Association of triglyceride-glucose index and its combination with adiposity-related indices with the incidence of myocardial infarction: a cohort study from the UK Biobank.

BACKGROUND: The triglyceride-glucose (TyG) index performs better at reflecting insulin resistance when combined with waist circumference (WC), body mass index (BMI), and waist-to-height ratio (WHtR) than when used alone. This study aimed to prospectively examine the relationships between TyG, TyG-BMI, TyG-WC, and TyG-WHtR with the incidence of myocardial infarction (MI) and its subtypes. METHODS: This cohort study included 370,390 participants from the UK Biobank. The Cox proportional hazards model and restricted cubic spline regression model were used to assess the associations of TyG, TyG-BMI, TyG-WC, and TyG-WHtR with MI, ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI). The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were employed to examine the predictive value of four indicators. RESULTS: The hazard ratios (HRs) and 95% confidence intervals (CIs) of MI in the highest quartiles for TyG, TyG-BMI, TyG-WC, and TyG-WHtR were 1.36 (1.28-1.44), 1.47 (1.39-1.56), 1.53 (1.43-1.64), and 1.58 (1.48-1.68) in the fully-adjusted model. Comparable findings were observed when the outcomes were reclassified as STEMI or NSTEMI. However, the associations of TyG-BMI, TyG-WC, and TyG-WHtR with the risk of STEMI were weaker than MI and NSTEMI. A linear dose-response association between TyG and the risk of MI and NSTEMI were demonstrated. TyG-BMI, TyG-WC, and TyG-WHtR all showed nonlinear patterns in their associations with the risk of MI, STEMI, and NSTEMI. TyG-WC was most effective in diagnosing MI (AUC: 0.648, 95% CI: 0.644-0.653), STEMI (AUC: 0.631, 95% CI: 0.622-0.639), and NSTEMI (AUC: 0.647, 95% CI: 0.641-0.654). CONCLUSION: The TyG index was linearly associated with increased risk of MI and NSTEMI, whereas TyG-BMI, TyG-WC, and TyG-WHtR were nonlinearly associated with increased risk of MI and NSTEMI. There were distinct patterns in the relationships between these indicators with STEMI. TyG-WC provided the best diagnostic effectiveness for MI, STEMI, and NSTEMI.

Investigating the causal association between obesity and risk of hepatocellular carcinoma and underlying mechanisms.

Obesity is a global health concern and independent risk factor for cancers including hepatocellular carcinoma (HCC). However, evidence on the causal links between obesity and HCC is limited and inconclusive. This study aimed to investigate the causal relationship between obesity-related traits and HCC risk and explore underlying mechanisms using bioinformatics approaches. Two-sample Mendelian randomization analysis was conducted leveraging publicly available genome-wide association study summary data on obesity traits (body mass index, body fat percentage, waist circumference, waist-to-hip ratio, visceral adipose tissue volume) and HCC. Associations of obesity with primary mechanisms (insulin resistance, adipokines, inflammation) and their effects on HCC were examined. Differentially expressed genes in obesity and HCC were identified and functional enrichment analyses were performed. Correlations with tumor microenvironment (TME) and immunotherapy markers were analyzed. Genetically predicted higher body mass index and body fat percentage showed significant causal relationships with increased HCC risk. Overall obesity also demonstrated causal links with insulin resistance, circulating leptin levels, C-reactive protein levels and risk of severe insulin resistant type 2 diabetes. Four differentially expressed genes (ESR1, GCDH, FAHD2A, DCXR) were common in obesity and HCC. Enrichment analyses indicated their roles in processes like RNA capping, viral transcription, IL-17 signaling and endocrine resistance. They exhibited negative correlations with immune cell infiltration and immunotherapy markers in HCC. Overall obesity likely has a causal effect on HCC risk in Europeans, possibly via influencing primary mechanisms. The identified differentially expressed genes may be implicated in obesity-induced hepatocarcinogenesis through regulating cell cycle, inflammation and immune evasion. Further research on precise mechanisms is warranted.

PolarFormer: A Transformer-based Method for Multi-lesion Segmentation in Intravascular OCT.

Several deep learning-based methods have been proposed to extract vulnerable plaques of a single class from intravascular optical coherence tomography (OCT) images. However, further research is limited by the lack of publicly available large-scale intravascular OCT datasets with multi-class vulnerable plaque annotations. Additionally, multi-class vulnerable plaque segmentation is extremely challenging due to the irregular distribution of plaques, their unique geometric shapes, and fuzzy boundaries. Existing methods have not adequately addressed the geometric features and spatial prior information of vulnerable plaques. To address these issues, we collected a dataset containing 70 pullback data and developed a multi-class vulnerable plaque segmentation model, called PolarFormer, that incorporates the prior knowledge of vulnerable plaques in spatial distribution. The key module of our proposed model is Polar Attention, which models the spatial relationship of vulnerable plaques in the radial direction. Extensive experiments conducted on the new dataset demonstrate that our proposed method outperforms other baseline methods. Code and data can be accessed via this link: https://github.com/sunjingyi0415/IVOCT-segementaion.

Hydrogen Sulfide Promotes Postnatal Cardiomyocyte Proliferation by Upregulating SIRT1 Signaling Pathway.

Hydrogen sulfide (H2S) has been identified as a novel gasotransmitter and a substantial antioxidant that can activate various cellular targets to regulate physiological and pathological processes in mammals. However, under physiological conditions, it remains unclear whether it is involved in regulating cardiomyocyte (CM) proliferation during postnatal development in mice. This study mainly aimed to evaluate the role of H2S in postnatal CM proliferation and its regulating molecular mechanisms. We found that sodium hydrosulfide (NaHS, the most widely used H2S donor, 50-200 µM) increased neonatal mouse primary CM proliferation in a dose-dependent manner in vitro. Consistently, exogenous administration of H2S also promoted CM proliferation and increased the total number of CMs at postnatal 7 and 14 days in vivo. Moreover, we observed that the protein expression of SIRT1 was significantly upregulated after NaHS treatment. Inhibition of SIRT1 with EX-527 or si-SIRT1 decreased CM proliferation, while enhancement of the activation of SIRT1 with SRT1720 promoted CM proliferation. Meanwhile, pharmacological and genetic blocking of SIRT1 repressed the effect of NaHS on CM proliferation. Taken together, these results reveal that H2S plays a promotional role in proliferation of CMs in vivo and in vitro and SIRT1 is required for H2S-mediated CM proliferation, which indicates that H2S may be a potential modulator for heart development in postnatal time window.

The dysregulation of biliary tract microflora is closely related to primary choledocholithiasis: a multicenter study.

Bile microecology changes play an important role in the occurrence and development of choledocholithiasis. At present, there is no clear report on the difference of bile microecology between asymptomatic patients with gallbladder polyps and choledocholithiasis. This study compared bile microecology between gallbladder polyp patients and patients with choledocholithiasis to identify risk factors for primary choledocholithiasis. This study was conducted in 3 hospitals in different regions of China. Bile samples from 26 patients with gallbladder polyps and 31 patients with choledocholithiasis were collected by laparoscopic cholecystectomy and endoscopic retrograde choledocholithiasis cholangiography (ERCP), respectively. The collected samples were used for 16S ribosomal RNA sequencing and liquid chromatography mass spectrometry analysis. The α-diversity of bile microecological colonies was similar between gallbladder polyp and choledocholithiasis, but the ß-diversity was different. Firmicutes, Proteobacteri, Bacteroidota and Actinobacteriota are the most common phyla in the gallbladder polyp group and choledocholithiasis group. However, compared with the gallbladder polyp patients, the abundance of Actinobacteriota has significantly lower in the choledocholithiasis group. At the genera level, the abundance of a variety of bacteria varies between the two groups, and Enterococcus was significantly elevated in choledocholithiasis group. In addition, bile biofilm formation-Pseudomonas aeruginosa was more metabolically active in the choledocholithiasis group, which was closely related to stone formation. The analysis of metabolites showed that a variety of metabolites decreased in the choledocholithiasis group, and the concentration of beta-muricholic acid decreased most significantly. For the first time, our study compared the bile of gallbladder polyp patients with patients with choledocholithiasis, and suggested that the change in the abundance of Actinobacteriota and Enterococcus were closely related to choledocholithiasis. The role of Pseudomonas aeruginosa biofilm in the formation of choledocholithiasis was discovered for the first time, and some prevention schemes for choledocholithiasis were discussed, which has important biological and medical significance.

Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with poor prognosis. Previous studies have implicated the gut microbiota in CCA, but evidence for causal mechanisms is lacking. AIM: To investigate the causal relationship between gut microbiota and CCA risk. METHODS: We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA. Genetic variants were used as instrumental variables. Multiple sensitivity analyses assessed result robustness. RESULTS: Fifteen gut microbial taxa showed significant causal associations with CCA risk. Higher genetically predicted abundance of genus Eubacteriumnodatum group, genus Ruminococcustorques group, genus Coprococcus, genus Dorea, and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA. Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae, genus Alistipes, order Enterobacteriales, and phylum Firmicutes. Protective effects against CCA were suggested for genus Collinsella, genus Eisenbergiella, genus Anaerostipes, genus Paraprevotella, genus Parasutterella, and phylum Verrucomicrobia. Sensitivity analyses indicated these findings were reliable without pleiotropy. CONCLUSION: This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk. Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.

Pan-cancer analysis revealing the multidimensional expression and prognostic and immunologic roles of TGFB1 in cancer.

OBJECTIVE: This study aimed to perform an integrated pan-cancer analysis to characterize the expression patterns, prognostic value, genetic alterations, and immunologic roles of transforming growth factor beta 1 (TGFB1) across diverse human cancer types. METHODS: Bioinformatics analyses were conducted using multiple public databases including The Cancer Genome Atlas, Genotype-Tissue Expression, Clinical Proteomic Tumor Analysis Consortium, TIMER2, GEPIA2, cBioPortal, StringDB, and others. Differential expression, survival, immune correlation, and protein interaction network analyses were performed. RESULTS: TGFB1 was overexpressed in several tumor types compared with that in normal tissues. High TGFB1 expression was associated with an advanced stage and poorer prognosis in certain cancers. TGFB1 mutations occurred in 1.3% of 10,967 cases surveyed. TGFB1 expression correlated with tumor-infiltrating immune cells and immunotherapy-related genes. CONCLUSIONS: This comprehensive multi-omics analysis revealed the complex expression and prognostic landscape of TGFB1 across cancers. TGFB1 is emerging as a potential immunotherapeutic target in certain contexts. Further research should elucidate its multifaceted tumor-promoting and tumor-suppressive mechanisms. Our pan-cancer analysis provides new insights into TGFB1 as a prognostic biomarker and immunotherapeutic target in human cancers, and our findings may guide future preclinical and clinical investigations of TGFB1-directed therapies.

Safety and Efficacy Analysis of PD-1 Inhibitors in Combination with Gemcitabine Plus Nab-Paclitaxel for Advanced Pancreatic Cancer: A Real-World, Single-Center Study.

Background: Pancreatic cancer is a deadly disease with a low five years survival rate, and chemotherapy remains the standard treatment for advanced cases. However, the efficacy of chemotherapy alone is limited, and there is a need for new treatment options. Recently, immune checkpoint inhibitors (ICIs), particularly programmed death-1 (PD-1) inhibitors, have shown promising results in various cancers, including pancreatic cancer. In this study, we explore the safety and efficacy of PD-1 inhibitors in combination with chemotherapy for advanced pancreatic cancer. Materials and Methods: A retrospective analysis was conducted on clinical data from 27 patients with advanced pancreatic cancer who were administered a combination of anti-PD-1 antibody and gemcitabine plus nab-paclitaxel (GnP) regimen. The study evaluated the safety of the treatment as well as the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: In this study, treatment with a combination of anti-PD-1 antibody and GnP regimen for pancreatic cancer resulted in partial response (PR) for 10 out of 27 (37.04%) patients, stable disease (SD) for 10 (37.04%) patients, and progressive disease (PD) for 7 (25.92%) patients. The study found that the median OS (mOS) for these patients was 16.4 months [standard error (SE) = 1.117, 95% confidence interval (CI) 14.211-18.589], while the median PFS (mPFS) was 6.4 months (SE = 1.217, 95% CI 3.981-8.752). Subgroup analysis revealed that pancreatic cancer patients' Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0 vs 1) and treatment cycles (≤6 cycles vs >6 cycles) significantly affected OS and PFS. Patients experienced mostly grade 1-2 adverse events (AEs), which were relieved through clinical treatment. Conclusion: The combination of GnP with anti-PD-1 antibodies shows promise as a potential treatment option for advanced pancreatic cancer.

Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis.

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver cancer with poor prognosis. The gut microbiota has been linked to ICC, but evidence for causality is lacking. Elucidating causal gut microbiota-ICC links could inform prevention and treatment strategies. Materials and methods: We performed a bidirectional two-sample Mendelian randomization (MR) study to investigate causal associations between gut microbiota and ICC risk. Genome-wide significant single nucleotide polymorphisms (SNPs) associated with gut microbiota abundances were utilized as instrumental variables (IVs). Multiple methods assessed causality and sensitivity analyses evaluated result robustness. Bioinformatics analysis of genetic loci linked to gut microbiota and ICC examined potential mechanisms. Results: Genetically predicted increases in Veillonellaceae, Alistipes, Enterobacteriales, and Firmicutes were suggestively associated with higher ICC risk, while increases in Anaerostipes, Paraprevotella, Parasutterella, and Verrucomicrobia appeared protective. Bioinformatics analysis revealed differentially expressed genes near gut microbiota-associated loci may influence ICC through regulating pathways and tumor immune microenvironment. Conclusion: Our findings provide suggestive evidence for causal links between specific gut microbiota and ICC risk.

Nanosecond pulsed electric field stimulates CD103+ DC accumulation in tumor microenvironment via NK-CD103+ DC crosstalk.

CD103+ DC is crucial for antitumor immune response. As a promising local therapy on cancers, nanosecond pulsed electric field (nsPEF) has been widely reported to stimulate anti-tumor immune response, but the underlying relationship between intratumoral CD103+ DC and nsPEF treatment remains enigmatic. Here, we focused on the behavior of CD103+ DC in response to nsPEF treatment and explored the underlying mechanism. We found that the nsPEF treatment led to the activation and accumulation of CD103+ DC in tumor. Depletion of CD103+ DC via Batf3-/- mice demonstrated CD103+ DC was necessary for intratumoral CD8+ T cell infiltration and activation in response to nsPEF treatment. Notably, NK cells recruited CD103+ DC into nsPEF-treated tumor through CCL5. Inflammatory array revealed CD103+ DC-derived IL-12 mediated the CCL5 secretion in NK cells. In addition, the boosted activation and infiltration of intratumoral CD103+ DC were abolished by cGAS-STING pathway inhibition, following IL-12 and CCL5 decreasing. Furthermore, nsPEF treatment promoting CD103+ DC-mediated antitumor response enhanced the effects of CD47 blockade strategy. Together, this study uncovers an unprecedented role for CD103+ DC in nsPEF treatment-elicited antitumor immune response and elucidates the underlying mechanisms.

Advanced hepatocellular carcinoma with MET-amplified contained excellent response to crizotinib: a case report.

Introduction: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Several novel therapeutic strategies have been developed to prolong the survival of patients with advanced HCC. However, therapeutic decision-making biomarkers owing to the extensive heterogeneity of HCC. Next-generation sequencing (NGS) is generally used in treatment decisions to help patients benefit from genome-directed targeting. Case presentation: A 56 year-old male with type-B hepatitis for more than 20 years was admitted to our department and underwent laparoscopic left lateral hepatic lobectomy for hepatocellular carcinoma. Unfortunately, the tumor recurred 1 year later. Despite multiple treatments, the tumor continued to progress and invaded the patient's 5th thoracic vertebras, leading to hypoesthesia and hypokinesia below the nipple line plane 2 years later. NGS revealed MET amplification, and crizotinib, an inhibitor of MET, was recommended. After administration for a month, tumor marker levels decreased, and the tumor shrunk. The patient has remained in remission since that time. Conclusions: We report that a patient with high MET amplification benefited from its inhibitor, which was recommended by NGS. This indicates the potential clinical decision support value of NGS and the satisfactory effect of MET inhibitors.

Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial.

BACKGROUND: Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. METHODS: This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. RESULTS: The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t = 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26-0.71, P <0.001) and 0.76 (95% CI: 0.57-0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05-0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39-0.95, P = 0.028) in the multivariable models. CONCLUSION: Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery. TRAIL REGISTRATION: ClinicalTrials.gov, No. NCT03075280.

Isolated pancreatic tuberculosis masquerading as malignancy in an immunocompetent host: a case report and review of the literature.

A 41-year-old man was admitted to our department with a 7-day history of jaundice of the skin. He was misdiagnosed with carcinoma because imaging tests showed a space-occupying lesion in the pancreatic head, and laboratory examinations showed elevated liver enzymes, and elevated serum bilirubin, alpha-fetoprotein, carbohydrate antigen 19-9, and ferroprotein levels. However, there was slight calcification in the lesion and a subsequent T-Spot test result was positive. The patient then underwent endoscopic retrograde cholangiopancreatography for biopsy and bile drainage. Histologically, the pancreatic mass showed granulomatosis, and the pathologic diagnosis of the isolated pancreatic neoplasm was tuberculosis. The patient accordingly received anti-tuberculosis agents, resulting in a significant decrease in the size of the pancreatic mass. The patient recovered well. Pancreatic tuberculosis can masquerade as malignancy; however, careful attention to a differential diagnosis can prevent the need for laparotomy.

Surgical treatment for recurrent hepatocellular carcinoma: Current status and challenges.

Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020. It includes hepatocellular carcinoma (HCC) (representing 75%-85% of cases), intrahepatic cholangiocarcinoma (representing 10%-15% of cases), and other rare types. The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years; however, high tumor recurrence rates continue to limit long-term survival, even after radical surgical resection (exceeding 50% recurrence). For resectable recurrent liver cancer, surgical removal [either salvage liver transplantation (SLT) or repeat hepatic resection] remains the most effective therapy that is potentially curative for recurrent HCC. Thus, here, we introduce surgical treatment for recurrent HCC. Areas Covered: A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022. Expert commentary: In general, long-term survival after the re-resection of recurrent liver cancer is usually beneficial. SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients; however, SLT is constrained by the supply of liver grafts. SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival. When considering the similar overall survival rate and the current situation of donor shortages, repeat liver resection remains an important option for recurrent HCC.

Association between gut microbiota and hepatocellular carcinoma from 2011 to 2022: Bibliometric analysis and global trends.

Background: Hepatocellular carcinoma (HCC) is a primary malignant tumor responsible for approximately 90% of all liver cancers in humans, making it one of the leading public health problems worldwide. The gut microbiota is a complex microbial ecosystem that can influence tumor formation, metastasis, and resistance to treatment. Therefore, understanding the potential mechanisms of gut microbiota pathogenesis is critical for the prevention and treatment of HCC. Materials and methods: A search was conducted in the Web of Science Core Collection (WoSCC) database for English literature studies on the relationship between gut microbiota and HCC from 2011 to 2022. Bibliometric analysis tools such as VOSviewer, CiteSpace, and R Studio were used to analyze global trends and research hotspots in this field. Results: A total of 739 eligible publications, comprising of 383 articles and 356 reviews, were analyzed. Over the past 11 years, there has been a rapid increase in the annual number of publications and average citation levels, especially in the last five years. The majority of published articles on this topic originated from China (n=257, 34.78%), followed by the United States of America (n=203, 27.47%), and Italy (n=85, 11.50%). American scholars demonstrated high productivity, prominence, and academic environment influence in the research of this subject. Furthermore, the University of California, San Diego published the most papers (n=24) and had the highest average citation value (value=152.17) in the study of the relationship between gut microbiota and HCC. Schnabl B from the USA and Ohtani N from Japan were the authors with the highest number of publications and average citation value, respectively. Conclusion: In recent years, research on the gut microbiota's role in HCC has made rapid progress. Through a review of published literature, it has been found that the gut microbiota is crucial in the pathogenesis of HCC and in oncotherapy.

TLR4 in POMC neurons regulates thermogenesis in a sex-dependent manner.

The rising prevalence of obesity has become a worldwide health concern. Obesity usually occurs when there is an imbalance between energy intake and energy expenditure. However, energy expenditure consists of several components, including metabolism, physical activity, and thermogenesis. Toll-like receptor 4 (TLR4) is a transmembrane pattern recognition receptor, and it is abundantly expressed in the brain. Here, we showed that pro-opiomelanocortin (POMC)-specific deficiency of TLR4 directly modulates brown adipose tissue thermogenesis and lipid homeostasis in a sex-dependent manner. Deleting TLR4 in POMC neurons is sufficient to increase energy expenditure and thermogenesis resulting in reduced body weight in male mice. POMC neuron is a subpopulation of tyrosine hydroxylase neurons and projects into brown adipose tissue, which regulates the activity of sympathetic nervous system and contributes to thermogenesis in POMC-TLR4-KO male mice. By contrast, deleting TLR4 in POMC neurons decreases energy expenditure and increases body weight in female mice, which affects lipolysis of white adipose tissue (WAT). Mechanistically, TLR4 KO decreases the expression of the adipose triglyceride lipase and lipolytic enzyme hormone-sensitive lipase in WAT in female mice. Furthermore, the function of immune-related signaling pathway in WAT is inhibited because of obesity, which exacerbates the development of obesity reversely. Together, these results demonstrate that TLR4 in POMC neurons regulates thermogenesis and lipid balance in a sex-dependent manner.

Soy protein/ß-glucan/tannic acid complex coacervates with different micro-structures play key roles in the rheological properties, tribological properties, and the storage stability of Pickering high internal phase emulsions.

Soy protein-glucan-tannic acid (S-G-T) complex coacervates were prepared by high-intensity ultrasonic processing (US), subcritical water (SW) treatment, and microfluidization homogenization with different pressures (DHPM 500 and 1000) to stabilize Pickering high internal phase emulsions (HIPEs). Our results show that different treatments affect the microstructure and interfacial properties of ternary coacervates by modifying the intermolecular associations between components. In particular, US and DHPM 500 resulted in the formation of ternary complexes with smaller particle sizes and compact network structures. These properties facilitate the capture of oil droplets. S-G-T (US)- and S-G-T (DHPM500)-stabilized HIPEs exhibit gel-like structures, good creaming stability, and high friction coefficients due to the formation of a three-dimensional network in the continuous phase. However, a more uniform droplet distribution, higher viscoelasticity, and reduced friction were observed after storage for 60 days. These results provide a strategy to improve the sensory characteristics of emulsion-based foods after processing.

The "No-touch" technique improves the survival of patients with advanced hepatocellular carcinomas treated by liver transplantation: A single-center prospective randomized controlled trial.

BACKGROUND: Liver transplantation (LT) is the best treatment for patients with hepatocellular carcinoma (HCC). However, the surgical technique needs to be improved. The present study aimed to evaluate the "no-touch" technique in LT. METHODS: From January 2018 to December 2019, we performed a prospective randomized controlled trial on HCC patients who underwent LT. The patients were randomized into two groups: a no-touch technique LT group (NT group, n = 38) and a conventional LT technique group (CT group, n = 46). Operative outcomes and survival in the two groups were analyzed. RESULTS: The perioperative parameters were comparable between the two groups (P > 0.05). There was no significant difference between the two groups in disease-free survival (DFS) (P = 0.732) or overall survival (OS) (P = 0.891). Of 36 patients who were beyond the Hangzhou criteria for LT, the DFS of the patients in the NT group was significantly longer than that in the CT group (median 402 vs. 126 days, P = 0.025). In 31 patients who had portal vein tumor thrombosis (PVTT), DFS and OS in the NT group were significantly better than those in the CT group (median DFS 420 vs. 167 days, P = 0.022; 2-year OS rate 93.8% vs. 66.7%, P = 0.043). In 14 patients who had diffuse-type HCCs, DFS and OS were significantly better in the NT group than those in the CT group (median DFS 141 vs. 56 days, P = 0.008; 2-year OS rate 75.0% vs. 33.3%, P = 0.034). Multivariate analysis showed that for patients with PVTT and diffuse-type HCCs, the no-touch technique was an independent favorable factor for OS (PVTT: HR = 0.018, 95% CI: 0.001-0.408, P = 0.012; diffuse-type HCCs: HR = 0.034, 95% CI: 0.002-0.634, P = 0.024). CONCLUSIONS: The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique. The no-touch technique may provide a new and effective LT technique for advanced HCCs.

Shulan Estimation Model: A New Formula for Estimation of Standard Liver Volume In Chinese Adults.

BACKGROUND: To establish a new and accurate model for standard liver volume (SLV) estimation and graft size prediction in liver transplantation for Chinese adults. METHODS: In this study, the data of morphologic indices and liver volume (LV) were retrospectively obtained on 507 cadaveric liver transplantation donors between June 2017 and September 2020 in Shulan (Hangzhou) Hospital. Linear regression analysis was performed to evaluate the impact of each parameter and develop a new SLV formula. The new formula was then validated prospectively on 97 donors between October 2020 and June 2021, and the prediction accuracy was compared with previous formulas. RESULTS: The average LV in all subjects was 1445.68 ± 309.94 mL. Body weight (BW) showing the strongest correlation (r = 0.453, P < .001). By stepwise multiple linear regression analysis, BW and age were the only 2 independent correlation factors for LV. Shulan estimation model derived: SLV (mL) = 13.266 × BW (kg) - 4.693 × age + 797.16 (R2 = 0.236, P < .001). In the validation cohort, our new model achieved no significant differences between the estimated SLV and the actual LV (P > .05), and showed the lowest mean percentage error of 0.33%. The proportions of estimated SLV within the actual LV ± 20%, ± 15%, and ± 10% percentage errors were 69.1%, 55.7%, and 40.2%, respectively. DISCUSSION: The Shulan SLV estimation model predicted LV more accurately than previous formulas on Chinese adults, which could serve as a simple screening tool during the initial assessment of graft volume for potential donors.