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.

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.

Rewriting DNA in the body lowers cholesterol.

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

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.

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.

Liver Transplantation in a Woman with Mahvash Disease.

Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.

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.

Seroprevalence of SARS-CoV-2 antibodies among healthcare workers in Dutch hospitals after the 2020 first wave: a multicentre cross-sectional study with prospective follow-up.

BACKGROUND: We aimed to estimate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and describe its determinants and associated symptoms among unvaccinated healthcare workers (HCWs) after the first wave of the pandemic. METHODS: HCWs from 13 Dutch hospitals were screened for antibodies against the spike protein of SARS-CoV-2 in June-July 2020 and after three months. Participants completed a retrospective questionnaire on determinants for occupational and community exposure to SARS-CoV-2 and symptoms suggestive of COVID-19 experienced since January 2020. The seroprevalence was calculated per baseline characteristic and symptom at baseline and after follow-up. Adjusted odds ratios (aOR) for seropositivity were determined using logistic regression. RESULTS: Among 2328 HCWs, 323 (13.9%) were seropositive at enrolment, 49 of whom (15%) reported no previous symptoms suggestive of COVID-19. During follow-up, only 1% of the tested participants seroconverted. Seroprevalence was higher in younger HCWs compared to the mid-age category (aOR 1.53, 95% CI 1.07-2.18). Nurses (aOR 2.21, 95% CI 1.34-3.64) and administrative staff (aOR 1.87, 95% CI 1.02-3.43) had a higher seroprevalence than physicians. The highest seroprevalence was observed in HCWs in the emergency department (ED) (aOR 1.79, 95% CI 1.10-2.91), the lowest in HCWs in the intensive, high, or medium care units (aOR 0.47, 95% CI 0.31-0.71). Chronic respiratory disease, smoking, and having a dog were independently associated with a lower seroprevalence, while HCWs with diabetes mellitus had a higher seroprevalence. In a multivariable model containing all self-reported symptoms since January 2020, altered smell and taste, fever, general malaise/fatigue, and muscle aches were positively associated with developing antibodies, while sore throat and chills were negatively associated. CONCLUSIONS: The SARS-CoV-2 seroprevalence in unvaccinated HCWs of 13 Dutch hospitals was 14% in June-July 2020 and remained stable after three months. A higher seroprevalence was observed in the ED and among nurses, administrative and young staff, and those with diabetes mellitus, while a lower seroprevalence was found in HCWs in intensive, high, or medium care, and those with self-reported lung disease, smokers, and dog owners. A history of altered smell or taste, fever, muscle aches and fatigue were independently associated with the presence of SARS-CoV-2 antibodies in unvaccinated HCWs.

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.

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.

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.

Serum PLA2R antibody as a predictive biomarker for venous thromboembolism risk in primary membranous nephropathy / El anticuerpo PLA2R sérico como biomarcador predictivo del riesgo de tromboembolia venosa en la nefropatía membranosa primaria

Background Patients with nephrotic syndrome are at high risk of venous thromboembolism (VTE), especially for primary membranous nephropathy (PMN). The phospholipase A2 receptor (PLA2R) is a marker of primary membranous nephropathy activity. This study investigated the predictive value of PLA2R antibodies in PMN for VTE.Methods In this retrospective study, we included 97 PMN patients and evaluated the predictive value of serum PLA2R antibodies for VTE risk. Lower extremity venous ultrasound, renal vein ultrasound, or spiral computed tomography pulmonary arteriography were used to assess VTE events. Serum anti-PLA2R antibodies were detected by enzyme-linked immunosorbent assay (ELISA). The risk of VTE was stratified according to serum albumin levels. Results Twenty PMN patients (21%) had thromboembolic events. Eight (15%) of patients with serum albumin >25g/l developed VTE, 6 of whom were positive for serum PLA2R antibodies. Positive serum PLA2R antibodies were significantly associated with VTE events in patients with serum albumin >25g/l (p=0.01). Age, sex, blood creatinine, serum albumin, and 24-h urine protein levels were not statistically different between the two groups. Kaplan–Meier analysis using the log-rank test revealed anti-PLA2R positive membranous nephropathy patients had more probability of VTE events than anti-PLA2R negative patients. Univariate Cox proportional hazards analysis revealed that lnPLA2R-Ab is an unfavorable predictor for VTE events in patients with serum albumin >25g/l (hazard ratio (HR) 2.1, p=0.01). Conclusions The PLA2R antibody was a risk predictor for thromboembolic events in patients with primary membranous nephropathy with serum albumin >25g/l (AU)

Antecedentes Los pacientes con síndrome nefrótico presentan un alto riesgo de tromboembolia venosa (TEV), especialmente en el caso de la nefropatía membranosa primaria (NMP). El receptor de fosfolipasa A2 (PLA2R) es un marcador de la actividad de la NMP. Este estudio investigó el valor predictivo de los anticuerpos PLA2R en NMP para TEV. Métodos En este estudio retrospectivo, se incluyeron 97 pacientes con NMP y se evaluó el valor predictivo de los anticuerpos PLA2R en suero para el riesgo de TEV. Se utilizaron la ecografía venosa de las extremidades inferiores, la ecografía de la vena renal o la arteriografía pulmonar por tomografía computarizada en espiral para evaluar los episodios de TEV. Los anticuerpos séricos anti-PLA2R se detectaron mediante un ensayo inmunoenzimático (ELISA). El riesgo de TEV se estratificó en función de los niveles de albúmina sérica. Resultados Veinte pacientes con NMP (21%) presentaron episodios tromboembólicos. Ocho (15%) de los pacientes con albúmina sérica>25g/l desarrollaron TEV, 6 de los cuales fueron positivos para anticuerpos PLA2R séricos. La positividad de los anticuerpos PLA2R séricos se asoció significativamente con episodios de TEV en pacientes con albúmina sérica>25g/l (p=0,01). La edad, el sexo, la creatinina en sangre, la albúmina sérica y los niveles de proteínas en orina de 24h no fueron estadísticamente diferentes entre los 2 grupos. El análisis de Kaplan-Meier mediante la prueba de rangos logarítmicos reveló que los pacientes con nefropatía membranosa positivos para anti-PLA2R tenían más probabilidad de sufrir TEV que los pacientes negativos para anti-PLA2R. El análisis univariante de riesgos proporcionales de Cox reveló que ln PLA2R-Ab es un predictor desfavorable de episodios de TEV en pacientes con albúmina sérica>25g/l (hazard ratio 2,1; p=0,01). Conclusiones El anticuerpo PLA2R fue un predictor de riesgo de episodios tromboembólicos en pacientes con NMP con albúmina sérica>25g/l (AU)

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)

[Correlation of expression of silencing information regulator 2 related enzyme 1 and tumor necrosis factor-like weak inducer of apoptosis in articular effusion and knee osteoarthritis].

OBJECTIVE: To analyze the correlation between the expression of silencing information regulator 2 related enzyme 1 (SIRT1), tumor necrosis factor like weak inducer of apoptosis (TWEAK) and knee osteoarthritis. METHODS: Total of 103 patients with knee joint (knee osteoarthritis group) from February 2019 to August 2021 were selected including 40 males and 63 females with an average age of (62.02±6.09) years;according to the modified Mankin score, 103 patients were divided into mild group (Mankin score 1-4 points, 31 cases) and moderate group (Mankin score 5-8 points, 40 cases) and severe group (Mankin score ≥9, 32 cases). Another 105 physical examination volunteers were selected as the control group including 46 males and 59 females with an average age of (62.11±6.34) years old. The levels of SIRT1 and TWEAK in articular effusion and serum were detected in the knee osteoarthritis group, while serum SIRT1 and TWEAK were detected in the control group only. The relationship between SIRT1, TWEAK and the occurrence and disease of knee osteoarthritis were analyzed. RESULTS: Articular cavity fluid TWEAK, serum TWEAK, CRP, IL-6, IL-1ß, white blood cell count and ESR were higher than those in the control group(P<0.05), articular cavity fluid SIRT1 and serum SIRT1 were lower than those in the control group(P<0.05). TWEAK level in the severe group was higher than that in the moderate and mild groups(P<0.05), SIRT1 was lower than that in the moderate and mild groups (P<0.05). The level of SIRT1 in articular cavity effusion was positively correlated with the serum level of SIRT1 (P<0.05), and negatively correlated with CRP, IL-6, IL-1ß, white blood cell count, modified Mankin score and ESR (P<0.05). TWEAK level in articular cavity fluid was positively correlated with serum TWEAK level (P<0.05), C-reactive protein(CRP), interleukin(IL)-6, IL-1ß, white blood cell count, modified Mankin score and erythrocyte sedimentation rate(ESR) (P<0.05). Body mass index, undertaking heavy physical work, and articular cavity fluid TWEAK were risk factors for the occurrence of knee osteoarthritis(P<0.05), and articular cavity fluid SIRT1 was a protective factor for the occurrence of knee arthritis (P<0.05). The area under curve(AUC) of SIRT1 and TWEAK for knee osteoarthritis was 0.641 and 0.653, and the AUC of SIRT1 and TWEAK for knee osteoarthritis was 0.879, which was higher than SIRT1 and TWEAK alone (z=6.105 and 6.225, P<0.05). CONCLUSION: The level of SIRT1 in articular fluid in patients with knee arthritis is decreased and the level of TWEAK is increased. Low SIRT1 and high TWEAK are associated with the onset and exacerbation of knee osteoarthritis.

[Correlation analysis of serum MMP-1 and MMP-2 levels with lower extremity deep venous thrombosis after operation for lower limb fracture].

OBJECTIVE: To investigate the relationship between serum matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-2(MMP-2) and the formation of deep venous thrombosis(LDVT) in lower extremity patients after surgery for lower extremity fracture, and to analyze the value of MMP-1 and MMP-2 in predicting the occurrence of LDVT after lower extremity fracture. METHODS: From June 2018 to December 2021, 352 patients who planned to receive surgical treatment of lower limb fracture in our hospital were selected as the research objects. Venous blood was collected at 1, 2 and 3 days after surgery, respectively, and serum MMP-1 and MMP-2 levels were detected. The incidence of LDVT during hospitalization was analyzed, and the risk factors of postoperative LDVT in patients with lower limb fracture surgery and the predictive value of MMP-1 and MMP-2 for LDVT were analyzed. RESULTS: LDVT occurred in 40 patients (LDVT group), the incidence of LDVT was 11.36%, and 312 patients did not occurred(no occurred group). The serum levels of MMP-1 and MMP-2 in LDVT group increased gradually after surgery; the serum levels of MMP-1 and MMP-2 in the no occurred group increased slightly after surgery at 2 days and then decreased at 3 days after surgery (P<0.01);the serum levels of MMP-1 and MMP-2 in LDVT group were higher than those in the no occurred group at 2 days and 3 days after surgery (P<0.05). Serum levels of MMP-1 and MMP-2 were positively correlated with serum levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor -α (TNF-α) in LDVT patients at 2 days and 3 days postoperatively (P<0.05). Operative time, MMP-1 and MMP-2 postoperative 3 days were related to the occurrence of LDVT after lower limb fracture (P<0.01). The area under the curve(AUC) predicted by MMP-1 and MMP-2 postoperative 3 days for LDVT after lower limb fracture was 0.738 and 0.744 respectively, and the AUC predicted by combined MMP-1 and MMP-2 was 0.910, which was higher than that predicted by single indicator(Z=2.819 and 2.025, P<0.05). CONCLUSION: High levels of MMP-1 and MMP-2 after lower extremity fracture are closely related to the occurrence of LDVT, and 3 d mMP-1 and MMP-2 after surgery maybe used as evaluation indexes for LDVT risk prediction.