The relationship between circulating metabolites and prostate hyperplasia: a Mendelian randomization study.

BACKGROUND: Circulating metabolites (CM) play a pivotal role in our overall health, yet the current evidence concerning the involvement of diverse CM in benign prostatic hyperplasia (BPH) remains limited. Mendelian randomization (MR) offers a promising avenue to explore the potential impact of CM on BPH. METHODS: In a forward MR analysis, a cohort of 249 circulating metabolites was employed as exposures to investigate their potential associations with BPH risk. Conversely, in a reverse MR analysis, BPH was employed as an exposure to assess its effects on CM. RESULTS: The forward MR analysis discerned a linkage between six metabolites and BPH, with careful consideration to excluding heterogeneity and pleiotropy. Subsequently, the reverse MR analysis unveiled that nine metabolic compounds, mainly comprising phospholipids and triglycerides, potentially exhibit elevated levels in BPH patients. CONCLUSION: Bidirectional MR analysis furnishes genetic insight into the interplay between CM and BPH. The prominence of lipids and triglycerides emerges as significant factors intricately linked to BPH risk.

Efficacy and safety of anlotinib plus XELOX regimen as first-line therapy for mCRC: a single-arm, multicenter, phase II study (ALTER-C-001).

Background: Anlotinib showed encouraging anti-tumor activity in metastatic colorectal cancer (mCRC). This study was designed to assess the efficacy and safety of anlotinib plus XELOX as first-line therapy in mCRC patients. Materials and Methods: Eligible patients aged ≥18 with mCRC were enrolled in this multicenter, single-arm, phase II, exploratory study. Patients received at least 6 cycles of anlotinib, oxaliplatin, and capecitabine as initial therapy. Subsequently, patients received anlotinib monotherapy as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Results: Thirty-one patients were included between December 2019 and March 2022. The median follow-up was 17.5 (95% CI, 3.0-17.5) months. The median PFS was 8.3 (95% CI, 6.3-10.0) months, with 6- and 12-month PFS rates of 82.3% (95% CI, 59.2%-93.0%) and 18.9% (95% CI, 4.8%-40.1%), respectively. Fifteen (48.4%) achieved partial response for an ORR of 48.4% (95% CI, 30.2%-66.9%). The disease control rate was 71.0% (95% CI, 52.0%-85.8%) due to 7 (22.6%) stable diseases. The median duration of response was 6.0 (95% CI, 3.6-8.0) months and 1 patient had the longest ongoing response of 17.3 months. Of 24 patients with evaluable imaging, 23 (74.2%) obtained tumor shrinkage. The median PFS (11.0 vs. 6.9 months) and ORR (66.7% vs. 60.0%) for patients with RAS/BRAF wild-type were numerically better than those with mutation. Three patients are still ongoing treatment. The grade 3 or more treatment-emergent adverse events (TEAEs) were mainly hypertension (12.9%) and decreased neutrophil count (12.9%). Four (12.9%) had serious TEAEs, primarily including abdominal pain and incomplete intestinal obstruction. Conclusion: Anlotinib plus XELOX as first-line therapy in patients with mCRC showed anti-tumor activity and safety profile, which is worth further investigation. Clinical Trial Registration: chictr.org.cn, identifier ChiCTR1900028417.

Reducing Target Volumes of Intensity Modulated Radiation Therapy After Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Long-Term Results of a Prospective, Multicenter, Randomized Trial.

PURPOSE: The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC + CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively. RESULTS: After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P = .045) and symptoms including dry mouth (P = .004), sticky saliva (P = .047), and feeling ill (P = .041). CONCLUSIONS: After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.

Trends in prevalence and all-cause mortality of metabolic dysfunction-associated fatty liver disease among adults in the past three decades: Results from the NHANES study.

BACKGROUND: Given the escalating epidemic of obesity and diabetes coupled with redefined diagnostic criteria, it is critical to identify the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD). We sought to determine the prevalence and mortality outcomes of MAFLD subtypes based on diagnostic criteria in the USA over the past three decades. METHODS: Eleven cycles of the National Health and Nutrition Examination Surveys (NHANES; 1988-1994 and 1999-2020) were used, and 72,224 participants were included. MAFLD was defined according to the 2020 International Expert Consensus. Based on diagnostic criteria and risk factors, MAFLD was categorized into seven subtypes: type 1 (obesity subtype), 2 (metabolic unhealthy subtype), 3 (diabetes subtype), 4 (metabolic unhealthy non-diabetes subtype), 5 (obesity and diabetes subtype), 6 (metabolic unhealthy non-obesity subtype), and 7 (mixed subtype). RESULTS: Over the study period, the estimated prevalence of MAFLD increased significantly from 22% in 1988-1994 to 36% in 2017-2020. The prevalence of Type 4 was the highest, followed by that of Type 7, whereas other types were low and almost unchanged over time. Individuals with MAFLD had 19% and 38% increased mortality risks from all causes and cardiovascular disease, respectively. Among them, the metabolically unhealthy participants with normal weight demonstrated a 116% higher risk for all-cause mortality [hazard ratio (HR): 2.16, 95% CI: 1.52-3.08] and a 222% higher risk for cardiovascular mortality (HR: 3.22, 95% CI: 1.72-6.04). Interestingly, stratification and interaction analyses demonstrated a significant impact of metabolic parameters on the relationship between MAFLD and all-cause mortality. CONCLUSIONS: In conclusion, our study identified an increase in MAFLD prevalence and a significant association between metabolic derangements in MAFLD and all-cause or cardiovascular mortality.

Effect of 3-Dimensional Interstitial High-Dose-Rate Brachytherapy With Regional Metastatic Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non-Small Cell Lung Cancer: 5-Year Follow-up of a Phase 2 Clinical Trial.

PURPOSE: We aimed to reveal the 5-year clinical outcomes of 3-dimensional (3D) interstitial high-dose-rate (HDR) brachytherapy with regional metastatic lymph node intensity modulated radiation therapy (IMRT) for locally advanced peripheral non-small cell lung cancer (NSCLC), which has been shown to have low toxicity and improved 2-year survival rates in patients with this disease. METHODS AND MATERIALS: In this phase 2, single-arm, open-label clinical trial, 83 patients with locally advanced peripheral NSCLC were enrolled (median follow-up [range], 53.7 [4.3-120.4] months). All eligible patients received 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT. The primary endpoint was overall survival (OS). Secondary endpoints were local recurrence-free survival, regional recurrence-free survival, progression-free survival, distant metastasis-free survival, toxicities, and quality of life. RESULTS: The final analysis included 75 patients (19 [25.3%] females, 56 [74.7%] males; median [range] age, 64 [44-80] years; stage IIIA, 34 [45.3%]; stage IIIB, 41 [54.7%]). At the latest follow-up, 32 (42.7%) patients had survived. The median OS was 38.0 months (5-year OS, 44.5%; 95% confidence interval [CI], 33.8%-58.6%). Local recurrence-free survival, recurrence-free survival, and distant metastasis-free survival at 5 years were 79.2% (95% CI, 68.5%-91.5%), 73.6% (95% CI, 61.5%-88.1%), and 50.3% (95% CI, 38.3%-66.1%), respectively. The dominant failure pattern was distant disease, corresponding to 40% (30 of 75) of patients and 65.2% (30 of 46) of all failures. Two (2.7%) patients developed grade 1 acute pneumonitis. Grade 2 and 3 acute esophagitis occurred in 11 (14.7%) and 4 (5.3%) patients, respectively. No late radiation-related grade ≥2 late adverse events were observed. CONCLUSIONS: 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT for locally advanced peripheral NSCLC shows significant OS and has a low toxicity rate. Additional evaluation in a phase 3 trial is recommended to substantiate these findings.

Regulatory mechanism of icariin in cardiovascular and neurological diseases.

Cardiovascular diseases (CVDs) and neurological diseases are widespread diseases with substantial rates of morbidity and mortality around the world. For the past few years, the preventive effects of Chinese herbal medicine on CVDs and neurological diseases have attracted a great deal of attention. Icariin (ICA), the main constituent of Epimedii Herba, is a flavonoid. It has been shown to provide neuroprotection, anti-tumor, anti-osteoporosis, and cardiovascular protection. The endothelial protection, anti-inflammatory, hypolipidemic, antioxidative stress, and anti-apoptosis properties of ICA can help stop the progression of CVDs and neurological diseases. Therefore, our review summarized the known mechanisms and related studies of ICA in the prevention and treatment of cardio-cerebrovascular diseases (CCVDs), to better understand its therapeutic potential.

Microbiota-derived short-chain fatty acids: Implications for cardiovascular and metabolic disease.

Cardiovascular diseases (CVDs) have been on the rise around the globe in the past few decades despite the existing guidelines for prevention and treatment. Short-chain fatty acids (SCFAs) are the main metabolites of certain colonic anaerobic bacterial fermentation in the gastrointestinal tract and have been found to be the key metabolites in the host of CVDs. Accumulating evidence suggest that the end-products of SCFAs (including acetate, propionate, and butyrate) interact with CVDs through maintaining intestinal integrity, anti-inflammation, modulating glucolipid metabolism, blood pressure, and activating gut-brain axis. Recent advances suggest a promising way to prevent and treat CVDs by controlling SCFAs. Hence, this review tends to summarize the functional roles carried out by SCFAs that are reported in CVDs studies. This review also highlights several novel therapeutic interventions for SCFAs to prevent and treat CVDs.

Beneficial effects of psyllium on the prevention and treatment of cardiometabolic diseases.

Cardiometabolic diseases are reaching epidemic proportions worldwide. Dietary fiber intake can improve the risk factors associated with CMD. Psyllium, especially its husk, is one of the most widely used dietary fiber supplements, which is often used to enrich cereals and other food products. Numerous pharmacological studies have investigated the active ingredients and therapeutic effects of psyllium and its extracts, including antioxidant, anti-tumor, antidiabetic, hypotensive, anti-inflammation, neuroprotection, antidiarrheal, and antiviral activities. In this review, we will summarize the available studies on the therapeutic potential and possible mechanisms of psyllium in treating CMDs, such as hyperlipidemia, diabetes mellitus, and its complications, hypertension, hyperuricemia and obesity, and its applications in food systems.

Glutamate excitotoxicity: Potential therapeutic target for ischemic stroke.

Glutamate-mediated excitotoxicity is an important mechanism leading to post ischemic stroke damage. After acute stroke, the sudden reduction in cerebral blood flow is most initially followed by ion transport protein dysfunction and disruption of ion homeostasis, which in turn leads to impaired glutamate release, reuptake, and excessive N-methyl-D-aspartate receptor (NMDAR) activation, promoting neuronal death. Despite extensive evidence from preclinical studies suggesting that excessive NMDAR stimulation during ischemic stroke is a central step in post-stroke damage, NMDAR blockers have failed to translate into clinical stroke treatment. Current treatment options for stroke are very limited, and there is therefore a great need to develop new targets for neuroprotective therapeutic agents in ischemic stroke to extend the therapeutic time window. In this review, we highlight recent findings on glutamate release, reuptake mechanisms, NMDAR and its downstream cellular signaling pathways in post-ischemic stroke damage, and review the pathological changes in each link to help develop viable new therapeutic targets. We then also summarize potential neuroprotective drugs and therapeutic approaches for these new targets in the treatment of ischemic stroke.

Roles and mechanisms of puerarin on cardiovascular disease：A review.

Cardiovascular diseases (CVDs) are now the leading cause of mortality and morbidity worldwide，resulting in a large global economic burden. Recently, complementary and alternative medicine, such as traditional Chinese medicine (TCM) have received great attention. Puerarin (Pue) is an isoflavone isolated from the roots of Pueraria lobata (Willd.) Ohwi (also named "Ge gen" in China), and is a versatile TCM herb used for the treatment of fever, diarrhea, diabetes mellitus CVDs and cerebrovascular diseases. Numerous lines ofin vitro studies, as well as in vivo animal experiments have established that Pue offers beneficial roles against the progression of atherosclerosis, ischemic heart diseases, heart failure hypertension and arrhythmia by inhibiting pathological processes, such as the mitigation of endothelium injury, protection against inflammation, the disturbance of lipid metabolism, protection against ischemic reperfusion injury, anti-myocardial remodeling and other effects. Here, we provide a systematic overview of the pharmacological actions and molecular targets of Pue in cardiovascular disease prevention and treatment, to provide insights into the therapeutic potential of Pue in treating cardiovascular diseases.

The molecular mechanisms of ferroptosis and its role in cardiovascular disease.

Ferroptosis is a programmed iron-dependent cell death characterized by accumulation of lipid peroxides (LOOH) and redox disequilibrium. Ferroptosis shows unique characteristics in biology, chemistry, and gene levels, compared to other cell death forms. The metabolic disorder of intracellular LOOH catalyzed by iron causes the inactivity of GPX4, disrupts the redox balance, and triggers cell death. Metabolism of amino acid, iron, and lipid, including associated pathways, is considered as a specific hallmark of ferroptosis. Epidemiological studies and animal experiments have shown that ferroptosis plays an important character in the pathophysiology of cardiovascular disease such as atherosclerosis, myocardial infarction (MI), ischemia/reperfusion (I/R), heart failure (HF), cardiac hypertrophy, cardiomyopathy, and abdominal aortic aneurysm (AAA). This review systematically summarized the latest research progress on the mechanisms of ferroptosis. Then we report the contribution of ferroptosis in cardiovascular diseases. Finally, we discuss and analyze the therapeutic approaches targeting for ferroptosis associated with cardiovascular diseases.

Association of Cholecystectomy With Liver Fibrosis and Cirrhosis Among Adults in the USA: A Population-Based Propensity Score-Matched Study.

Background and Aims: Cholecystectomy is the "gold standard" for treating diseases of the gallbladder. In addition, non-alcoholic fatty liver disease (NAFLD), liver fibrosis or cirrhosis, are major causes of morbidity and mortality across the world. However, the association between cholecystectomy and these diseases is still unclear. We assessed the association among US adults and examined the possible risk factors. Methods: This cross-sectional study used data from 2017 to 2018 National Health and Nutrition Examination Survey, a population-based nationally representative sample of US. Liver fibrosis and cirrhosis were defined by median stiffness, which was assessed by transient elastography. Furthermore, patients who had undergone cholecystectomy were identified based on the questionnaire. In addition, Propensity Score Matching (PSM, 1:1) was performed based on gender, age, body mass index (BMI) and diabetes. Results: Of the 4,497 included participants, cholecystectomy was associated with 60.0% higher risk of liver fibrosis (OR:1.600;95% CI:1.278-2.002), and 73.3% higher risk of liver cirrhosis (OR:1.733, 95% CI:1.076-2.792). After PSM based on age, gender, BMI group and history of diabetes, cholecystectomy was associated with 139.3% higher risk of liver fibrosis (OR: 2.393;95% CI: 1.738-3.297), and 228.7% higher risk of liver cirrhosis (OR: 3.287, 95% CI: 1.496-7.218). Conclusions: The present study showed that cholecystectomy is positively associated with liver fibrosis and cirrhosis in US adults. The discovery of these risk factors therefore provides new insights on the prevention of NAFLD, liver fibrosis, and cirrhosis.

Beneficial effects of cinnamon and its extracts in the management of cardiovascular diseases and diabetes.

Cardiovascular diseases (CVDs) and diabetes are the leading causes of death worldwide, which underlines the urgent necessity to develop new pharmacotherapies. Cinnamon has been an eminent component of spice and traditional Chinese medicine for thousands of years. Numerous lines of findings have elucidated that cinnamon has beneficial effects against CVDs in various ways, including endothelium protection, regulation of immune response, lowering blood lipids, antioxidative properties, anti-inflammatory properties, suppression of vascular smooth muscle cell (VSMC) growth and mobilization, repression of platelet activity and thrombosis and inhibition of angiogenesis. Furthermore, emerging evidence has established that cinnamon improves diabetes, a crucial risk factor for CVDs, by enhancing insulin sensitivity and insulin secretion; regulating the enzyme activity involved in glucose; regulating glucose metabolism in the liver, adipose tissue and muscle; ameliorating oxidative stress and inflammation to protect islet cells; and improving diabetes complications. In this review, we summarized the mechanisms by which cinnamon regulates CVDs and diabetes in order to provide a theoretical basis for the further clinical application of cinnamon.

Intestinal Microbiota, Anti-Inflammatory, and Anti-Oxidative Status of Broiler Chickens Fed Diets Containing Mushroom Waste Compost By-Products.

This study investigated the effects of using mushroom waste compost as the residue medium for Pleurotus eryngii planting, which was used as a feed replacement; its consequent influence on broiler chickens' intestinal microbiota, anti-inflammatory responses, and anti-oxidative status was likewise studied. A total of 240 male broilers were used and allocated to four treatment groups: the basal diet-control group (corn-soybean); 5% replacement of a soybean meal via PWMC (Pennisetum purpureum Schum No. 2 waste mushroom compost); 5% replacement of a soybean meal via FPW (Saccharomyces cerevisiae fermented PWMC); 5% replacement of a soybean meal via PP (Pennisetum purpureum Schum No. 2). Each treatment had three replicates and 20 birds per pen. The levels of glutathione peroxidase and superoxide dismutase mRNA as well as protein increased in the liver and serum in chickens, respectively; mRNA levels of inflammation-related genes were also suppressed 2 to 10 times in all treatments as compared to those in the control group. The tight junction and mucin were enhanced 2 to 10 times in all treatment groups as compared to those in the control, especially in the PWMC group. Nevertheless, the appetite-related mRNA levels were increased in the PWMC and FPW groups by at least two times. In ileum and cecum, the Firmicutes/Bacteroidetes ratios in broilers were decreased in the PWMC, FPW, and PP groups. The Lactobacillaceae in the ileum were increased mainly in the PWMC and control groups. Overall, high-fiber feeds (PWMC, FPW, and PP) could enhance the broilers' health by improving their antioxidant capacities and decreasing their inflammatory response as compared to the control. Based on the results, a 5% replacement of the soybean meal via PWMC is recommended in the broiler chickens' diet.

Assessment of Intestinal Immunity and Permeability of Broilers on Partial Replacement Diets of Two-Stage Fermented Soybean Meal by Bacillus velezensis and Lactobacillus brevis ATCC 367.

The effect of soybean peptides from fermented soybean meal on the intestinal immunity and tight junction of broilers was assessed. Roughly, two-stage fermented soybean meal prepared with Bv and Lb (FSBMB+L), which has nearly three times higher soluble peptides than soybean meal (SBM), and reduced galacto-oligosaccharide (GOS) content and allergen protein. The one-stage fermented by Bv (FSBMB) has the highest soluble peptides, while commercial lactic acid bacteria (FSBML) has the highest Lactic acid bacteria count; these were used to compare the differences in the process. Ross308 broilers (n = 320) were divided into four groups: SBM diet and a diet replaced with 6% FSBMB+L, FSBMB, or FSBML. The growth performance was recorded during the experiment, and six birds (35-day-old) per group were euthanized. Analysis of their jejunum and ileum showed that the fermented soybean meal significantly improved the villus height in the jejunum (p < 0.05) and reduced the crypt hyperplasia. The FSBMB group had the highest reducing crypt depth; however, the FSBMB+L group had the highest villus height/crypt depth in the ileum (p < 0.05). In the jejunum, the relative mRNA of CLDN-1 and Occludin increased 2-fold in the treatments, and ZO-1 mRNA increased 1.5 times in FSBML and FSBMB+L (p < 0.05). Furthermore, the level of NF-κB and IL-6 mRNAs in FSBML increased, respectively, by 4 and 2.5 times. While FSBMB, along with FSBMB+L, had a 1.5-fold increase in the mRNA of IL-10, that of NF-κB increased 2-fold. FSBMB+L and FSBMB singly led to a 2- and 3-fold increase in IL-6 mRNA, respectively (p < 0.05). FSBMB and FSBMB+L can also upregulate MUC2 in the jejunum (p < 0.05). In short, using the soybean peptides from two-stage fermented soybean meal can ameliorate the negative factors of SBM and effectively regulate immune expression and intestinal repair, which will help broilers maintain intestinal integrity.

The Potential Utilization of High-Fiber Agricultural By-Products as Monogastric Animal Feed and Feed Additives: A Review.

With the increase in world food demand, the output of agricultural by-products has also increased. Agricultural by-products not only contain more than 50% dietary fiber but are also rich in functional metabolites such as polyphenol (including flavonoids), that can promote animal health. The utilization of dietary fibers is closely related to their types and characteristics. Contrary to the traditional cognition that dietary fiber reduces animal growth, it can promote animal growth and maintain intestinal health, and even improve meat quality when added in moderate amounts. In addition, pre-fermenting fiber with probiotics or enzymes in a controlled environment can increase dietary fiber availability. Although the use of fiber has a positive effect on animal health, it is still necessary to pay attention to mycotoxin contamination. In summary, this report collates the fiber characteristics of agricultural by-products and their effects on animal health and evaluates the utilization value of agricultural by-products.

Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments.

Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion is currently the standard intervention. However, the reperfusion may lead to further myocardial damage, known as myocardial ischemia/reperfusion injury (MI/RI). Oxidative stress is one of the most important pathological mechanisms in reperfusion injury, which causes apoptosis, autophagy, inflammation, and some other damage in cardiomyocytes through multiple pathways, thus causing irreversible cardiomyocyte damage and cardiac dysfunction. This article reviews the pathological mechanisms of oxidative stress involved in reperfusion injury and the interventions for different pathways and targets, so as to form systematic treatments for oxidative stress-induced myocardial reperfusion injury and make up for the lack of monotherapy.

Prevalence and Effect of Cerebral Small Vessel Disease in Stroke Patients With Aspirin Treatment Failure-A Hospital-Based Stroke Secondary Prevention Registry.

Background: Breakthrough strokes during treatment with aspirin, termed clinical aspirin treatment failure (ATF), is common in clinical practice. The burden of cerebral small vessel disease (SVD) is associated with an increased recurrent ischemic stroke risk. However, the association between SVD and ATF remains unclear. This study investigated the prevalence and clinical characteristics of SVD in stroke patients with ATF. Methods: Data from a prospective, and multicenter stroke with ATF registry established in 2018 in Taiwan were used, and 300 patients who developed ischemic stroke concurrent with regular use of aspirin were enrolled. White matter lesions (WMLs) and cerebral microbleeds (CMBs) were identified using the Fazekas scale and Microbleed Anatomical Rating Scale, respectively. Demographic data, cardiovascular comorbidities, and index stroke characteristics of patients with different WML and CMB severities were compared. Logistic regression analyses were performed to explore the factors independently associated with outcomes after ATF. Results: The mean patient age was 69.5 ± 11.8 years, and 70.0% of patients were men. Among all patients, periventricular WML (PVWML), deep WML (DWML), and CMB prevalence was 93.3, 90.0, and 52.5%, respectively. Furthermore, 46.0% of the index strokes were small vessel occlusions. Severe PVWMLs and DWMLs were significantly associated with high CMB burdens. Patients with moderate-to-severe PVWMLs and DWMLs were significantly older and had higher cardiovascular comorbidity prevalence than did patients with no or mild WMLs. Moreover, patients with favorable outcomes exhibited significantly low prevalence of severe PVWMLs (p = 0.001) and DWMLs (p = 0.001). After logistic regression was applied, severe WMLs predicted less favorable outcomes independently, compared with those with no to moderate PVWMLs and DWMLs [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.25-0.87 for severe PVWMLs; OR, 0.40; 95% CI, 0.21-0.79 for severe DWMLs]. Conclusions: SVD is common in stroke patients with ATF. PVWMLs and DWMLs are independently associated with functional outcomes in stroke patients with ATF. The burden of SVD should be considered in future antiplatelet strategies for stroke patients after ATF.

Association of Serum Vitamin C With NAFLD and MAFLD Among Adults in the United States.

BACKGROUND AND AIMS: Despite the remarkable progress of metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named non-alcoholic fatty liver disease (NAFLD), the disease remains poorly improved. Since increased oxidative stress and inflammation contribute to the initiation and progression of fatty liver disorders, vitamin C (VC), an antioxidant agent, might be a suitable treatment option for MAFLD. However, the lack of clinically confirmed benefits makes clinicians challenging to recommend antioxidant supplements for MAFLD individuals. METHODS: Herein, the nationally representative National Health and Nutrition Examination Survey 2017-2018 data were collected to evaluate the potential association between the serum VC levels with the risk of different categories of NALFD and the newly proposed MAFLD terminology. Hepatic steatosis was defined as controlled attenuated parameter scores ≥ 263 dB/m, whereas liver fibrosis (LF) status was defined as F0-F4, with the cutoff values of median liver stiffness being 6.3, 8.3, 10.5, and 12.5 (KPa), respectively. A cross-sectional analysis was performed to calculate the odds rate and determine the potential beneficial effects of VC. RESULTS: A total of 4,494 participants aged more than 18 years and conducted transient elastography examinations were included. Our findings demonstrated that participants with increased serum VC status were more likely to be female predominant, more educated, and moderate drinkers. Interestingly, female participants tended to have a lower prevalence of NAFLD, MAFLD, LF, and liver cirrhosis (LC) after stratification by gender. Moreover, our results revealed that participants from the quartile three group (quartile 3: 50.5-67.0 µmol/L) experienced a slightly lower risk of MAFLD than the risk of NAFLD. Of note, the serum concentration of VC (quartile 2: 30.9-50.5 µmol/L) inversely associated with LF and LC was lower than the serum VC level (quartile 3) associated with NAFLD and MAFLD. Notably, individuals from the quartile 3 group experienced a statistically significant 32.5, 42.0, 45.7, and 71% decrease in risk of NAFLD, MAFLD, LF, and LC, respectively. CONCLUSION: In summary, our findings suggested an inverse association between serum VC levels and NAFLD, MAFLD, LF, or LC. Additionally, adjustment of VC supplementation according to age, gender, and ethnicity may be a promising candidate for these diseases.

Totally laparoscopic anatomic S7 segmentectomy using in situ split along the right intersectoral and intersegmental planes.

BACKGROUND: The traditional open or laparoscopic segmentectomy of liver segment 7 (S7) requires exposing and controlling the root of the right hepatic vein(RHV)after full mobilization and lifting up of the right liver before liver transection. This approach violates the "no-touch" principle for malignant tumors, and makes laparoscopic resection technically challenging. So reports on isolated totally laparoscopic anatomic S7 segmentectomy have rarely been reported. This study describes our experience in laparoscopic anatomic S7 segmentectomy using in situ split along the right intersectoral and intersegmental planes of the liver. To our knowledge, this is the first description of this novel approach. METHODS: From September 2017 to May 2019, patients who underwent laparoscopic anatomic S7 segmentectomy for hepatocellular carcinoma at the HPB Surgery Department, Sun Yat-Sen Memorial Hospital entered into this retrospective study. This in situ split approach was designed using main vessels as the plane markers of right intersectoral and intersegmental planes, along which liver transection was carried out. There was no need to mobilize the right liver and control the root of RHV. RESULTS: There were 9 women and 15 men. The average diameter of the tumors on preoperative CT/MR was 3.4 cm (range 2-6 cm). All the procedures were successfully carried out laparoscopically. There was no perioperative death. The average operative time was 216.5 min (range 180-310 min). The average blood loss was 320 ml (range 120-620 ml). Pathological study showed all the operations to be R0 resections. CONCLUSION: Laparoscopic anatomic S7 segmentectomy using the in situ split approach resulted in R0 liver resection in all our patients with primary liver cancer. The operation was technically feasible and it provided a better view and increased maneuverability in the cramped operative space compared with the traditional open/laparoscopic approach. The approach also better complies with the "no-touch" principle for malignant tumors. Its long-term oncological outcomes require further studies.