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Abstract Background Non-invasive risk stratification contributes to the precise treatment of prostate cancer (PCa). In previous studies, lymphocyte subsets were used to differentiate between low-/intermediate-risk and high-risk PCa, with limited clinical value and poor interpretability. Based on functional subsets of peripheral lymphocyte with the largest sample size to date, this study aims to construct an easy-to-use and robust nomogram to guide the tripartite risk stratifications for PCa. Methods We retrospectively collected data from 2039 PCa and benign prostate disease (BPD) patients with 42 clinical characteristics on functional subsets of peripheral lymphocyte. After quality control and feature selection, clinical data with the optimal feature subset were utilized for the 10-fold cross-validation of five Machine Learning (ML) models for the task of predicting low-, intermediate- and high-risk stratification of PCa. Then, a novel clinic-ML nomogram was constructed using probabilistic predictions of the trained ML models via the combination of a multivariable Ordinal Logistic Regression analysis and the proposed feature mapping algorithm. Results 197 PCa patients, including 56 BPD, were enrolled in the study. An optimal subset with nine clinical features was selected. Compared with the best ML model and the clinic nomogram, the clinic-ML nomogram achieved the superior performance with a sensitivity of 0.713 (95% CI 0.573–0.853), specificity of 0.869 (95% CI 0.764–0.974), F1 of 0.699 (95% CI 0.557–0.841), and AUC of 0.864 (95% CI 0.794–0.935). The calibration curve and Decision Curve Analysis (DCA) indicated the predictive capacity and net benefits of the clinic-ML nomogram were improved. Conclusion Combining the interpretability and simplicity of a nomogram with the efficacy and robustness of ML models, the proposed clinic-ML nomogram can serve as an insight tool for preoperative assessment of PCa risk stratifications, and could provide essential information for the individual diagnosis and treatment in PCa patients.

Immune cells are important for the development of schistosomiasis japonica and are also critical for the treatment of schistosomiasis. The immune cells in the peripheral blood help assess the immune state. The peripheral lymphocytes in schistosomiasis mansoni were well studied; however, immune cells in patients with different stages of schistosomiasis japonica are not well analysed. Here, we performed a preliminary study to explore characteristics of peripheral lymphocyte subsets in patients with different stages of schistosomiasis japonica. 135 patients with Schistosoma japonicum infection and 25 healthy volunteers were included in this study, including 84 patients with chronic S. japonicum infection and 51 patients with advanced S. japonicum infection. Flow cytometry analysis was performed to evaluate peripheral lymphocytes including T cells, B cells, and natural killer (NK) cells. Blood routine and liver function test data were analysed. Ultrasound examination was used to access liver fibrosis according to the World Health Organization standard about ultrasound in schistosomiasis. Demographic data analysis suggested there was no difference in age and gender in patients with S. japonicum infection and health control group. Liver function tests showed that patients with advanced schistosomiasis had a higher incidence of liver function abnormality and blood lipid than those with chronic schistosomiasis. Blood routine results reflected that haemoglobin, red blood cells, platelets, as well as lymphocytes in the advanced group were significantly less than that in the chronic group. Furthermore, flow cytometry analysis indicated that the percentage of CD4+ T cells was lower in the advanced group, but the percentage of CD19+ B cells was higher in the advanced group. In addition, the number of CD3+ T cells, CD3+ CD4+ T cells, CD3+ CD8+ T cells, and NK cells was less in the advanced group when compared with those in the chronic group. In addition, there was a correlation between the decrease in CD4+ T cells and more severe fibrosis on ultrasound images. Our results indicated that the immune state in the peripheral is different in different stages of S. japonicum infection. Lymphocyte subset analysis has potential to facilitate differential diagnosis of different stages of schistosomiasis japonica and even to be a prognostic factor. [ABSTRACT FROM AUTHOR]

Background: Non-invasive risk stratification contributes to the precise treatment of prostate cancer (PCa). In previous studies, lymphocyte subsets were used to differentiate between low-/intermediate-risk and high-risk PCa, with limited clinical value and poor interpretability. Based on functional subsets of peripheral lymphocyte with the largest sample size to date, this study aims to construct an easy-to-use and robust nomogram to guide the tripartite risk stratifications for PCa. Methods: We retrospectively collected data from 2039 PCa and benign prostate disease (BPD) patients with 42 clinical characteristics on functional subsets of peripheral lymphocyte. After quality control and feature selection, clinical data with the optimal feature subset were utilized for the 10-fold cross-validation of five Machine Learning (ML) models for the task of predicting low-, intermediate- and high-risk stratification of PCa. Then, a novel clinic-ML nomogram was constructed using probabilistic predictions of the trained ML models via the combination of a multivariable Ordinal Logistic Regression analysis and the proposed feature mapping algorithm. Results: 197 PCa patients, including 56 BPD, were enrolled in the study. An optimal subset with nine clinical features was selected. Compared with the best ML model and the clinic nomogram, the clinic-ML nomogram achieved the superior performance with a sensitivity of 0.713 (95% CI 0.573–0.853), specificity of 0.869 (95% CI 0.764–0.974), F1 of 0.699 (95% CI 0.557–0.841), and AUC of 0.864 (95% CI 0.794–0.935). The calibration curve and Decision Curve Analysis (DCA) indicated the predictive capacity and net benefits of the clinic-ML nomogram were improved. Conclusion: Combining the interpretability and simplicity of a nomogram with the efficacy and robustness of ML models, the proposed clinic-ML nomogram can serve as an insight tool for preoperative assessment of PCa risk stratifications, and could provide essential information for the individual diagnosis and treatment in PCa patients. [ABSTRACT FROM AUTHOR]

Background: Rosemary plant, with phenolic compounds, is known as an antioxidant herb and able to scavenge free radical agents in the biological environment; therefore, it is expected that the rosemary essential oil (R-EO) shows the radioprotective effect to protect individuals who are physically in contact with ionizing radiation. Objective: This study aimed to assess the radioprotective effect of R-EO on human peripheral blood mononuclear cells (PBMCs).Material and Methods: In this experimental study, the toxicity of the rosemary essential oil on PBMCs was assessed by the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. The cells were irradiated at 0. 25 and 200 cGy using a 6 MV X-ray linear accelerator. The survival, apoptosis, necrosis, and survival enhancement factors of cells were analyzed by MTT and flow cytometry analyses with a non-toxic concentration of the rosemary essential oil (IC10). Results: Irradiation of cells in the presence of R-EO caused a significant increase in cell survival compared with the control in both 25 and 200 cGy radiation doses. Also, the percentages of apoptosis and necrosis of cells showed a significant decrease compared with the control. Conclusion: Rosemary essential oil as a natural and non-toxic compound could show favorable radioprotective effects in such a way that significantly increases the survival rate and decreases the percentage of apoptosis and necrosis of PBMCs.

Background: Rosemary plant, with phenolic compounds, is known as an antioxidant herb and able to scavenge free radical agents in the biological environment; therefore, it is expected that the rosemary essential oil (R-EO) shows the radioprotective effect to protect individuals who are physically in contact with ionizing radiation. Objective: This study aimed to assess the radioprotective effect of R-EO on human peripheral blood mononuclear cells (PBMCs). Material and Methods: In this experimental study, the toxicity of the rosemary essential oil on PBMCs was assessed by the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. The cells were irradiated at 0. 25 and 200 cGy using a 6 MV X-ray linear accelerator. The survival, apoptosis, necrosis, and survival enhancement factors of cells were analyzed by MTT and flow cytometry analyses with a non-toxic concentration of the rosemary essential oil (IC10). Results: Irradiation of cells in the presence of R-EO caused a significant increase in cell survival compared with the control in both 25 and 200 cGy radiation doses. Also, the percentages of apoptosis and necrosis of cells showed a significant decrease compared with the control. Conclusion: Rosemary essential oil as a natural and non-toxic compound could show favorable radioprotective effects in such a way that significantly increases the survival rate and decreases the percentage of apoptosis and necrosis of PBMCs. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine whether different radiotherapy (RT) fractionation schemes induce disparate effects on lymphocyte and its subsets in breast cancer patients.Methods: 60 female patients diagnosed with breast cancer were recruited in this study after receiving modified radical mastectomy and were randomly divided into two groups. One group received irradiation at a standard dose of 50 Gy in 25 fractions and the other at a dose of 40.3 Gy in 13 fractions. Both total lymphocyte count and its composition were recorded at three timepoints: right before the radiation treatment (T0), immediately after the last fraction of radiotherapy (T1) and 6 months after irradiation therapy ended (T2).Results: Both groups experienced temporal lymphopenia after finishing local radiation (T1) (13F T0 vs. T1 1570.6 ± 243.9 vs. 940.6 ± 141.8, **p < 0.01; 25F T0 vs. T1 1620.5 ± 280.2 vs. 948.5 ± 274.6, **p < 0.01), while the lymphocyte count recovered at follow-up time (T2), and the cell count in the hypofractionation group (13F) was higher than the standard fraction group (25F) (13F vs. 25F 1725.6 ± 225.6 vs. 1657.5 ± 242.4, *p < 0.05). With respect to the composition of lymphocyte, we found T cell, B cell, and NK cell reacted differently to different radiotherapy protocols.Conclusions: Different RT protocols impose different impacts on immunity, leading us to further explore the optimal radiotherapy regimes to synergy with immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Programmed death 1 (PD-1) and CD4 + CD25 + FoxP3 + expression in peripheral blood T-cells has been previously reported in various types of cancer. However, the specific variation tendency during surgery and chemotherapy, as well as their relationship in gastric cancer patients, still remain unclear. Understanding this aspect may provide some novel insights for future studies on tumor recurrence and tumor immune escape, and also serve as a reference for determining the optimal timing and dose of clinical anti-PD-1 antibodies., Aim: To observe and analyze the expression characteristics of peripheral lymphocyte PD-1 and FoxP3 + regulatory T cells (FoxP3 + Tregs) before and after surgery or chemotherapy in gastric cancer patients., Methods: Twenty-nine stomach cancer patients undergoing chemotherapy after a D2 gastrectomy provided 10 mL peripheral blood samples at each phase of the perioperative period and during chemotherapy. This study also included 29 age-matched healthy donors as a control group. PD-1 expression was detected on lymphocytes, including CD4 + CD8 + CD45RO + , CD4 + CD45RO + , and CD8 + CD45RO + lymphocytes as well as regulatory T cells., Results: We observed a significant increase of PD-1 expression on immune subsets and a larger number of FoxP3 + Tregs in gastric cancer patients ( P < 0.05). Following D2 gastrectomy, peripheral lymphocytes PD-1 expression and the number of FoxP3 + Tregs notably decrease ( P < 0.05). However, during postoperative chemotherapy, we only observed a decrease in PD-1 expression on lymphocytes in the CD8 + CD45RO + and CD8 + CD45RO + populations. Additionally, linear correlation analysis indicated a positive correlation between PD-1 expression and the number of CD4 + CD45RO + FoxP3 high activated Tregs (aTregs) on the total peripheral lymphocytes ( r = 0.5622, P < 0.0001)., Conclusion: The observed alterations in PD-1 expression and the activation of regulatory T cells during gastric cancer treatment may offer novel insights for future investigations into tumor immune evasion and the clinical application of anti-PD-1 antibodies in gastric cancer., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Neonatal lesion in the ventral hippocampus (NLVH) is a validated animal model to study schizophrenia from a neurodevelopmental perspective. This animal model is also used to investigate how neonatal lesions may alter the genetic expression of dopaminergic receptors. The present study compares mRNA expression levels of dopamine receptors (drd2 and drd3) in lymphocytes and brain of NLVH animals at two different age stages: young and adult. Methods: The NLVH procedure was performed on 20 male Wistar rats at postnatal days 5-7. The mRNA expression levels of drd2 and drd3 genes in lymphocytes, nucleus accumbens, hippocampus and prefrontal cortex were measured and analyzed at postnatal days 45 and 90. The results were compared and contrasted with respective sham groups. Results: In lymphocytes, only in NLVH-adult group we observed drd2 mRNA expression, while drd2 mRNA expression was not observed in the NLVH-juvenile rats; on the other hand, the drd3 mRNA expression did not show significant statistical differences. In hippocampus no differences were observed between drd2 mRNA or drd3 mRNA expression when comparing juvenile/adult shams with NLVH groups. In the prefrontal area, a decrease in drd2 mRNA expression levels were observed in the NLVH-adult group (F(1,3) = 52.83, p = 0,005) in comparison to the sham-adult group. Finally, in the nucleus accumbens, a strong decrease of drd3 mRNA expression was observed in the NLVH-adult group in comparison to the sham-adult group (F(1,3) = 123,2, p < 0.001). Conclusions: Our results show that differences in drd2 and drd3 mRNA levels in NLVH-adults are patent when compared to the sham-adult group or with the NLVH-juvenile group. These findings suggest that the expression levels may be regulated during adulthood, leading to behavioral and neurochemical changes related to schizophrenia. Therefore, more studies are necessary to determine the role of dopamine receptors as possible molecular markers for neurodevelopmental changes associated with schizophrenia. [ABSTRACT FROM AUTHOR]

Introduction: Ionizing radiation induces various kinds of DNA damage in which may lead to chromosomal aberrations (CA). Inspite of growing importance in the risk assessment, the dose yield kinetics of CA and their implications for dose assessment are not well established in exposures to low level radiation. In the present study, cytochalasin-B blocked micronucleus assay and metaphase analysis were used as test system to monitor hospital radiation workers who received chronic low dose ionizing radiation below dose limit. Materials and Methods: Heparinized blood samples were taken from healthy non-smoker radiology and radiotherapy workers occupationally exposed to X and gamma rays and healty population whose duties do not expose them to radiation sources and chemical agents. The whole body dose was measured by film badge. Lymphocytes were cultured in RPMI-1640 supplemented with 15% FBS, and metaphase spread was prepared using standard cytogenetic method. Cytochalasine-B (3 mg/ml)treatment was used for binuclei micronuclei assay. 100 mitoses and 1000 binuclei lymphocytes were scored for CA and micronuclei (MN) respectively. Results: Results show a high frequency of CA mainly deletions and simple breaks in radiation workers compared to control (p

Response to drug treatment of major depression is variable and biomarkers of response are needed. Cyclic AMP response element binding protein (CREB) is considered a key mediator of antidepressant drug effect. We studied CREB in T-lymphocytes as a potential predictor of response to a selective serotonin reuptake inhibitor (SSRI) in 69 Korean depressed patients. We determined total CREB (tCREB), phosphorylated CREB (pCREB) and CRE-DNA binding using immunoblot and electrophoretic mobility shift assays, at baseline and after 6 wk treatment. Thirty-four healthy controls were also studied. The rate of response was 36 of 69 cases (52%). Baseline levels of tCREB and pCREB were lower in the total depressed group compared to controls (p = 0.044 and p<0.001, respectively). Baseline tCREB values in responders were significantly reduced in comparison to non-responders and to controls. After 6 wk treatment, median values of change of all CREB measures were greater in responders (36) than in non-responders (33; p<0.001 for tCREB, p = 0.003 for pCREB, and p=0.072 for CRE-DNA binding). Similar but less robust changes in CREB variables distinguished remitters from non-remitters. The optimum value of baseline tCREB predicted response with a positive predicted value of 0.778 [21/27; 95% confidence intervals (CI) 0.621–0.935], negative predictive value of 0.643 (27/42; 95% CI 0.498–0.788) and accuracy of 0.695 (48/69; 95% CI 0.586–0.804). Patients with low baseline tCREB had a significantly greater rate of response (78%) than patients with high baseline tCREB (36%), p < 0.001. Moreover, the greatest changes in tCREB with treatment were observed in subjects who did respond. This preliminary study suggests that T-lymphocytic CREB biomarkers are reduced in depressed patients and may assist in the prediction of response to SSRI drugs in depression. [ABSTRACT FROM PUBLISHER]

In this study, we identify molecular mediators that participate in the regulation of the immune response during corticosterone-induced stress in chickens. At 7 weeks of age, 120 chickens were exposed for 1 week to corticosterone treatment. Cytokine and chemokine mRNA expression levels were evaluated in peripheral blood and splenic lymphocytes. Expression levels of interleukin (IL)-1β, IL-6, IL-18 and transforming growth factor (TGF)-β4 mRNA were significantly up-regulated in lymphocytes 3 h after first treatment with corticosterone. TGF-β4 and IL-18 remained elevated 1 week post-initial treatment. Compared with controls, corticosterone-treated birds showed greater expression levels of chemokine (CC) mRNA, particularly for CCLi2, CCL5 (RANTES), CCL16 and CXCLi1, in peripheral and splenic lymphocytes 3 h post-initial exposure. CCLi2 mRNA was highly expressed in splenocytes at all time-points. Administration of corticosterone significantly increased circulating corticosterone concentrations and decreased total lymphocyte counts at 3, 24 h and 1 week post-initiation of corticosterone treatment. There was a positive correlation between plasma corticosterone concentrations and CCL5 and CCL16 mRNA at 3 h post-initial administration. At 1 week post-initial treatment, corticosterone concentrations correlated positively with CCL5 and negatively with IL-18 mRNA level. Conditions associated with significant changes in corticosterone levels might therefore affect the immune response by increasing pro-inflammatory responses, leading to potential modulation of the Th1/Th2 balance. [ABSTRACT FROM AUTHOR]

Abstract: Crude water-soluble polysaccharides (ASP) were separated from Angelica sinensis (Oliv.) Diels by hot water extraction. They were fractionated into neutral and acidic polysaccharides by anion-exchange chromatography. The neutral polysaccharide (ASP1) was rich in glucose, galactose, and arabinose suggesting a mixture of glucan and arabinogalactan. The acidic polysaccharide (ASP2, ASP3) consisted mainly of galacturonic acid along with rhamnose, arabinose, and galactose indicating a pectic polysaccharide. The degree of esterification of ASP and ASP3 were 54.06% and 47.14% for the crude and purified sample, respectively. ASP3, with a molecular weight of 3.4×104 Da determined by high-performance size-exclusion chromatography (HPSEC), was the major constituent for the crude extracts. The radioprotective effect of the pectic polysaccharide ASP3 was studied in murine models. ASP3 pretreated mice exhibited a significant decrease of apoptosis (P &#60;0.05, dosage of 200mg/kgd body weight) in peripheral lymphocytes compared to the irradiated control. The results showed that ASP3 can protect leucocytes and lymphocytes of mice against radiation induced damage, which has potential radioprotective effect on acute radiation injured mice. [Copyright &y& Elsevier]

To investigate impairment of cellular immunity in severe acute pancreatitis, alterations of peripheral lymphocytes in acute pancreatitis were examined. In 48 patients with severe acute pancreatitis, the mean peripheral lymphocyte count on admission was 959 +-105/mm 3, and it was significantly decreased in the patients with subsequent infection (623 +-90/mm 3) in comparison to those without infection (1084 +- 135/ram3). According to an analysis of lymphocyte subsets, although both B and T lymphocytes were decreased in peripheral circulation in the patients with infection, it was primarily CD8-positive lymphocytes that decreased in these subsets. Cell cycle analysis of lymphocytes collected from these patients indicated that apoptotic changes occurred after 24 hours’ incubation in lymphocytes from patients with severe pancreatitis but not in lymphocytes from healthy control subjects. In a rat model of experimental necrotizing pancreatitis, total peripheral lymphocytes and T lymphocytes were significantly decreased 5 hours after induction of pancreatitis. In severe pancreatitis, peripheral lymphocytes are eliminated from systemic circulation possibly as a result of apoptosis. It has been suggested that impairment of cellular immunity due to peripheral lymphocyte apoptosis is linked to the development of subsequent infectious complications in acute pancreatitis. [ABSTRACT FROM AUTHOR]

Tumor-infiltrating lymphocytes (TILs) have been reported to reflect the anti-tumor immune status of patients and to be correlated with their prognosis and therapeutic outcomes. However, the characteristics of the local immune status in metastatic tumors is poorly understood, as primary tumors have been the focus in most previous studies. In addition, the local immune status may be influenced by preoperative chemotherapy. The present study aimed therefore to investigate the relationship between the degree of TIL infiltration and the prognosis in patients with curative resection of colorectal cancer liver metastases and to examine the effects of preoperative chemotherapy on the function of immune cells. A total of 108 patients who underwent curative resection of colorectal cancer liver metastases in our department between May 1996 and January 2017 were enrolled in the present study. Peripheral blood samples were obtained within two weeks before surgery. TIL infiltration was evaluated by immunohistochemical staining of surgically resected specimens of liver metastases using anti-CD8/CD3 antibodies. The mean number of TILs in five different fields was calculated, and patients were classified into a high-TIL group and a low-TIL group. Furthermore, patients were divided into three groups as follows: i) A group of patients who did not receive preoperative chemotherapy; ii) a group of patients who received short-term preoperative chemotherapy for <6 months; and iii) a group of patients who received long-term preoperative chemotherapy for ≥6 months. The results demonstrated that the density of TILs in colorectal liver metastases was not correlated with the absolute peripheral lymphocyte count in all patients. Furthermore, the degree of CD8+TIL infiltration in liver metastases was significantly lower in the recurrence group compared with the recurrence-free group following hepatectomy. In all patients with colorectal liver metastases, the degree of CD8+TIL infiltration was significantly associated with the relapse-free and overall survival. In patients without preoperative chemotherapy, the degree of CD8+TIL infiltration was significantly associated with the relapse-free survival, and a high CD8+TIL presence tended to have a better effect on the overall survival than a low CD8+TIL presence. In the short-term chemotherapy group, the degree of CD8+TIL infiltration was significantly associated with the relapse-free and overall survival. In the long-term chemotherapy group, there were no significant differences between the high- and low- CD8+TIL groups in the relapse-free and overall survival. In contrast to CD8+TILs, CD3+TILs showed a poor prognostic ability. In summary, the degree of CD8+TIL infiltration in colorectal cancer liver metastases may be correlated with patient prognosis. However, in patients who received long-term chemotherapy before surgery, the degree of TIL infiltration was not necessarily associated with prognosis as the anti-tumor effects of TILs may decrease. The degree of CD8+TIL infiltration may therefore be considered as a useful prognostic factor in patients with colorectal liver metastases, but the prognostic accuracy may decrease in patients who received long-term chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: To study whether sewage workers are exposed to genotoxic substances. An increased risk of cancers among sewage workers has been noted. If this increased risk is due to an exposure to genotoxic agents, primarily DNA damage could be used as a biological marker of exposure.Methods: In a cross sectional study, DNA damage in peripheral lymphocytes from 35 sewage workers and 30 controls was compared with alkaline single cell gel electrophoresis, a technique for detecting single strand breaks and alkali labile sites in DNA. The controls were selected from among municipal workers matched for age and smoking habit. Information about occupational exposures and possible confounders was collected by means of a questionnaire.Results: No increase in DNA damage was found among the sewage workers when compared with the unexposed controls.Conclusions: The failure to detect increased damage to DNA in peripheral lymphocytes by alkaline single cell gel electrophoresis suggests that the sewage workers studied here were not exposed to genotoxic agents to a greater extent than other municipal workers. It may be, however, that the lymphocyte is not the appropriate target cell to study, or that sewage workers are exposed to carcinogens which do not damage the genetic material. [ABSTRACT FROM AUTHOR]