Cell Count Research Articles

Saccharomyces cerevisiae strains L7 contribute to flavor and deacidification in Suanyu, a Chinese traditional fermented fish

Saccharomyces cerevisiae L7 was found to be an excellent starter and biological deacidification strain for Suanyu, however, the underlying mechanisms remain poorly understood. This study aimed to investigate the acid inhibition mechanism of S. cerevisiae L7. The strain enhances the sensory and flavor characteristics of Suanyu. The growth of Lactiplantibacillus plantarum is inhibited due to competition for carbon sources, resulting in a decrease in cell count from 9.00 Lg CFU/mL at 48 h to 7.70 Lg CFU/mL in co-culture. The addition of yeast reduces acidity, decreasing it from 5.83 g/kg to 0.82 g/kg at 48 h, while increasing sugar utilization to 94.52%. We found that cell contact was the main method of inhibition between the two microbials. Transcriptome analysis revealed that multiple pathways were affected under co-culture, ultimately leading to a decrease in lactic acid production. These findings provide valuable insights into the microbial interactions involved in biological deacidification.

Risk Factors of the Severity of COVID-19 Infection in Infants

Background: The global COVID-19 crisis has profoundly affected populations worldwide. While it is widely accepted that older individuals are at greater risk of severe illness, data indicate that in newborns and infants, the disease is generally not fatal. Objectives: This cross-sectional study aimed to examine the roles of laboratory tests and clinical symptoms in determining the severity of COVID-19 infection in infants younger than three months. Methods: This study included all infants less than three months old with positive PCR tests for COVID-19 admitted to the Children's Medical Center between October 2020 and March 2022. We analyzed the association between disease severity and clinical symptoms, as well as laboratory findings. Results: Sixty-four neonates and infants under three months of age with COVID-19 participated in the study. Our findings suggest that lower birth weight and gestational age are associated with increased disease severity. Infants with underlying medical conditions were found to have a higher risk of reaching stage IIb or greater severity. Among laboratory and clinical findings, only white blood cell (WBC) count and cough symptoms showed a significant correlation with disease severity. Conclusions: Clinical evaluations, along with factors such as birth weight, gestational age, and underlying conditions, appear more effective in guiding decision-making for COVID-19 severity in infants. Further studies are necessary to explore the influence of these factors on COVID-19 severity in this age group.

Analytical performance of a point-of-care CBC hematology analyzer, including a 5-part differential: A prospective study to evaluate a microfluidic flow cytometry–based analyzer in waived settings

Abstract Objectives A microfluidic flow cytometer–based point-of-care (POC) analyzer was validated against an in-laboratory hematology analyzer (Sysmex XN Automated Hematology System). Concordance on a full complete blood cell count (CBC) with 5-part differential, as performed by operators with no prior clinical laboratory experience, was evaluated. Methods We prospectively collected 376 venous blood specimens (376) from individuals with self-reported medical conditions and from apparently healthy individuals. Forty-six additional remnant specimens were acquired to ensure coverage of analytic measuring ranges. Parallel testing was performed, with up to 7 hours between testing on the POC and Sysmex XN analyzers. Results Regression analysis resulted in r values of 0.998 to 0.932 for all parameters of a 5-part differential CBC other than basophils (0.709). The mean percentage bias from the reference method, inclusive of the upper and lower reporting limits, was less than 2% for parameters other than lymphocytes (–6.4%), monocytes (25.9%), eosinophils (12.2%), and basophils (–15%). Overall agreement on abnormal flagging was 93.3%. Conclusions The Cito CBC microflow cytometer (CytoChip Inc) provides a CBC with a 5-part differential with accuracy, precision, and abnormal flagging equivalent to a moderate-complexity hematology analyzer. It has the key features required of a POC device that can be operated in a waived setting: minimum space requirements, rapid results, single-action measurement (no sample processing or dilution), ease of use, and minimal blood volume.

Association between serum glucose potassium ratio and mortality in critically ill patients with intracerebral hemorrhage

The effect of serum glucose-to-potassium ratio (GPR) on cerebrovascular diseases has been previously validated. However, the value of the GPR in patients with severe intracerebral hemorrhage (ICH) requiring ICU admission remains unclear. This study aimed to investigate the association between the GPR and the clinical prognosis of critically ill patients with ICH. This study identified patients with severe ICH requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-IV) database and divided them into quartiles based on GPR levels. Outcomes included 30-day, 90-day, and 1-year mortality rates. The association between the GPR and clinical outcomes in critically ill patients with ICH was elucidated using Cox proportional hazards regression analysis and restricted cubic splines. In total, 2018 patients (53.8% male), with a median age of 70 years, were enrolled in the study. The 30-day, 90-day, and 1-year mortality rates were 23.9%, 30.1%, and 38.4%, respectively. Per multivariate Cox proportional hazards analysis, an elevated GPR was significantly associated with all-cause mortality. After adjusting for age, sex, Charlson Comorbidity Index, white blood cell count, red blood cell count, platelet count, and Glasgow Coma Scale, patients with an elevated GPR had a higher 30-day mortality (hazard ratio [HR]: 1.32; 95% confidence interval [CI]: 1.22–1.42; P < 0.001), 90-day mortality (HR: 1.27; 95% CI: 1.18–1.37; P < 0.001) and 1-year mortality (HR: 1.22; 95% CI: 1.14–1.31; P < 0.001) when analyzed as a continuous variable. Furthermore, analysis using restricted cubic splines demonstrated a consistent and progressive escalation in the risk of all-cause mortality with an elevated GPR. The GPR was significantly associated with short- and long-term all-cause mortality in critically ill patients with ICH. This finding demonstrates that GPR may be useful in identifying patients with ICH at a high risk of all-cause mortality.

Belimumab safety in adult and paediatric Chinese patients with systemic lupus erythematosus: A Phase 4, multicentre, observational study

Objective Although belimumab has been widely used in patients with systemic lupus erythematosus (SLE) globally, real-world safety data among Chinese patients are limited, particularly for children. This study assessed the safety and tolerability of belimumab in adult and paediatric patients with SLE in China in real-world clinical practice. Methods This Phase 4, multicentre, prospective, observational study enrolled patients prescribed intravenous belimumab by their physicians in tertiary hospitals, independent of a clinical study, during routine clinical visits between May 2021 and May 2022. Patients could have been receiving belimumab prior to enrolment. The primary objective was to describe the incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs) and AEs of special interest (AESIs) over the 24-week follow-up period. Data were collected at enrolment and approximately 4, 12 and 24 weeks post-enrolment, during routine clinical visits. AEs, ADRs and SAEs were collected as independent events. The safety population comprised patients who received ≥1 dose of belimumab and completed ≥1 follow-up visit. Results Overall, 417 patients were included in the analysis (safety population); 89.2% were female and mean (standard deviation) age was 35.5 (11.9) years. AEs were reported in 158 patients (37.9%) and were mostly mild (79.1%). The most common AEs were upper respiratory tract infections ( n = 19, 4.6%) and hypokalaemia ( n = 18, 4.3%; all mild). Among 22 patients (5.3%) with SAEs, four patients (1.0%) had drug-related SAEs (pneumonia, respiratory tract infection, gingivitis and decreased white blood cell and neutrophil count). ADRs were experienced by 25 patients (6.0%), most commonly urinary tract infections ( n = 5, 1.2%). There were no fatal SAEs. AESIs occurred in 14 patients (3.4%), including infections of interest ( n = 5, 1.2% all herpes zoster), serious selected psychiatric events ( n = 3, 0.7%) and infusion-related systemic and anaphylactic reactions ( n = 7, 1.7%). Of 14 paediatric patients enrolled, six experienced AEs, zero ADRs, two SAEs and one AESI. Conclusion Belimumab was generally well tolerated in adult and paediatric patients with SLE in this real-world setting in China, with no new safety signals identified. Future assessment of long-term belimumab safety in China beyond 24 weeks will extend this current body of evidence.

Sarcopenia is associated with new-onset acute biliary infection within 1 year in patients with hepatitis B virus-related decompensated cirrhosis

Backgrounds: Malnutrition and sarcopenia are prevalent complications in cirrhosis. The relationship between sarcopenia and biliary infection in cirrhotic patients is not well understood. Our study aims to clarify this association. Methods: In this study, we leveraged data from a tertiary care hospital, enrolling patients with hepatitis B virus (HBV)-induced cirrhosis from 2022. An acute biliary tract infection was defined as the onset of acute cholecystitis or cholangitis within a year. Sarcopenia was identified based on established criteria and assessed using the L3 skeletal muscle index (SMI). A multivariate logistic regression model was constructed to analyze the relationship between sarcopenia and acute biliary tract infection. Receiver operating characteristic (ROC) curve analysis and smooth curve fitting were also conducted. Results: This study enrolled a total of 262 patients with HBV-related cirrhosis, with an average age of 60 years and including 173 males. The primary causes for hospital admission were ascites and hepatic encephalopathy. Within the group with biliary infection, patients typically presented with higher white blood cell counts, lower platelet levels, and poorer indicators of liver and kidney function. In the multivariate analysis, after adjusting for various confounding factors, sarcopenia was associated with an odds ratio of 1.55 (P = 0.002) for acute biliary infection. Smooth curve fitting revealed an approximately linear positive relationship between L3 SMI and acute biliary infection, with the area under the ROC curve for L3 SMI reaching 0.89, indicating a strong predictive value. Conclusion: Sarcopenia is associated with acute biliary infection in patients with HBV-related cirrhosis.

The intervention effect of psychological care combined with ondansetron, dexamethasone, and promethazine hydrochloride on chemotherapy in breast cancer surgical patients

BACKGROUND: Breast cancer (BC) is one of the most common malignancies in women and imposes a significant health burden globally. According to data from the World Health Organization, the incidence of BC has been increasing steadily over the years. It has become one of the leading causes of cancer-related death among women worldwide. OBJECTIVE: This work was to evaluate the combined intervention effect of psychological care along with the use of ondansetron, dexamethasone, and promethazine hydrochloride in breast cancer (BC) patients undergoing chemotherapy, including their impact on nausea and vomiting control, quality of life (QoL), and psychological status. METHODS: 64 BC patients undergoing chemotherapy were collected and randomly rolled into a control group (Group C) and an intervention group (Group I). Group C received ondansetron combined with routine psychological support and counseling therapy, while Group I received a combination of ondansetron, dexamethasone, promethazine hydrochloride, and psychological care therapy. Self-assessment scores for anxiety, QoL ratings, white blood cell counts, and incidence of adverse reactions were assessed and compared between the two groups. RESULTS: Group I showed better control of nausea and vomiting versus Group C (P&lt; 0.05). Marked improvements were also observed in the self-rating anxiety scale (SAS) scores, white blood cell counts, and nursing satisfaction in Group I versus Group C (P&lt; 0.05). Nevertheless, the two groups had no significant difference regarding QoL scores (P&gt; 0.05). CONCLUSION: the combination of psychological care with ondansetron, dexamethasone, and promethazine hydrochloride effectively controls nausea and vomiting symptoms in BC patients undergoing chemotherapy and provides higher levels of clinical nursing satisfaction.

In vitro plaque formation model to unravel biofilm formation dynamics on implant abutment surfaces

ABSTRACT Background Biofilm formation on implant-abutment surfaces can cause inflammatory reactions. Ethical concerns often limit intraoral testing, necessitating preliminary in vitro or animal studies. Here, we propose an in vitro model using human saliva and hypothesize that this model has the potential to closely mimic the dynamics of biofilm formation on implant-abutment material surfaces in vivo. Methods A saliva stock was mixed with modified Brain-Heart-Infusion medium to form biofilms on Titanium-Aluminum-Vanadium (Ti6Al4V) and Yttria-partially Stabilized Zirconia (Y-TZP) discs in 24-well plates. Biofilm analyses included crystal violet staining, intact cell quantification with BactoBox, 16S rRNA gene analysis, and short-chain fatty acids measurement. As a control, discs were worn in maxillary splints by four subjects for four days to induce in vivo biofilm formation. Results After four days, biofilms fully covered Ti6Al4V and Y-TZP discs both in vivo and in vitro, with similar cell viability. There was a 60.31% overlap of genera between in vitro and in vivo biofilms in the early stages, and 41% in the late stages. Ten key oral bacteria, including Streptococcus, Haemophilus, Neisseria, Veillonella, and Porphyromonas, were still detectable in vitro, representing the common stages of oral biofilm formation. Conclusion This in vitro model effectively simulates oral conditions and provides valuable insights into biofilm dynamics.

Amino acid deletions at positions 893 and 894 of cytotoxin-associated gene A protein affect Helicobacter pylori gastric epithelial cell interactions

BACKGROUND Helicobacter pylori (H. pylori ) persistently colonizes the human gastric mucosa in more than 50% of the global population, leading to various gastroduodenal diseases ranging from chronic gastritis to gastric carcinoma. Cytotoxin-associated gene A (CagA) protein, an important oncoprotein, has highly polymorphic Glu-Pro-Ile-Tyr-Ala segments at the carboxyl terminus, which play crucial roles in pathogenesis. Our previous study revealed a significant association between amino acid deletions at positions 893 and 894 and gastric cancer. AIM To investigate the impact of amino acid deletions at positions 893 and 894 on CagA function. METHODS We selected a representative HZT strain from a gastric cancer patient with amino acid deletions at positions 893 and 894. The cagA gene was amplified and mutated into cagA -NT and cagA -NE (sequence characteristics of strains from nongastric cancer patients), cloned and inserted into pAdtrack-CMV, and then transfected into AGS cells. The expression of cagA and its mutants was examined using real-time polymerase chain reaction and Western blotting, cell elongation via cell counting, F-actin cytoskeleton visualization using fluorescence staining, and interleukin-8 (IL-8) secretion via enzyme-linked immunosorbent assay. RESULTS The results revealed that pAdtrack/cagA induced a more pronounced hummingbird phenotype than pAdtrack/cagA -NT and pAdtrack/cagA -NE (40.88 ± 3.10 vs 32.50 ± 3.17, P &lt; 0.001 and 40.88 ± 3.10 vs 32.17 ± 3.00, P &lt; 0.001) at 12 hours after transfection. At 24 hours, pAdtrack/cagA- NE induced significantly fewer hummingbird phenotypes than pAdtrack/cagA and pAdtrack/cagA- NT (46.02 ± 2.12 vs 53.90 ± 2.10, P &lt; 0.001 and 46.02 ± 2.12 vs 51.15 ± 3.74, P &lt; 0.001). The total amount of F-actin caused by pAdtrack/cagA was significantly lower than that caused by pAdtrack/cagA- NT and pAdtrack/cagA- NE (27.54 ± 17.37 vs 41.51 ± 11.90, P &lt; 0.001 and 27.54 ± 17.37 vs 41.39 ± 14.22, P &lt; 0.001) at 12 hours after transfection. Additionally, pAdtrack/cagA induced higher IL-8 secretion than pAdtrack/cagA- NT and pAdtrack/cagA- NE at different times after transfection. CONCLUSION Amino acid deletions at positions 893 and 894 enhance CagA pathogenicity, which is crucial for revealing the pathogenic mechanism of CagA and identifying biomarkers of highly pathogenic H. pylori .

Alanyl-Glutamine Inhibits the Epithelial-Mesenchymal Transition of Airway Epithelial Cells in Asthmatic Mice via DPP4-SIRT1 Pathway

Introduction: Alanyl-glutamine (Ala-Gln) is a compound known for its protective effects in various tissue injuries. However, its role in asthma-related lung injuries remains underexplored. This study investigates the mechanisms by which Ala-Gln modulates sDPP4-induced airway epithelial-mesenchymal transition and ovalbumin (OVA)-induced asthma in a mouse model. Methods: An asthma model was established in female C57BL/6 J mice by using OVA. CD4+ T cells and bronchial epithelial cells (BECs) were isolated from the spleen and bronchi of the mice, respectively. Interventions included recombinant sCD26/sDPP4 protein, Ala-Gln, and EX527 (a SIRT1 inhibitor). Flow cytometry was used to assess Th17 and Treg cell populations. Mice were treated with Ala-Gln, EX527, and budesonide (BUD). Histopathological changes in lung tissues were evaluated using hematoxylin-eosin and Masson staining. White blood cell counts were measured with a hematology analyzer. The expression levels of DPP4, IL-17, SIRT1, SMAD2/3, N-cadherin, E-cadherin, MMP9, and α-SMA proteins were analyzed. Results: Treatment with recombinant sCD26/sDPP4 resulted in decreased E-cadherin expression in BECs and increased levels of α-SMA, MMP9, and N-cadherin, effects that were mitigated by Ala-Gln. Ala-Gln also prevented the reduction in SIRT1 expression in BECs and the increase in Th17 cell differentiation induced by recombinant sCD26/sDPP4. EX527 administration alongside Ala-Gln reversed these changes and enhanced the phosphorylation of SMAD2/3 through SIRT1 signaling. BUD alone reduced inflammation and fibrosis in bronchial tissue and lowered the Th17/Treg ratio in peribronchial lymph nodes. The therapeutic effect of BUD was further improved with concurrent Ala-Gln treatment. Conclusion: Ala-Gln can inhibit BEC fibrosis and Th17 cell differentiation mediated by recombinant sCD26/sDPP4 through the SIRT1 pathway. Combined with BUD, Ala-Gln enhanced therapeutic efficacy in OVA-induced asthma in mice, which could offer improved outcomes for asthmatic patients with elevated DPP4 levels.

Burden of liver steatosis and liver fibrosis in a large cohort of people living with HIV.

Liver steatosis (LS) and liver fibrosis (LF) can increase the risk of cardiovascular disease in people with HIV, but their prevalence and associated factors are poorly understood. This study aimed to assess the prevalence of and factors associated with LS and LF in a large cohort of people with HIV. We conducted a cross-sectional study of consecutive people with HIV attending the Clinic of Barcelona from September 2022 to September 2023, excluding those with chronic B or/and C hepatitis virus coinfection. LS was assessed using the Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI), and LF was assessed using the Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS), Fibrosis-4 score (FIB-4), and the European AIDS Clinical Society (EACS) algorithm in both the whole cohort (cohort 1) and in a specific cohort more susceptible to liver disease (cohort 2). We identified independent variables associated with LS and LF using logistic regression. Cohort 1 included 4664 people with HIV; 76% and 37% of them had available HSI and FLI data, LS was present in 28% and 19%, respectively. LF risk was present in 1%, 2%, and 1% of people with HIV according to NFS, FIB-4, and EACS algorithm scores, respectively. Cohort 2 included 1345 people with HIV; 60% and 30% of them had available HSI and FLI data, LS affected 55% and 43% and LF 2%, 5%, or 3%, respectively. Factors associated with LS included current CD4 cell count, diabetes, and hypertension, whereas LF was associated with previous exposure to dideoxynucleoside drugs and current CD4 to LF. Current integrase strand transfer inhibitor (INSTI) therapy appeared protective for LF in cohort 1. In this study, one in four people with HIV had LS, and the prevalence rose to one in two in those with cardiovascular risk factors. The prevalence of LF was low, but it should be considered in older people with HIV with low CD4 counts or high aspartate transaminase levels. A possible protective effect from INSTIs deserves further investigation.

Liver Regeneration Following Thermal Ablation Using Nanocarrier Mediated Targeted Mesenchymal Stem Cell Therapy

Abstract Purpose To test the efficacy of nanocarrier (NC) mediated mesenchymal stem cell (MSC) therapy for liver regeneration following thermal ablation of porcine livers. Materials and Methods Liver radiofrequency ablation was performed in 18 swines divided into MSC, MSC + NC and control groups. The test groups received infusion of MSC or MSC + NC labeled with enhanced green fluorescent protein (eGFP) via hepatic artery. MSC + NC group had MSCs coated with dendrimer nanocarrier complexed with I-Domain of lymphocyte function-associated antigen-1 (LFA-1). Nanocarriers direct homing of MSCs by binding to its counterpart protein, intercellular adhesion molecule-1 (ICAM-1), which is overexpressed at the periablation margins from inflammation. Ablation cavity reduction by CT volumetry was used as surrogate marker for liver regeneration. Cell proliferation was assessed with Ki67 and HepPar-1 stains. GFP identified MSC derived cells. Results Total number of ablations in control animals were 13 across 4 animals. In the MSC group, there were 23 ablations across 6 animals, and in MSC + NC group there were 21 ablations across 6 animals. Ablation cavity volume reduction from day 0 to 30 were 64.4 ± 15.0%, 61.5 ± 12.9% and 80.3 ± 9.4% for control, MSC and MSC + NC groups, respectively (MSC + NC vs MSC: p &lt; 0.001, MSC + NC vs. control: p = 0.001). GFP+ cell count at margins was 426.8 ± 193.2 for MSC group and 498.6 ± 235.2 for MSC + NC group (p = 0.01). The mean Ki67 and HepPar-1 staining at margins were 9.81 ± 4.5% and 6.12 ± 4.2% for MSC + NC group versus 7.59 ± 3.7% and 5.09 ± 3.7% for MSC group, respectively (P &lt; 0.001 and P = 0.09, respectively). Conclusion Nanocarrier-mediated MSC therapy promotes liver regeneration by engrafting MSCs at ablation margins, potentially making liver-directed therapy viable for patients with severe liver dysfunction. This technology may also benefit other solid organs. Graphical Abstract

Exploring the Role of Gut Vascular Barrier Proteins in HIV-Induced Mucosal Damage: A Comparative Study.

This study aims to compare intestinal mucosal damage and the expression levels of occludin, zonula occludens-1 (ZO-1), vascular endothelial (VE)-cadherin, β-catenin, and plasmalemma vesicle-associated protein (PLVAP) in the gut vascular barrier (GVB) among people living with HIV (PLWH), asymptomatic PLWH, and healthy volunteers (non-PLWH). Three groups were selected for the study: PLWH, asymptomatic PLWH, and healthy volunteers. Colonic mucosal tissue samples were collected via colonoscopy from all participants. Histological examination of the colonic mucosa was conducted using hematoxylin and eosin staining. The expression levels of occludin, ZO-1, VE-cadherin, β-catenin, and PLVAP were assessed using RT-qPCR, immunohistochemistry, and western blot analyses. Pathological scores of colonic mucosa in PLWH and asymptomatic PLWH were significantly higher than those in non-PLWH (p < .001 and p = .0056, respectively). CD4+ T cell counts in asymptomatic PLWH and non-PLWH were significantly higher than in PLWH (p < 0.05). The CD4+/CD8+ T cell ratio in non-PLWH significantly exceeded those in PLWH and asymptomatic PLWH (p < .05). Analysis of protein and mRNA expression revealed: (1) no statistically significant differences in PLVAP-mRNA expression across all groups (p > .05); (2) higher PLVAP protein levels in PLWH compared with asymptomatic PLWH and non-PLWH (p < .05), with no significant differences between asymptomatic PLWH and non-PLWH (p = .632); (3) significantly higher PLVAP expression in the colonic mucosa of PLWH and asymptomatic PLWH compared with non-PLWH (p = .034 and p = .011, respectively), with no significant differences between PLWH and asymptomatic PLWH (p > .999). ZO-1 expression was significantly lower in PLWH than in non-PLWH (p = .012), with no notable differences between asymptomatic PLWH and other groups. PLWH, compared with healthy controls, exhibit significant inflammatory changes in the intestinal mucosa. PLVAP expression serves as a potential indicator to assess the extent of GVB damage and disease progression in PLWH.

Histopathological substrate of increased T2 signal in the anterior temporal lobe white matter in temporal lobe epilepsy associated with hippocampal sclerosis.

This study was undertaken to analyze the histology underlying increased T2 signal intensity (iT2SI) in anterior temporal lobe white matter (aTLWM) epilepsy due to hippocampal sclerosis (TLE/HS). Twenty-three patients were included: 16 with increased T2 signal in the aTLWM and seven with HS only. Magnetic resonance imaging (MRI) findings were consistent across two neuroradiologists (kappa = .89, p < .001). Quantification of neuronal cells, astrocytes, oligodendrocytes, and vacuolization in the white matter of temporal lobe specimens was performed by immunohistochemistry (neuronal nuclear antigen, glial fibrillary acidic protein, oligodendrocyte transcription factor, and basic myelin protein, respectively). Surgical specimens from TLE/HS patients with and without iT2SI in the aTLWM were compared. Samples of aTLWM were divided into three groups, according to MRI features: G1 = samples of iT2SI, G2 = samples with normal T2 signal intensity from patients without white matter imaging abnormalities, and G3 = samples with normal T2 signal intensity adjacent to areas with iT2SI. Patients with increased T2 signal had a significantly younger age at epilepsy onset (p < .035). Histological analysis revealed a higher percentage of vacuolar area in these patients (p < .004) along with a lower number of ectopic neurons (p = .042). No significant differences were found in astrocyte or oligodendrocyte counts among groups. A higher proportion of vacuoles in regions with iT2SI may be the histopathologic substrate of this signal alteration in the white matter of the temporal lobe in patients with TLE/HS. This method of quantifying vacuoles using digital image analysis proved reliable and cost-effective.

Splitting apheresis platelets as a contingency measure for inventory shortages.

Splitting apheresis platelet (PLT) units increase available inventory during shortages. The impact of prolonged storage in gas-impermeable aliquot bags on PLT quality in vitro and transfusion outcomes in patients remains uncertain. We assessed in vitro PLT quality and thromboelastography (TEG) in PLTs stored for 8 or 24 h in aliquot bags compared with baseline (T0). Retrospective assessment of response (PLT increment and corrected count increment (CCI)) was conducted among adults (≥18 years) transfused with split platelet units from January 2021 to June 2022. No differences were observed in PLT and white blood cell (WBC) counts, mean platelet volume, or TEG parameters during storage, except for an increase in TEG R time (mean ± SD) at 24 h (6.1 ± 0.5 min) compared to T0 (4.4 ± 0.8 min), p = 0.0031 one-way ANOVA. Eighty-one patients were transfused 119 split units with a median [IQR] PLT yield of 2.1 × 1011[1.9 × 1011 to 2.3 × 1011] and storage duration of 1.6[0.7-9.1] h. The overall median PLT count increment was 6.0 × 103/uL and CCI was 5.0 × 103, correlating negatively with split unit storage duration (Spearman rho = -0.218, p = 0.017). Compared with split transfusions of pathogen-reduced (PR) PLTs, non-PR splits were associated with higher median platelet count increments (7.0 × 103/μL vs. 4.0 × 103/μL, p = 0.0263 Mann-Whitney U) and higher CCIs (6.5 × 103 vs. 3.9 × 103, p = 0.0116 Mann-Whitney U) despite no differences in PLT yields (2.1 × 1011/μL vs. 2.1 × 1011/μL). Storing PLTs in aliquot bags for 8 or 24 h does not adversely affect their quality in vitro. Splitting apheresis PLTs are feasible for adult transfusions during shortages. It may be advisable to prioritize non-PR PLTs for splitting given improved patient responses.

Rbbp6-Mediated Bmal1 Ubiquitination Inhibits YAP1 Signaling Pathway to Promote Ferroptosis in Diabetes-Induced Testicular Damage.

Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Somatic cell count in dairy goats I: association with infectious and non-infectious factors

BackgroundIntramammary infections negatively affect milk quality, animal welfare and productivity in the dairy industry. Somatic cell count (SCC) is the most used screening tool to detect subclinical mastitis caused by intramammary infections. In dairy goats, SCC is greatly influenced by non-infectious factors, which complicates the interpretation. The aim of this research paper was to determine the association between SCC, intramammary infections and non-infectious factors including parity, season, lactation stage, and milk yield in dairy goats. In this longitudinal study, 451 goats from four Norwegian dairy goat herds were sampled for bacteriology and SCC up to nine times during two lactations. Factors like parity, milk yield, and stage of lactation were retrieved from the Norwegian goat recording system.ResultsThe most prevalent udder pathogen findings were Staphylococcus caprae (6.8%), Staphylococcus warneri (6.3%), and Staphylococcus epidermidis (3.8%), all of which had a mild but significant impact on SCC. Staphylococcus aureus was detected in 3.6% of the udder halves and had a major effect on SCC. Parity, stage of lactation, season, and milk yield significantly influenced SCC.ConclusionsThis study highlights that intramammary infections caused by Staphylococcus aureus, along with factors such as increasing parity and the seasonal effects of pasturing, significantly influence the SCC. Understanding these key contributors is essential for improving udder health management and improving milk quality in goat milk production.

Efficacy of disitamab vedotin in non-small cell lung cancer with HER2 alterations: a multicenter, retrospective real-world study

BackgroundNon-small cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) alterations poses a substantial treatment challenge. Current HER2-targeted therapies offer limited efficacy. Antibody-drug conjugates (ADCs) targeting HER2 have emerged as a promising therapeutic strategy. This study aimed to evaluate the clinical response to a novel ADC drug Disitamab vedotin (RC48) in advanced NSCLC with HER2 alterations.MethodsThis study conducted a retrospective review of patients harboring HER2 alterations treated with RC48 in the real world. Clinical outcomes were evaluated in terms of objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).ResultsOut of 22 patients, 21 (95.5%) received RC48 combination therapy, while one received RC48 monotherapy. The ORR of all patients reached 45.5%, and the DCR stood at 90.9%. The median PFS (mPFS) was 7.5 months. Among patients receiving RC48 combination therapy, the ORR was 47.7%, and the mPFS of 8.1 months. The combination of RC48 with platinum+/- bevacizumab resulted in the highest ORR of 71.4% (5 out of 7 patients), with HER2 TKI following at a 50.0% ORR (4 out of 8 patients). First-line (1L) treatment with RC48 showed an ORR of 62.5% (5 out of 8 patients), second-line (2L) treatments had a 57.1% ORR (4 out of 7 patients), and beyond second-line (&amp;gt;2L) treatments exhibited a 14.3% ORR (1 out of 7 patients). Patients with 1L, 2L, or &amp;gt;2L treatment had a mPFS of 8.1 months, 7.2 months, and 7.4 months, respectively. Patients with HER2 mutations or amplifications, and those with concurrent mutations and amplifications at baseline, showed mPFS of 8.1 months, 9.4 months, and 7.4 months, respectively. The mPFS was significantly longer in patients with HER2 amplification. The most common adverse events included hand-foot syndrome (54.5%), asthenia (50.0%), decreased white blood cell count (45.5%), and liver impairment (45.5%). Grade 3 adverse events occurred in one (4.5%) patient.ConclusionRC48, particularly in combination regimens, demonstrates promising efficacy in advanced NSCLC with HER2 alterations. These findings underscore the need for further research to validate RC48’s application in clinical practice.

Identification of miR-451 target genes as prognostic markers in diffuse large B-cell lymphoma

ABSTRACT Background B-cell lymphoma, a diverse malignancy, is intricately regulated by multiple factors. MicroRNAs (miRNAs) have been demonstrated to be important regulators of the initiation and progression of human B-cell lymphoma, but their functions need to be further explored. Research design and methods Two B-cell lymphoma cell lines, Romas and HBL-1, were engineered to overexpress miR-451, with cell proliferation assessed via cell counting assays. Flow cytometry was used to study the effects of miR-451 on cell cycle and apoptosis. Bioinformatics analyses were performed using GEO datasets (GSE181063, GSE32918, GSE56315) to identify DEGs, and potential miR-451 target genes were predicted using tools like ENCORI, TargetScan, and R packages. A risk model for DLBCL prognosis was developed using Cox and LASSO regression. qRT-PCR validated the expression of these target genes. Results This study revealed that miR-451 inhibited cell proliferation, arrested the cell cycle, and induced apoptosis in human DLBCL cell lines. Bioinformatics analysis identified 9 target genes (MMP9, AQP9, RIN2, EOMES, LCP2, SELPLG, MAL, SOCS5, S1PR3) significantly associated with DLBCL prognosis, suggesting a potential mechanism by which miR-451 suppresses DLBCL development. Conclusions Our study indicates that a specific set of miR-451 target genes may significantly influence DLBCL patient outcomes.

Systemic Immune Inflammatory Index as Predictor of Blood Pressure Variability in Newly Diagnosed Hypertensive Adults Aged 18–75

Background: Accumulating evidence from clinical trials, large registries, and meta-analyses of population studies shows that increased Blood Pressure Variability (BPV) is predictive of Cardiovascular (CV) outcomes, independently of the average Blood Pressure (BP) values. One of the mechanisms explaining the relationship between BPV and target organ damage is the inflammatory response. The Systemic Immune Inflammation Index (SII), which relies on peripheral blood cell counts, including platelets, neutrophils, and lymphocytes, has emerged as a predictor of prognosis and outcomes in various diseases. The aim of this study was to investigate the association of the SII with Ambulatory Blood Pressure Variability (ABPV) in newly diagnosed hypertensive patients. Methods: This study was designed as a cross-sectional observational study. A total of 1606 consecutive newly diagnosed Hypertension (HT) patients were included in the study. The population was evaluated across 3 different categories according to HT grades (5 groups), eligibility for antihypertensive therapy (2 groups) and ABPV levels (2 groups). Results: Significant differences were observed between ABPV groups in terms of Neutrophil to Lymphocyte ratio, Platelet to Lymphocyte ratio, glucose, SII, high-sensitive CRP, HT grade, Inter-Ventricular Septum, Posterior Wall thickness, and Left Ventricular Mass (p &lt; 0.005). There was a significant relationship between SII and ABPV (r: 0.619, p &lt; 0.05). At the cutoff value of 580.49, SII had 77% sensitivity and 71% specificity for ABPV &gt; 14 (AUC: 0.788). Conclusions: SII may assist in developing an early treatment approach to minimize complications in patients with high ABPV who are at a higher risk of CV events.