Direct competitive assay for HER2 detection in human plasma using Bloch surface wave-based biosensors.

The overexpression and/or amplification of the HER2/neu oncogene has been proposed as a prognostic marker in breast cancer. The detection of the related peptide HER2 remains a grand challenge in cancer diagnosis and for therapeutic decision-making. Here, we used a biosensing device based on Bloch Surface Waves excited on a one-dimensional photonic crystal (1DPC) as valid alternative to standard techniques. The 1DPC was optimized to operate in the visible spectrum and the biosensor optics has been designed to combine label-free and fluorescence operation modes. This feature enables a real-time monitoring of a direct competitive assay using detection mAbs conjugated with quantum dots for an accurate discrimination in fluorescence mode between HER2-positive/negative human plasma samples. Such a competitive assay was implemented using patterned alternating areas where HER2-Fc chimera and reference molecules were bio-conjugated and monitored in a multiplexed way. By combining Label-Free and fluorescence detection analysis, we were able to tune the parameters of the assay and provide an HER2 detection in human plasma in less than 20 min, allowing for a cost-effective assay and rapid turnaround time. The proposed approach offers a promising technique capable of performing combined label-free and fluorescence detection for both diagnosis and therapeutic monitoring of diseases.

Association between insulin resistance and serum insulin-like growth factor 1 levels in patients with non-remitting major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is linked to an increased risk of diabetes; however, the underlying pathomechanism remains unknown. Although insulin-like growth factor 1 (IGF-1) is involved in the pathogenesis of both insulin resistance (IR) and MDD, no studies have investigated the relationship between IGF-1 and IR in patients with MDD. METHODS: We recruited 120 patients with MDD (84 non-remitting patients and 36 remitting patients) and 99 control participants. Blood samples were collected after overnight fasting to investigate associations between serum and clinical factors, such as serum IGF-1 levels and homeostasis model assessment-insulin resistance (HOMA-IR). RESULTS: Serum IGF-1 levels were higher in patients with non-remitting MDD than in control participants and patients with remitting MDD (P = 0.001 and P = 0.007, respectively). There were no significant differences in HOMA-IR between the three groups. HOMA-IR was positively correlated with serum IGF-1 levels in patients with non-remitting MDD (R = 0.355; P= 0.001) but not in control participants or patients with remitting MDD. A stepwise multiple regression analysis with various clinical factors revealed a positive association of serum IGF-1 levels and body mass index with HOMA-IR in patients with non-remitting MDD. LIMITATIONS: This is a cross-sectional study and therefore we cannot draw firm conclusions about causal associations. CONCLUSIONS: Serum IGF-1 levels may play a role in IR in patients with MDD who fail to achieve remission. Further studies, including longitudinal studies, are needed to determine the relationship between high serum IGF-1 levels and subsequent IR and diabetes risk.

Beneficial effects of coconut oil (Cocos nucifera) on hematobiochemicl and histopathological markers in CCL4-intoxicated rabbits / Efeitos benéficos do óleo de coco (Cocos nucifera) em marcadores hematobioquímicos e histopatológicos em coelhos intoxicados com CCL4

The study was designed to investigate the effect of Coconut Oil on the levels of some liver and hematological parameters in carbon tetrachloride intoxicated rabbits. Also the antioxidant capacity of Coconut Oil for various concentrations was assessed on the basis of percent scavenging of (DPPH) free radical. Experimental animals were divided into five groups, eight rabbits in each group. These were: group A (Normal control), group B (Toxic control), group C (Standard control), group D (Treated with Coconut Oil 50 mL/kg body weight after CCl4 intoxication), group E (Treated with Coconut Oil 200 mL/kg body weight after CCl4 intoxication). The effects observed were compared with a standard hepatoprotective drug silymarine (50 mL/kg body weight). The Coconut Oil (200 mL/kg body weight) significantly (P<0.05) reduced the elevated serum levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) when compared to a toxic control rabbits. The results of extract treated rabbits were similar to silymarine administered rabbits group. Treatment with Coconut Oil root and silymarine caused no significant changes in RBC, Platelets, (Hb), (MCH) concentration and (HCT) values. However, significant (P<0.05) increase was observed in the total WBC count. The present study suggested that Coconut Oil can be used as an herbal alternative (need further exploration i.e to detect its bioactive compound and its efficacy) for hepatoprotective activit.

O estudo foi desenhado para investigar o efeito do óleo de coco nos níveis de alguns parâmetros hepáticos e hematológicos em coelhos intoxicados com tetracloreto de carbono. Também a capacidade antioxidante do óleo de coco para várias concentrações foi avaliada com base na porcentagem de eliminação de radicais livres (DPPH). Os animais experimentais foram divididos em cinco grupos, oito coelhos em cada grupo. Estes foram: grupo A (controle normal), grupo B (controle tóxico), grupo C (controle padrão), grupo D (tratado com óleo de coco 50 mL/kg de peso corporal após intoxicação por CCl4), grupo E (tratado com óleo de coco 200 mL/kg de peso corporal após intoxicação por CCl4). Os efeitos observados foram comparados com um fármaco hepatoprotetor padrão silimarina (50 mL/kg de peso corporal). O óleo de coco (200 mL/kg de peso corporal) reduziu significativamente (P<0,05) os níveis séricos elevados de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP), quando comparado a um coelho controle tóxico. Os resultados dos coelhos tratados com extrato foram semelhantes aos do grupo de coelhos administrados com silimarina. O tratamento com raiz de óleo de coco e silimarina não causou alterações significativas nos valores de RBC, Plaquetas, (Hb), (MCH) e (HCT). No entanto, observou-se aumento significativo (P<0,05) na contagem total de leucócitos. O presente estudo sugeriu que o óleo de coco pode ser usado como uma alternativa fitoterápica (precisa de mais exploração, ou seja, para detectar seu composto bioativo e sua eficácia) para atividade hepatoprotetora.

The association of genetic factors with serum calretinin levels in asbestos-related diseases.

BACKGROUND: Asbestos exposure is associated with different asbestos-related diseases, including malignant mesothelioma (MM). MM diagnosis is confirmed with immunohistochemical analysis of several markers, including calretinin. Increased circulating calretinin was also observed in MM. The aim of the study was to determine if CALB2 polymorphisms or polymorphisms in genes that can regulate calretinin expression are associated with serum calretinin levels or MM susceptibility. SUBJECTS AND METHODS: The study included 288 MM patients and 616 occupationally asbestos-exposed subjects without MM (153 with asbestosis, 380 with pleural plaques and 83 without asbestos-related disease). Subjects were genotyped for seven polymorphisms in CALB2, E2F2, MIR335, NRF1 and SEPTIN7 genes using competitive allele-specific polymerase chain reaction (PCR). Serum calretinin was determined with ELISA in 545 subjects. Nonparametric tests, logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis. RESULTS: Carriers of at least one polymorphic CALB2 rs889704 allele had lower calretinin levels (P = 0.036). Carriers of two polymorphic MIR335 rs3807348 alleles had higher calretinin (P = 0.027), while carriers of at least one polymorphic NRF1 rs13241028 allele had lower calretinin levels (P = 0.034) in subjects without MM. Carriers of two polymorphic E2F2 rs2075995 alleles were less likely to develop MM (odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.43-0.96, P = 0.032), but the association was no longer significant after adjustment for age (P = 0.093). Optimal serum calretinin cut-off values differentiating MM patients from other subjects differed according to CALB2, NRF1, E2F2, and MIR335 genotypes. CONCLUSIONS: The results of presented study suggest that genetic variability could influence serum calretinin levels. These findings could contribute to a better understanding of calretinin regulation and potentially to earlier MM diagnosis.

Association between serum cholinesterase and the prevalence of atrial fibrillation in Chinese hypertensive population: a cross-sectional study.

BACKGROUND: Atrial fibrillation (AF) is a very common arrhythmia with significant incidence rate and mortality. Several studies have shown a notable correlation between non-alcoholic fatty liver disease (NAFLD) and AF. It has been observed that serum cholinesterase (SChE) levels are elevated in individuals with fatty liver. However, the relationship between the SChE index and AF is still unclear. Therefore, the purpose of this study is to explore the association between the SChE index and the prevalence of AF in patients with hypertension. METHOD: We collected cross-sectional data from January 2018 to April 2021 based on a retrospective study of cardiovascular disease. A total of 748 patients with hypertension were included, of whom 165 had AF. We used logistic regression models to test the relationship between SChE and the prevalence of AF in hypertensive patients. RESULT: In hypertensive patients, the SChE index was significantly associated with AF (OR = 0.723, P < 0.001). After adjusting for potential confounding factors, this correlation was still significant (OR = 0.778, P < 0.001). The stability of the model was verified by adjusting the variable type of SChE. The data were further stratified according to whether the patient had fatty liver. In the stratified data, the correlation between SChE and atrial fibrillation was still significant (P < 0.05). CONCLUSION: Our study showed that SChE was significantly negatively correlated with the occurrence of AF in patients with hypertension. And this correlation was not affected by whether the patient had fatty liver.

Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis.

Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in CORIN, the gene encoding atrial natriuretic peptide (ANP)-converting enzyme. A plasma sample obtained from one of the siblings had no detectable levels of corin or N-terminal pro-ANP but had elevated levels of B-type natriuretic peptide (BNP) and one of the two protein markers of fibrosis that we tested. These and other findings support the hypothesis that BNP cannot fully compensate for a lack of activation of the ANP pathway and that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis.

A novel score of IL-13 and age predicts 90-day mortality in severe alcohol-associated hepatitis: A multicenter plasma biomarker analysis.

BACKGROUND: Severe alcoholic hepatitis (AH) has a high short-term mortality rate. The MELD assesses disease severity and mortality; however, it is not specific for AH. We screened plasma samples from patients with severe AH for biomarkers of multiple pathological processes and identified predictors of short-term mortality. METHODS: Plasma was collected at baseline from 85 patients with severe AH (MELD≥20, Maddrey's discriminant function≥32) enrolled in the Defeat Alcoholic Steatohepatitis clinical trial (investigating IL-1 receptor antagonist+pentoxifylline+zinc vs. methylprednisolone+placebo). Samples were analyzed for 43 biomarkers and the markers' association with 28- and 90-day mortalities was assessed. RESULTS: Thirty-one (36.5%) patients died during the 90-day follow-up with similar ratios in the treatment groups. Eight biomarkers showed an association with mortality. IL-6, IL-22, interferon-α2, soluble TNF receptor 1, lipocalin-2, and α-fetoprotein levels were associated with 28-day mortality, while IL-6, IL-13, and endotoxin levels with 90-day mortality. In multivariable Cox regression, encephalopathy, lipocalin-2, and α-fetoprotein levels were independent predictors of 28-day mortality, and IL-6, IL-13, international normalized ratio levels, and age were independent predictors of 90-day mortality. The combination of IL-13 and age had superior performance in predicting 90-day mortality compared with MELD in the total cohort and the individual treatment groups. CONCLUSIONS: We identified predictors of short-term mortality in a cohort exclusively involving patients with severe AH. We created a composite score of IL-13 and age that predicts 90-day mortality regardless of the treatment type with a performance superior to MELD in severe AH.

Serum C-reactive protein level and sleep characteristics in obstructive sleep apnea syndrome comorbid with panic disorder: a preliminary study.

OBJECTIVE: Investigate the sleep characteristics of patients with obstructive sleep apnea syndrome (OSAS) comorbidity with panic disorder (PD), exploring its potential association with serum C-reactive protein (CRP) levels. PATIENTS AND METHODS: Fifty-four patients (25 OSAS patients with PD and 29 without PD) and 25 healthy controls (HCs) were included. The Self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Pittsburgh sleep quality index (PSQI) were used to assess the mood and sleep quality of the subjects. All patients had circulating CRP levels and polysomnography was performed. RESULTS: OSAS with PD had higher SAS, SDS, PSQI than the OSAS without PD. Compared to OSAS without PD, OSAS with PD had higher percentage of non- rapid eye movement sleep 1 and 2 (N1 and N2%), sleep latency, and a lower percentage of rapid eye movement sleep (REM%). Respiratory-related microarousal index, AHI, and time below 90% oxygen saturation (T90) were low, and the lowest oxygen saturation (LO2) was high. Serum CRP levels in OSAS patients with PD were lower than that in OSAS patients without PD, but higher than that in HCs. In OSAS patients with PD, serum CRP levels were negatively correlated with wake time after sleep onset and SAS scores but positively correlated with sleep efficiency and N2%. Serum CRP levels were positively correlated with T90 and negatively correlated with LO2. CONCLUSION: OSAS patients with PD had worse sleep quality, less severe OSAS, and low serum CRP levels. Serum CRP levels in OSAS patients with PD were associated with poorer sleep quality and duration of hypoxia rather than AHI.

PCT, IL-6, and IL-10 facilitate early diagnosis and pathogen classifications in bloodstream infection.

BACKGROUND: In the diagnosis of bloodstream infection (BSI), various inflammatory markers such as C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL), white blood cell count (WBC), neutrophil percentage (NE%), platelet count (PLT), and erythrocyte sedimentation rate (ESR) have been extensively utilized. However, their specific roles in distinguishing BSI from local bacterial infection (LBI) and in classifying BSI pathogens remain uncertain. METHODS: A historical cohort study was conducted, involving the enrollment of 505 patients with BSI and 102 patients with LBI. To validate the reliability of the clinical data obtained from this cohort, mouse models of BSI were utilized. RESULTS: Our findings revealed that patients with BSI had significantly higher levels of inflammatory markers, including CRP, PCT, IL-6, IL-10, WBC, NE%, and ESR, compared to those with LBI (p < 0.05). The receiver operating characteristic (ROC) curve analysis demonstrated that CRP, PCT, IL-6, IL-10, ESR and NE% exhibited excellent diagnostic efficacy for BSI. Additionally, we observed significant differences in CRP, PCT, IL-6, and IL-10 levels between patients with BSI caused by Gram-positive bacteria (GP-BSI) and Gram-negative bacteria (GN-BSI), but no significant variations were found among specific bacterial species. Furthermore, our study also found that CRP, PCT, and IL-10 have good discriminatory ability for vancomycin-resistant Enterococcus (VRE), but they show no significant diagnostic efficacy for other multidrug-resistant organisms (MDROs) such as carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and methicillin-resistant Staphylococcus aureus (MRSA). In our mouse model experiments, we observed a remarkable increase in PCT, IL-6, and IL-10 levels in mice with GN-BSI compared to those with GP-BSI. CONCLUSION: Our study has confirmed that PCT, IL-6, and IL-10 are efficient biomarkers for distinguishing between BSI and LBI. Furthermore, they can be utilized to classify BSI pathogens and differentiate between VRE and vancomycin-susceptible Enterococcus. These findings are extremely valuable for clinicians as they enable timely initiation of empiric antibiotic therapies and ultimately lead to improved clinical outcomes for patients with BSI.

Intronic Variants of the Angiotensin-Converting Enzyme 2 Gene Modulate Plasma ACE2 Levels and Possibly Confer Protection against Severe COVID-19.

Membrane-bound angiotensin-converting enzyme 2 (ACE2) receptor acts as the entry point for the novel coronavirus, SARS-CoV-2. Polymorphisms in the ACE2 gene may alter viral binding, regulate the expression of ACE2, and thus, affect disease severity. In this study, 68 COVID-19 patients with varying degrees of severity and 40 healthy controls were enrolled. The genetic landscape of the ACE2 gene was explored by whole exome sequencing of 29 individuals, and specific regions of ACE2 were analyzed for the rest of the participants via PCR, followed by barcode-tagged sequencing. The mean soluble ACE2 level in the plasma of healthy controls and patients did not vary significantly but was higher in the patient group (3.77 ± 1.55 ng/mL vs. 3.94 ± 1.42 ng/mL). Analysis of exon 1, exon 2, and exon 8 of the ACE2 gene revealed that these regions are highly conserved in our population. Investigation of exon 11 and its flanking intronic region revealed that deletions in a stretch of 18T nucleotides in the noncoding region significantly decrease ACE2 levels in plasma, as individuals harboring wild-type variants had higher plasma ACE2 levels compared to those harboring T1del, T2del, and T3del variants. However, the intronic variants were not found to be significantly associated with disease severity.

The effect of genetic variation and mRNA expression of interleukin-17A gene on susceptibility to asthma.

Analyzing the genetic variation and mRNA expression of interleukin-17A (IL-17A) gene and its impact on asthma susceptibility was the purpose of this study. 120 asthma patients were selected as the asthma group, and another 120 healthy individuals who underwent physical examination were selected as the health group; Compare the cytokine levels and mRNA expression of IL-17A between two groups, as well as the clinical indicator total immunoglobulin E (TIgE) levels; The genotype and allele distribution frequency of IL-17A Single-nucleotide polymorphism locus rs2275913 and rs8193036 were compared between the two groups; Compare the serum IL-17A and TIgE levels of different genotypes at rs2275913 and rs8193036 loci; and logistic regression was used to evaluate the impact of IL-17A on asthma susceptibility. The serum levels of IL-17A, TIgE, and IL-17AmRNA expression in the asthma group were higher than those in the healthy group (P<0.05). There were three genotypes of AA, AG and GG at rs2275913 locus, and the frequency distribution between the two groups was significant (P<0.05), and the frequency of A Allele frequency in asthma group was higher than that in healthy group (P<0.05). There are three genotypes of CC, CT, and TT at the rs8193036 locus, and there was no significant difference in the frequency distribution between the two groups (P>0.05). There is no difference in the frequency distribution of alleles C and T between the two groups (P>0.05). The levels of IL-17A and TIgE in the rs2275913AA genotype were higher than those in the AG and GG genotypes (P<0.05); There was no difference in IL-17A and TIgE levels among different genotypes of rs8193036 (P>0.05). The rs2275913 polymorphism was associated with asthma susceptibility and is an independent risk parameter for asthma susceptibility. Upregulation of serum IL-17A and TIgE, as well as overexpression of IL-17A mRNA, were closely related to asthma susceptibility in asthma patients. The rs2275913 polymorphism had a significant role in increasing the risk of asthma, and variant allele A may be a susceptibility factor for increasing asthma risk.

Molecular species profiles of plasma ceramides in different clinical types of X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder associated with peroxisomal dysfunction. Patients with this rare disease accumulate very long-chain fatty acids (VLCFAs) in their bodies because of impairment of peroxisomal VLCFA ?-oxidation. Several clinical types of X-ALD, ranging from mild (axonopathy in the spinal cord) to severe (cerebral demyelination), are known. However, the molecular basis for this phenotypic variability remains largely unknown. In this study, we determined plasma ceramide (CER) profile using liquid chromatography-tandem mass spectrometry. We characterized the molecular species profile of CER in the plasma of patients with mild (adrenomyeloneuropathy;AMN) and severe (cerebral) X-ALD. Eleven X-ALD patients (five cerebral, five AMN, and one carrier) and 10 healthy volunteers participated in this study. Elevation of C26:0 CER was found to be a common feature regardless of the clinical types. The level of C26:1 CER was significantly higher in AMN but not in cerebral type, than that in healthy controls. The C26:1 CER level in the cerebral type was significantly lower than that in the AMN type. These results suggest that a high level of C26:0 CER, along with a control level of C26:1 CER, is a characteristic feature of the cerebral type X-ALD. J. Med. Invest. 70 : 403-410, August, 2023.

Relationship between Serum Homocysteine Concentration and Dietary Factors in Young Japanese Women.

Homocysteine is a methionine metabolism intermediate and its increased blood levels are associated with a higher risk of noncommunicable diseases. Reportedly, blood homocysteine levels increase with inadequate folate, vitamin B6, and vitamin B12 intake; however, its relationship with dietary factors other than these three vitamins remains unknown. Thus, we investigated the relationship of homocysteine with other nutrient intake. We performed a dietary survey on 227 young women using a food record with approximate amounts for 7 consecutive days in conjunction with digital imaging. We collected early morning fasting blood samples the day after the dietary survey was completed and analyzed the serum homocysteine levels. We observed that the serum homocysteine concentrations were significantly negatively associated with soluble, insoluble, and total fiber intake. In addition, participants with high fruit and mushroom intake displayed lower serum homocysteine concentrations, suggesting dietary fiber involvement from these foods. However, we observed no serum homocysteine concentration-related association with cereals and vegetables (well-documented dietary fiber sources) or with fruits and mushrooms. In conclusion, fiber quality-related differences could thus be caused by different sources, including antioxidant components such as fruit polyphenols and mushroom antioxidant and anti-inflammatory factors.

Combined Age with Mean Decrease Rates of Total Bilirubin and MELD Score as a Novel and Simple Clinical Predictor on 90-Day Transplant-Free Mortality in Adult Patients with Acute Liver Failure Undergoing Plasma Exchange: A Single-Center Retrospective Study.

Background: Acute liver failure (ALF), previously known as fulminant hepatic failure, has become a common, rapidly progressive, and life-threatening catastrophic hepatic disease in intensive care unit (ICU) due to the continuous increase in drug abuse, viral infection, metabolic insult, and auto-immune cause. At present, plasma exchange (PE) is the main effective alternative treatment for ALF in ICU clinical practice, and high-volume plasma exchange (HVP) has been listed as a grade I recommendation for ALF management in the American Society for Apheresis (ASFA) guidelines. However, no existing models can provide a satisfactory performance for clinical prediction on 90-day transplant-free mortality in adult patients with ALF undergoing PE. Our study aims to identify a novel and simple clinical predictor of 90-day transplant-free mortality in adult patients with ALF undergoing PE. Methods: This retrospective study contained adult patients with ALF undergoing PE from the Medical ICU (MICU) in the Second Affiliated Hospital of Harbin Medical University between January 2017 and December 2020. Baseline and clinical data were collected and calculated on admission to ICU before PE, including gender, age, height, weight, body mass index (BMI), etiology, total bilirubin, direct bilirubin, indirect bilirubin, prothrombin activity, model for end-stage liver disease (MELD) score, and sequential organ failure assessment (SOFA) score. Enrolled adult patients with ALF undergoing PE were divided into a survival group and a death group at discharge and 90 days on account of medical records and telephone follow-up. After each PE, decreased rates of total bilirubin and MELD score and increased rates of prothrombin activity were calculated according to the clinical parameters. In clinical practice, different patients underwent different times of PE, and thus, mean decrease rates of total bilirubin and MELD score and mean increase rate of prothrombin activity were obtained for further statistical analysis. Results: A total of 73 adult patients with ALF undergoing 204 PE were included in our retrospective study, and their transplant-free mortality at discharge and 90 days was 6.85% (5/73) and 31.51% (23/73), respectively. All deaths could be attributed to ALF-induced severe and life-threatening complications or even multiple organ dysfunction syndrome (MODS). Most of the enrolled adult patients with ALF were men (76.71%, 56/73), with a median age of 48.77 years. Various hepatitis virus infections, unknown etiology, auto-immune liver disease, drug-induced liver injury, and acute pancreatitis (AP) accounted for 75.34%, 12.33%, 6.85%, 4.11%, and 1.37% of the etiologies in adult patients with ALF, respectively. Univariate analysis showed a significant difference in age, mean decrease rates of total bilirubin and MELD score mean increase rate of prothrombin activity, decrease rates of total bilirubin and MELD score, and increase rate of prothrombin activity after the first PE between the death group and survival group. Multivariate analysis showed that age and mean decrease rates of total bilirubin and MELD score were closely associated with 90-day transplant-free mortality in adult patients with ALF undergoing PE. The 90-day transplant-free mortality was 1.081, 0.908, and 0.893 times of the original value with each one-unit increase in age and mean decrease rates of total bilirubin and MELD score, respectively. The areas under the receiver operatingcharacteristic (ROC) curve of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 0.689, 0.225, 0.123, and 0.912, respectively. The cut-off values of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 61.50, 3.12, 1.21, and 0.33, respectively. The specificity and sensitivity of combined age with mean decrease rates of total bilirubin and MELD score for predicting 90-day transplant-free mortality in adult patients with ALF undergoing PE were 87% and 14%. Conclusion: Combined age with mean decrease rates of total bilirubin and MELD score as a novel and simple clinical predictor can accurately predict 90-day transplant-free mortality in adult patients with ALF undergoing PE, which is worthy of application and promotion in clinical practice, especially in the identification of potential transplant candidates.

Rewriting DNA in the body lowers cholesterol.

Verve Therapeutics says its base-editing approach may help prevent heart disease in many people.

Immune checkpoint inhibitors and cellular immunotherapy for advanced gastric, gastroesophageal cancer: a long pathway

Although the incidence rate and mortality of gastric/gastroesophageal cancer (G/GEJC) are declining globally, G/GEJC remains a health issue in East Asia. When diagnosed as advanced stage, treatment after serial lines of chemotherapy is limited, with a median overall survival of less than 1 year. Immunotherapy, including immune checkpoint inhibitors (ICIs) and cellular immunotherapy, has changed the prospects of cancer therapy by reversing immune suppression in the tumor microenvironment. As part of this review, we enumerated the clinical uses of ICIs related to the immunosuppressive signaling axis PD-1/PD-L1 and CTLA-4/B7. ICIs were initially approved as a secondary treatment option for patients with severe pretreating advanced gastric and gastroesophageal cancer (AG/GEJC). Till now, it has become the mainstream therapy in combination with chemotherapy and targeted therapy for patients identified by biomarkers. Numerous evidence showed microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden (TMB) and Epstein–Barr virus (EBV) status might be indicative to the use of ICIs. In addition, we discussed the current limitations and prospects of ICIs in AG/GGEJC, as well as the first clinical application of novel CAR-T cell therapies (AU)