the treatment of in-stent restenosis (ISR) and small vessels. However, its role in the treatment of de novo lesions in large vessels is less settled. Aims: To estimate the efficacy and safety of drug-coated balloon versus stent in the treatment of de novo lesions in large coronary arteries. Methods: We searched the literature until April 2023. We judged the safety of DCB based on major adverse cardiovascular events (MACEs), cardiac death, all-cause mortality, non-fatal myocardial infarction, target lesion revascularization (TLR), and bleeding event; and efficacy according to late lumen loss (LLL), minimum lumen diameter (MLD). We conducted subgroup analyses according to stent type and whether urgent PCI was required. Results: A total of 10 RCTs were included. Overall, LLL (mean difference (MD) = -0.19, 95 % confidence interval (CI): -0.32 to -0.06, P = 0.003) was lower in the DCB group than in the Stent arm. This effect was consistent in subgroup analysis regardless of stent type and disease type. In terms of safety indicators, there were no significant differences between DCB and stent. The subgroup analyses found that safety indicators showed no significant differences between DCB and drug-eluting stent (DES), but TLR was lower in the DCB than in the bare metal stent (BMS). Moreover, in ST-elevation myocardial infarction (STEMI), safety indicators and LLL showed no significant differences between DCB and DES, but MLD in the DCB was smaller. While in patients with excluded STEMI, MACE and TLR was lower in the DCB compared with the overall stent. Conclusions: DCB could be a promising alternative for treating de novo lesions in large coronary arteries with satisfactory efficacy and low risk, superior to BMS and not inferior to DES, with a trend toward lower late lumen loss.

Genome-Wide Association Analysis of Protein-Coding Variants in IgA Nephropathy.

SIGNIFICANCE STATEMENT: Genome-wide association studies have identified nearly 20 IgA nephropathy susceptibility loci. However, most nonsynonymous coding variants, particularly ones that occur rarely or at a low frequency, have not been well investigated. The authors performed a chip-based association study of IgA nephropathy in 8529 patients with the disorder and 23,224 controls. They identified a rare variant in the gene encoding vascular endothelial growth factor A (VEGFA) that was significantly associated with a two-fold increased risk of IgA nephropathy, which was further confirmed by sequencing analysis. They also identified a novel common variant in PKD1L3 that was significantly associated with lower haptoglobin protein levels. This study, which was well-powered to detect low-frequency variants with moderate to large effect sizes, helps expand our understanding of the genetic basis of IgA nephropathy susceptibility. BACKGROUND: Genome-wide association studies have identified nearly 20 susceptibility loci for IgA nephropathy. However, most nonsynonymous coding variants, particularly those occurring rarely or at a low frequency, have not been well investigated. METHODS: We performed a three-stage exome chip-based association study of coding variants in 8529 patients with IgA nephropathy and 23,224 controls, all of Han Chinese ancestry. Sequencing analysis was conducted to investigate rare coding variants that were not covered by the exome chip. We used molecular dynamic simulation to characterize the effects of mutations of VEGFA on the protein's structure and function. We also explored the relationship between the identified variants and the risk of disease progression. RESULTS: We discovered a novel rare nonsynonymous risk variant in VEGFA (odds ratio, 1.97; 95% confidence interval [95% CI], 1.61 to 2.41; P = 3.61×10 -11 ). Further sequencing of VEGFA revealed twice as many carriers of other rare variants in 2148 cases compared with 2732 controls. We also identified a common nonsynonymous risk variant in PKD1L3 (odds ratio, 1.16; 95% CI, 1.11 to 1.21; P = 1.43×10 -11 ), which was associated with lower haptoglobin protein levels. The rare VEGFA mutation could cause a conformational change and increase the binding affinity of VEGFA to its receptors. Furthermore, this variant was associated with the increased risk of kidney disease progression in IgA nephropathy (hazard ratio, 2.99; 95% CI, 1.09 to 8.21; P = 0.03). CONCLUSIONS: Our study identified two novel risk variants for IgA nephropathy in VEGFA and PKD1L3 and helps expand our understanding of the genetic basis of IgA nephropathy susceptibility.

Poly(A)-specific ribonuclease protein promotes the proliferation, invasion and migration of esophageal cancer cells.

BACKGROUND: Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear. AIM: To investigate the relationship between PARN and the proliferation, migration and invasion of EC cells. METHODS: The EC tissues of 91 patients after EC surgery and 63 paired precancerous healthy tissues were collected. PARN mRNA levels were measured using a tissue microarray, and the PARN expression level was evaluated using immunohistochemistry to analyze the relationship between PARN expression and clinicopathologic features as well as the survival and prognosis of patients. In addition, the effects of PARN gene knockout on tumor cell proliferation, invasion and migration were studied by using shRNA during the in vitro culture of EC cell lines Eca-109 and TE-1, and the effects of the PARN gene on tumor growth in vivo were verified by a xenotransplantation nude mice model. RESULTS: The expression of PARN in EC tissues was higher than that in adjacent normal tissues, and the level of PARN expression was significantly positively correlated with lymphatic metastasis. Patients with high PARN levels had poor overall survival. BIM, IGFBP-5 and p21 levels were significantly increased in the PARN knockout group, while the expression levels of the antiapoptotic proteins Survivin and sTNF-R1 were significantly decreased in the apoptotic antibody array data. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 in the downstream signaling pathway regulating EC progression were significantly decreased. The culture of EC cell lines confirmed that the apoptosis rate of EC cells was significantly increased, the growth and proliferation of tumor cells were significantly inhibited, and the invasion and migration ability of tumor cells were significantly decreased after PARN gene knockout. In vivo experiments of BALB/c nude mice transfected with Eca-109 cells expressing control shRNA (sh-NC) and PARN shRNA (sh-PARN) showed that the tumor volume and weight of nude mice treated with sh-PARN were significantly decreased compared with those of nude mice treated with sh-NC, indicating that PARN knockdown significantly inhibited tumor growth in vivo. CONCLUSION: PARN has antiapoptotic effects on EC cells and promotes their proliferation, invasion and migration, which is associated with the development of EC and poor patient prognosis. PARN may become a potential target for the diagnosis, prognosis prediction and treatment of EC.

PD98059 protects SH-SY5Y cells against oxidative stress in oxygen-glucose deprivation/reperfusion.

Mitochondria play a key role in the cerebral ischemia-reperfusion injury. Although the extracellular signal-regulated kinase 1/2 inhibitor PD98059 (PD) is a selective and reversible flavonoid that can protect the mitochondria in a rat model of cardiac arrest/cardiopulmonary resuscitation, its role requires further confirmation. In this study, we investigated whether PD could maintain mitochondrial homeostasis and decrease reactive oxygen species (ROS) production in neuroblastoma (SH-SY5Y) cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R). PD improved the mitochondrial morphology and function, reversed the increase in ROS production and cell apoptosis, and reduced total-superoxide dismutase and Mn-superoxide dismutase activities induced by OGD/R. PD decreases ROS production and improves mitochondrial morphology and function, protecting SH-SY5Y cells against OGD/R-induced injury.

Inhibition of ERK downregulates autophagy via mitigating mitochondrial fragmentation to protect SH-SY5Y cells from OGD/R injury.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is the main cause leading to high mortality and neurological disability in patients with cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Our previous study found that extracellular signal-regulated kinase (ERK) activation, dynamin-related protein1 (Drp1)/Mitofusin2 (Mfn2)-dependent mitochondrial dynamics imbalance, and excessive autophagy were involved in the mechanism of nerve injury after CA/CPR. However, the specific pathological signaling pathway is still unknown. This study aimed to explore the molecular function changes of ERK-Drp1/Mfn2-autophagy signaling pathway in SH-SY5Y cell oxygen-glucose deprivation/reoxygenation (OGD/R) model, to further clarify the pathophysiological mechanism of CIRI, and to provide a new strategy for cerebral protection after CIRI. METHODS: SH-SY5Y cells were pretreated with drugs 24 h before OGD/R. The Drp1 and Mfn2 knockdown were adopted small interfering RNAs. The overexpression of p-Drp1S616 and Mfn2 were used recombinant plasmids. The expression levels of mitochondrial dynamics proteins (p-Drp1, Drp1, Mfn2, Mfn1 and Opa1) and autophagy markers (LC3, Beclin1 and p62) were measured with the Western blotting. The mRNA levels after transfection were determined by PCR. Cell injury and viability were evaluated with released LDH activity and CCK8 assay kits. Mitochondria morphology and autophagosome were observed under transmission electron microscopy. Mitochondrial function was detected by the mitochondrial permeability transition pore assay kit. The co-expression of p-ERK, p-Drp1 and LC3 was assessed with multiple immunofluorescences. One-way analysis of variance followed by least significance difference post hoc analysis (for equal homogeneity) or Dunnett's T3 test (for unequal homogeneity) were used for statistical tests. RESULTS: ERK inhibitor-PD98059 (PD) protects SH-SY5Y cells from OGD/R-induced injury; while ERK activator-TPA had the opposite effect. Similar to autophagy inhibitor 3-MA, PD downregulated autophagy to improve cell viability; while autophagy activator-rapamycin further aggravated cell death. PD and Drp1-knockdown synergistically attenuated OGD/R-induced Drp1 activation, mPTP opening and cell injury; overexpression of Drp1S616E or ablating Mfn2 partly abolished the protective effects of PD. Multiple immunofluorescences showed that p-ERK, p-Drp1 and LC3 were co-expressed. CONCLUSION: Inhibition of ERK downregulates autophagy via reducing Drp1/Mfn2-dependent mitochondrial fragmentation to antagonize mitochondrial dysfunction and promotes cell survival in the SH-SY5Y cells OGD/R model. Video Abstract.

Efficacy and Safety of Sevelamer Carbonate in Chinese Nondialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized, Double-Blind, Parallel-Group Study.

Introduction: Previous studies suggested that sevelamer carbonate is well tolerated with a favorable efficacy and safety profile in both dialysis and nondialysis patients in Europe; however, the efficacy remains controversial, and few studies have examined sevelamer carbonate therapy in other ethnic nondialysis CKD patients. This study assessed the efficacy and safety of sevelamer carbonate in Chinese nondialysis CKD patients with hyperphosphatemia. Methods: The multicenter, randomized, double-blind, parallel-group, placebo-controlled, and phase 3 clinical trial enrolled 202 Chinese nondialysis CKD patients with serum phosphorus ≥1.78 mmol/L. Patients were randomly assigned 1:1 to receive sevelamer carbonate (2.4-12 g per day) or placebo for 8 weeks. The primary outcome was the change in serum phosphorous between baseline and week 8. Results: Totally 482 Chinese patients were screened and 202 were randomized (sevelamer carbonate, n = 101; placebo, n = 101). The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate compared with placebo (-0.22 ± 0.47 vs. 0.05 ± 0.44 mmol/L, p < 0.0001). Significantly (p < 0.0001), decreases of serum total cholesterol, low-density lipoprotein cholesterol, and calcium-phosphorus (Ca × P) product levels from baseline to week 8 were shown in sevelamer carbonate group compared with placebo group. Serum intact parathyroid hormone was not significantly changed in the sevelamer carbonate group (p = 0.83). Patients in the sevelamer carbonate group experienced similar adverse events as the placebo group. Conclusion: Sevelamer carbonate is an effective and well-tolerated phosphate binder in advanced nondialysis CKD Chinese patients with hyperphosphatemia.

Calpain inhibitor MDL28170 alleviates cerebral ischemia­reperfusion injury by suppressing inflammation and autophagy in a rat model of cardiac arrest.

Cerebral ischemia-reperfusion injury (CIRI) is associated with a poor neurological prognosis in patients who have experienced cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The aim of the current study was to investigate the potential role of a calpain inhibitor in CIRI using a rat model of CA. CA was induced in adult male Sprague-Dawley rats, and MDL28170 (a calpain inhibitor) was administered to the rats within 30 min after the return of spontaneous circulation. Differences between groups were evaluated by measuring survival rate, CPR duration and neurological deficit score. Hematoxylin-eosin staining and Nissl staining were performed to assess cerebral injury, and microstructure and autophagy were assessed by transmission electron microscopy. The levels of calpain-1, calpain-2, calpastatin, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, P62, beclin-1 and LC3 in the brain tissues were determined using western blotting and double immunofluorescence staining. There was no significant difference in CPR duration or survival rate among the groups. At 24 h after CPR, the CA group demonstrated damaged tissue morphology; decreased neurological deficit scores, and P62 expression; and upregulated calpain-2, IL-1ßp17, TNF-α, beclin-1 and LC3 levels in the cortex. However, MDL28170 improved neuronal function and suppressed inflammation and autophagy by inhibiting calpain-2 level, but there were no differences in the calpain-1 and calpastatin levels. These results suggest that calpain-2, inflammation and autophagy are involved in CA-induced CIRI. MDL28170 inhibited calpain-2 expression, inflammation and autophagy, which suggests its potential efficacy in treating post-CA nerve damage.

Effect of Red Cell Distribution Width on the Prognosis of Patients with Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: The link between red cell distribution width (RDW) and prognosis of traumatic brain injury (TBI) is controversial. Whether RDW can increase the prognostic value of established predictors remains unknown. This study aimed to provide supportive evidence for the prognostic value of RDW. METHODS: Clinical data of 1488 patients with TBI were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database and classified into 2 groups: 1) one with RDW <14.5% (n = 1061) and 2) the other with RDW ≥14.5% (n = 427). Multivariable logistic regression models were used to estimate the relationship between RDW and outcomes. Stratified analyses and interactions were also performed. We compared the area under the receiver operating characteristic curve of the International Mission for Prognoses and Clinical Trial Design in TBI (IMPACT) core and extended models with and without RDW. RESULTS: After adjusting for confounding factors, RDW was an independent risk consideration for TBI prognoses; the odds ratios were 1.62 (95% confidence interval (CI): 1.05, 2.50) and 1.89 (95% CI: 1.35, 2.64) for hospital mortality and 6-month mortality, respectively. This association was crucial for patients with a Glasgow Coma Score of 3-12 (odds ratio, 2.79; 95% CI: 1.33, 5.87). For 6-month mortality, when RDW was added to the core and extended IMPACT models, the area under the receiver operating characteristic curve increased from 0.833 to 0.851 (P = 0.001) and from 0.842 to 0.855 (P = 0.002), respectively. CONCLUSIONS: Elevated RDW is an independent risk consideration for hospital and 6-month mortality rates. When RDW was added to the IMPACT core and extended models, it improved its predictive ability for 6-month mortality in patients with TBI.

Conventional disease-modifying anti-rheumatic drugs combined with Chinese Herbal Medicines for rheumatoid arthritis: A systematic review and meta-analysis.

Rheumatoid Arthritis (RA) remains a major global public health challenge. Disease-modifying anti-rheumatic drugs (DMARDs) are standard therapeutic drugs for RA. Conventional DMARDs (c-DMARDs) are a subgroup of approved synthetic DMARDs. The c-DMARDs experienced lesser response with longer disease duration or drug exposure, and unwanted adverse events (AEs). The combination treatments (CTs) of c-DMARDs and Chinese Herbal Medicines (CHMs) were often used in RA clinical trials for increasing the therapeutic effectiveness and reducing the AEs. This systematic review aimed to evaluate the efficacy and safety of the CTs for RA. Databases were searched from inception to October 2020 for identification of randomized controlled trials (RCTs) that investigated the CTs in the management of RA. Twenty-three RCTs with 2,441 participants were included. The assessments and analyses found CTs improved American College of Rheumatology (ACR) 20 (RR: 1.33, 95% CI [1.21, 1.45], 10 studies, n=1,075) and alleviated AEs (RR: -0.40, 95% CI [-0.30, -0.53], 19 studies, n=2,011) in comparison with c-DMARDs. The CTs also significantly improved RA symptoms and patient-reported outcomes; reduced disease activity score (DAS) 28, serum acute-phase reactants and RA biomarkers. The five most commonly used herbs in included studies were Angelicae Sinensis Radix, Paeoniae Radix Alba, Cinnamomi Ramulus, Glycyrrhizae Radix et Rhizoma, and Clematidis Radix et Rhizoma. Pharmacological studies indicated these CHMs could contribute to the outcomes. The integrated CHMs potentially increased the overall effectiveness of c-DMARDs and alleviated AEs in management of RA. Large sample and rigorously designed RCTs are required for future studies.

Impact of adding opioids to paravertebral blocks in breast cancer surgery patients: A systematic review and meta-analysis.

BACKGROUND: Several breast cancer studies have reported the use of adjuvant opioids with the paravertebral block (PVB) to improve outcomes. However, there is no level-1 evidence justifying its use. AIM: To elucidate if the addition of opioids to PVB improves pain control in breast cancer surgery patients. METHODS: We conducted an electronic literature search across PubMed, Embase, Scopus, and Google Scholar databases up to October 20, 2020. Only randomized controlled trials (RCTs) comparing the addition of opioids to PVB with placebo for breast cancer surgery patients were included. RESULTS: Six RCTs were included. Our meta-analysis indicated significantly reduced 24-h total analgesic consumption with the addition of opioids to PVB as compared to placebo [standardized mean difference (SMD) -1.57, 95% confidence interval (CI): -2.93, -0.21, I 2 = 94%]. However, on subgroup analysis, the results were non-significant for studies using single PVB (SMD: -1.76, 95%CI: -3.65, 0.13 I 2 = 95.09%) and studies using PVB infusion (SMD: -1.30, 95%CI: -4.26, 1.65, I 2 = 95.49%). Analysis of single PVB studies indicated no significant difference in the time to first analgesic request between opioid and placebo groups (mean difference -11.28, 95%CI: -42.00, 19.43, I 2 = 99.39%). Pain scores at 24 h were marginally lower in the opioid group (mean difference -1.10, 95%CI: -2.20, 0.00, I 2 = 0%). There was no difference in the incidence of postoperative nausea and vomiting between the two groups. CONCLUSION: Current evidence suggests a limited role of adjuvant opioids with PVB for breast cancer surgery patients. Further homogenous RCTs with a large sample size are needed to clarify the beneficial role of opioids with PVB.

Tracing the pollution and human risks of potentially toxic elements in agricultural area nearby the cyanide baths from an active private gold mine in Hainan Province, China.

Mining activities are well-known sources of potentially toxic elements (PTEs) pollution, which often jeopardize the biosphere, pedosphere, and hydrosphere. However, the soil and groundwater pollution caused by active private mining activities has long been neglected. This study investigated the occurrence of PTEs and cyanide (CN) in agricultural soils, mine tailings, and groundwater nearby the cyanide baths from a private gold mine in Hainan Province, southern China. Results indicated that concentrations of Pb, As, Cd, Hg, and CN in different soil depths and mine tailings were up to ten thousand mg/kg, and relatively higher content of As and Pb was detected in groundwater. The chemical forms of Cd, Pb, As, and Hg varied greatly in different soil depths; over 80% of Cd distributed in the water-soluble fraction, suggesting its higher mobility in soils, while approximately 60-90% of Pb, As, and Hg distributed in other chemical fractions, indicating relatively lower mobility in soils. The pollution indices also revealed the serious pollution and deterioration of site quality in this area. Human risk assessments also reflected a high non-carcinogenic/carcinogenic health risk in this area. The framework of integrated management strategies for private metal mines was proposed to mitigate PTEs pollution and reduce health risks.

The effect of high-intensity interval training on exercise capacity in post-myocardial infarction patients: a systematic review and meta-analysis.

AIMS: Exercise-based cardiac rehabilitation has been recommended a treatment for patients with cardiovascular disease. Nevertheless, it remains controversial which exercise characteristics are most beneficial for post-myocardial infarction (MI) patients. We performed a systematic review and meta-analysis to investigate the effects of high-intensity interval training (HIIT) in these patients. METHODS AND RESULTS: We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang Dataset (from the earliest date available to February 2021) for randomized controlled trials and cohort studies that evaluated the effects of HIIT on post-MI patients. Studies were selected according to inclusion and exclusion criteria. Data synthesis was performed with R software version 4.0.1. Eight studies met the study criteria, including 387 patients. Compared to the control group [moderate-intensity continuous training (MICT) and/or routine physical activity], HIIT significantly improved peak oxygen uptake (peak VO2) [mean difference = 3.83 mL/kg/min, 95% confidence interval (CI) (3.25, 4.41), P < 0.01]. No significant difference in systolic and diastolic blood pressures, peak and resting heart rate, left ventricular ejection fraction, left ventricular end-diastolic volume, and the quality of life was found between HIIT group and control group. The duration of follow-up ranged from 6 to 12 weeks. The incidence of adverse events was similar between groups [risk difference = 0.01, 95% CI (-0.02, 0.04), P = 0.53]. CONCLUSION: Compared with MICT and routine physical activity, HIIT could significantly improve exercise capacity in post-MI patients, and appears to be safe.

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

A survey of cognitive function in peritoneal dialysis patients.

INTRODUCTION: The aim of this study was to investigate how peritoneal dialysis and other influencing factors affect patients' cognitive function. METHODS: The 85 subjects in the study group were regular patients in our center. The control group included 88 age and gender matched healthy individuals who were with normal renal function. The study subjects' cognitive levels and related factors were analyzed using several screening instruments: the cognitive function was measured using the Montreal Cognitive Assessment Scale and statistical analysis was conducted based on the relevant data. RESULTS: The results showed that cognitive impairment was higher in peritoneal dialysis patients than in non-dialysis subjects. Age and educational background were single factors that affected cognitive function, which was more likely to be impaired at a higher age level and/or a lower educational level. CONCLUSION: Cognitive function can be impaired by peritoneal dialysis, and age and education levels are influencing factors.

A retrospective study: do patients with left ventricular ejection fraction ≤50% benefit from heart valve surgery?

Background: Left ventricular ejection fraction (LVEF) is an indicator of heart failure, and it is controversial whether patients with reduced preoperative left ventricular ejection fraction can benefit from heart valve surgery. We aimed to assess the differences in clinical characteristics after surgery in patients with different grades of reduced preoperative LVEF to guide clinical management. Methods: A total of 100 heart valve disease patients with low LVEF (≤50%) who had undergone valve surgery in the Department of Cardiology. The patients were divided into three groups according to their LVEF measured by echocardiography before surgery, with LVEF ≤40% as group A, 40%< LVEF ≤45% as group B, and 45%< LVEF ≤50% as group C. Clinical characteristics such as postoperative LVEF values, oxygenation index, liver function and inflammatory index, intra-aortic balloon pump (IABP) utilization rate, and mortality were compared among the three groups of patients. Results: There was no statistically significant difference in the preoperative baseline data between the three groups of patients (P>0.05). The clinical outcomes of patients in group A (n=28) were similar to those of patients in groups B (n=39) and C (n=33) (P>0.05). The vasoactive-inotropic score (VIS), postoperative ventilator use time, length of stay in the care unit, IABP use rate, and mortality rate on the first postoperative day were higher in group A. By comparing the preoperative and postoperative (within 48 hours and 3 months after surgery) cardiac echocardiograms of the three groups, we learned that LVEF increased, LV end-systolic internal diameter and LV end-diastolic internal diameter decreased, and ventricular remodeling improved after surgery compared with the preoperative period (P<0.05). The postoperative improvement was more obvious in group A than in groups B and C. Three months after surgery, LVEF increased to 55%, the LV end-systolic internal diameter decreased to 39 mm, and the LV end-diastolic internal diameter decreased to about 55 mm in each group (P>0.05). Conclusions: Patients with heart valve disease and low LVEF should be actively treated with heart valve surgery, which can significantly improve the patient's left ventricular reverse remodeling and cardiac function, thereby facilitating survival.

Anti-Inflammatory and Antimicrobial Volatile Oils: Fennel and Cumin Inhibit Neutrophilic Inflammation via Regulating Calcium and MAPKs.

Neutrophilic inflammatory diseases, such as chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), or psoriasis, exert a huge burden on the global health system due to the lack of safe and effective treatments. Volatile oils from terrestrial plants showed impressive therapeutic effects against disorders of the skin, digestive system, lungs, liver, metabolism, and nervous system. However, their effect on the immune system and neutrophil function is still elusive. Fennel, cumin, marjoram, lavender, caraway, and anise are the common nutraceuticals that are widely used in the Mediterranean diet. The volatile oils of these herbs were screened for various biological activities, including anti-inflammatory, anti-allergic, antimicrobial, and antiviral effects. Several oils showed anti-inflammatory and antimicrobial potential. Fennel (Foeniculum vulgare) and cumin (Cuminum cyminum) fruits' volatile oils significantly suppressed the activation of human neutrophils, including respiratory burst and the degranulation induced by formyl peptide receptor agonists fMLF/CB and MMK1 in the human neutrophils (IC50, 3.8-17.2 µg/ml). The cytotoxic effect and free-radical scavenging effects (ABTS, DPPH) of these oils did not account for the observed effects. Both fennel and cumin volatile oils significantly shortened calcium influx recovery time and inhibited phosphorylation of mitogen-activated protein kinases (p38, JNK, and ERK) expression. The gas chromatography-mass spectrometry analysis of these oils revealed the presence of estragole and cuminaldehyde as the major components of fennel and cumin volatile oils, respectively. Our findings suggested that cumin and fennel, common in the Mediterranean diet, hold the potential to be applied for the treatment of neutrophilic inflammatory diseases.

High-volume hemofiltration reduces short-term mortality with no influence on the incidence of MODS, hospital stay, and hospitalization cost in patients with severe-acute pancreatitis: A meta-analysis.

This study aimed to investigate the efficiency, safety and cost-efficiency of blood purification (BP) in treating patients with severe-acute pancreatitis (SAP). A literature search was conducted using PubMed, OVID, International Clinical Trials Register (ICTRP), and Cochrane Central Register of Controlled Trials (CENTRAL). A total of 11 prospective studies and 6 retrospective studies, which reported the mortality of 1279 SAP patients, were included for analysis. Decreased short-term mortality and incidence rate of infection were observed in the high-volume hemofiltration (HVHF) group, but not in patients treated with other types of BP. There was no significant difference in the incidence of multiple-organ dysfunction (MODS), duration of hospital stay, or cost of hospitalization between the BP and non-BP groups. The starting time point, substitution fluid flow rate, filter membrane type, hemofilter change interval, anticoagulation, and sustaining times of BP varied across studies. In conclusion, HVHF may reduce the short-term mortality (<4 weeks), not long-term mortality, of SAP patients by decreasing the incidence of infection, while other types of BP did not show a significant beneficial effect. Neither HVHF nor other BP patterns affect the duration of hospital stay, cost of hospitalization, or incidence of MODS in SAP patients.

Biological effects and mechanisms of matrine and other constituents of Sophora flavescens in colorectal cancer.

The plant Sophora flavescens Ait. has been used in the clinical management of colorectal cancer (CRC). Its constituent compounds, notably the alkaloids matrine, oxymatrine, and sophoridine, have received considerable research attention in experimental models of CRC in vivo and in vitro. This review found that extracts of S. flavescens and/or its constituent compounds have been reported to inhibit CRC cell proliferation by inducing cell-cycle arrest at the G1 phase, inducing apoptosis via the intrinsic pathway, interfering in cancer metabolism, inhibiting metastasis and angiogenesis, regulating senescence and telomeres, regulating the tumour microenvironment and down-regulating cancer-related inflammation. In addition, matrine and oxymatrine reversed multi-drug resistance and enhanced the effects of chemotherapies. These anti-cancer effects were associated with regulation of several cellular signalling pathways including: MAPK/ERK, PI3K/AKT/mTOR, p38MAPK, NF-κB, Hippo/LATS2, TGF-ß/Smad, JAK/STAT3, RhoA/ROC, and Wnt/ ß-catenin pathways. These multiple actions in CRC suggest the alkaloids of S. flavescens may be therapeutic candidates for CRC management. Nevertheless, there remains considerable scope for future research into its flavonoid constituents, the effects of combinations of compounds, and the interaction between these compounds and anti-cancer drugs. In addition, more research is needed to investigate likely drug ligand-receptor interactions for each of the bioactive compounds.