Two new megastigmane glycosides from the leaves of Nicotiana tabacum and their anti-inflammatory activities.

Two new megastigmane glycosides, (6 R,7E,9R)-3-oxo-α-ionyl-9-O-α-L-rhamnopyranosyl-(1''→4')-ß-D-glucopyranoside (1) and (6 R,7E,9R)-3-oxo-α-ionyl-9-O-ß-D-glucopyranosyl-(1''→6')-ß-D-glucopyranoside (2), together with six known analogues (3-8) were isolated from the leaves of Nicotiana tabacum. The structures of all metabolites were determined by comprehensive analysis of NMR and MS spectroscopic data as well as by comparison with those of previously reported. The in vitro anti-inflammatory activity of all isolates was evaluated using a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model, and the compounds 1, 3, 7, and 8 exhibited inhibition of LPS-induced NO production in RAW264.7 macrophage cells with IC50 values of 42.3-61.7 µM (positive control, dexamethasone, IC50 = 21.3 ± 1.2 µM).

A Promising Application of Injectable Hydrogels in Nerve Repair and Regeneration for Ischemic Stroke.

Ischemic stroke, a condition that often leads to severe nerve damage, induces complex pathological and physiological changes in nerve tissue. The mature central nervous system (CNS) lacks intrinsic regenerative capacity, resulting in a poor prognosis and long-term neurological impairments. There is no available therapy that can fully restore CNS functionality. However, the utilization of injectable hydrogels has emerged as a promising strategy for nerve repair and regeneration. Injectable hydrogels possess exceptional properties, such as biocompatibility, tunable mechanical properties, and the ability to provide a supportive environment for cell growth and tissue regeneration. Recently, various hydrogel-based tissue engineering approaches, including cell encapsulation, controlled release of therapeutic factors, and incorporation of bioactive molecules, have demonstrated great potential in the treatment of CNS injuries caused by ischemic stroke. This article aims to provide a comprehensive review of the application and development of injectable hydrogels for the treatment of ischemic stroke-induced CNS injuries, shedding light on their therapeutic prospects, challenges, recent advancements, and future directions. Additionally, it will discuss the underlying mechanisms involved in hydrogel-mediated nerve repair and regeneration, as well as the need for further preclinical and clinical studies to validate their efficacy and safety.

Plant-based diets and the risk of pancreatic cancer: a large prospective multicenter study.

BACKGROUND: Plant-based diets have been recommended for improving health outcomes, including cancer. However, previous studies on plant-based diets and the risk of pancreatic cancer are scarce and fail to consider plant food quality. OBJECTIVES: We sought to examine the potential associations of 3 plant-based diet indices (PDIs) with the risk of pancreatic cancer in a US population. METHODS: A population-based cohort of 101,748 US adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The overall PDI, healthful PDI (hPDI), and unhealthful PDI (uPDI) were constructed to qualify adherence to overall, healthy, and less healthy plant-based diets, respectively, with higher scores indicating better adherence. Multivariable Cox regression was used to compute hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was conducted to identify the potential effect modifiers. RESULTS: Over a mean follow-up of 8.86 years, 421 pancreatic cancer cases occurred. Participants in the highest compared with the lowest quartiles of overall PDI had a lower risk of pancreatic cancer [HRquartile 4 versus 1: 0.74; 95% confidence interval (CI): 0.57, 0.96; Ptrend = 0.023]. A stronger inverse association was observed for hPDI (HRquartile 4 versus 1: 0.56; 95% CI: 0.42, 0.75; Ptrend < 0.001). Conversely, uPDI was positively associated with the risk of pancreatic cancer (HRquartile 4 versus 1: 1.38; 95% CI: 1.02, 1.85; Ptrend = 0.012). Subgroup analyses revealed a stronger positive association for uPDI in participants with BMI <25 (HRquartile 4 versus 1: 3.22; 95% CI: 1.56, 6.65) than in those with BMI ≥25 (HRquartile 4 versus 1: 1.08; 95% CI: 0.78, 1.51) (Pinteraction = 0.001). CONCLUSIONS: In this US population, adherence to a healthy plant-based diet confers a lower risk of pancreatic cancer, whereas adherence to a less healthy plant-based diet confers a higher risk. These findings highlight the importance of considering plant food quality in preventing pancreatic cancer.

Study on the correlation between early three-dimensional gait analysis and clinical efficacy after robot-assisted total knee arthroplasty.

PURPOSE: Robot-assisted technology is a forefront of surgical innovation that improves the accuracy of total knee arthroplasty (TKA). But whether the accuracy of surgery can improve the clinical efficacy still needs further research. The purpose of this study is to perform three-dimensional (3D) analysis in the early postoperative period of patients who received robot-assisted total knee arthroplasty (RATKA), and to study the trend of changes in gait parameters after RATKA and the correlation with the early clinical efficacy. METHODS: Patients who received RATKA in the Center of Joint Surgery, the First Hospital Affiliated to Army Military Medical University from October 2020 to January 2021 were included. The imaging parameters, i.e., hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, posterior condylar angle were measured 3 months post-TKA. The 3D gait analysis and clinical efficacy by Western Ontario Mac Master University Index (WOMAC) score were performed pre-TKA, 3 and 6 months post-TKA. The differences in spatiotemporal parameters of gait, kinetic parameters, and kinematic parameters of the operated limb and the contralateral limb were compared. The correlation between gait parameters and WOMAC scores was analyzed. Paired sample t-test and Wilcoxon rank-sum test were used to analyze the difference between groups, and Spearman correlation coefficient was used to analyze the correlation. RESULTS: There were 31 patients included in this study, and the imaging indexes showed that all of them returned to normal post-TKA. The WOMAC score at 3 months post-TKA was significantly lower than that pre-TKA, and there was no significant difference between at 3 and 6 months. The 3D gait analysis results showed that the double support time of the operated limb reduced at 3 and 6 months (all p < 0.05), the maximum extension and maximum external rotation of the knee joint increased at stance phase, and the maximum flexion angle, the range of motion and the maximum external rotation increased at swing phase. Compared with the preoperative data, there were significant improvements (all p < 0.05). Compared with the contralateral knee joint, the maximum external rotation of the knee joint at swing phase was smaller than that of the contralateral side, and the maximum flexion and extension moment was greater than that of the contralateral knee. The maximum external rotation moment of the joint was greater than that of the contralateral knee joint (p < 0.05). There was a negative correlation between the single support time pre-TKA and the WOMAC score at 3 months (p = 0.017), and the single support time at 3 months was negatively correlated with the WOMAC score at 6 months (p = 0.043). The cadence at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.031). The maximum knee extension at stance phase at 6 months was negatively correlated with the WOMAC score at 6 month (p = 0.048). The maximum external rotation at stance phase at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.024). CONCLUSION: The 3D gait analysis of RATKA patients is more sensitive than WOMAC score in evaluating the clinical efficacy. Trend of changes in gait parameters shows that the knee joint support, flexion and extension function, range of motion, external rotation and varus deformity moment of the patient were significantly improved at 3 months after surgery, and continued to 6 months after surgery. Compared with the contralateral knee, the gait parameters of the operated limb still has significant gaps in functionality, such as the external rotation and flexion and extension. The single support time, cadence, knee extension, and knee external rotation of the operated limb have a greater correlation with the postoperative WOMAC score. Postoperative rehabilitation exercises should be emphasized, which is of great value for improving the early efficacy of RATKA.

Early diagnosis of intracranial atherosclerotic large vascular occlusion: A prediction model based on DIRECT-MT data.

Aims: This study aimed to build a prediction model to early diagnose intracranial atherosclerosis (ICAS)-related large vascular occlusion (LVO) in acute ischemic stroke patients before digital subtractive angiography. Methods: Patients enrolled in the DIRECT-MT trial (NCT03469206) were included in our secondary analysis and distributed into ICAS-LVO and non-ICAS-LVO groups. We also retrieved demographic data, medical histories, clinical characteristics, and pre-operative imaging data. Hypothesis testing was used to compare data of the two groups, and univariate logistic regression was used to identify the predictors of ICAS-LVO primarily. Then, we used multivariate logistic regression to determine the independent predictors and formulate the prediction model. Model efficacy was estimated by the area under the receiver operating characteristic (ROC) curve (AUC) and diagnostic parameters generated from internal and external validations. Results: The subgroup analysis included 45 cases in the ICAS-LVO group and 611 cases in the non-ICAS-LVO group. Variates with p < 0.1 in the comparative analysis were used as inputs in the univariate logistic regression. Next, variates with p < 0.1 in the univariate logistic regression were used as inputs in the multivariate logistic regression. The multivariate logistic regression indicated that the atrial fibrillation history, hypertension and smoking, occlusion located at the proximal M1 and M2, hyperdense artery sign, and clot burden score were related to the diagnosis of ICAS-LVO. Then, we constructed a prediction model based on multivariate logistics regression. The sensitivity and specificity of the model were 84.09 and 74.54% in internal validation and 73.11 and 71.53% in external validation. Conclusion: Our current prediction model based on clinical data of patients from the DIRECT-MT trial might be a promising tool for predicting ICAS-LVO.

A Newly Designed "SkyWalker" Robot Applied in Total Knee Arthroplasty: A Retrospective Cohort Study for Femoral Rotational Alignment Restoration.

OBJECTIVE: This study explored whether robotic arm-assisted total knee arthroplasty (RATKA) has the advantage of restoring femoral rotational alignment compared to conventional total knee arthroplasty (COTKA). METHODS: Sixty patients (45 women and 15 men) attending our department from May 2019 to December 2020 were selected and divided into two groups, with 30 patients in each group, according to whether they underwent COTKA or RATKA. Femoral rotational alignment results, such as, posterior condylar angle (PCA), patella transverse axis-femoral transepicondylar axis angle (PFA), radiological findings, such as, hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA), and operative data (operation time, intraoperative blood loss, tourniquet time, and length of stay (LOS), and clinical outcomes, such as maximum knee flexion angle (MKFA), Knee Society Score (KSS), and Western Ontario Mac Master University Index Score (WOMAC) were compared within and between the two groups. RESULTS: PCA and PFA in the RATKA group were (0.6 ± 0.3)° and (0.9 ± 0.3)°, respectively, which were smaller than (1.5 ± 2.0)° and (3.1 ± 1.1)° in the COTKA group (P < 0.05), and were closer to 0°; the differences in HKA, LDFA, and MPTA were not statistically significant. With the exception of the LDFA, the HKA, MPTA, PCA, and PFA improved in both groups after surgery (P < 0.05). The blood loss and the LOS of RATKA group were 192.3 ± 23.1 mL and 8.2 ± 1.4 days, which were less than 203.7 ± 29.8 mL and 9.3 ± 1.1 days of the COTKA group, but the operation time showed no statistically significant difference, and the tourniquet time was longer (P < 0.05). The MKFA in the RATKA group was (123.0 ± 3.7)°, which was greater than (116.3 ± 4.6)° in the COTKA group (P < 0.05). In terms of scores, the postoperative results were better than the preoperative results in both groups (P < 0.05). However, there was no statistically significant difference between the groups. CONCLUSION: The accuracy of femoral rotational alignment reconstructed achieved by RATKA is significantly better than that of COTKA and is more conducive to the recovery of knee flexion function after surgery; although RATKA reduces intraoperative blood loss and postoperative LOS, the short-term clinical efficacy comparison has not yet demonstrated the advantages of robotic technology, and a more optimized design is needed to improve the efficiency of RATKA surgery.

Occludin facilitates tumour angiogenesis in bladder cancer by regulating IL8/STAT3 through STAT4.

Bladder cancer (BLCA) is a common genitourinary cancer in patients, and tumour angiogenesis is indispensable for its occurrence and development. However, the indepth mechanism of tumour angiogenesis in BLCA remains elusive. According to recent studies, the tight junction protein family member occludin (OCLN) is expressed at high levels in BLCA tissues and correlates with a poor prognosis. Downregulation of OCLN inhibits tumour angiogenesis in BLCA cells and murine xenografts, whereas OCLN overexpression exerts the opposite effect. Mechanistically, the RT-qPCR analysis and Western blotting results showed that OCLN increased interleukin-8 (IL8) and p-signal transducer and activator of transcription 3 (STAT3) levels to promote BLCA angiogenesis. RNA sequencing analysis and dual-luciferase reporter assays indicated that OCLN regulated IL8 transcriptional activity via the transcription factor STAT4. In summary, our results provide new perspectives on OCLN, as this protein participates in the development of BLCA angiogenesis by activating the IL8/STAT3 pathway via STAT4 and may serve as a novel and unique therapeutic target.

Egg consumption and risks of all-cause and cause-specific mortality: a dose-response meta-analysis of prospective cohort studies.

CONTEXT: Current dietary guidelines recommend eggs as a part of a healthy diet. However, whether egg consumption is associated with risk of mortality remains controversial. Moreover, the dose-response association of egg consumption with risk of mortality has not been determined. OBJECTIVE: To determine the potential dose-response association of egg consumption with risk of mortality in the general population. DATA SOURCES: The PubMed and Embase databases were searched for publications meeting eligibility criteria through November 2021. DATA EXTRACTION: Required data were extracted by 1 reviewer and then checked for accuracy by another reviewer. A random-effects dose-response meta-regression model was used to calculate the pooled risk estimates. A restricted cubic spline model was used to test nonlinearity. The certainty of evidence was assessed using the GRADE system. DATA ANALYSIS: Nineteen prospective cohort studies, involving 1 737 893 participants, were included. The pooled hazard ratios for an increase of 1 egg/d were 1.08 (95%CI, 1.01-1.15) for all-cause mortality, 1.07 (95%CI, 0.97-1.18) for cardiovascular disease-caused mortality, and 1.16 (95%CI, 1.04-1.30) for cancer-caused mortality. The certainty of evidence for these observations was rated as very low. Nonlinear dose-response associations were found for egg consumption and all-cause, cardiovascular disease-caused, and cancer-caused mortality. Moreover, the positive association between egg consumption and all-cause mortality was more pronounced in studies with adjustment for blood cholesterol-related covariates than those without (Pinteraction = 0.011). CONCLUSIONS: Greater amount of egg consumption confers higher risks of death from all causes, cardiovascular disease, and canc er in a nonlinear dose-response pattern. These findings should be treated with caution and need to be confirmed by future studies.

Tight junction protein 1 promotes vasculature remodeling via regulating USP2/TWIST1 in bladder cancer.

Bladder cancer (BLCA) is the most common malignant tumor of the urinary system and is characterized by high metastatic rates and poor prognosis. The expression of tight junction protein 1 (TJP1) is associated with bladder cancer invasion; however, the mechanism by which TJP1 affects vasculature remodeling remains unknown. In this study, we found that TJP1 expression correlated with tumor angiogenesis and poor overall survival in clinical samples. Furthermore, TJP1 overexpression promoted tumor angiogenesis in BLCA cells and stimulated recruitment of macrophages to tumors by upregulating CCL2 expression. Mechanistically, TJP1 interacted with TWIST1 and enhanced the transcriptional activity of CCL2. The impairment of tumor angiogenesis caused by knockdown of TJP1 was dramatically rescued by overexpression of TWIST1. Furthermore, TJP1 recruited USP2, which deubiquitinated TWIST1, thereby protecting TWIST1 from proteasome-mediated protein degradation. In conclusion, our results suggest that TJP1 controls angiogenesis in BLCA via TWIST1-dependent regulation of CCL2. We demonstrate that TJP1 functions as a scaffold for the interaction between USP2 and TWIST1 and this may provide potential therapeutic targets in bladder cancer.

Type 2 Diabetes-Prevention Diet and All-Cause and Cause-Specific Mortality: A Prospective Study.

We aimed to examine whether type 2 diabetes-prevention diet, a dietary pattern previously developed for reducing type 2 diabetes risk, was associated with mortality in a US population. A population-based cohort of 86,633 subjects was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2015). Dietary information was collected with a food frequency questionnaire. A dietary diabetes risk-reduction score was calculated to reflect adherence to this dietary pattern, with higher scores representing better adherence. Hazard ratios (HRs) and absolute risk differences (ARDs) in mortality rates per 10,000 person-years were calculated. After a mean follow-up of 13.6 years, 17,532 all-cause deaths were observed. Participants with the highest versus the lowest quintiles of dietary diabetes risk-reduction score were observed to have decreased risks of death from all causes (HR = 0.76, 95% CI: 0.72, 0.80; ARD: -81.94, 95% CI: -93.76, -71.12), cardiovascular disease (HR = 0.73, 95% CI: 0.66, 0.81; ARD: -17.82, 95% CI: -24.81, -11.30), and cancer (HR = 0.85, 95% CI: 0.78, 0.94; ARD: -9.92, 95% CI: -15.86, -3.59), which were modified by sex, smoking status, or alcohol consumption in subgroup analyses (P for interaction < 0.05 for all). In conclusion, a type 2 diabetes-prevention diet confers reduced risks of death from all causes, cardiovascular disease, and cancer in this US population.

Type 2 diabetes prevention diet and the risk of pancreatic cancer: A large prospective multicenter study.

BACKGROUND & AIMS: Type 2 diabetes prevention diet confers a lower risk of type 2 diabetes, which exhibits overlapping mechanisms with pancreatic cancer. We performed a prospective study to examine whether adherence to this dietary pattern is associated with a reduced risk of pancreatic cancer. METHODS: A population-based cohort of 101,729 American adults was identified. A dietary diabetes risk reduction score was computed to reflect adherence to this dietary pattern, with higher scores representing greater adherence. Cox regression was used to compute hazard ratios (HRs) for pancreatic cancer incidence. Prespecified subgroup analyses were used to identify the potential effect modifiers. RESULTS: After an average follow-up of 8.86 years (900,871.67 person-years), a total of 402 pancreatic cancer cases were observed. In the fully adjusted model, participants in the highest quartile of dietary diabetes risk reduction score were found to have a reduced risk of pancreatic cancer compared with those in the lowest quartile [HRquartiles 4versus1: 0.62; 95% confidence interval (CI): 0.44, 0.86; Ptrend = 0.004], which remained in a series of sensitivity analyses. Subgroup analyses further found that this favorable association was more pronounced in current or former smokers (HRquartiles 4versus1: 0.48; 95% CI: 0.30, 0.77) than in never smokers (HRquartiles 4versus1: 0.71; 95% CI: 0.44, 1.15), although the interaction test did not reach statistical significance (Pinteraction = 0.095). CONCLUSIONS: Greater adherence to type 2 diabetes prevention diet is associated with a lower risk of pancreatic cancer in this US population. More studies are needed to confirm our findings.

Chocolate consumption and all-cause and cause-specific mortality in a US population: a post hoc analysis of the PLCO cancer screening trial.

Few studies with mixed results have examined the association between chocolate consumption and mortality. We aimed to examine this association in a US population. A population-based cohort of 91891 participants aged 55 to 74 years was identified. Chocolate consumption was assessed via a food frequency questionnaire. Cox regression was used to estimate risk estimates. After an average follow-up of 13.5 years, 19586 all-cause deaths were documented. Compared with no regular chocolate consumption, the maximally adjusted hazard ratios of all-cause mortality were 0.89 [95% confidence interval (CI) 0.84-0.94], 0.84 (95% CI 0.79-0.90), 0.86 (95% CI 0.81-0.93), and 0.87 (95% CI 0.82-0.93) for >0-0.5 servings/week, >0.5-1 serving/week, >1-2 servings/week, and >2 servings/week, respectively (Ptrend = 0.009). A somewhat stronger inverse association was observed for mortality from cardiovascular disease and Alzheimer's disease. A nonlinear dose-response pattern was found for all-cause and cardiovascular mortality (all Pnonlinearity < 0.01), with the lowest risk observed at chocolate consumption of 0.7 servings/week and 0.6 servings/week, respectively. The favorable associations with all-cause and cardiovascular mortality were found to be more pronounced in never smokers than in current or former smokers (all Pinteraction < 0.05). In conclusion, chocolate consumption confers reduced risks of mortality from all causes, cardiovascular disease, and Alzheimer's disease in this US population.

Dietary Vitamin K Intake and the Risk of Pancreatic Cancer: A Prospective Study of 101,695 American Adults.

No epidemiologic studies have been conducted to assess the association of intake of dietary vitamin K with the risk of pancreatic cancer. We used prospective data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial between 1993 and 2009 to fill this gap. A total of 101,695 subjects were identified. Dietary intakes of phylloquinone (vitamin K1), menaquinones (vitamin K2), and dihydrophylloquinone (dihydrovitamin K1) were assessed using a food frequency questionnaire. Cox regression was applied to calculate hazard ratios and 95% confidence intervals. During a mean follow-up of 8.86 years (900,744.57 person-years), 361 cases of pancreatic cancer were documented. In the fully adjusted model, dietary intakes of phylloquinone (for quartile 4 vs. quartile 1, hazard ratio (HR) = 0.57, 95% confidence interval (CI): 0.39, 0.83; P for trend = 0.002) and dihydrophylloquinone (for quartile 4 vs. quartile 1, HR = 0.59; 95% CI: 0.41, 0.85; P for trend = 0.006), but not menaquinones (for quartile 4 vs. quartile 1, HR = 0.93; 95% CI: 0.65, 1.33; P for trend = 0.816), were found to be inversely associated with the risk of pancreatic cancer in a nonlinear dose-response manner (all P values for nonlinearity < 0.05), and this was not modified by predefined stratification factors and remained in sensitivity analyses. In conclusion, dietary intakes of phylloquinone and dihydrophylloquinone, but not menaquinones, confer a lower risk of pancreatic cancer. Future studies should confirm our findings.

New lymphatic cell formation is associated with damaged brain tissue clearance after penetrating traumatic brain injury.

We characterized the tissue repair response after penetrating traumatic brain injury (pTBI) in this study. Seventy specific pathogen-free Kunming mice were randomly divided into the following groups: normal control, 1, 3, 7, 15, 21, and 30 days after pTBI. Hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence were performed to examine and monitor brain tissue morphology, and the distribution and expression of lymphatic-specific markers lymphatic vessel endothelial receptor-1 (LYVE-1), hematopoietic precursor cluster of differentiation 34 (CD34) antigen, and Prospero-related homeobox-1 (PROX1) protein. H&E staining revealed that damaged and necrotic tissues observed on day 1 at and around the injury site disappeared on day 7, and there was gradual shrinkage and disappearance of the lesion on day 30, suggesting a clearance mechanism. We explored the possibility of lymphangiogenesis causing this clearance as part of the post-injury response. Notably, expression of lymphangiogenesis markers LYVE-1, CD34, and PROX1 was detected in damaged mouse brain tissue but not in normal tissue. Moreover, new lymphatic cells and colocalization of LYVE-1/CD34 and LYVE-1/PROX1 were also observed. Our findings of the formation of new lymphatic cells following pTBI provide preliminary insights into a post-injury clearance mechanism in the brain. Although we showed that lymphatic cells are implicated in brain tissue repair, further research is required to clarify the origin of these cells.

Reconstruction and analysis of correlation networks based on GC-MS metabolomics data for hypercholesterolemia.

BACKGROUND AND AIMS: Hypercholesterolemia is characterized by the elevation of plasma total cholesterol level, especially low-density lipoprotein (LDL) cholesterol. This disease is usually caused by a mutation in genes such as LDL receptor, apolipoprotein B, or proprotein convertase subtilisin/kexin type 9. However, a considerable number of patients with hypercholesterolemia do not have any mutation in these candidate genes. In this study, we examined the difference in the metabolic level between patients with hypercholesterolemia and healthy subjects, and screened the potential biomarkers for this disease. METHODS: Analysis of plasma metabolomics in hypercholesterolemia patients and healthy controls was performed by gas chromatography-mass spectrometry and metabolic correlation networks were constructed using Gephi-0.9.2. RESULTS: First, metabolic profile analysis confirmed the distinct metabolic footprints between the patients and the healthy ones. The potential biomarkers screened by orthogonal partial least-squares discrimination analysis included l-lactic acid, cholesterol, phosphoric acid, d-glucose, urea, and d-allose (Variable importance in the projection > 1). Second, arginine and methionine metabolism were significantly perturbed in hypercholesterolemia patients. Finally, we identified that l-lactic acid, l-lysine, l-glutamine, and l-cysteine had high scores of centrality parameters in the metabolic correlation network. CONCLUSION: Plasma l-lactic acid could be used as a sensitive biomarker for hypercholesterolemia. In addition, arginine biosynthesis and cysteine and methionine metabolism were profoundly altered in patients with hypercholesterolemia.

Dietary Acid Load and the Risk of Pancreatic Cancer: A Prospective Cohort Study.

BACKGROUND: Modern Western diets are rich in acidogenic foods. Human and in vitro studies suggest a potential link between dietary acid load and cancer risk. However, no epidemiologic studies have investigated the association of dietary acid load with the risk of pancreatic cancer. Therefore, we conducted a prospective cohort study to fill this gap. METHODS: A population-based cohort of 95,708 American adults was identified. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) were used to assess dietary acid load of each subject, with greater values indicating greater dietary acid load. Cox regression was used to estimate risk estimates for pancreatic cancer incidence. Predefined subgroup analysis was used to identify the potential effect modifiers. RESULTS: A total of 337 pancreatic cancer cases were observed during 848,534.0 person-years of follow-up. PRAL score was found to be positively associated with the risk of pancreatic cancer [fully adjusted HRquartile 4 vs. 1: 1.73; 95% confidence interval (95% CI), 1.21-2.48; P trend = 0.001] in a nonlinear dose-response pattern (P nonlinearity = 0.012). Subgroup analysis found that the positive association of PRAL score with the risk of pancreatic cancer was more pronounced in subjects aged <65 years than in those ≥65 years (P interaction = 0.018). Similar results were obtained for NEAP score. CONCLUSIONS: Higher dietary acid load is associated with a higher risk of pancreatic cancer. Future studies should validate our findings in other populations and settings. IMPACTS: This is the first epidemiologic study suggesting that reducing dietary acid load may be useful in primary prevention of pancreatic cancer.

Low-carbohydrate diets and the risk of pancreatic cancer: a large prospective cohort study.

Low-carbohydrate diets have become a popular approach for weight loss in recent years. However, whether low-carbohydrate diets are associated with the risk of pancreatic cancer remains to be elucidated. Hence, we examined the association of low-carbohydrate diets with the risk of pancreatic cancer in a US population. A population-based cohort of 95 962 individuals was identified. A low-carbohydrate-diet score was calculated to quantify adherence to this dietary pattern, with higher scores indicating greater adherence. Cox regression was used to calculate risk estimate for the association of the low-carbohydrate-diet score with the risk of pancreatic cancer. Subgroup analysis was used to identify the potential effect modifiers. After an average follow-up of 8.87 years (875856.9 person-years), we documented a total of 351 pancreatic cancer cases. In the fully adjusted model, the highest versus the lowest quartiles of the overall low-carbohydrate-diet score were found to be associated with a reduced risk of pancreatic cancer (hazard ratioquartile 4 versus 1: 0.61; 95% confidence interval: 0.45, 0.82; Ptrend < 0.001). Subgroup analysis found that the inverse association of low-carbohydrate diets with the risk of pancreatic cancer was more pronounced in individuals aged ≥65 years than in those aged <65 years (Pinteraction = 0.015). Similar results were obtained for animal and vegetable low-carbohydrate-diet scores. In conclusion, low-carbohydrate diets, regardless of the type of protein and fat, are associated with a lower risk of pancreatic cancer in the US population, suggesting that adherence to low-carbohydrate diets may be beneficial for pancreatic cancer prevention. Future studies should validate our findings in other populations.

Higher Baseline Cortical Score Predicts Good Outcome in Patients With Low Alberta Stroke Program Early Computed Tomography Score Treated with Endovascular Treatment.

BACKGROUND: Patients with large vessel occlusion and noncontrast computed tomography (CT) Alberta Stroke Program Early CT Score (ASPECTS) <6 may benefit from endovascular treatment (EVT). There is uncertainty about who will benefit from it. OBJECTIVE: To explore the predicting factors for good outcome in patients with ASPECTS <6 treated with EVT. METHODS: We retrospectively reviewed 60 patients with ASPECTS <6 treated with EVT in our center between March 2018 and June 2019. Patients were divided into 2 groups because of the modified Rankin Score (mRS) at 90 d: good outcome group (mRS 0-2) and poor outcome group (mRS ≥3). Baseline and procedural characteristics were collected for unilateral variate and multivariate regression analyses to explore the influent variates for good outcome. RESULTS: Good outcome (mRS 0-2) was achieved in 24 (40%) patients after EVT and mortality was 20% for 90 d. Compared with the poor outcome group, higher baseline cortical ASPECTS (c-ASPECTS), lower intracranial hemorrhage, and malignant brain edema after thrombectomy were noted in the good outcome group (all P < .01). Multivariate logistic regression showed that only baseline c-ASPECTS (≥3) was positive factor for good outcome (odds ratio = 4.29; 95% CI, 1.21-15.20; P = .024). The receiver operating characteristics curve indicated a moderate value of c-ASPECTS for predicting good outcome, with the area under receiver operating characteristics curve 0.70 (95% CI, 0.56-0.83; P = .011). CONCLUSION: Higher baseline c-ASPECTS was a predictor for good clinical outcome in patients with ASPECTS <6 treated with EVT, which could be helpful to treatment decision.

A Delta-radiomics model for preoperative evaluation of Neoadjuvant chemotherapy response in high-grade osteosarcoma.

BACKGROUND: The difficulty of assessment of neoadjuvant chemotherapeutic response preoperatively may hinder personalized-medicine strategies that depend on the results from pathological examination. METHODS: A total of 191 patients with high-grade osteosarcoma (HOS) were enrolled retrospectively from November 2013 to November 2017 and received neoadjuvant chemotherapy (NCT). A cutoff time of November 2016 was used to divide the training set and validation set. All patients underwent diagnostic CTs before and after chemotherapy. By quantifying the tumor regions on the CT images before and after NCT, 540 delta-radiomic features were calculated. The interclass correlation coefficients for segmentations of inter/intra-observers and feature pair-wise correlation coefficients (Pearson) were used for robust feature selection. A delta-radiomics signature was constructed using the lasso algorithm based on the training set. Radiomics signatures built from single-phase CT were constructed for comparison purpose. A radiomics nomogram was then developed from the multivariate logistic regression model by combining independent clinical factors and the delta-radiomics signature. The prediction performance was assessed using area under the ROC curve (AUC), calibration curves and decision curve analysis (DCA). RESULTS: The delta-radiomics signature showed higher AUC than single-CT based radiomics signatures in both training and validation cohorts. The delta-radiomics signature, consisting of 8 selected features, showed significant differences between the pathologic good response (pGR) (necrosis fraction ≥90%) group and the non-pGR (necrosis fraction < 90%) group (P < 0.0001, in both training and validation sets). The delta-radiomics nomogram, which consisted of the delta-radiomics signature and new pulmonary metastasis during chemotherapy showed good calibration and great discrimination capacity with AUC 0.871 (95% CI, 0.804 to 0.923) in the training cohort, and 0.843 (95% CI, 0.718 to 0.927) in the validation cohort. The DCA confirmed the clinical utility of the radiomics model. CONCLUSION: The delta-radiomics nomogram incorporating the radiomics signature and clinical factors in this study could be used for individualized pathologic response evaluation after chemotherapy preoperatively and help tailor appropriate chemotherapy and further treatment plans.

BCLAF1 promotes cell proliferation, invasion and drug-resistance though targeting lncRNA NEAT1 in hepatocellular carcinoma.

AIMS: In the present research, we aimed to investigate the effect of Bcl-2-associated transcription factor 1 (BCLAF1) on hepatocellular carcinoma and further explore the special molecular mechanism. MAIN METHODS: The expression of BCLAF1 was analyzed in tumor tissues and different hepatocellular cancer cell lines by real-time RT-PCR and Western blot. Cell proliferation and invasion was explored using MTT and Transwell assay respectively. In addition, luciferase reporter assay was performed to determine the binding activity of BCLAF1 and Nuclear enrichment-rich transcription factor 1 (NEAT1) promoter. Finally, the IC50 for 5-Fluorouracil (5-Fu) was measured by MTT assay, and Western blot was used to determine the expression of P-glycoprotein (P-gp) and multidrug resistance protein1 (MRP1). KEY FINDING: The result revealed that BCLAF1 was highly expressed in hepatocellular carcinoma tissues and cells. In addition, BCLAF1-siRNA inhibited the proliferation and invasion of hepatocellular carcinoma cells, and overexpression of BCLAF1 promoted proliferation and invasion. Furthermore, luciferase reporter assay demonstrated that BCLAF1 directly interact with lncNEAT1 promoter and improved NEAT1 expression, and BCLAF1 promoted proliferation and invasion through targeting lncRNA NEAT1. What's more, BCLAF1 promoted 5-Fu resistance and the expression of P-gp and MRP1 in hepatocellular carcinoma cells by targeting NEAT1. SIGNIFICANCE: The results of the present study suggested that BCLAF1 might be a new gene related to proliferation and drug-resistance of hepatocellular carcinoma. In the future, the search for a deep and reasonable mechanism for the role of BCLAF1 will help us to understand its function more comprehensively, and finally find a new method for the treatment of human cancer.