Tolerance Group Research Articles

Predictors of tolerability for postoperative adjuvant S1 plus docetaxel chemotherapy for gastric cancer: a multicenter retrospective study.

Adjuvant docetaxel plus S1 (DS) chemotherapy after gastrectomy with D2 lymph node dissection is the standard treatment for stage III gastric cancer in Japan; however, some patients are unable to receive adequate drug administration because of the deterioration of their conditions. This study aimed to investigate the correlation between tolerability for postoperative adjuvant DS chemotherapy and prognosis, and the factors affecting tolerability. This retrospective study involved patients with stage III gastric cancer who underwent curative resection between 2018 and 2021 from a multicenter database. Patients with a cumulative dose of docetaxel and S1 greater than 120 and 8400mg/m2, respectively, were considered tolerable. The prognostic impact and factors predicting tolerability were analyzed. Of the 103 patients, the tolerable group comprised of 63 (61%) patients and had a significantly better 3-year recurrence-free survival than the intolerable group (83% vs. 64%, P = 0.02). Among the preoperative factors, only performance status (PS, P = 0.04) was significantly correlated with tolerability in the univariate analysis. Among the postoperative factors, PS (P = 0.001) and perioperative weight loss rate (P = 0.02) were significantly correlated with tolerability in the univariate analysis. The multivariate analysis showed significant differences in the PS (odds ratio [OR]: 4.94, 95% confidence interval [CI] 1.79-14.98, P = 0.002) and weight loss rate (OR: 1.10, 95% CI 1.01-1.21, P = 0.03). Tolerance to postoperative adjuvant DS chemotherapy has a significant prognostic impact. Postoperative PS and perioperative weight loss rates were independent predictors of tolerability.

Mechanism of CXCL8 regulation of methionine metabolism to promote angiogenesis in gliomas

BackgroundGliomas are the most common malignant brain tumors characterized by angiogenesis and invasive growth. A detailed understanding of its molecular characteristics could provide potential therapeutic targets. In the present study, we sought to explore the key gene CXCL8 in methionine metabolism in gliomas and its potential role in angiogenesis.MethodsU251 glioma cells were divided into control and methionine-restriction tolerant (constructed with 1/4 of the standard level of methionine in the culture medium) groups for transcriptome and metabolome analysis. To confirm the functions and mechanism of CXCL8 in glioma, heat map, volcano map, Go enrichment, gene set enrichment analysis (GSEA), protein–protein interaction network analysis, RT-PCR, western blotting assays, chicken embryo chorioallantoic membrane (CAM) test, chicken embryo yolk sac membrane (YSM) test and transplantation tumor nude mice model were performed. The TCGA database, CGGA database and clinical tissue samples were used to analyze CXCL8’s significance on prognosis for patients with glioma.ResultsCXCL8 expression was significantly up-regulated in methionine-restricted tolerance cells, it also activated vascular system development and triggered angiogenesis. CXCL8 expression is negatively correlated with survival prognosis in gliomas.ConclusionsGlioma cells promote angiogenesis in methionine-restricted environments through the activation of CXCL8, compensating for nutrient deprivation, and possibly contributing to the failure of antiangiogenic therapy.

Evaluation of right ventricular mechanics using exercise echocardiography in asymptomatic patients with severe mitral stenosis.

We aimed to evaluate the effect of exercise echocardiography (EE) on Right ventricular (RV) deformation parameters in asymptomatic patients with severe rheumatic mitral stenosis (MS) (mitral valve area ≤ 1.5 cm2, stage C) and to determine the relation between symptoms and severity of MS. 38 rheumatic MS patients in stage C underwent EE. 20 Patients were defined; as an exercise intolerance group who couldn't reach a maximum heart rate according to their age during exercise due to developing dyspnea The remaining 18 patients who reached a maximum heart rate without dyspnea were defined; as an exercise tolerance group. RV echocardiographic parameters at baseline and peak exercise were compared between the groups. While RV global strain (RV GLS) (21.02 ± 3.33 vs. 21.92 ± 3.03) and RV free wall longitudinal strain (RV FWLS) (23.41 ± 5.66 vs. 25.08 ± 5.00) at baseline were similar in both groups (P = 0.390 P = 0.343), RV GLS (23.38 ± 4.30 vs. 26.05 ± 3.24) and RV FWLS (24.24 ± 5.78 vs. 28.05 ± 4.62) at peak exercise were reduced in exercise intolerance group (P = 0.040 P = 0.033). The best correlations were found between exercise capacity and RV FWLS at baseline and peak exercise in all MS patients (respectively; r = 0.627 P < 0.001; r = 0.697 P < 0.001). RV mechanics has approved the reliability of EE in patients with asymptomatic patients with severe MS. During exercise RV contractile reserve could diminish in MS patients with stage C who develop dyspnea. Moreover, since our study has a close relationship between exercise capacity and RV mechanics, using RV mechanics during exercise echocardiography may be useful for risk stratification in MS patients with severe MS.

Heterogeneity of gestational diabetes and risk for adverse pregnancy outcome: a cohort study.

Diabetes has increasingly been recognized as a heterogeneous disease, with clinical characteristics and outcomes risk varying across different phenotypes. Evidence on heterogeneity of gestational diabetes (GDM) is yet to be provided. To investigate the insulin physiology and pregnancy outcomes of GDM phenotypes characterized by fasting hyperglycemia or postload hyperglycemia. A total of 2050 women who underwent a 75-g oral glucose tolerance test were prospectively recruited and followed up until delivery. Women were categorized into normoglycemia (NGT, n = 936), isolated impaired fasting glucose (gestational-IFG, n = 378), and isolated impaired postload glucose tolerance (gestational-IGT, n = 736) groups. Fasting blood sample at mid-pregnancy were collected to measure C-peptide and insulin concentrations. Homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were used to evaluate insulin physiology. Maternal and neonatal outcomes were recorded. Gestational-IFG had greater insulin resistance (HOMA-IR 3.11 vs. 2.25, QUICKI-CP 0.94 vs. 1.03, both P < 0.01), and gestational-IGT had worse β-cell function (C-peptide 2.00 vs. 2.26 ng/ml, P < 0.05) when compared to one another. Gestational-IFG was more strongly associated with excessive gestational weight gain (RR 1.62, 95% CI 1.18-2.23) and large-for-gestational-age infants (RR 1.45, 95% CI 1.03-2.03) than gestational-IGT. The risk for neonatal brain injury was increased in gestational-IGT (RR 2.03, 95% CI 1.04-4.09), but not in gestational-IFG (P = 0.439). Gestational-IGT showed a stronger association with the risk of preterm birth compared to gestational-IFG (RR 1.80, 95% CI 1.02-3.36). GDM exhibits distinct insulin physiology profiles. Pregnancy outcome varies between each phenotype. These findings provide evidence on risk stratification and diverse strategies for the treatment of GDM.

Screening of drought tolerance indices for selection of resistance wheat (Triticum aestivum L.) landraces under drought stress conditions

Abstract During the cropping season 2016-2017, an experiment was conducted in a split plot design to study the response of 25 wheat genotypes to drought stress under irrigated and minimal irrigation conditions. Different drought tolerance indices for 25 bread wheat (Triticum aestivum L.) genotypes were evaluated. The calculation drought tolerance indices was based on the grain yield of wheat under irrigated and water stress conditions. The result indicated a significant effect of drought stress on the yield of different wheat genotypes based on mean values of different drought tolerance indices. Among the studied different indices, mean productivity (MP), stress tolerance index (STI), and geometric mean productivity (GMP) were more efficient to discriminate between drought sensitive and drought tolerant genotypes based on the calculation of correlation coefficient and multivariate analysis. Twenty-five genotypes were classified into tolerant and susceptible groups through drought tolerance indices using cluster analysis. Among the genotypes, C-306, WH 1236, WH 1235, and GW 477 having higher yields under drought conditions which showing their stability under stress conditions. The most yield stable genotypes under adverse environment were identified by multivariate analysis of drought tolerance indices individually or in combination. From the result, we concluded that GMP, MP and STI are more efficient drought tolerance indices among other indices to identify stable genotypes under stress conditions.

Dynamics of inflammatory markers in patients with normal and impaired glucose metabolism during lung exacerbation treatment

Cystic fibrosis (CF) is one of the most common autosomal-recessive inherited diseases. The primary genetic defect in CF is aligned CFTR gene mutation which encodes a membrane protein functioning as cAMP-depended chloride channel. Classic phenotypical manifestations of CF include chronic obstructive pulmonary disease with bronchiectasis, persisting infection (St. aureus, Ps. aeruginosa, B. cepacia) and aberrant inflammatory response, as well as exocrine pancreatic insufficiency with malabsorption, hypotrophy and growth retardation. CFTR deficiency is also accompanied by β-cell pancreatic dysfunction, causing glucose metabolism disturbances and CF-related diabetes. The aim of the study was the comparison of inflammatory markers dynamics in patients with normal and disturbed glucose metabolism during pulmonary exacerbation treatment. The study included 10 patients with impaired glucose tolerance (Group 1) and 24 patients with normal carbohydrate metabolism (Group 2). Patients of the two groups did not significantly differ in demographic characteristics, pulmonary function test and body mass index parameters, as well as in the number of F508del mutation carriers and in the number of those who were infected with Ps. aeruginosa and B. cepacia complex. Blood sampling was performed twice: before and after a routine course of antibiotic therapy. Plasma levels of biomarkers including the antibodies to single- and double-stranded DNA (ss-DNA-IgG, ds-DNA-IgG, respectively), the hormones (dehydroepiandrosterone (DHEA) and DHEA sulfate), C-reactive protein (CRP), Mn-dependent superoxide dismutase (Mn-SOD), and the cytokines (tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), IFNα, tissue growth factor-β1 (TGF-β1), interleukin-4 (IL-4), IL-6, IL-10, IL-17A) were assessed using commercial immunoassay kits. Our study shows that antibiotic treatment did not have a sufficient influence on levels of inflammatory markers in patients with disturbances of glucose metabolism while patients with normal glucose tolerance demonstrated a significant reduction in inflammatory marker values after the therapy. The data may suggest both impaired effectivity of antibiotic treatment and aberrant inflammatory response in patients with glucose intolerance.

Lipid profile is similar in both subjects with high 1-hour postload glucose and 2-hour postload glucose and is related to cardio-metabolic profile in prediabetes

AimThe study aimed to investigate a lipid profile in people with normal glucose tolerance (NGT), NGT and 1hrOGTT > 8.6 mmol/l, and impaired glucose tolerance (IGT); and to assess its association with some cardio-metabolic parameters. Material and methodsA total of 90 subjects, of mean age 46.7 ± 10.5 years and mean BMI of 32.0 ± 6.3 kg/m2 were enrolled. They were divided into 3 groups: 19 with NGT, 22 with NGT and 1hrOGTT > 8.6 mmol/l, and 49 with IGT; and subdivided into 2 subgroups according to HOMA-IR: 40 with HOMA-IR < 2.5 and 50 with HOMA-IR ≥ 2.5. Body composition (Inbody 720) and advanced glycation end products (AGE Reader) were assessed. Two functional tests (OGTT; MMTT) were performed and AUC for glucose, insulin and triglycerides were calculated. ResultsThere was no difference across the glucose tolerance groups for all evaluated lipids. The results showed higher AUCinsulin during OGTT (p = 0.037 and 0.020), AUCtriglycerides during MMTT (p = 0.048) and triglycerides/HDL ratio (p = 0.064 and 0.016) in the 1hrOGTT and IGT subgroups with HOMA-IR ≥ 2.5 in comparison to those with HOMA-IR < 2.5. AUCtriglycerides during OGTT is independently related to body composition, b-cell function and insulin sensitivity; and AUCtriglycerides during MMTT is independently related to blood pressure and hsCRP in prediabetes. Triglycerides/HDL-C ratio emerged as an independent contributor to glycaemia and insulinemia. ConclusionOur results demonstrate a similar lipid profile in subjects with 1hrOGTT > 8.6 mmol/l and IGT, whereas increased AUCtriglycerides during OGTT, AUCtriglycerides during MMTT and triglycerides/HDL-C ratio have been found in the subgroups with insulin resistance. The triglycerides/HDL-C ratio outlined as an independent predictor of insulin secretion and action, and postload triglycerides appear to be independently related to most of the metabolic parameters.

Glycated CD59 is a potential biomarker for gestational diabetes mellitus.

To explore the diagnostic value of glycated CD59 (gCD59) in gestational diabetes mellitus (GDM). A total of 707 pregnant women who underwent the first visit in the obstetric outpatient clinic of the Affliated Suqian Hospital of Xuzhou Medical University from January 2022 to July 2023 were included, and were grouped according to the International Association of the Diabetes and Pregnancy Study Groups(IADPSG) diagnostic criteria, and finally 113 cases in the GDM group and 559 cases in the normal glucose tolerance (NGT) group were included, and the concentration of gCD59 was determined by enzyme-linked immunosorbent assay (ELISA). The baseline data characteristics of the two groups were compared, the risk factors for GDM were explored by multivariate binary logistic analysis, and the diagnostic value of gCD59 in predicting GDM was explored by receiver operating characteristic (ROC) curve analysis. The level of gCD59 in the GDM group was significantly higher than that in the NGT group (1.49 SPU vs 0.87 SPU). Multivariate regression analysis showed that gCD59, diastolic blood pressure (DBP) and thyroid stimulating hormone (TSH) were independent risk factors for GDM.The area under the curve (AUC) of gCD59 for the diagnosis of GDM was 0.681 (95% CI: 0.583-0.717), with a sensitivity of 71.7% and a specificity of 58.3%. In combination with fasting glucose, gCD59 effectively diagnosed GDM with higher AUC of 0.871 (95% CI: 0.708-1.000). gCD59 is an independent risk factor for GDM and a good biomarker for the diagnosis of GDM.

Salt stress effects on growth, physiology, and ionic concentrations in hydroponically grown barley genotypes

Soil salinity is a major abiotic stress that severely affects crop production in different regions of the globe. Barley is an essential cereal crop and there is a significant genetic variation among barley varieties for tolerance towards salt stress. Understanding of salinity tolerance mechanisms assists in developing salt tolerant barley varieties in a hydroponics experiment. There were twelve barley varieties and two NaCl stress levels (Control, 100 and 200 mM) in this study. The nursery of barley was seeded in sand and at two-leaf stage; plants were transplanted into hydroponic tubs. The plants were grown under salt stress for 65 days and data regarding several morpho-physiological parameters were collected. The statistical analysis of the collected data was implemented by using completely randomized design (CRD) with factorial arrangement. Exposure to NaCl stress significantly reduced shoot and root growth and relative leaf water contents (RLWC), while increasing Na+ concentration, with B-9006 showing the highest root dry weight (0.39 g) and YSM1 recorded the lowest root dry weight (0.10 g) under 100 mM NaCl. The maximum (232 ppm) Na+ concentration in leaf sap was observed in variety B-15011 (70 % from control) and minimum was observed in B-15018. Maximum K+ mM concentration in leaf sap was found as 72 % in Aia-03 and minimum was observed as 50 % in B-15035. At stress level of 200 mM, highest shoot dry weight (2.52 g) was observed in ZP2 (73 % decreased from control) while minimum shoot dry weight (0.19 g) (96 % decrease from control) was recorded in Franklin genotype. Maximum root dry weight (0.24 g) was observed in B-9006 genotype while minimum root dry weight (0.04 g) was recorded in Gairdner. Maximum K+/Na+ ratio (1.20) was recorded in B-15018 and minimum (0.14) was seen in B-15035. Therefore, based on our results, barley genotypes can be classified into salt-tolerant (B-9006, B-15018, Yerong, Aia-03), salt-sensitive (Gairdner, Franklin, B-15035, B-05011), and moderately tolerant groups at both 100 and 200 mM NaCl levels.

A measurement model of pedestrian tolerance time under signal-controlled conditions

The tolerance of pedestrians to red light signals is a crucial factor in urban residents’ travel experiences and road traffic safety. To address the current lack of research on methods for measuring pedestrian red light tolerance time at crossings, this paper proposes a stacking model for predicting the red light tolerance time of individual pedestrians. The model employs the XGBoost (XGB), random forest (RF), support vector machine regression (SVR), and multilayer perceptron (MLP) models as primary models, with a multiple linear regression model as the secondary-layer meta-model, as well as Bayesian hyperparameter tuning. Using random survival forest (RSF) and K-means clustering methods, the dataset was divided into three categories: the low, medium, and high tolerance groups. The feature variables influencing the red light tolerance time were grouped accordingly. Stacking models were established for each tolerance and feature group. The experimental results demonstrated that the feature group voted on by multiple machine learning models performed the best in all three tolerance groups. In the low tolerance group, the mean squared error (MSE), mean absolute error (MAE), and mean absolute percentage error (MAPE) were 6.58, 1.91, and 19.78%, respectively. For the medium tolerant group, the MSE, MAE, and MAPE were 4.82, 1.53, and 7.63%, respectively. For the high tolerance group, the MSE, MAE, and MAPE were 33.32, 3.89, and 10.14%, respectively. Individual XGB, RF, SVR, MLP, and ungrouped stacking models were established for comparative analysis of the test set. The results indicated that the proposed grouped stacking model outperformed the other models overall. The method provides a means of obtaining the probability distribution function of the length of the waiting crowd’s tolerance time for each red light range and thus determining the duration of the red light at the crossing signal for different personnel compositions.

A Skin Testing Strategy for Non–IgE-Mediated Reactions Associated With Vancomycin

Vancomycin infusion reaction (VIR), reportedly mediated through Mas-Related G Protein-Coupled Receptor-X2, is the primary vancomycin-induced immediate drug reaction. Clinically, distinguishing the underlying drug-induced immediate drug reaction mechanisms is crucial for future treatment strategies, including drug restriction, re-administration, and pretreatment considerations. However, the lack of validated diagnostic tests makes this challenging, often leading to unnecessary drug restriction. To determine whether intradermal tests (IDTs) and, separately, the basophil activation test (BAT) differentiate VIR from vancomycin-tolerant subjects. This was a cross-sectional study of vancomycin-exposed adults with and without a history of VIR. Data on demographics, allergy-related comorbidities, history of vancomycin exposures, and VIR characteristics were collected. IDT with vancomycin was performed. IDT dose-response EC50, IDT-related local symptoms, and BAT results were compared between groups. A total of 11 VIR and 10 vancomycin-tolerant subjects were enrolled. The most reported VIR symptoms were pruritus (82%), flushing (82%), hives (46%), angioedema (27%), and dyspnea (19%). The IDT dose-response mean EC50 was 328 μg/mL (95% CI, 296-367) in the VIR versus 1166 μg/mL (95% CI, 1029-1379) in the tolerant group (P < .0001). All VIR subjects reported IDT-related local pruritus compared with 60% of tolerant subjects (P= .0185). The %CD63+ basophils were consistently less than 2%, without significant differences between groups (P < .54). Variations in skin test methodologies could help identify other immediate drug reaction mechanisms beyond IgE. This skin test protocol holds the potential for identifying VIR, particularly in cases where patients have received multiple drugs while BAT is insufficient. Future studies will validate and delineate its predictive value, assessing the risk of VIR.

Insulin sensitivity, disposition index and insulin clearance in cystic fibrosis: a cross-sectional study

Aims/hypothesisThe aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency.MethodsIn a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups. We used three different oral minimal models to assess insulin secretion, insulin sensitivity and insulin clearance during the OGTT. We evaluated insulin secretion using total secretion (Φ total), first-phase secretion (Φ dynamic) and second-phase secretion (Φ static) from the model, and we estimated the disposition index by multiplying Φ total and insulin sensitivity.ResultsAmong 61 participants (NGT 21%, EGI 33%, IGT 16%, CFRD 30%), insulin secretion indices (Φ total, dynamic and static) were significantly lower in the CFRD group compared with the other groups. Insulin sensitivity declined with worsening in glucose tolerance (p value for trend <0.001) and the disposition index declined between NGT and EGI and between IGT and CFRD. Those with CFRD had elevated insulin clearance compared with NGT (p=0.019) and low insulin secretion (Φ total) was also associated with high insulin clearance (p<0.001).Conclusions/interpretationIn individuals with PI-CF, disposition index declined with incremental impairment in glucose tolerance due to a reduction in both insulin secretion and insulin sensitivity. Moreover in CF, reduced insulin secretion was associated with higher insulin clearance.Graphical

Small Stomates and Xylem Vessels Associated With Freeze Tolerance in Winter Barley

ABSTRACTFreeze tolerance is a complex agronomic trait that is difficult to evaluate in the field because of year‐to‐year variation in weather. Discovering plant characteristics closely related to freeze tolerance would enable more effective selection for this important trait. To explore possible physiological mechanisms and search for useful characteristics related to freeze tolerance in winter barley, we conducted field and growth chamber experiments with seven freeze‐tolerant and seven freeze‐susceptible genotypes that exhibited contrasting winter survival in preliminary field screenings. In a 2‐year field experiment, malondialdehyde, proline and water‐soluble carbohydrate concentrations were measured during cold acclimation and deacclimation to investigate differences in osmoregulation and membrane stability between freeze‐tolerant and freeze‐sensitive genotypes. All parameters varied by sampling year, and significant differences between freeze tolerance groups were found mainly during cold deacclimation in the spring. In growth chamber experiments, the size of xylem vessels and stomates was measured with and without cold acclimation. Freeze‐tolerant genotypes had smaller xylem vessels and stomates than freeze‐sensitive genotypes with and without cold acclimation, and small stomatal length was associated with a small xylem vessel area. Thus, it may be possible to improve freeze tolerance in winter barley by selecting smaller xylem and stomate cells. This study also validated germplasms of winter barley with differential freeze tolerance for future projects on breeding for improving winter hardiness and on plant physiology and genetics in response to freezing stress.

A - 42 Differences in Exercise Tolerance and Autonomic Function Based on Concussion Clinical Profile

Abstract Purpose This study examined differences in clinical profiles (e.g., post-traumatic migraine, vestibular, anxiety/mood, oculomotor, and cognitive) between exercise tolerance groups determined by the Buffalo Concussion Bike Test (BCBT). We hypothesized the exercise-intolerant group would be more likely to have anxiety and/or vestibular profiles. Method Patients (18–49 years; 8 days to 6 months from concussion) completed demographic and medical history, the Clinical Profile Screen, Brief Symptom Inventory-18, and BCBT. Participants were adjudicated into one or more clinical profiles and classified as exercise tolerant or intolerant. Independent-sample t-tests and chi-square tests were used to compare demographics, clinical profiles, reasons for stopping the BCBT, and ANS metrics. Results One hundred six participants (mean age = 27.9¬ ± 8.1, 62.3% female) were included in the study (71 exercise-intolerant; 35 exercise-tolerant). No demographic or medical history differences were noted between groups. The exercise-intolerant group had significantly lower odds of having an adjudicated headache profile (OR = 0.39, 95%CI = 0.16–0.93, p = 0.03) and significantly greater odds of having an adjudicated autonomic profile (OR = 2.28, 95%CI = 1.01–5.21, p = 0.04). A greater proportion of those with the vestibular profile stopped the BCBT due to symptom exacerbation than those without (90.5% vs. 9.5%, p = 0.04). Conclusions Adjudicated clinical profiles and ANS metrics were similar between exercise-tolerant and intolerant groups. Vestibular sensitivities have a considerable contribution to symptom provocation during the BCBT, as a significant proportion of participants with the vestibular profile discontinued the BCBT due to symptom exacerbation. These findings corroborate previous research and suggest that exercise intolerance is pervasive across all concussion clinical profiles and should be considered in all evaluations.

ROLE OF HIGH-TEMPERATURE PROTEIN G IN THE VIRULENCE AND DEVELOPMENT OF ANTIMICROBIAL RESISTANCE IN SOME ORAL BACTERIAL ISOLATES

A marked increase in antimicrobial resistance among common bacterial pathogens has made the search for new therapeutic targets highly imperative. The present study was aimed to analyse the potential of bacterial chaperone high-temperature protein G (HtpG) as a therapeutic target by determining its role in virulence and antibiotic resistance. Two bacterial isolates obtained from the oral cavity of healthy human subjects were characterized and tentatively identified as Staphylococcus aureus and Streptococcus mutans. Survival assays of these isolates showed induction of thermotolerance with around 24% increase in survival at lethal temperature after preconditioning. Protein profile studies revealed prominent expression of proteins of 99, 77 and 40 kDa in thermo tolerance group as compared to the control. HtpG inhibition was achieved by using a pharmacological inhibitor of human Hsp90, geldanamycin (GA). In disc diffusion assays, there was no significant inhibitory impact of HtpG on antibiotic susceptibility to six antimicrobial compounds in both the isolates as compared to the control. An 18-19% reduction in biofilm-forming capacity was observed for both isolates after GA treatment. This study lays strong experimental evidence to the involvement of HtpG in the development of anti-microbial resistance through biofilm formation.

Roles of M1 and M2 macrophage infiltration in post-renal transplant antibody-mediated rejection

BackgroundWe aimed to analyze the roles of M1 and M2 macrophage infiltration in post-renal transplant antibody-mediated rejection (AMR). MethodsA total of 102 recipients who underwent renal allotransplant from January 2020 to February 2023 were divided into an immune tolerance group (n = 56) and a rejection group (n = 46). The transplant renal biopsy specimens were harvested by ultrasound-guided puncture. The M1 and M2 macrophages in renal tissues were counted, and the M1/M2 ratio was calculated. The numbers of M1 and M2 macrophages and M1/M2 ratios in patients with different severities of interstitial fibrosis/tubular atrophy (IF/TA) and different degrees of tubulointerstitial inflammatory cell infiltration were compared. The predictive values of M1 and M2 macrophages and M1/M2 ratio for post-renal transplant AMR were clarified. ResultsThe rejection group had significantly more M1 and M2 macrophages and higher M1/M2 ratio than those of the immune tolerance group (P < 0.05). In the rejection group, infiltrating macrophages were mainly distributed in the glomerular and interstitial capillaries, with M1 macrophages being the predominant type. With increasing severity of IF/TA, the numbers of M1 and M2 macrophages and M1/M2 ratio rose in patients with post-renal transplant AMR (P < 0.05). The numbers and ratio had significant positive correlations with the levels of blood urea nitrogen and serum creatinine (P < 0.05). The areas under the curves (AUCs) of numbers and M1 and M2 macrophages and M1/M2 ratio for predicting post-renal transplant AMR were 0.856, 0.839 and 0.887, respectively. The combined detection had AUC of 0.911 (95% CI: 0.802–0.986), sensitivity of 90.43% and specificity of 83.42%. ConclusionsSignificant macrophage infiltration is present in the case of post-renal transplant AMR, and closely related to the severity of IF/TA and the degree of tubulointerstitial inflammatory cell infiltration.

Evaluation of Allergic Reactions and Tolerance with Fruit and Vegetable Allergy in Children

Introduction: Despite the increasing prevalence of fruit and vegetable allergies in childhood over the past decades, the clinical course of reaction types and tolerance remain unclear. Our aim was to evaluate the clinical course, demographic characteristics, and tolerance rate of allergic reactions induced by fruits or vegetables. Methods: We conducted a retrospective, descriptive, cross-sectional study on patients who presented with suspected allergic reactions to fruit or vegetables. We used patient records to identify demographic data, skin prick test, prick-to-prick test, and oral food challenge test results and laboratory findings. Results: The study included 78 children with a median age of 61.5 months. Class 1 and 2 allergies were found in 65 and 13 cases, respectively. The most common allergens were potato (21.8%), banana (15.4%), peach (14.1%), and tomato (12.8%). Clinical symptoms included urticaria (75.6%), oral allergy syndrome (15.4%), angioedema (7.7%), and anaphylaxis (1.3%). Thirteen children achieved tolerance, while 61.7% did not. The median time to tolerance was 13.5 months after diagnosis, with a minimum of 9 months. Significant differences in reaction type, clinical presentation, pan-allergy to aeroallergens, and serum total IgE levels were found between the tolerant and non-tolerant groups (p = 0.006, 0.009, 0.005, and 0.001, respectively). Conclusion: This is the first study to provide guidance on the tolerance rate and resolution time of fruit and vegetable allergies based on demographic and diagnostic parameters. Further research is needed to deepen our understanding of fruit and vegetable allergy.

Tsc22d3 promotes morphine tolerance in mice through the GPX4 ferroptosis pathway.

Morphine tolerance refers to gradual reduction in response to drug with continuous or repeated use of morphine, requiring higher doses to achieve same effect. The morphine tolerance dataset GSE7762 profiles, obtained from gene expression omnibus (GEO) database, were used to identify differentially expressed genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) was applied to explore core modules of DEGs related to morphine tolerance. Core genes were input into Comparative Toxicogenomics Database (CTD). Animal experiments were performed to validate role of Tsc22d3 in morphine tolerance and its relationship with ferroptosis-related pathway. 500 DEGs were identified. DEGs were primarily enriched in negative regulation of brain development, neuronal apoptosis processes, and neurosystem development. Core gene was identified as Tsc22d3. Tsc22d3 gene-associated miRNAs were mmu-miR-196b-5p and mmu-miR-196a-5p. Compared to Non-morphine tolerant group, Tsc22d3 expression was significantly upregulated in Morphine tolerant group. Tsc22d3 expression was upregulated in Morphine tolerant+Tsc22d3_OE, expression of HIF-1alpha, GSH, GPX4 in GPX4 ferroptosis-related pathway showed a more pronounced decrease. As Tsc22d3 expression was downregulated in Morphine tolerant+Tsc22d3_KO, expression of HIF-1alpha, GSH, GPX4 in GPX4 ferroptosis-related pathway exhibited a more pronounced increase. Upregulation of Tsc22d3 in Morphine tolerant+Tsc22d3_OE led to a more pronounced increase in expression of apoptosis proteins (P53, Caspase-3, Bax, SMAC, FAS). The expression of inflammatory factors (IL6, TNF-alpha, CXCL1, CXCL2) showed a more pronounced increase with upregulated Tsc22d3 expression in Morphine tolerant+Tsc22d3_OE. Tsc22d3 is highly expressed in brain tissue of morphine-tolerant mice, activating ferroptosis pathway, enhancing apoptosis, promoting inflammatory responses in brain cells.

Validation of Methotrexate Intolerance Severity Score (MISS) questionnaire to measure methotrexate intolerance among rheumatoid arthritis Egyptian patients

BackgroundRheumatoid arthritis (RA) is a systemic autoimmune chronic inflammatory disease, causing progressive disability. Methotrexate (MTX) is the gold standard drug treatment for RA. Long-term use of MTX is associated with intolerance including gastrointestinal effects. In addition, anticipatory, associative, and behavioral symptoms such as anxiety and irritability are also observed which are often inadequately managed, leading to discontinuation of treatment. Methotrexate Intolerance Severity Score (MISS) questionnaire designed to measure MTX intolerance. The work aims to validate the MISS questionnaire Arabic version for the detection of MTX intolerance among Egyptian RA patients to halt the progression of the disease.ResultsA total of 80 patients were involved in this study. Of those, 67 (83.8%) were females with a mean disease duration of 6.9 ± 6.1 years. Forty-eight patients (60%) were intolerant to MTX and 32 patients (40%) were tolerant. Comparison between the tolerant group (n = 32) to MTX and the intolerant group (n = 48) revealed a statistically significant difference between them regarding the DAS28 score and HAQ score. Behavioral intolerance is the predominant factor that directs MTX intolerance.ConclusionThe MISS questionnaire has a good predictive ability to detect MTX intolerance among Egyptian RA patients. Due to its good reliability, serves as an invaluable tool as it detects anticipatory and associative symptoms.

Study on the relationship between hemoglobin glycosylation index and arteriosclerosis- related blood lipids

Objective: To study the relationship between hemoglobin glycation index (HGI) and blood lipid indices such as low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and plasma atherogenic index (AIP). Methods: This cross-sectional study included 16 049 participants from the Beijing Apple Garden community between December 2011 and August 2012. The subjects were divided into three groups based on the HGI quartile: low (n=5 388), medium (n=5 249), and high (n=5 412). The differences in blood lipid indicators between different HGI groups were compared and multivariate logistic regression model was established to analyze the association between HGI and dyslipidemia. And multivariate logistic regression model was established to analyze the relationship between HGI and blood lipid indicators in different glucose metabolism populations. Results: There were 16 049 participants in all (mean age: 56 years), including 10 452 women (65.1%). They were classified into normal glucose tolerance (9 093 cases), prediabetes (4 524 cases), and diabetes (2 432 cases) based on glucose tolerance status. In the general population, with the increase of HGI, LDL-C, non-HDL-C, and AIP gradually increased (all P values for trends were <0.05), and the proportion of abnormalities increased significantly (χ2=101.40, 42.91, 39.80; all P<0.001). A multivariate logistic regression model was established, which suggested a significant correlation between HGI and LDL-C, non-HDL-C, and AIP (all P<0.05), after adjusting for factors such as age, sex, fasting blood glucose, hypertension, body mass index, smoking, and alcohol consumption. In the overall population, normal glucose tolerance group, and diabetes group, HGI had the highest correlation with non-HDL-C (OR values of 1.325, 1.678, and 1.274, respectively); in the prediabetes group, HGI had a higher correlation with LDL-C (OR value: 1.510); and in different glucose metabolism groups, AIP and HGI were both correlated (OR: 1.208-1.250), but not superior to non-HDL-C and LDL-C. Conclusion: HGI was closely related to LDL-C, non HDL-C, and AIP in the entire population and people with different glucose metabolism, suggesting that HGI may be a predictor of atherosclerotic cardiovascular disease.