Peripheral White Blood Cell Count Research Articles

Oral administration of tilapia hydrolysate peptides ameliorates the immune-related side effects of cyclophosphamide in BALB/c mice

Bioactive peptide derived from fish is a novel and promising immunomodulating agent. However, the use of tilapia peptides as adjuvant therapy to ameliorate chemotherapy-induced immunosuppression in vivo has not been previously studied. In this study, tilapia hydrolysate peptides (THP) with a low molecular weight distribution (<3 kDa) were obtained from tilapia processing byproducts using Flavourzyme hydrolysis. These peptides showed no cytotoxicity to RAW264.7 macrophage cells and splenocytes. THP promoted the proliferation of RAW264.7 macrophage cells under basal conditions and enhanced mitogen-induced splenocyte proliferation. When treated with LPS-induced RAW264.7 macrophage cells, THP exhibited anti-inflammatory properties by inhibiting iNOS expression and NO production. To evaluate the in vivo immunomodulatory activity of THP, BALB/c mice were assigned to four groups (n = 7) and received either water (Control and CY group) or THP at doses of 400 mg/kg (Low-THP) and 800 mg/kg (High-THP) body weight through oral gavage for total 12 days. All groups, except the control, were injected with 100 mg/kg BW of cyclophosphamide (CY) on day 7. The high dose of THP positively influenced the recovery of peripheral white blood cell counts. Both doses of THP improved the proliferation ability of splenic T cells and immune organ indices. Additionally, the results of pro-inflammatory gene expression and histological examination suggested that both doses of THP alleviated CY-induced spleen damage. Consequently, oral administration of THP effectively ameliorated the immune-related side effects of CY, including reductions of peripheral white blood cell count, inhibition of splenic lymphocytes proliferation, atrophy of the spleen and thymus, and spleen damage.

Enterovirus Meningitis without Pleocytosis: a Retrospective Observational Study in Adults.

Reverse-transcription polymerase chain reaction (RT-PCR)-confirmed enterovirus (EV) meningitis without pleocytosis has only been previously reported in children. In this study, we examined the frequency of EV meningitis without pleocytosis in adults and compared its clinical features. We retrospectively analyzed the data of adult patients with EV meningitis confirmed using cerebrospinal fluid (CSF) RT-PCR. Among the 17 patients included in this study, 58.8% showed no pleocytosis. The median age and clinical symptoms did not differ between the pleocytosis and non-pleocytosis groups. There were no statistically significant differences in seasonal variation or time from the onset of meningitis symptoms to lumbar puncture. The peripheral white blood cell (WBC) count in patients with pleocytosis was significantly higher than that in patients without pleocytosis. The median CSF pressure showed a higher trend in the non-pleocytosis group. Patients with CSF pressures higher than normal were more common in the non-pleocytosis group. The median CSF protein values were higher than the normal values in both groups. We confirmed the high frequency of EV meningitis without pleocytosis in adults. Accurate diagnosis using RT-PCR is necessary when meningitis symptoms are prominent during an EV epidemic, and CSF protein levels and pressure are high, even if the CSF WBC count is normal.

CLL Cell-Derived Exosomes Impair Immune Function and Normal Hematopoiesis in CLL

CLL is characterized by immune and hematopoietic abnormalities such as T-cell dysfunction, hypogammaglobulinemia, increased levels of inflammatory cytokines, aberrant monocyte polarity, anemia, neutropenia, and low-grade bone marrow fibrosis. As a result, CLL patients become susceptible to increased rates of infection and/or second neoplasms. Exosomes are nanovesicles that participate in bidirectional communication between neoplastic cells and their microenvironment. Using electron microscopy, we found that CLL cells produce and release CD19 +/CD5 +exosomes, and in agreement with other investigators, we detected high levels of CLL cell-derived exosomes in the plasma of patients with CLL. By using bead-assisted flow cytometry, we found that at least 50% of circulating extracellular vesicles are CLL cell-derived exosomes, identified as CD63 +/CD41a - particles co-expressing CD19 +/CD5 +, whereas only a small proportion of CLL patients' plasma-derived exosomes expressed T-cell or endothelial cell surface markers. Furthermore, we found a positive correlation between levels of CLL cell-derived exosomes in the plasma of patients with CLL and the patients' peripheral white blood cell counts, indicating that CLL cells are the primary source of circulating exosomes. To investigate the effects of CLL cell-derived exosomes, we conducted an analysis of CLL cells and CLL cell-derived exosomes from a cohort of 78 previously untreated patients. To identify the molecular profiles of CLL cell-derived exosomes, we analyzed their RNA transcripts using RNA-seq and qRT-PCR. Our data revealed that CLL cell-derived exosomes expressed significant levels of oncogenic micro-RNAs. Additionally, we identified 1052 differentially expressed genes, and enrichment analysis further unveiled the significant upregulation of gene clusters associated with p53, NF-κB, MAPK, mTOR, and interleukin signal transduction pathways, consistent with their neoplastic cell origin. The distinctive transcriptional profile of CLL cell-derived exosomes led us to explore their effects on normal cell populations. We labeled ultra-centrifuged CLL cell-derived exosomes with fluorescent markers and incubated them with various cell types in culture conditions conducive to their physiological activity. Using confocal microscopy and flow cytometry, we observed significant uptake of CLL cell-derived exosomes by normal monocytes, fibrocytes, B cells, T cells, and CLL cells. Furthermore, incubation with CLL exosomes resulted in notable alterations in normal CD14 + monocyte polarity and subset-specific shifts in the expression of inflammatory cytokines. Remarkably, CLL cell-derived exosomes induced overexpression of the T-cell makers CD5 and CD8 in normal CD19 + cells, suggesting that CLL exosomes may promote immune-evasive reprogramming of normal B cells. Moreover, when normal T cells were incubated with CLL cell-derived exosomes, CyTOF analysis using 46 markers revealed elevated levels of immune checkpoints, including PD1, CTLA4, and LAG3, in both CD4 + and CD8 + subsets, indicating that exosomes derived from CLL cells induce T-cell dysfunction. Given their profound effect on immune cells, we wondered whether CLL exosomes affect hematopoietic cells. We previously found that normal monocyte derived fibrocytes stimulate hematopoietic colony proliferation. In sharp contrast to control fibrocytes, fibrocytes preincubated with CLL exosomes and CLL cell-derived exosomes inhibited normal BFU-E and CFU-GM colony formation, suggesting that CLL exosomes might contribute to CLL patients' anemia or neutropenia. Wondering whether CLL cell-derived exosomes affect the viability of other cell types, we found that they induced a dose-dependent apoptosis of CD19 + B cells, CLL cells but not normal T cells. In summary, CLL cell-derived exosomes exert a profound effect on gene and cell surface protein expression in immune and tissue-remodeling cells, leading to functional modifications, alteration of inflammatory cytokine levels, and suppression of normal hematopoiesis. The impact of CLL exosomes may vary across different cell types; however, as the leukemic cell mass increases, exosome levels escalate, invariably affecting CLL cell environment. The identification of exosomes with distinct molecular signatures holds promising potential for novel therapeutic interventions in future treatment of CLL.

Association between white blood cell count and adverse pregnancy outcomes: a retrospective cohort study from a tertiary hospital in China

ObjectivesThis study aimed to clarify the relationship between white blood cell (WBC) and adverse pregnancy outcomes.DesignA total of 25 270 pregnant women underwent peripheral blood white blood cell count tests...

Differentiate Clinical Characteristics Between Viral Pneumonia and Mycoplasma pneumoniae and Nomograms for Predicting Mycoplasma pneumoniae : A Retrospective Study in Primary Hospitals.

To identify the difference in clinical characteristics between viral pneumonia and Mycoplasma pneumoniae , providing cues on their differential diagnosis for primary hospitals with the insufficient pathogen detection capacity. We retrospectively reviewed the medical records of hospitalized children with acute respiratory tract infections, and pathogenic microbes test results were analyzed. Clinical characteristics, routine blood parameters and hospitalization duration and fee were compared between M. pneumoniae and viral pneumonia. We used in the multivariable logistic regression to predict the probability of children with M. pneumoniae and graphically represented by a dynamic nomogram. The discrimination and clinical utility of the model were confirmed by receiver operating characteristic and decision curve analysis curves. A total of 375 children with community-acquired pneumonia were included. Mycoplasma infection accounted for the largest proportion (22.13%). The incidence of both hypothermia and vomiting was lower in M. pneumoniae compared to viral pneumonia (hypothermia: 10.50% vs. 0.00%; vomiting: 7.90% vs. 0.00%). The prevalence of hyperthermia was higher in M. pneumoniae (hyperthermia: 89.5% vs. 100%). Procalcitonin, peripheral blood white blood cell count and lymphocyte levels were higher in the viral pneumonia group, and eosinophil levels were conversely lower. As for the duration of illness, the mean length of stay was 5.20 ± 2.12 (viral pneumonia) and 6.27 ± 2.48 days ( M. pneumoniae ). Children with M. pneumoniae had higher overall hospital costs and required more medical treatment. The above were all statistically significant with a P < 0.05. The scoring system was established based on the above results. Receiver operating characteristic curves showed good model-discrimination ability with 0.844 of the area under the curve in the training set and 0.778 in the test set. Decision curve analysis curves demonstrated the discriminative superiority of this model. The web-based dynamic nomogram calculator is accessible at https://zhxylxy0160128.shinyapps.io/Nomogram/ . Nomograms have satisfactory discrimination, and clinical utility may benefit in predicting the probability of developing M. pneumoniae in children. Children with M. pneumoniae have a higher burden than those with viral pneumonia and may require more intensive in-hospital monitoring.

Evaluation on the Sex-Specific Association Between Cigarette Smoke Exposure and Inflammation Markers-C-Reactive Protein and White Blood Cell Count.

Cigarette smoke increases peripheral white blood cell (WBC) count. However, the dose-dependent association between smoking and C-reactive protein (CRP), an important inflammatory marker, has been reported as inconsistent. Here, we evaluated the associations between smoking and CRP using both smoking questionnaires and urine cotinine as exposure markers. The Korea National Health and Nutrition Examination Survey data were used for analyzing the associations. Multiple regression analyses were performed to examine the associations between cigarette smoke exposure, as assessed by questionnaires and urine cotinine, and health effects, as measured by CRP and WBC count, controlling for potential confounders. The confounders, including age, sex, body mass index, blood pressure, cholesterol, glucose, alanine aminotransferase, and uric acid, were selected a priori based on the literature. A total of 11 435 participants were included for analysis. For the exposure-response relationship, the results indicated a significant increase in CRP levels in male smokers compared to male nonsmokers (p = .002), whereas no significant increase was found in female smokers compared to female nonsmokers (p = .680). For the dose-response relationship, a significant positive association was observed between urine cotinine and CRP in male smokers (p = .018), whereas no significant association was found in female smokers (p = .508). WBC count consistently showed significant exposure-response and dose-response relationships in both sexes. WBC count was found to be a consistent effect marker of cigarette smoke exposure, while the association between CRP level and smoking was inconsistent and varied by sex. The sex-specific response to cigarette smoke exposure warrants further exploration in future studies. Cigarette smoke exposure is known to increase inflammation and has been thought to increase CRP, a significant inflammation marker. However, recent studies have reported conflicting results regarding the dose-dependent association between cigarette smoke exposure and CRP. This study found that the association between smoking and CRP is inconsistent and varies by sex, showing significant exposure response in men but not in women. Furthermore, the study suggests that WBC count is a more consistent marker for cigarette smoke exposure.

The Distinct Pattern of Granulomatous Lobular Mastitis with Erythema Nodosum: More Severe Conditions and Extensive Lesions

Purpose Granulomatous lobular mastitis (GLM) is a benign inflammatory disease of the mammary gland with unknown etiology. Erythema nodosum (EN) is a rare, extramammary symptom of GLM. The purpose of this article was to investigate the clinical features of EN associated with GLM. Methods We recruited 102 GLM patients diagnosed between December 2018 and December 2021 at Renmin Hospital of Wuhan University. The clinical characteristics and laboratory indices of the EN group (n = 12) and the non-EN group (n = 90) were compared. Results The proportion of GLM patients with lesions involving ≥2 quadrants and high peripheral white blood cell count, absolute neutrophil count and neutrophil-to-lymphocyte ratio (NLR) was larger in the EN group than in the non-EN group (p = 0.002, 0.025, 0.014, 0.002, respectively). The duration of EN was longer in GLM patients with EN than in GLM patients without EN (p = 0.005). GLM patients with EN had more abscesses and sinus tracts than those without EN (p = 0.003, 0.038). Lesions involving ≥2 quadrants and the NLR were positively associated with the occurrence of EN (R = 0.304, 0.0302, p = 0.002, 0.002). Receiver operating characteristic curve analysis revealed that the area under the curve of the NLR was 0.770. When NLR > 5.73, the sensitivity and specificity of predicting EN were 66.67% and 87.78%, respectively. Conclusion Our findings suggest that GLM concomitant with EN suggests the presence of a more severe condition and extensive lesions.

[Clinical characteristics and related factors analysis of adrenal crisis occurred in children with primary nephrotic syndrome].

Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P>0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month,U=25.50, P=0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U=27.00,P=0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L,t=-6.22,P<0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×109 vs. (11±5)×109/L,t=4.26,P=0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19,t=2.56,P=0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0,P=0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.

The effect of Dipeptidyl peptidase 4 (DPP-4) inhibitors on hemoglobin level in diabetic kidney disease: A retrospective cohort study.

Anemia typically develops early in the course of diabetic kidney disease (DKD). There are data to show that dipeptidyl-peptidase-4 (DPP-4) inhibitors affect hematopoietic growth factor activity and hemoglobin level. We retrospectively reviewed 443 DKD patients who were started on DDP-4 inhibitor therapy in 2019. Their hemoglobin level at baseline (6-12 months before treatment), pretreatment (0-6 months before treatment), and post-treatment periods (within 6 months after DPP-4 inhibitor), concomitant estimated glomerular filtration rate (eGFR), HbA1c, peripheral blood white cell and platelet counts were reviewed. The severity of kidney failure was classified according to the Kidney Disease: Improving Global Outcomes stages. The hemoglobin level had a small but significant decline from 11.98 ± 2.07 to 11.87 ± 2.12 g/dL from pretreatment to post-treatment period (paired Student t test, P < .0001). From the pre- to post-treatment period, the decline of hemoglobin level was 0.10 ± 0.89 g/dL, which was significantly less than that from baseline to pretreatment period (0.24 ± 0.90 g/dL, P = .0008). The change in hemoglobin level had a positive correlation with the change in HbA1c level (R = 0.218, P < .0001), but did not correlate with the type of DPP-4 inhibitor or pretreatment eGFR. There was no significant change in peripheral blood white cell or platelet count during the same period. DPP-4 inhibitor ameliorates hemoglobin decline in DKD. The effect of DPP-4 inhibitor on hemoglobin is statistically significant but clinically modest, and did not correlate with the concomitant change in kidney function.

Distinguishing clinical characteristics of central nervous system tuberculosis in immunodeficient and non-immunodeficient individuals: a 12-year retrospective study

BackgroundCentral nervous system tuberculosis (CNS TB) is a severe Mycobacterium tuberculosis (MTB) infection. It is unclear whether a patient’s immune status alters the clinical manifestations and treatment outcomes of CNS TB.MethodsBetween January 2007–December 2018, chart reviews of CNS TB, including tuberculous meningitis (TBM), tuberculoma/abscess, and TB myelitis, were made. Subjects were categorized as immunodeficient (ID) and non-immunodeficient (NID).ResultsOf 310 subjects, 160 (51.6%) were in the ID group—132 (42.6%) had HIV and 28 (9.0%) had another ID, and 150 (48.4%) were in the NID group. The mean age was 43.64 ± 16.76 years, and 188 (60.6%) were male. There were 285 (91.9%) TBM, 16 (5.2%) tuberculoma/abscess, and 9 (2.9%) myelitis cases. The TBM characteristics in the ID group were younger age (p = 0.003), deep subcortical location of tuberculoma (p = 0.030), lower hemoglobin level (p < 0.001), and lower peripheral white blood cell count (p < 0.001). Only HIV individuals with TBM had an infection by multidrug-resistant MTB (p = 0.013). TBM mortality was varied by immune status —HIV 22.8%, other ID 29.6%, and NID 14.8% (p < 0.001). Factors significantly associated with unfavorable outcomes in TBM also differed between the HIV and NID groups.ConclusionsTBM is the most significant proportion of CNS TB. Some of the clinical characteristics of TBM, such as age, radiographic findings, hematological derangement, and mortality, including factors associated with unfavorable outcomes, differed between ID and non-ID patients.

Pharmacokinetics and Pharmacodynamics of Burixafor Hydrobromide (GPC-100), a Novel C-X-C Chemokine Receptor 4 Antagonist and Mobilizer of Hematopoietic Stem/Progenitor Cells, in Mice and Healthy Subjects.

Adequate mobilization of hematopoietic stem cells (HSCs), especially CD34+ cells, is necessary for stem cell transplantation in patients with hematological malignancies or autoimmune diseases. Burixafor is an inhibitor of the C-X-C Chemokine Receptor 4 that disrupts the C-X-C motif chemokine 12 (CXCL12)/CXCR4 axis in the bone marrow, releasing HSCs into circulation. In mice, a single intravenous dose of burixafor was rapidly absorbed (time to maximum concentration, 5minutes) and increased peripheral white blood cell counts within 30minutes. Additionally, burixafor was administered to 64 healthy subjects in a randomized, double-blind, placebo-controlled, single-ascending-dose study to evaluate safety, pharmacokinetics, and pharmacodynamics. Subjects received burixafor intravenous doses ranging from 0.10 to 4.40mg/kg in 8 cohorts. Single doses were generally safe and well tolerated. Gastrointestinal events were reported at doses of 2.24mg/kg or greater. Exposure (maximum concentration and area under the concentration-time curve) increased in an approximately dose-proportional manner. Time to maximum concentration occurred with a median of 0.26-0.30hours that was not dose proportional. As expected, white blood cell, CD133+ cell, and CD34+ cell concentrations generally increased with the increases in burixafor dose from 0.10 to 3.14mg/kg. At maximal levels, the CD34+ cell counts increased 3- to 14-fold from baseline levels. These results provide support for continued clinical development of burixafor.

[Clinical characteristics and risk factors for bronchoscopic airway mucus hypersecretion in childhood pneumonia infected by different pathogens].

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×106 vs. 490 (210, 1 510)×106/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.

[Analysis of CSF3R Gene Mutations and Clinical Characteristics in Patients with t(8;21) Acute Myeloid Leukemia].

To investigate the occurrence of CSF3R mutation in patients with t(8;21) acute myeloid leukemia (AML) and its correlation with some clinical parameters. The clinical and laboratory data of 167 newly diagnosed AML patients with t(8;21) translocation were analyzed retrospectively. High-throughput DNA sequencing technology combined with Sanger sequencing method was used to detect 112 gene mutations. The occurrence of CSF3R gene mutation and its influence on the remission rate after chemotherapy were analyzed. Among 167 patients with t(8;21) AML, 15 patients (9.0%) carried CSF3R mutations, including 6 cases of membrane proximal region mutations and 9 cases of truncation mutations in the cytoplasmic tail. The most common coexisting mutations of CSF3R were KIT (40.0%), TET2 (33.3%), DNMT3A (26.7%), FLT3 (20.0%), CBL (20.0%), IDH1 (13.3%), etc. Compared with the wild type, the CSF3R mutant group had a higher mutation rate of DNA methylation-related genes（P <0.001）. The median peripheral white blood cell (WBC) count of patients with CSF3R gene mutation was 5.80 (3.20-8.56)×109/L at initial diagnosis, which was significantly lower than 8.80 (5.26-19.92)×109/L of the CSF3R wild-type patients (P =0.017). There was no significant difference between the two groups in sex, median age, FAB classification, hemoglobin level, platelet count, etc. (P >0.05). The CR rate of the CSF3R gene mutation group (100%) was significantly higher than that of the wild-type group (86.8%), but the difference was not statistically significant (P >0.05). The CSF3R gene mutation group had a significantly higher CD19 positive rate and a higher -X rate than the wild group (86.7% vs 47.4%, P =0.004; 33.3% vs 13.2%, P =0.037). There is a high incidence of CSF3R mutation in t (8;21) AML patients. The clinical characteristics and coexisting mutation genes of CSF3R mutation-positive patients are different from those of wild-type patients.

Moderate body lipid accumulation in mice attenuated benzene-induced hematotoxicity via acceleration of benzene metabolism and clearance

Recent population and animal studies have revealed a correlation between fat content and the severity of benzene-induced hematologic toxicity. However, the precise impact of lipid deposition on benzene-induced hematotoxicity and the underlying mechanisms remain unclear. In this study, we established a mouse model with moderate lipid accumulation by subjecting the mice to an 8-week high-fat diet (45% kcal from fat, HFD), followed by 28-day inhalation of benzene at doses of 0, 1, 10, and 100 ppm. The results showed that benzene exposure caused a dose-dependent reduction of peripheral white blood cell (WBC) counts in both diet groups. Notably, this reduction was less pronounced in the HFD-fed mice, suggesting that moderate lipid accumulation mitigates benzene-related hematotoxicity. To investigate the molecular basis for this effect, we performed bioinformatics analysis of high-throughput transcriptome sequencing data, which revealed that moderate lipid deposition alters mouse metabolism and stress tolerance towards xenobiotics. Consistently, the expression of key metabolic enzymes, such as Cyp2e1 and Gsta1, were upregulated in the HFD-fed mice upon benzene exposure. Furthermore, we utilized a real-time exhaled breath detection technique to monitor exhaled benzene metabolites, and the results indicated that moderate lipid deposition enhanced metabolic activation and increased the elimination of benzene metabolites. Collectively, these findings demonstrate that moderate lipid deposition confers reduced susceptibility to benzene-induced hematotoxicity in mice, at least in part, by accelerating benzene metabolism and clearance.

Leukopenia in autosomal dominant polycystic kidney disease: a single-center cohort of kidney transplant candidates with post-transplantation follow-up.

Autosomal dominant polycystic kidney disease (ADPKD) has occasionally been associated with lower peripheral white blood cell (WBC) counts. This study aimed to investigate the peripheral blood cell counts in a large cohort of kidney transplant recipients before and after kidney transplantation and its potential impact on post-transplant outcomes. This was a retrospective study with long-term follow-up data of 2090 patients who underwent a first kidney transplantation in the Leuven University Hospitals, of whom 392 had ADPKD. In total, 2090 patients who underwent a first kidney transplantation in the Leuven University Hospitals were included, of whom 392 had ADPKD. Both pre- and post-transplantation, ADPKD patients had significantly lower total WBC counts, and more specifically lower neutrophil, lymphocyte and eosinophil counts compared with the non-ADPKD patients. This observation was independent of potential confounders such as level of inflammation, smoking habit, vitamins and pre-transplant medication. Overall survival and kidney transplant survival were significantly better in ADPKD vs non-ADPKD transplant recipients and a longer time to first infection was observed. However, no association between blood cell counts and outcome differences was found. In conclusion, this large single-center study reports a strong and independent association between ADPKD and lower peripheral WBC counts both before and after kidney transplantation. Considering the role of inflammation in disease progression, further investigation into the role of WBC in ADPKD is needed.

Effect of Nasal Irrigation in Children With Omicron Variant of COVID-19 Infection.

Objective: To explore the effect of nasal irrigation on the disappearance of symptoms and nucleic acid conversion in children with Omicron variant. Methods: This quasi-experimental study included children diagnosed with asymptomatic, mild, and moderate Omicron variant infection during the isolation observation period in the Shandong Public Health Clinical Center between April 1, 2022 and May 1, 2022. The children were divided into a routine group (received Lianhua Qingwen (LhQw) Granules), isotonic saline group (received LhQw Granules combined with isotonic saline nasal irrigation), and hypertonic saline group (received LhQw Granules combined with 3% hypertonic saline nasal irrigation), respectively. The primary outcomes were the time of symptom disappearance and nucleic acid conversion time. The secondary outcomes were peripheral white blood cell count (WBC), lymphocyte count (LYM), neutrophil count (NEU), and C-reactive protein (CRP) levels. Results: A total of 60 children (7.26 ± 3.15years old) were included (20 per group). The average time of nucleic acid conversion in the 2 saline nasal irrigation groups was significantly reduced compared with the routine group (all P < 0.001), while the fever time and cough duration among the 3 groups were comparable (all P > 0.05). LYM count in the 2 saline nasal irrigation groups was significantly increased after treatment compared to before treatment and was significantly higher than in the routine group (all P < 0.05). There was no significant difference in LYM count between the isotonic and hypertonic saline groups (P = 0.76). Additionally, all children in the saline group well tolerated the treatment, and no adverse events occurred in the isotonic saline group. Conclusions: Timely use of saline nasal irrigation may promote nucleic acid conversion in children with Omicron virus infection.

Dupilumab aggravates Sézary syndrome: The importance of accurate pathological diagnosis

We report a case of Sézary syndrome aggravated by dupilumab. Although a diagnosis of atopic dermatitis was made previously, our retrospective diagnosis was cutaneous T-cell lymphoma. A 72-year-old woman was referred for evaluation of erythema over her entire body. She had received a diagnosis of atopic dermatitis (AD) based on skin biopsy elsewhere 7 years earlier. Since her symptoms were resistant to topical corticosteroids and oral antihistamines, dupilumab was started. She noticed peripheral lymph node enlargement 11 months after the commencement of dupilumab. Physical examination revealed generalized erythroderma with desquamation (Figure 1A,B) and lymphadenopathy in the neck, axilla, and inguinal region. A biopsy from her abdomen showed dense infiltrations of atypical lymphoid cells in the upper dermis with epidermotropism (Figure 1C,D). Immunohistochemically, the infiltrating cells were positive for CD3 and CD4; CD8 was almost negative. There was a 50% deletion of CD7 (Figure 1E–H). Her peripheral blood (PB) white blood cell count was 7660/μL, with 35% abnormal lymphocytes (2681/μL). Although CD4+/CD26− or CD4+/CD7− cells were not assessed, CD4/CD8 ratio was 10.59.1, 2 Human T-lymphotropic virus-1 antibody was negative. Monoclonal gene rearrangement of T-cell receptor β-chain was identified in her PB by Southern blot analysis. Inguinal lymph node biopsy showed partial effacement by atypical lymphocytes. The diagnosis was Sézary syndrome (SS), stage IVA2 (T4N3MXB2). Taking into account the risk of tumor lysis syndrome due to high tumor burden, we selected conventional multiagent chemotherapy as an initial therapy before using a molecular-targeted drug. Dupilumab was discontinued; cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) were started. After two cycles of CHOP, biweekly intravenous mogamulizumab was introduced. Her skin lesions gradually improved. The PB abnormal lymphocyte count decreased. Her disease was well controlled with mogamulizumab for 17 months. We reviewed the previous biopsy specimen. Dense dermal infiltrates with atypical cells and epidermotropism were seen (Figure 1I,J). These infiltrates were positive for CD3 and CD4. CD8-positive cells were sparse. There was a 30% deletion of CD7 (Figure 1K–N). The atypical cells were CCR4+ and CD68−. Although a diagnosis of AD was made previously, our retrospective diagnosis was cutaneous T-cell lymphoma (CTCL). Dupilumab is a monoclonal antibody which inhibits both IL-4 and IL-13 signaling pathways by binding specifically to the α subunit of the IL-4 receptor. Several cases of CTCL that developed or worsened after dupilumab use have been reported. A proposed mechanism of CTCL due to dupilumab is the involvement of IL-13 receptor α2 (IL-13Rα2), which is expressed on CTCL cells and promotes tumor progression. When dupilumab blocks IL-4 and IL-13 receptors, serum IL-13 levels increase. Because dupilumab inhibits IL-13Rα1 but not IL-13Rα2 signaling, increased IL-13 levels due to dupilumab stimulate IL-13Rα2, leading to the activation and proliferation of lymphoma cells.3 To our knowledge, there are 36 cases3-19 of CTCL worsened by dupilumab based on the diagnosis of AD or eczema have been reported. Of these 36 patients, 18 underwent skin biopsy prior to dupilumab therapy; no evidence of CTCL was described in 16 patients.3-10 In one remaining patient, the authors re-evaluated the biopsy specimen taken before dupilumab treatment and revised the diagnosis to early CTCL-not otherwise specified.10 In another patient, the first skin biopsy taken before dupilumab was compatible with AD; however, the diagnosis of mycosis fungoides was made by the second biopsy taken on the first day of dupilumab treatment. After 6 months of dupilumab treatment, the third biopsy turned out CD30-positive anaplastic large-cell lymphoma.11 When using dupilumab for AD, clinicians should be alert to the development or worsening of CTCL. Skin biopsy with immunohistochemical examination is strongly recommended before dupilumab therapy, especially in patients with erythroderma and elderly patients. The authors declare no conflict of interest. Approval of the research protocol: N/A. Informed Consent: N/A. Registry and the Registration No.: N/A. Animal Studies: N/A.

Nonlinear low dose hematotoxicity of benzene; a pooled analyses of two studies among Chinese exposed workers

BackgroundImpairment of the hematopoietic system is one of the primary adverse health effects from exposure to benzene. We previously have shown that exposure to benzene at low levels (<1 ppm) affects the blood forming system and that these effects were proportionally stronger at lower versus higher levels of benzene exposure. This observation is potentially explained by saturation of enzymatic systems. MethodsHere we extend these analyses by detailed modeling of the exposure response association of benzene and its major metabolites (i.e. catechol, muconic acid, phenol, and hydroquinone) on peripheral white blood cell (WBC) counts and its major cell-subtypes (i.e. granulocytes, lymphocytes, and monocytes) using two previously published cross-sectional studies among occupationally exposed Chinese workers. ResultsSupra-linear exposure response associations were observed between air benzene concentrations (range ∼ 0.1 – 100 ppm) and WBC counts and its cell-subtypes, with a larger than proportional decrease in cell counts at lower than at higher levels of benzene exposure. The hematotoxicity associations were largely similar in shape when the analyses were repeated with benzene urinary metabolites suggesting that enzymatic saturation is not a full explanation of the observed non-linearity with WBC endpoints. DiscussionWe hypothesize that the flattening of the exposure response curve especially at higher benzene exposure levels may reflect a response by the bone marrow to maintain hematopoietic homeostasis. Toxicity to the bone marrow and an induced hyper-proliferative response could both contribute to risk of subsequently developing a hematopoietic malignancy. Additional work is needed to explore this hypothesis.

[Risk Factors and Prognosis of Cardiovascular Damage in Hypereosinophilia].

To investigate the risk factors and prognosis of cardiovascular damage in hypereosinophilia (HE). The clinical data of 62 patients with HE in Gansu Provincial Hospital from January 2015 to December 2020 were retrospectively analyzed, including clinical characteristics and laboratory indicators, and the influencing factors of survival and prognosis were also analyzed. In this study, there were 34 males and 28 females, with a median age of 53.5 (20-79) years, 35 patients without cardiovascular damage, 27 patients with cardiovascular damage, including 22 patients with abnormal electrocardiogram (ECG) (81.5%), 18 patients with abnormal echocardiography (ECHO) (66.7%), 9 patients with single ECG abnormality, 5 patients with single ECHO abnormality, and other 13 patients with multiple abnormalities. In cardiovascular damage group, peripheral white blood cell count, absolute value of eosinophils, troponin T (TNT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin (IL)-4 and IL-5 levels at initial diagnosis were significantly higher than those in the non-cardiovascular damage group (P <0.01), while hemoglobin, IL-2 and interferon-γ levels were significantly lower (P <0.01). There were no significant differences in age, sex, course of disease, etiological classification, platelet count, serum creatine kinase, serum creatine kinase isoenzyme and lactate dehydrogenase between the two groups (P >0.05). The 5-year overal survival rate of patients with cardiovascular damage was 88.9%, and that of patients without cardiovascular damage was 100%, the difference was statistically significant (P =0.012). The 5-year event-free survival (EFS) rate of patients with cardiovascular damage was 59.3%, and the median time was 37 (21-52) months, while that of patients without cardiovascular damage was 80%, and the median time was 63 (51-74) months (P =0.002). Age (>60 years old), course of disease (>24 months), NT-proBNP (>3 000 pg/ml), TNT (>100 ng/L), elevated IL-4 and IL-5 were associated with EFS shortening in patients with cardiovascular damage, which were independent risk factors for EFS. The EFS rate in HE patients without cardiovascular damage is significantly higher than patients with cardiovascular damage. Age, course of disease, NT-proBNP, TNT, IL-4 and IL-5 are independent risk factors affecting EFS of patients with cardiovascular damage.

Etiological analysis of patients with sudden sensorineural hearing loss: a prospective case–control study

Sudden sensorineural hearing loss (SSNHL) is a multifactorial emergency disease. Until now, the etiology of SSNHL is still unknown. Previous studies regarding the etiology of SSNHL are clinical studies depending on clinical data collection and analysis. Due to the insufficient sample size or various selective bias in clinical studies, the results of these studies may be inaccurate. This prospective case–control study aimed at exploring the possible etiology and risk factors of SSNHL. We enrolled 255 SSNHL patients and 255 sex-, age- and residence-matched non-SSNHL subjects in the control group. Our study shows that there was no significant difference in the prevalence of comorbidities including hypertension and diabetes, as well as the incidence of smoking and drinking habits between the case and control groups (P > 0.05). In addition, the peripheral blood white blood cell count, neutrophil count, platelet-to-lymphocyte ratio (PLR) and fibrinogen level of the case group were significantly higher than those in the control group (P < 0.05). These findings suggest smoking, drinking, hypertension and diabetes may not be related to the onset of SSNHL. However, hypercoagulable state and inner ear vascular microthrombosis related to an elevated fibrinogen level might be the risk factors of the disease. In addition, inflammation play an important role of SSNHL onset.Trial Registration: Chinese Clinical Trial Registry. Registration number: ChiCTR2100048991.