Childhood obesity has been escalating in Asian countries in recent decades resulting in the younger age groups being diagnosed with metabolic syndrome (MetS). Brassicaceae vegetables that contain high bioactive compounds with anti-inflammatory and anti-oxidative properties might be beneficial in preventing MetS. This narrative review presents; (a) the consumption of vegetables in the world population and the availability of bitter-taste vegetables in Asian culture; (b) the interaction between food preference and childhood obesity and (c) potential associations between the consumption of bitter-taste vegetables in Asian culture and clinical outcomes. A number of online searches were conducted for publications in the English language from the year 1990 until October 2022 with a two-step search strategy adopted: initial searches were conducted in four electronic databases (MEDLINE, CINAHL, EMBASE, and Cochrane Library), and a second search using all identified keywords and indexes by including two additional electronic databases (ProQuest and Scopus). The keywords included “bitter”; “vegetables”; “weight status”; “metabolic profile”, “Asia”, “culture”, and “children”. Brassica vegetables in Asian countries are abundantly available and commonly consumed, yet the overall vegetable intake in children was inadequate or below the recommended daily intake. Childhood obesity can be influenced by their preference for and consumption of bitter-taste vegetables, and excessive body weight is associated with the risk of developing MetS. It remains inconclusive whether brassicas vegetables play a dominant role in the group. Future longitudinal studies to investigate the taste sensitivity, vegetable acceptance, and effect of brassicas vegetables on the risk of MetS in Asian children are warranted.

Patients with secondary mitral regurgitation (SMR), the majority of which is ischemic, often have atherosclerotic ascending aorta and left ventricular (LV) dysfunction. In these patients, restrictive mitral annuloplasty is associated with a high rate of MR recurrence, aortic cross-clamping increases the stroke rate, and cardioplegic arrest increases postoperative low cardiac output syndrome. To avoid these complications, beating heart mitral valve replacement without aortic cross-clamping has been proposed. Here, we describe two male patients, aged 71 and 54 years, with severe SMR and low left ventricle ejection fraction (LVEF) (24% and 30%, respectively). Beating-heart mitral valve replacement with total chordal sparing was performed without aortic cross-clamping through a full sternotomy. Weaning from cardiopulmonary bypass was easily achieved without use of inotropes. The duration of mechanical ventilation (3 and 6 hours, respectively) and intensive care (24 and 48 hours, respectively) was short. Neither patient presented with postoperative neurological disorders. After a mean follow-up of 66 months, both patients were asymptomatic, without prosthetic valve dysfunction, and their LVEF reached 42% and 51%, respectively. This cases study indicates that for patients with SMR with impaired LV function who are at high risk for cardioplegic arrest, clampless beating heart mitral valve replacement with total preservation of the subvalvular apparatus could reduce stroke incidence, preserve peri-operative LVEF, and allow reverse LV remodeling.

We aimed to perform a network meta-analysis (NWM) to examine comparative effectiveness of non-selective beta blockers (NSBBs) on prophylaxis of gastroesophageal variceal bleeding (GVB) and mortality benefit.

MEDLINE (OVID) and EMBASE databases were searched for eligible randomized clinical trials (RCTs) from inception to July 3, 2021. Outcomes of interest included primary/secondary prophylaxis of GVB, failure to achieve hepatic venous pressure gradient (HVPG) decremental response, liver-related and all-cause mortality. A Bayesian NWM was performed to derive relative risk (RR) with 95% credible intervals (CrIs). The ranking probability of each NSBB was assessed by surface under cumulative ranking curve (SUCRA).

Thirty-three RCTs including 3,188 cirrhosis patients with gastroesophageal varices were included. Compared with placebo, nadolol ranked first for reducing variceal bleeding [RR:0.25, (95% CrI:0.11–0.51); SUCRA:0.898], followed by carvedilol [RR:0.33, (95% CrI: 0.11–0.88); SUCRA:0.692] and propranolol [RR:0.52, (95% CrI:0.37–0.75); SUCRA:0.405]. Carvedilol was more effective than propranolol in achieving HVPG decremental response [RR:0.43, (95% CrI: 0.26–0.69)]. Carvedilol ranked first for reducing all-cause mortality [RR: 0.32, (95% CrI:0.17–0.57); SUCRA:0.963), followed by nadolol [RR:0.48, (95% CI:0.29–0.77); SUCRA:0.688], and propranolol [RR:0.77, (95% CI:0.58–1.02); SUCRA: 0.337]. Similar findings were observed for liver-related mortality. Carvedilol ranked the safest. The RR of adverse events was 4.38, (95% CrI:0.33–161.4); SUCRA:0.530, followed by propranolol [RR: 7.54, (95% CrI:1.90–47.89); SUCRA:0.360], and nadolol [RR: 18.24, (95% CrI:91.51–390.90); SUCRA:0.158].

Carvedilol is the preferred NSBB with better survival benefit and lower occurrence of adverse events among patients with gastroesophageal varices.

Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities. These mutations have not been thoroughly investigated in Mexico. This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations.

This cross-sectional study analyzed 158 samples. HBV DNA was extracted, amplified, and sequenced in serum samples using the spin column method, PCR assay, and Sanger’s sequencing, respectively. HBV genotypes were determined, and HBV mutations were tested using the Geno2pheno tool.

Overall, 68.4% (108/158) of HBV patients were infected with genotype H, followed by G (11.4%, 18/158), A2 (10.8%, 17/158), F1b (6.9.0%, 11/158), D (1.9%, 3/158), and E (0.6%, 1/158), and 5.1% (8/158) had evidence of recombination. The prevalence of resistance mutations was 8.2% (13/158) and the most common combined mutation was rt180M+rt204V. Notably, we found the combinations rt180M+rt204V+rt173L (n=2) and rt180M+rt204V+rt202G (n=1) that confer multidrug resistance to 3TC, LdT, and ETV. Resistance mutations were found in genotypes A2 (11.8%, 2/17), and H (10.2%, 11/108), and escape mutations were detected in HBV genotypes A2 (11.8%, 2/17), H (10.2%, 11/108), F1b (9.1%, 1/11) and G (5.6%, 1/18).

The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H. The earliest cases of HBV multidrug resistance were detected in Mexico.

Gastrointestinal (GI) malignancies account for over a quarter of all new cancer diagnoses worldwide, and pose a significant burden on public health. As endoscopes are improved over the years, upgraded high-definition cameras have allowed for better polyp detection. Due to the absence of symptoms in GI malignancy, lesions are often incidentally detected in various stages by endoscopists. Careful polyp morphology evaluation and classification is paramount when selecting the most appropriate endoscopic (or surgical) resection method. The technique that would allow for an en bloc or R0 resection is preferred (endoscopic submucosal dissection [ESD]), while those that present with lower risk features can be reasonably removed in a piecemeal fashion or hybrid fashion with care in ablating clean margins to decrease recurrence. Although Eastern and European endoscopists have more experience in ESD, this expertise is not widely available in North America. The present study aims to explore the following questions: (1) Is ESD always necessary? (2) In which scenarios are ESD always indicated? (3) Can endoscopic mucosal resection be used to achieve resection goals, since this expertise is more widely available and has an easier learning curve?

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease affecting a large population worldwide. No clinically approved drugs are available. In this minireview, we discuss the heterogeneous nature of NASH and lack of consensus in outcome measures among clinical trials. We summarize NASH therapeutic targets and candidate drugs. We compare the efficacy of 33 published clinical trials that evaluated noninvasive biomarkers and liver biopsy. Currently, phase II trial results of fibroblast growth factor 21 (FGF21) and phase III trial results of resmetirom and pioglitazone are encouraging.

Liver ischemia-reperfusion (IR) injury is a common pathological process in liver surgery. Ferroptosis, which is closely related to lipid peroxidation, has recently been confirmed to be involved in the pathogenesis of IR injury. However, the development of drugs that regulate ferroptosis has been slow, and a complete understanding of the mechanisms underlying ferroptosis has not yet been achieved. Fucoidan (Fu) is a sulfated polysaccharide that has attracted research interest due to its advantages of easy access and wide biological activity.

In this study, we established models of IR injury using erastin as an activator of ferroptosis, with the ferroptosis inhibitor ferrostatin-1 (Fer-1) as the control. We clarified the molecular mechanism of fucoidan in IR-induced ferroptosis by determining lipid peroxidation levels, mitochondrial morphology, and key pathways in theta were involved.

Ferroptosis was closely related to IR-induced hepatocyte injury. The use of fucoidan or Fer-1 inhibited ferroptosis by eliminating reactive oxygen species and inhibiting lipid peroxidation and iron accumulation, while those effects were reversed after treatment with erastin. Iron accumulation, mitochondrial membrane rupture, and active oxygen generation related to ferroptosis also inhibited the entry of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus and reduced downstream heme oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPX4) protein levels. However, fucoidan pretreatment produced adaptive changes that reduced irreversible cell damage induced by IR or erastin.

Fucoidan inhibited ferroptosis in liver IR injury via the Nrf2/HO-1/GPX4 axis.

Alcohol-associated liver disease (ALD) is one of the most common liver diseases and indications for liver transplantation (LT). Alcohol use disorder (AUD), a frequent accompaniment in ALD patients, may also be associated with psychiatric comorbidities such as depression and anxiety. Identification of ALD at an earlier stage, and treatment of AUD may help prevent progression to advanced stage of ALD such as cirrhosis and alcoholic hepatitis. Screening for alcohol use and AUD treatment in ALD patients is often not performed due to several barriers at the level of patients, clinicians, and administrative levels. This review details the integrated multidisciplinary care model especially on the specific role of the hepatologist, psychiatrist, addiction counselor, and social worker in providing complete management for the dual pathology of liver disease and of AUD. Laboratory assessment, pharmacological and behavioral therapies, and recommended assessments for follow-up care by the respective specialists is outlined. We provide perspective along with the literature support, with the goal of providing team based comprehensive care of patients with ALD.

Portal hypertension in cirrhosis is defined as an increase in the portal pressure gradient (PPG) between the portal and hepatic veins and is traditionally estimated by the hepatic venous pressure gradient (HVPG), which is the difference in pressure between the free-floating and wedged positions of a balloon catheter in the hepatic vein. By convention, HVPG≥10 mmHg indicates clinically significant portal hypertension, which is associated with adverse clinical outcomes. Nonalcoholic fatty liver disease (NAFLD) is a common disorder with a heterogeneous clinical course, which includes the development of portal hypertension. There is increasing evidence that portal hypertension in NAFLD deserves special considerations. First, elevated PPG often precedes fibrosis in NAFLD, suggesting a bidirectional relationship between these pathological processes. Second, HVPG underestimates PPG in NAFLD, suggesting that portal hypertension is more prevalent in this condition than currently believed. Third, cellular mechanoresponses generated early in the pathogenesis of NAFLD provide a mechanistic explanation for the pressure-fibrosis paradigm. Finally, a better understanding of liver mechanobiology in NAFLD may aid in the development of novel pharmaceutical targets for prevention and management of this disease.

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with the metabolic syndrome and type 2 diabetes and independently contributes to long-term complications. Being often asymptomatic but reversible, it would require population-wide screening, but direct diagnostics are either too invasive (liver biopsy), costly (MRI) or depending on the examiner’s expertise (ultrasonography). Hepatosteatosis is usually accommodated by features of the metabolic syndrome (e.g. obesity, disturbances in triglyceride and glucose metabolism), and signs of hepatocellular damage, all of which are reflected by biomarkers, which poorly predict NAFLD as single item, but provide a cheap diagnostic alternative when integrated into composite liver fat indices. Fatty liver index, NAFLD LFS, and hepatic steatosis index are common and accurate indices for NAFLD prediction, but show limited accuracy for liver fat quantification. Other indices are rarely used. Hepatic fibrosis scores are commonly used in clinical practice, but their mandatory reflection of fibrotic reorganization, hepatic injury or systemic sequelae reduces sensitivity for the diagnosis of simple steatosis. Diet-induced liver fat changes are poorly reflected by liver fat indices, depending on the intervention and its specific impact of weight loss on NAFLD. This limited validity in longitudinal settings stimulates research for new equations. Adipokines, hepatokines, markers of cellular integrity, genetic variants but also simple and inexpensive routine parameters might be potential components. Currently, liver fat indices lack precision for NAFLD prediction or monitoring in individual patients, but in large cohorts they may substitute nonexistent imaging data and serve as a compound biomarker of metabolic syndrome and its cardiometabolic sequelae.

Over the last decade, epidemiological studies have discovered a link between hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and non-Hodgkin lymphoma (NHL). The regression of HCV-associated NHL after HCV eradication is the most compelling proof supporting HCV infection’s role in lymphoproliferative diseases. HBV infection was found to significantly enhance the incidence of NHL, according to the epidemiological data. The exact mechanism of HCV leading to NHL has not been fully clarified, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HCV and cytokines; (2) Direct mechanisms: oncogenic effects mediated by intracellular HCV proteins; (3) hit-and-run mechanism: permanent genetic B lymphocytes damage by the transitional entry of HCV. The specific role of HBV in the occurrence of NHL is still unclear, and the research on its mechanism is less extensively explored than HCV, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HBV; (2) Direct mechanisms: oncogenic effects mediated by intracellular HBV DNA. In fact, it is reasonable to consider direct-acting antivirals (DAAs) as first-line therapy for indolent HCV-associated B-NHL patients who do not require immediate chemotherapy. Chemotherapy for NHL is affected by HBV infection and replication. At the same time, chemotherapy can also activate HBV replication. Following recent guidelines, all patients with HBsAg positive/HBV DNA≥2,000 IU/mL should be treated for HBV. The data on epidemiology, interventional studies, and molecular mechanisms of HCV and HBV-associated B-NHL are systematically summarized in this review.

Disease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease (MAFLD) remains elusive. This study assessed the fibrosis stages and features of MAFLD between different items. We also aimed to investigate the associations between advanced fibrosis and risk factors.

This multicenter cross-sectional study enrolled adults participating in liver disease screening in the community. Patients were stratified following MAFLD diagnostic criteria, to group A (395 patients) for type 2 diabetes, group B (1,818 patients) for body mass index (BMI)>23 kg/m2, and group C (44 patients) for BMI≤23 kg/m2 with at least two metabolic factors. Advanced fibrosis was defined as a fibrosis-4 index>2.67.

Between 2009 and 2020, 1,948 MAFLD patients were recruited, including 478 with concomitant liver diseases. Advanced fibrosis was observed in 125 patients. A significantly larger proportion of patients in group C (25.0%) than in group A (7.6%) and group B (5.8%) had advanced fibrosis (p<0.01). Logistic regression analysis found that hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection (odds ratio [OR]: 12.14, 95% confidence interval [CI]: 4.04–36.52; p<0.01), HCV infection (OR: 7.87, 95% CI: 4.78–12.97; p<0.01), group C (OR: 6.00, 95% CI: 2.53–14.22; p<0.01), and TC/LDL-C (OR: 1.21, 95% CI: 1.06–1.38; p<0.01) were significant predictors of advanced fibrosis.

A higher proportion of lean MAFLD patients with metabolic abnormalities had advanced fibrosis. HCV infection was significantly associated with advanced fibrosis.

Ferroptosis is a programmed cell death mainly manifested as accumulation of ferrous ions and cell lipid peroxidation. Ferroptosis is well regulated by multiple signaling pathways, of which SLC7A11/GPX4 axis is the key pathway negatively regulating ferroptosis by eliminating lipid peroxidation. While disorder of iron homeostasis catalyzes the lipid peroxidation by supplying ferrous iron. Lipid metabolism participates in ferroptosis by offering lipid substrates. In addition, transsulfuration pathway and FSP1/CoQ10 also involve in ferroptosis. Evading ferroptosis is one strategy that cancer bypasses cell death and develops resistance to chemotherapy or radiotherapy, making ferroptosis inducers the potential treatment for cancer. The objective of this review is to summarize the ferroptosis signaling pathways and ferroptosis inducers, thus exploring the opportunities and challenges of inducing ferroptosis in cancer.

Donors with fatty livers are considered to address the shortage of livers for transplantation, but those livers are particularly sensitive to ischemia-reperfusion injury (IRI), and an increased incidence of graft failure is observed. Kupffer cells account for 20–35% of liver nonparenchymal cells, and have been shown to participate in the process of IRI and inflammatory reactions of hepatic steatosis. NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) is an intracellular sensor activated by Kupffer cells to promote generation and participates in IRI. Dynamics-associated protein 1 (Drp1) is one of the main proteins regulating mitochondrial division and exacerbates IRI by affecting mitochondrial dynamics. The mechanism of interaction of Kupffer cells with Drp1 and NLRP3 to aggravate IRI has not been clarified.

A mouse model of hepatic steatosis was established by feeding the mice with a high-fat diet. In vitro experiments were performed using AML12 normal mouse liver cells and RAW264.7 mononuclear macrophage cells cultured in medium with palmitate and oleic acid. Western blotting and immunohistochemical (IHC) staining were used to detect the expression of NLRPP3 and Drp1 in IRI in the control and high-fat diet groups. The expression of F4/80+ cells during IRI in hepatic steatosis was verified by IHC staining, and the role of NLRPP3 and Drp1 in Kupffer-cell mediated IRI was investigated by targeting Drp-1 inhibition.

Drp1 and NLRP3 expression was increased during IRI in hepatic steatosis, and the expression of Drp1 and NLRP3 were decreased after the elimination of Kupffer cells. That indicated Kupffer cells were involved in the process of IRI in hepatic steatosis through the action of Drp1 and NLRP3. After Drp1 inhibition, liver function was restored and NLRP3 expression level was reduced.

Kupffer cells aggravated IRI in hepatic steatosis via NLRP3 and Drp1. Drp1 inhibitors might be useful as specific therapeutics to alleviate IRI in hepatic steatosis and may have promise in case of liver donor shortage.

This study aimed to analyze the effects of baicalin (BC) and geniposide (GP) in combination (7:3) on the activation of microglia (MG) and 5-lipoxygenase (5-LOX) expression in rats during the recovery period after cerebral ischemia and to determine whether inhibition of the 5-LOX pathway is beneficial for M1-to-M2 polarization of MG.

Sprague Dawley rats were divided into five groups: control, model, and BC/GP (7:3) at 30, 45, and 60 mg/kg. A permanent middle artery occlusion model was established using the thread embolism method, and recovery after cerebral ischemia was monitored for 5 weeks. The effects on microglial activation and 5-LOX expression were evaluated by the neurofunctional score and immunofluorescence double labeling. The gene expression of 5-LOX in MG was determined by quantitative polymerase chain reaction before and after drug administration. The gene expression of tumor necrosis factor alpha, inducible nitric oxide synthase, interleukin 10, and cluster of differentiation 206 in MG was determined after the administration of zileuton (depressor). Western blotting was performed to determine the protein expression of 5-LOX, cysteinyl leukotriene receptor 1, cysteinyl leukotriene receptor 2, leukotriene B4 receptor 1, and leukotriene B4 receptor 2 before and after the administration of zileuton.

The activation of MG and the expression of 5-LOX were both increased after cerebral ischemia. BC/GP in combination inhibited the activation of microglia-reduced expression of 5-LOX and induced M2 polarization of MG.

The combination of BC and GP downregulates the 5-LOX inflammatory pathway by inhibiting activation of MG and promotes M1-to-M2 polarization of MG. Neurons are protected by the M2-type polarization, resulting in alleviation of cerebral ischemia.

This study aimed to determine the key points in the design of clinical trial protocols for coronavirus disease 2019 (COVID-19) following the PICOS principle.

A randomized, double-blind, placebo-controlled study of Cangma Huadu Granules in the treatment of mild COVID-19 will be carried out.

We recommend a randomized controlled trial as the study type. The inclusion criteria should not only define the diagnostic criteria of Western medicine and the syndrome types of Chinese medicine but also define the course of the disease. The definition of high-risk groups in the exclusion criteria needs to specify the diseases and laboratory test indicators to avoid excluding patients with common underlying diseases. Preclinical studies on the experimental product and the traditional Chinese medicine theory of indications should be outlined to clarify the trial rationale. A placebo combined with basic treatment is recommended as a control. Outcomes can refer to the core outcome set for clinical trials on COVID-19, and it is recommended to set the main outcome indicators around the clinical symptoms. In addition, homogeneous Chinese medicine during the experiment should be avoided, and the online registration should be completed in a timely manner.

Chinese Clinical Trial Registry, ChiCTR2300070933. Registered on 26 April 2023, www.chictr.org.cn .

Hepatocellular carcinoma (HCC) is a common tumor. Although the diagnosis and treatment of HCC have made great progress, the overall prognosis remains poor. As the core component of artificial intelligence, machine learning (ML) has developed rapidly in the past decade. In particular, ML has become widely used in the medical field, and it has helped in the diagnosis and treatment of cancer. Different algorithms of ML have different roles in diagnosis, treatment, and prognosis. This article reviews recent research, explains the application of different ML models in HCC, and provides suggestions for follow-up research.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) have common features and differences. This real-life study investigated their characteristics, treatment modalities, and prognoses.

This retrospective comparative study was performed in 1,075 patients seen at one tertiary center between January 2008 and December 2020. Overall survival (OS) was estimated by the Kaplan-Meier method. Subclassification of iCCAs after histological and radiological review, and molecular profiling was performed.

HCCs patients were more likely to have early-stage disease than iCCA patients. iCCA patients were more likely to be female, especially those patients without cirrhosis (43% vs. 17%). Cirrhosis was prominent among HCC patients (89% vs. 34%), but no difference in underlying liver disease among cirrhotic patients was found. OS of HCC patients was 18.4 (95% CI: 6.4, 48.3) months, that of iCCA patients was 7.0 (95% CI: 3.4, 20.1) months. OS of Barcelona Clinic Liver Cancer C HCC patients was 7.8 (95% CI: 4.3, 14.2) months, that of advanced/metastatic iCCA patients was 8.5 (95% CI: 5.7, 12.3) months. In patients treated with sorafenib, OS was longer in HCC patients who received subsequent tyrosine kinase inhibitor therapies. No significant OS difference was found between iCCA patients with and without cirrhosis or according to histological subtype. A targetable molecular alteration was detected in 50% of the iCCA patients.

In this French series, cirrhosis was common in iCCA, which showed etiological factors comparable to those of HCC, implying a distinct oncogenic pathway. Both entities had a dismal prognosis at advanced stages. However, systemic therapies sequencing in HCC and molecular profiling in iCCA offer new insights.