Elaidic acid leads to mitochondrial dysfunction via mitochondria-associated membranes triggers disruption of mitochondrial calcium fluxes

Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome,and sustained Ca^(2+)transfer can result in mitochondrial dysfunction.We focused on KCs to explore the damage to mitochondria by EA.After EA stimulation,cells produced an oxidative stress(OS)response with a significant increase in ROS release.Immunoprecipitation experiments and the addition of inhibitors revealed that the increase in the level of intracellular Ca^(2+)led to Ca^(2+)accumulation in the mitochondrial matrix via mitochondria-associated membranes(MAMs).This was accompanied by a significant release of m ROS,loss of MMP and ATP,and a significant increase in mitochondrial permeability transition pore opening,ultimately leading to mitochondrial instability.These findings confirmed the mechanism that EA induced mitochondrial Ca^(2+)imbalance in KCs via MAM,ultimately leading to mitochondrial dysfunction.Meanwhile,EA induced OS and the decrease of MMP and ATP in rat liver,and significant lesions were found in liver mitochondria.Swelling of the inner mitochondrial cristae and mitochondrial vacuolization occurred,with a marked increase in lipid droplets.

Frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students

AIM:To investigate the frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students.METHODS:Totally 158 student volunteers underwent routine vision examination in the optometry clinic of Guangxi Medical University.Their data were used to identify the different types of accommodation and nonstrabismic binocular vision dysfunction and to determine their frequency.Correlation analysis and logistic regression were used to examine the factors associated with these abnormalities.RESULTS:The results showed that 36.71%of the subjects had accommodation and non-strabismic binocular vision issues,with 8.86%being attributed to accommodation dysfunction and 27.85%to binocular abnormalities.Convergence insufficiency(CI)was the most common abnormality,accounting for 13.29%.Those with these abnormalities experienced higher levels of eyestrain(χ2=69.518,P<0.001).The linear correlations were observed between the difference of binocular spherical equivalent(SE)and the index of horizontal esotropia at a distance(r=0.231,P=0.004)and the asthenopia survey scale(ASS)score(r=0.346,P<0.001).Furthermore,the right eye's SE was inversely correlated with the convergence of positive and negative fusion images at close range(r=-0.321,P<0.001),the convergence of negative fusion images at close range(r=-0.294,P<0.001),the vergence facility(VF;r=-0.234,P=0.003),and the set of negative fusion images at far range(r=-0.237,P=0.003).Logistic regression analysis indicated that gender,age,and the difference in right and binocular SE did not influence the emergence of these abnormalities.CONCLUSION:Binocular vision abnormalities are more prevalent than accommodation dysfunction,with CI being the most frequent type.Greater binocular refractive disparity leads to more severe eyestrain symptoms.

Metabolic dysfunction-associated steatotic liver disease:A silent pandemic

The worldwide epidemiology of non-alcoholic fatty liver disease(NAFLD)is showing an upward trend,parallel to the rising trend of metabolic syndrome,owing to lifestyle changes.The pathogenesis of NAFLD has not been fully understood yet.Therefore,NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide.Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication.Lifestyle changes are the main treatment modality.Recently,clinical trial using drugs that target‘insulin resistance’which is the driving force behind NAFLD,have shown promising results.Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets.The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively.Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.

Effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease:Clinical implications

In this editorial,we comment on the article by Chen et al recently published in 2024.We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase(ALT)would effectively identify cases of fibrosis in metabolic-dysfunction associated fatty liver disease(MAFLD).This is important given the increasing prevalence of MAFLD and obesity globally.Currently,a suitable screening test to identify patients in the general population does not exist and most patients are screened after the finding of an abnormal ALT.The authors of this paper challenge the idea of what a normal ALT is and whether that threshold should be lowered,particularly as their study found that 83.12%of their study population with a diagnosis of MAFLD had a normal ALT.The main advantages of screening would be to identify patients and provide intervention early,the mainstay of this being changing modifiable risk factors and monitoring for liver fibrosis.However,there is not enough suitable therapeutic options available as of yet although this is likely to change in the coming years with more targets for therapy being discovered.Semaglutide is one example of this which has demonstrated benefit with an acceptable side effect profile for those patients with MAFLD and obesity,although studies have not yet shown a significant improvement in fibrosis regression.It would also require a huge amount of resource if a reduced ALT level alone was used as criteria;it is more likely that current scoring systems such as fibrosis-4 may be amended to represent this additional risk.Currently,there is not a good argument to recommend wide-spread screening with a reduced ALT level as this is unlikely to be cost-effective.This is compounded by the fact that there is a significant heterogeneity in what is considered a normal ALT between laboratories.Although studies previously have suggested a more pragmatic approach in screening those over the age of 60,this is likely to change with the increasing incidence of obesity within the younger age groups.The main message from this study is that those who have hypercholesterolemia and high body metabolic index should have these risk factors modified to maintain a lower level of ALT to reduce the risk of progression to fibrosis and cirrhosis.

Interplay between metabolic dysfunction-associated fatty liver disease and renal function: An intriguing pediatric perspective

Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.

Metabolic dysfunction-associated fatty liver disease and low muscle strength: A comment

The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.

A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction

Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver disease.Despite notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients.Unfortunately,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD.Herein,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages.Comparison of the 75231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))natural killer cells,and S100 calcium binding protein A12^(+)(S100A12^(+))neutrophils.Moreover,we verified this immune niche and its association with EAD occurrence in two independent cohorts.Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.

Effect of exogenous free N^(ε)-(carboxymethyl)lysine on diabetes-associated cognitive dysfunction:neuroinflammation,and metabolic disorders

Diabetes-associated cognitive dysfunction has already been attracted considerable attention.Advanced glycation end products(AGEs)from daily diets are thought to be a vital contributor to the development of this diseases.However,the effect of one of the best-characterized exogenous AGEs N^(ε)-(carboxymethyl)lysine(CML)on cognitive function is not fully reported.In the present study,diabetical Goto-Kakizaki(GK)rats were treated with free CML for 8-weeks.It was found that oral consumption of exogenous CML significantly aggravated diabetes-associated cognitive dysfunction in behavioral test.In details,exogenous CML increased levels of oxidative stress,promoted the activation of glial cells in the brain,up-regulated the release of inflammatory cytokines interleukin-6,inhibited the protein expression of the brain-derived neurotrophic factor and thus led to neuroinflammation.Furthermore,exogenous CML promoted the amyloidogenesis in the brain of GK rats,and inhibited the expression of GLUT4.Additionally,several tricarboxylic acid cycle and glutamate-glutamine/γ-aminobutyric acid cycle intermediates including pyruvate,succinic acid,glutamine,glutamate were significantly changed in brain of GK rats treated with exogenous free CML.In conclusion,exogenous free CML is a potentially noxious compounds led to aggravated diabetes-associated cognitive dysfunction which could be possibly explained by its effects on neuroinflammation,energy and neurotransmitter amino acid homeostasis.

Sarcopenia and metabolic dysfunction associated steatotic liver disease:Time to address both

Sarcopenia and metabolic dysfunction associated steatotic liver disease(MASLD)are closely intertwined.Sarcopenia,traditionally a disease of the older adult and chronic disease population,has been closely studied as one of the pathophysiologic conditions at play in the development of MASLD.They share similar risk factors of insulin resistance and physical inactivity.Given similar pathophysiology along the liver-muscle axis,sarcopenia has been studied as a risk factor for MASLD,and vice versa.Current research suggests a bidirectional relationship.Given the chronicity of MASLD as a chronic inflammatory liver disease,it can break down muscle mass and lead to sarcopenia,while sarcopenia promotes intramuscular lipid accumulation that releases cytokines that can aggravate inflammation in the liver.However,for the longest time,a lack of consensus definition for MASLD and sarcopenia made it difficult to study their relationship and outcomes.A recent nomenclature update to diagnosing MASLD has made it easier for researchers to identify cohorts for study.However,no gold standard technique to measure muscle mass or consensus sarcopenia definition has been identified yet.Future studies are needed to reach a consensus and reduce diagnostic variation.With similar pathophysiology and shared risk factors between the two diseases,future research may also identify potential therapeutic targets along the liver-muscle axis that would benefit both sarcopenia and MASLD in order to maximize their outcomes.

Prognostic factors associated with gastrointestinal dysfunction after gastrointestinal tumor surgery:A meta-analysis

BACKGROUND Explore the risk factors of gastrointestinal dysfunction after gastrointestinal tumor surgery and to provide evidence for the prevention and intervention of gastrointestinal dysfunction in patients with gastrointestinal tumor surgery.AIM To investigate the potential risk factors for gastrointestinal dysfunction following gastrointestinal tumor surgery and to present information supporting the prevention and management of gastrointestinal dysfunction in surgery patients.METHODS Systematically searched the relevant literature from PubMed,Web of Science,Cochrane Library,Embase,CNKI,China Biomedical Database,Wanfang Database,and Weipu Chinese Journal Database self-established until October 1,2022.Review Manager 5.3 software was used for meta-analysis after two researchers independently screened literature,extracted data,and evaluated the risk of bias in the included studies.RESULTS A total of 23 pieces of literature were included,the quality of which was medium or above,and the total sample size was 43878.The results of meta-analysis showed that the patients were male(OR=1.58,95%CI:1.25-2.01,P=0.002)and≥60 years old(OR=2.60,95%CI:1.76-2.87,P<0.001),physical index≥25.3 kg/m2(OR=1.6,95%CI:1.00-1.12,P=0.040),smoking history(OR=1.89,95%CI:1.31-2.73,P<0.001),chronic obstructive pulmonary disease(OR=1.49,95%CI:1.22-1.83,P<0.001),enterostomy(OR=1.47,95%CI:1.26-1.70,P<0.001),history of abdominal surgery(OR=2.90,95%CI:1.67-5.03,P<0.001),surgical site(OR=1.2,95%CI:1.40-2.62,P<0.001),operation method(OR=1.68,95%CI:1.08-2.62,P=0.020),operation duration(OR=2.65,95%CI:1.92-3.67,P<0.001),abdominal adhesion grade(OR=2.52,95%CI:1.90-3.56,P<0.001),postoperative opioid history(OR=5.35,95%CI:3.29-8.71,P<0.001),tumor TNM staging(OR=2.58,95%CI:1.84-3.62,P<0.001),postoperative blood transfusion(OR=2.92,95%CI:0.88-9.73,P=0.010)is a risk factor for postoperative gastrointestinal dysfunction in patients with gastrointestinal tumors.CONCLUSION There are many factors affecting gastrointestinal dysfunction in gastrointestinal patients after surgery.Clinical staff should identify relevant risk factors early and implement targeted intervention measures on the basis of personalized assessment to improve the clinical prognosis of patients.

Ethanol extract of cassia seed alleviates metabolic dysfunction-associated steatotic liver disease by acting on multiple lipid metabolism-related pathways

Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD is an important risk factor for cardiovascular and cerebrovascular diseases,including coronary heart disease,stroke,and tumors,with no specific therapeutic drugs currently available.The ethanol extract of cassia seed(CSEE)has shown promise in lowering blood lipids and improving hepatic steatosis,but its mechanism in treating MASLD remains underexplored.This study aims to investigate the therapeutic effects and mechanisms of CSEE.Methods:MASLD models were established in male Wistar rats and golden hamsters using a high fat diet(HFD).CSEE(10,50,250 mg/kg)was administered via gavage for six weeks.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),as well as liver TC and TG,were measured using biochemical kits.Histopathological changes in the liver were evaluated using Oil Red O staining,Hematoxylin-eosin(H&E)staining,and transmission electron microscopy(TEM).HepG2 cell viability was assessed using the cell counting kit-8(CCK8)and Calcein-AM/PI staining.Network pharmacology was used to analyze drug-disease targets,and western blotting was used to confirm these predictions.Results:CSEE treatment significantly reduced serum levels of TC,TG,LDL-C,ALT,and AST,and improved liver weight,liver index,and hepatic lipid deposition in rats and golden hamsters.In addition,CSEE alleviated free fatty acid(FFA)-induced lipid deposition in HepG2 cells.Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK,p-ACC,PPARα,CPT1A,PI3K P110 and p-AKT,while decreasing the protein levels of SREBP1,FASN,C/EBPα,and PPARγ,thus improving hepatic lipid metabolism and reducing lipid deposition.The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro.Conclusion:CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK,PPARα,and PI3K/AKT signaling pathways.

Metabolic dysfunction-associated steatotic liver disease-associated fibrosis and cardiac dysfunction in patients with type 2 diabetes

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in the presence of liver fibrosis,increases the risk of cardiovascular morbidity and mortality,but the nature of the cardio-hepatic interaction in the context type 2 diabetes mellitus(T2DM)is not fully understood.AIM To evaluate the changes in cardiac morphology and function in patients with T2DM and MASLD-associated liver fibrosis.METHODS T2DM patients with MASLD underwent a medical evaluation that included an assessment of lifestyle,anthropometric measurements,vital signs,an extensive laboratory panel,and a standard echocardiography.Liver fibrosis was evaluated using two scores[Fibrosis-4(FIB4)and Non-alcoholic fatty liver disease-Fibrosis Score(NFS)],and subjects were classified as having advanced fibrosis,no fibrosis,or an indeterminate risk.The correlations between structural and functional cardiac parameters and markers of liver fibrosis were evaluated through bivariate and multiple regression analyses.Statistical significance was set at P<0.05.RESULTS Data from 267 T2DM-MASLD subjects with complete assessment was analyzed.Patients with scores indicating advanced fibrosis exhibited higher interventricular septum and left ventricular(LV)posterior wall thickness,atrial diameters,LV end-systolic volume,LV mass index(LVMi),and epicardial adipose tissue thickness(EATT).Their mean ejection fraction(EF)was significantly lower(49.19%±5.62%vs 50.87%±5.14%vs 52.00%±3.25%;P=0.003),and a smaller proportion had an EF≥50%(49.40%vs 68.90%vs 84.21%;P=0.0017).Their total and mid LV wall motion score indexes were higher(P<0.05).Additionally,they had markers of diastolic dysfunction,with a higher E/e’ratio[9.64±4.10 vs 8.44(2.43-26.33)vs 7.35±2.62;P=0.026],and over 70%had lateral e’values<10 cm/second,though without significant differences between groups.In multiple regression analyses,FIB4 correlated with left atrium diameter(LAD;β=0.044;P<0.05),and NFS with both LAD(β=0.039;P<0.05)and right atrium diameter(β=0.041;P<0.01),Moreover,LVMi correlated positively with age and EATT(β=1.997;P=0.0008),and negatively with serum sex-hormone binding protein(SHBP)concentrations(β=-0.280;P=0.004).SHBP also correlated negatively with LAD(β=-0.036;P<0.05).CONCLUSION T2DM patients with markers of MASLD-related liver fibrosis exhibit lower EF and present indicators of diastolic dysfunction and cardiac hypertrophy.Additionally,LVMi and LAD correlated negatively with serum SHBP concentrations.

Effect of the traditional Chinese medicine fumigation combined with the meibomian gland squeezer for treatment of dry eye associated with meibomian gland dysfunction

Background:To observe the effect of traditional Chinese medicine fumigation combined with the meibomian gland squeezer for the treatment of dry eye associated with meibomian gland dysfunction(MGD).Methods:This is a randomized,controlled,non-masked,single-center study.Seventy-four cases(74 eyes)of dry eye associated with MGD were randomly divided into two groups.Thirty-seven patients were chosen as the treatment group was treated by the traditional Chinese medicine fumigation 3 times a week combined with the meibomian gland squeezer once a week for one month.The other 37 cases were sorted as the control group and only treated with the meibomian gland squeezer once a week for one month.Both groups received the primary treatment for 1 month,including Tobradex eye ointment once a day and 0.1%sodium hyaluronate eye drops 4-6 times daily.Patients were evaluated at baseline and 2-week and 1-month visits for the ocular symptom scores,international ocular surface disease index(OSDI),fluorescein tear break-up time(TBUT),corneal fluorescein staining test(CFS),Schirmer I test,meibum quality and meibum expressibility.Results:Sixty-seven patients were followed in the study,and the mean age was 57(±12.6)years.Thirty-three patients(11 males)in the treatment group and 34 patients(8 males)in the control group were followed in the study,and the mean age of the two groups was 45.36±15.02 years and 43.68±13.43 years,respectively.Before treatment,there was no significant difference between the two groups in gender,age,ocular symptom scores,OSDI,TBUT,CFS,Schirmer I test,meibum quality,and meibum expressibility(P>0.05).Compared with baseline,the 2 groups had different degrees of improvement in the ocular symptom scores,OSDI,TBUT,CFS,meibum quality,and meibum expressibility at the 2-week and 1-month visits(P<0.05),and the treatment group showed a more significant improvement in the ocular symptom scores,OSDI,TBUT,CFS,meibum quality and meibum expressibility compared with the control group(P<0.05).In addition,no serious adverse events were observed in each group.Conclusions:The traditional Chinese medicine fumigation combined with the meibomian gland squeezer may be safe,effective,and helpful for the treatment of dry eye associated with MGD.

Lower synaptic density and its association with cognitive dysfunction in patients with obsessive-compulsive disorder

Background Understanding synaptic alteration in obsessive-compulsive disorder(OCD)is crucial for elucidating its pathological mechanisms,but in vivo research on this topic remains limited.Aims This study aimed to identify the synaptic density indicators in OCD and explore the relationship between cognitive dysfunction and synaptic density changes in OCD.Methods This study enrolled 28 drug-naive adults with OCD aged 18-40 years and 16 healthy controls(HCs).Three-dimensional T1-weighted structural magnetic resonance imaging and 18F-SynVesT-1 positron emission tomography were conducted.Cognitive function was assessed using the Wisconsin Cart Sorting Test(WCST)in patients with OCD and HCs.Correlative analysis was performed to examine the association between synaptic density reduction and cognitive dysfunction.Results Compared with HCs,patients with OCD showed reduced synaptic density in regions of the cortico-striatothalamo-cortical circuit such as the bilateral putamen,left caudate,left parahippocampal gyrus,left insula,left parahippocampal gyrus and left middle occipital lobe(voxel p<0.001,uncorrected,with cluster level above 50 contiguous voxels).The per cent conceptual-level responses of WCST were positively associated with the synaptic density reduction in the left middle occipital gyrus(R^(2)=0.1690,p=0.030),left parahippocampal gyrus(R^(2)=0.1464,p=0.045)and left putamen(R^(2)=0.1967,p=0.018)in patients with OCD.Conclusions Adults with OCD demonstrated lower 18Flabelled difluoro analogue of 18F-SynVesT-1 compared with HCs,indicating potentially lower synaptic density.This is the first study to explore the synaptic density in patients with OCD and provides insights into potential biological targets for cognitive dysfunctions in OCD.

Implications of metabolic dysfunction associated fatty liver disease in COVID-19

Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the world population.In 2020,the coronavirus disease 2019(COVID-19)crisis was unprecedented,and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2.MAFLD patients are frequently obese with added metabolic menace like diabetes,hypertension,and dyslipidemia leading to greater jeopardy of COVID-19.MAFLD patients are 4 to 6-fold more prone towards infections.COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin.Hence,MAFLD in COVID-19 patients worsens the condition significantly.The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission.Direct hepatic injury,enhanced levels of inflammatory cytokines,declined hepatic mitochondrial activity,and compromised immunity are considered as some underlying mechanisms.The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients.The review systematically analyzes the effect of striking two worldwide pandemics(MAFLD and COVID-19)together in the present era.

Insulin resistance and adipose tissue interactions as the cornerstone of metabolic(dysfunction)-associated fatty liver disease pathogenesis

The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.

Gastrointestinal dysfunction is associated with mortality in severe burn patients:a 10-year retrospective observational study from South China

Background:Data on severe and extensive burns in China are limited,as is data on the prevalence of a range of related gastrointestinal(GI)disorders[such as stress ulcers,delayed defecation,opioid-related bowel immotility,and abdominal compartment syndrome(ACS)].We present a multicentre analysis of coincident GI dysfunction and its effect on burn-related mortality.Methods:This retrospective analysis was conducted on patients with severe[≥20%total burn surface area(TBSA)]and extensive(>50%TBSA or>25%full-thickness TBSA)burns admitted to three university teaching institutions in China between January 1,2011 and December 31,2020.Both 30-and 90-day mortality were assessed by collating demographic data,burn causes,admission TBSA,%full-thickness TBSA,Baux score,Abbreviated Burn Severity Index(ABSI)score,and Sequential Organ Failure Assessment(SOFA)score,shock at admission and the presence of an inhalation injury.GI dysfunction included abdominal distension,nausea/vomiting,diarrhoea/constipation,GI ulcer/haemorrhage,paralytic ileus,feeding intolerance and ACS.Surgeries,length of intensive care unit(ICU)stay,pain control[in morphine milligram equivalents(MME)]and overall length of hospital stay(LOHS)were recorded.Results:We analyzed 328 patients[75.6%male,mean age:(41.6±13.6)years]with a median TBSA of 62.0%(41.0%–80.0%);256(78.0%)patients presented with extensive burns.The 90-day mortality was 23.2%(76/328),with 64(84.2%)of these deaths occurring within 30 d and 25(32.9%)occurring within 7 d.GI dysfunction was experienced by 45.4%of patients and had a significant effect on 90-day mortality[odds ratio(OR)=14.070,95%confidence interval(CI)5.886–38.290,P<0.001].Multivariate analysis showed that GI dysfunction was associated with admission SOFA score and%full-thickness TBSA.Overall,88.2%(67/76)of deceased patients had GI dysfunction[hazard ratio(HR)for death of GI dysfunction=5.951],with a survival advantage for functional disorders(diarrhoea,constipation,or nausea/vomiting)over GI ulcer/haemorrhage(P<0.001).Conclusion:Patients with severe burns have an unfavourable prognosis,as nearly one-fifth died within 90 d.Half of our patients had comorbidities related to GI dysfunction,among which GI ulcers and haemorrhages were independently correlated with 90-day mortality.More attention should be given to severe burn patients with GI dysfunction.

Death-associated protein kinase 1 is associated with cognitive dysfunction in major depressive disorder

We previously showed that death-associated protein kinase 1(DAPK1)expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's disease.In addition,depression is a risk factor for developing Alzheimer's disease,as well as an early clinical manifestation of Alzheimer's disease.Meanwhile,cognitive dysfunction is a distinctive feature of major depressive disorder.Therefore,DAPK1 may be related to cognitive dysfunction in major depressive disorder.In this study,we established a mouse model of major depressive disorder by housing mice individually and exposing them to chronic,mild,unpredictable stressors.We found that DAPK1 and tau protein levels were increased in the hippocampal CA3 area,and tau was hyperphosphorylated at Thr231,Ser262,and Ser396 in these mice.Furthermore,DAPK1 shifted from axonal expression to overexpression on the cell membrane.Exercise and treatment with the antidepressant drug citalopram decreased DAPK1 expression and tau protein phosphorylation in hippocampal tissue and improved both depressive symptoms and cognitive dysfunction.These results indicate that DAPK1 may be a potential reason and therapeutic target of cognitive dysfunction in major depressive disorder.

Frequency and Associated Factors of Erectile Dysfunction among Patients with Liver Cirrhosis in Parakou, Republic of Benin in 2022

Introduction: Erectile dysfunction is a pathology less expressed by patients, but it affects their quality of life. The objective of this work is to study erectile dysfunction among patients with cirrhosis in Parakou in 2022. Patients and Methods: This was a descriptive and analytical cross-sectional study with prospective data collection, conducted from February 1 to June 30, 2022 at the Teaching Hospital of Borgou/Alibori and the Military Teaching Hospital of Parakou. Men with liver cirrhosis who gave their informed verbal consent were included. Erectile dysfunction was diagnosed using IIEF-5 score. The prognosis of cirrhosis was assessed using Child-Pugh score. The data were analyzed by Epi Data analysis 2.3 software. Results: A total of 64 patients were included. Their mean age was 43.53 ± 13.13 years. Cirrhosis was secondary to chronic hepatitis B virus infection in 55 patients (85.94%). In this study, 42 patients (65.63%) had at least one decompensation of cirrhosis. Among the 64 patients included, 27 (42.18%) had erectile dysfunction. This erectile dysfunction was moderate in 12 patients (44.44%). The other sexual disorders found in these patients were decreased libido and ejaculation disorders. After multivariate analysis, the factors statistically associated with erectile dysfunction were: age (p Conclusion: Erectile dysfunction is common in patients with liver cirrhosis. It is more frequent when the cirrhosis is complicated and the patients are elderly. Nevertheless, it should be systematically sought in any patient with liver cirrhosis.

Sexual dysfunction and associated factors in Thai patients with psychiatric disorders

Background Sexual dysfunction is common among patients with psychiatric disorders but might be under-reported due to Asian sociocultural factors.Recognition of sexual dysfunction and associated factors in this vulnerable population would help clinicians properly assess and manage related conditions.Aims We aimed to examine the prevalence of sexual dysfunction and its associated factors among patients with psychiatric disorders in Thailand.Methods This was a cross-sectional study.We enrolled participants aged 18 and older who visited the psychiatry clinic at King Chulalongkorn Memorial Hospital in Bangkok,Thailand between August 2020 and December 2021.Demographic and clinical data were assessed,and all psychiatric disorders and sexual dysfunctions were diagnosed by clinical interview using the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.Statistical analysis was done to explore the association between sexual dysfunction and related factors.Results Sexual dysfunction was diagnosed in 101(50.0%)of the total 202 participants.The mean(standard deviation,SD)age was 30.2(9.0)years,and the majority of patients were men(54.5%),single(81.2%),employed(47.5%)and had a coexisting depressive disorder(48.0%).Multivariable logistic regression analysis showed a significant association between sexual dysfunction and quality of life,unemployment,and the dosage of antidepressants and benzodiazepines.Conclusions The prevalence of sexual dysfunction among this population was relatively high.However,the findings may represent only a portion of affected psychiatric patients for others with sexual dysfunction symptoms but without functional impairment did not meet the diagnostic criteria for sexual dysfunction.Improvement of quality of life and optimising antidepressant/benzodiazepine dosage should be further investigated for promoting sexual function in patients with mental disorders.