Reticulocyte hemoglobin content associated with the risk of iron deficiency anemia.

Background/Objective: Reticulocyte hemoglobin content (MCHr) was recognized as a rapid and reliable marker for investigating iron deficiency (ID). We hypothesized that MCHr was associated with the risk of iron deficiency anemia in adults. Methods: This is a dual-center case-control study. A total of 806 patients and healthy individuals were recruited from Ruijin Hospital and Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine between January 2021 and December 2021. The participants were categorized into iron deficiency anemia (IDA) group (n = 302), non-IDA group (n = 366), and healthy control group (n = 138). According to the MCHr level, the participants were divided into two groups, i.e. normal MCHr (≥25 pg) and decreased MCHr (<25 pg) group. Multivariate logistic regression analysis and adjusted subgroup analysis were conducted to estimate the relative risk between MCHr and IDA, with confounding factors including age, sex, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), Hematocrit (HCT), serum iron (Fe), ferritin (Ferrit), and total iron binding capacity (TIBC). Results: Compared with the non-IDA, the MCHr level with IDA decreased significantly. ROC curve analysis showed that MCHr had the largest area under the AUC curve. After comprehensive adjustment for confounding factors, individuals with normal level of MCHr exhibited a decreased risk of IDA (OR = 0.68 [0.60, 0.77], P < 0.01), while the risk of IDA was up to 5 times higher for those with decreased MCHr. Conclusion: Our findings supported the hypothesis that MCHr was associated with the risk of IDA in adults and could serve as an indicator of IDA severity. MCHr holds clinical value as an auxiliary diagnostic indicator, providing valuable insights into whether invasive examinations are warranted in the assessment of IDA.

[Research progress in drugs targeting 5-lipoxygenase for age-related diseases].

With the acceleration of aging society, delaying aging or promoting healthy aging has become a major demand for human health. 5-Lipoxygenase (5-LOX) is a key enzyme catalyzing arachidonic acid into leukotrienes (LTs), which is a potent mediator of the inflammatory response. Previous studies showed that abnormal activation of 5-LOX and overproduction of LTs are closely related to the occurrence and development of aging-related inflammatory diseases. Therefore, inhibiting 5-LOX activation is a possibly potential strategy for treating age-related diseases. In this paper, the latest research progress in 5-LOX activation, 5-LOX in mediating aging-related diseases and its small molecule inhibitors is briefly reviewed to provide scientific theoretical basis and new ideas for the prevention and treatment of aging-related inflammatory diseases.

Processed Multiparameter Electroencephalogram-Guided General Anesthesia Management Can Reduce Postoperative Delirium Following Carotid Endarterectomy: A Randomized Clinical Trial.

Background: Patients undergoing carotid endarterectomy (CEA) for severe carotid stenosis are vulnerable to postoperative delirium, a complication frequently associated with poor outcome. This study investigated the impact of processed electroencephalogram (EEG)-guided anesthesia management on the incidence of postoperative delirium in patients undergoing CEA. Methods: This single-center, prospective, randomized clinical trial on 255 patients receiving CEA under general anesthesia compared the outcomes of patient state index (PSI) monitoring [SEDLine Brain Function Monitor (Masimo, Inc, Irvine, CA)] (standard group, n = 128) with PSI combined with density spectral array(DSA) -guided monitoring (intervention group, n = 127) to reduce the risk of intraoperative EEG burst suppression. All patients were monitored by continuous transcranial Doppler ultrasound (TCD) and near-infrared spectroscopy (NIRS) to avoid perioperative cerebral hypoperfusion or hyperperfusion. According to the surgical process, EEG suppression time was calculated separately for three stages: S1 (from anesthesia induction to carotid artery clamping), S2 (from clamping to declamping), and S3 (from declamping to the end of surgery). The primary outcome was incidence of postoperative delirium according to the Confusion Assessment Method algorithm during the first 3 days post-surgery, and secondary outcomes were other neurologic complications and length of hospital stay. Results: There were no episodes of cerebral hypoperfusion or hyperperfusion according to TCD and NIRS monitoring in either group during surgery. The incidence of postoperative delirium within 3 days post-surgery was significantly lower in the intervention group than the standard group (7.87 vs. 28.91%, P < 0.01). In the intervention group, the total EEG suppression time and the EEG suppression time during S2 and S3 were shorter (Total, 0 "0" vs. 0 "1.17" min, P = 0.04; S2, 0 "0" vs. 0 "0.1" min, P < 0.01; S3, 0 "0" vs. 0 "0" min, P = 0.02). There were no group differences in incidence of neurologic complications and length of postoperative hospital stay. Conclusion: Processed electroencephalogram-guided general anesthesia management, consisting of PSI combined with DSA monitoring, can significantly reduce the risk of postoperative delirium in patients undergoing CEA. Patients, especially those exhibiting hemodynamic fluctuations or receiving surgical procedures that disrupt cerebral perfusion, may benefit from the monitoring of multiple EEG parameters during surgery. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03622515.

Correlation between narrow-band imaging endoscopy results and hPTTG expression indicated by angiogenensis and its distribution in the initial phase of colorectal adenoma-carcinoma sequence.

The aim of the present study was to investigate the correlation between vascular characteristics under narrow band imaging endoscopy (NBI) and the expression of angiogenic factors of colorectal carcinoma and adenoma, and to evaluate the feasibility and validity of NBI in vivo visualizing angiogenesis. Patients with colorectal polyps, which were pathologically confirmed as early carcinoma, adenoma and hyperplastic polyp, were recruited and examined by NBI. The endoscopic vascular pattern was classified by Showa classification. Immunohistochemical staining was performed by cluster of differentiation (CD34), microvessel density (MVD) and Human Pituitary Tumor-Transforming Gene (hPTTG). The histologic results were compared with the vascular pattern under NBI. Overall, 83 colorectal lesions including 9 intramucosal colorectal carcinomas, 44 adenomas (18 tubular adenomas, 26 tubulovillous adenomas) and 30 hyperplastic polyps were recruited and examined by NBI. A higher proportion (88.6%, 47/53) of intramucosal carcinomas and adenomas were more likely to have the dense pattern (DP) or network pattern (NP), while that of hyperplastic polyps was only 30.0% (9/30). There was an obvious increase in the MVD-CD34 counting from hyperplastic polyps, to adenoma to carcinoma, and a significant difference among the three groups as well. Also, a clear difference can be seen in the expression of hPTTG, which was expressed more in carcinoma than in adenoma and HP group (P < 0.05). Conclusion: NBI might be a useful tool as in vivo visualizing angiogenesis. hPTTG expression in colorectal adenoma and carcinoma is related to angiogenesis.

Ectopic repression of receptor tyrosine kinase-like orphan receptor 2 inhibits malignant transformation of ovarian cancer cells by reversing epithelial-mesenchymal transition.

Receptor tyrosine kinase-like orphan receptor 2 is an enzyme-linked receptor which specifically modulates WNT5A signaling and plays an important role in tumorigenesis, invasion, and metastasis; however, the precise role of receptor tyrosine kinase-like orphan receptor 2 in cancer is controversial. The purpose of this study was to investigate the expression and role of receptor tyrosine kinase-like orphan receptor 2 in ovarian carcinoma and clarify the biological functions and interactions of receptor tyrosine kinase-like orphan receptor 2 with non-canonical Wnt pathways in ovarian cancer. The result of the human ovary tissue microarray revealed that the receptor tyrosine kinase-like orphan receptor 2-positive rate increased in malignant epithelial ovarian cancers and was extremely higher in the metastatic tumor tissues, which was also higher than that in the malignant ovarian tumor tissues. In addition, high expression of receptor tyrosine kinase-like orphan receptor 2 was closely related with ovarian cancer grading. The expression of receptor tyrosine kinase-like orphan receptor 2 protein was higher in SKOV3 and A2780 cells than OVCAR3 and 3AO cells. Knockdown of receptor tyrosine kinase-like orphan receptor 2 inhibited ovarian cancer cell proliferation, migration, invasion, and induced morphologic as well as digestive state alterations in stably transfected SKOV3 cells. Detailed study further revealed that silencing of receptor tyrosine kinase-like orphan receptor 2 reversed the epithelial-mesenchymal transition and inhibited non-canonical Wnt signaling. Our findings suggest that receptor tyrosine kinase-like orphan receptor 2 may be an important regulator of epithelial-mesenchymal transition, primarily regulated the non-canonical Wnt signaling pathway in ovarian cancer cells, and may display a promising therapeutic target for ovarian cancer.

Correlation between microvascular characteristics and the expression of MVD, IGF-1 and STAT3 in the development of colonic polyps carcinogenesis.

The aim of the present study was to investigate the correlation between vascular characteristics under narrow band imaging (NBI) and the expression of angiogenic factors of colorectal carcinoma and adenoma, and to evaluate the feasibility of NBI in vivo visualizing angiogenesis. Patients with colorectal polyps, which were pathologically confirmed as early carcinoma and adenoma, were recruited and examined by NBI. The vascular pattern was classified into type I (invisible or faintly visible vasculature), type II (clearly visible microvasculature that is regularly arranged in a round, oval honeycomb-like pattern) and type III (clearly visible microvasculature that is irregularly arranged in size and caliber or has irregular winding). Immunohistochemical staining was performed by cluster of differentiation (CD)34, insulin-like growth factor (IGF)-1 and signal transducer and activator of transcription 3 (STAT3). The histological results were compared with the vascular pattern under NBI. Overall, 64 sites (15 adenocarcinomas, 29 adenomas and 20 normal) from 58 patients were recruited in the study and examined by NBI. A higher proportion of adenomas (82.1%, 23/28) and adenocarcinomas (66.7%, 10/15) had vascular patterns II and III, respectively. The expression of microvessel density (MVD)-CD34 and IGF-1 in normal mucosa compared with adenomas and adenocarcinomas was significantly different (P<0.0001 and P=0.0062, respectively). MVD-CD34, IGF-1 and STAT3 expression in the sites displayed with vascular patterns I, II, and III was different significantly (P<0.0001, P=0.0010 and P=0.0055, respectively). The spearman correlation coefficient between NBI vascular pattern and MVD-CD34, IGF-1 and STAT3 expression was 0.67, 0.41 and 0.40, respectively. In conclusion, vascular-pattern analysis and the use of an NBI system may be a promising tool for evaluating angiogenesis of colorectal lesions in real-time endoscopy.

Intractable epilepsy and the P-glycoprotein hypothesis.

Epilepsy is a serious neurological disorder that affects more than 60 million people worldwide. Intractable epilepsy (IE) refers to approximately 20%-30% of epileptic patients who fail to achieve seizure control with antiepileptic drug (AED) treatment. Although the mechanisms underlying IE are not well understood, it has been hypothesized that multidrug transporters such as P-glycoprotein (P-gp) play a major role in drug efflux at the blood-brain barrier, and may be the underlying factor in the variable responses of patients to AEDs. The main goal of the present review is to show evidence from different areas that support the idea that the overexpression of P-gp is associated with IE. We discuss here evidence from animal studies, pharmacology, clinical cases and genetic studies.

CD19+CD24hiCD38hiBregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer.

Regulatory B cells (Bregs) play a critical role in inflammation and autoimmune disease. We characterized the role of Bregs in the progression of gastric cancer. We detected an increase in Bregs producing IL-10 both in peripheral blood mononuclear cells (PBMCs) and in gastric tumors. Multicolor flow cytometry analysis revealed that a subset of CD19+CD24hiCD38hi B cells produces IL-10. Functional studies indicated that increased Bregs do not inhibit the proliferation of CD3+T cells or CD4+ helper T cells (Th cells). However, Bregs do suppress the secretion of IFN-γ and TNF-α by CD4+Th cells. CD19+CD24hiCD38hiBregs were also found to correlate positively with CD4+FoxP3+ regulatory T cells (Tregs). Neutralization experiments showed that Bregs convert CD4+CD25- effector T cells to CD4+FoxP3+Tregs via TGF-ß1. Collectively, these findings demonstrate that increased Bregs play a immunosuppressive role in gastric cancer by inhibiting T cells cytokines as well as conversion to Tregs. These results may provide new clues about the underlying mechanisms of immune escape in gastric cancer.

Vitamin D deficiency contributes to the reduction and impaired function of naïve CD45RA⁺ regulatory T cell in chronic heart failure.

The effect of vitamin D pertinent to cardiovascular health on the heart itself is considered to shift toward an anti-inflammatory response in chronic heart failure (CHF); however, its underlying mechanism is not completely understood. In this study, we demonstrated that plasma 25(OH)D level, negatively associated with NT-ProBNP, correlated with the decreased Treg in CHF compared to the patients with other cardiovascular diseases and healthy and older donors. Naïve Treg cell (CD4(+)CD45RA(+)Foxp3(lo)T) subset, rather than whole Treg cells, contributes to the reduction of Treg in CHF. 1,25(OH)2D treatment maintained partial expression of CD45RA on CD4(+)T cell after αCD3/CD28 monoclonal antibodies activation and ameliorated the impaired CD4(+)CD45RA(+)T cell function from CHF patients through upregulating Foxp3 expression and IL-10 secretion in vitro. Low level of vitamin D receptor (VDR) was detected in CD4(+)CD45RA(+)T cell of CHF than control, while 1,25(OH)2D treatment increased the VDR expression to exert its immunosuppression on T cell. The results of this study might provide tangible evidence to our knowledge of the impact of vitamin D supplementation on naïve Tregs, which may offer new means of preventing and treating CHF.

3-Deazaneplanocin A is a promising therapeutic agent for ovarian cancer cells.

BACKGROUND: Recent studies have shown that 3-deazaneplanocin A (DZNep), a well-known histone methyltransferase inhibitor, disrupts polycomb-repressive complex 2 (PRC2), and induces apoptosis, while inhibiting proliferation and metastasis, in cancer cells, including acute myeloid leukemia, breast cancer and glioblastoma. However, little is known about effects of DZNep on ovarian cancer cells. MATERIALS AND METHODS: We here therefore studied DZNep-treated A2780 ovarian cancer cells in vitro. Proliferation of ovarian cancer cells under treatment of DZNep was assessed by MTT and apoptosis by flow cytometry. Cell wound healing was applied to detect the migration. Finally, we used q-PCR to assess the migration-related gene, E-cadherin. RESULTS: DZNep could inhibit the proliferation of A2780 and induce apoptosis Furthermore, it inhibited migration and increased the expression of E-cadherin (P<0.05). CONCLUSION: DZNep is a promising therapeutic agent for ovarian cancer cells, with potential to inhibite proliferation, induce apoptosis and decrease migration.

Glioma in the third trimester of pregnancy: Two cases and a review of the literature.

We present two cases of glioma (WHO grade III) in pregnant females presenting in the third trimester. Gliomas during pregnancy are rare. At present, the association between gliomas and pregnancy is poorly understood and little has been reported with regard to the management of patients with gliomas in pregnancy. Management of these cases presents a medical dilemma. Gliomas during pregnancy pose a risk to maternal and fetal life. The benefit-to-risk ratio should be carefully evaluated and discussed prior to surgery. In the present cases, caesarean section (CS) followed by craniotomy was performed under the same general anesthesia at 34 weeks' gestation. The mothers received radiotherapy and chemotherapy following surgery. They have been followed up to the present date and remain in good health. These two cases indicate that early CS followed by craniotomy is an effective choice in pregnant patients with gliomas at ≥34 weeks' gestation. In the present study, we describe these two cases and review the literature with regard to gliomas during pregnancy.

[The feasibility of training anesthesiologists with hemodynamic models of miniature pigs].

OBJECTIVE: To investigate the feasibility of training anesthesiologists with hemodynamic models of miniature pigs. METHODS: Eight miniature experimental pigs were chosen; ECG, SpO2, PetCO2, ABP, CVP, SV, SVV and PAP were monitored after anesthesia. The research was divided into two parts. Part one: the blood of pig was taken from its artery, air was injected into its body thought jugular vein, 15%KCl and 0.75% bupivacaine were given by peripheral vein respectively. The resuscitation would not be implemented unless the monitoring data changes were significantly and were recorded. Trainees looked on only during that time. Part two: Trainees were trained for placement of Swan-Ganz catheter after the sheath had been success- fully intubated into pig's right jugular vein. Trainees were trained for placement of femoral artery guided by ultrasound.Scores related to trainees' performance were written down. RESULTS: (1) Monitoring data (ABP, SV, SVV, CVP, PetCO2, PAP, SpO2 , ECG) changes were significantly ( P < 0.05 or P < 0.01), which indicated that the models had been successfully established. The evaluation scale displays: 81.3% of trainees thought this research improved their under- standing of hemodynamic changes; 78.2% thought that it helped them know how to deal with these circumstances; 71.9% thought this training was meaningful. (2) It was improved for students' skill to place Swan-Ganz catheter (P < 0.05), whereas the skill for placement of artery catheter by ultrasound was not significantly improved (P > 0.05). CONCLUSION: It was feasible to use a hemodynamic model of miniature pigs as an assisted teaching method to improve resident anesthesiologists' ability to understand and cope with clinical hemodynamic changes.

Association of dopaminergic/GABAergic genes with attention deficit hyperactivity disorder in children.

Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioral disorder in children and adolescents; however, its etiology is unknown. In this study, we investigated the association of five polymorphisms in dopaminergic/GABAergic genes with ADHD using polymerase chain reaction-restriction fragment length polymorphism in a group of 54 children with ADHD and 67 healthy controls. The distribution of AA genotype and A allele frequencies of rs5320 in the dopamine beta-hydroxylase gene in ADHD children differed significantly from that in healthy controls; however, no associations were found between four other polymorphisms in dopaminergic/GABAergic genes and ADHD. We also identified the best model consisting of four loci. We conclude that the rs5320 polymorphism may be considered as a genetic risk factor of ADHD, but the other four polymorphisms were not confirmed to be related directly to ADHD. The multilocus of dopaminergic/GABAergic genes acted in combination to affect susceptibility to ADHD in the children studied.

[Effect of occupational combined exposure of chromium and iron on erythrocyte metabolism].

OBJECTIVE: To investigate the effect of combined occupational exposure of chromium and iron on erythrocyte metabolism, and the possible mechanism. METHODS: A total of 115 chromate production workers were selected in a chemical factory of Jinan as exposure group, Dec, 2008, and 60 healthy residents from a community which was far away from the factory were enrolled as control group. Environmental concentrations of chromium and iron were collected by filter membrane sampling and determined. The peripheral blood of subjects were collected for determination of chromium, iron, copper in whole blood and folate, vitamin B12 in serum, mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) and correlation analysis was conducted. RESULTS: The median (quartile interval) concentration of air-chromium and air-iron in workplace were 9.0 (10.5) and 11.2 (10.1) µg/m³, respectively, which were significantly higher than that of the control (0.1 (0.1) and 7.2 (2.5) µg/m³) (all P values < 0.01). Blood-chromium and blood-iron of the exposed group were 15.5 (14.1) µg/L and (895.1 ± 90.2) mg/L, which were significantly higher than the counterpart of the control (3.6(2.0) µg/L, (563.7 ± 49.3) mg/L) (all P values < 0.01). Serum folate ((6.9 ± 2.5) µg/L), serum vitamin B12 ((396.4 ± 177.0) µg/L) and blood copper ((777.6 ± 103.5) µg/L) of the exposed group were all significantly lower comparing to the control group ((558.0 ± 330.8), (8.1 ± 3.8), (812.1 ± 94.6) µg/L) (all P values < 0.05). The relationships between blood chromium and serum folate, serum vitamin B12 were statistical significant (r = -0.319 and -0.293, P < 0.01). Both serum vitamin B12 and blood copper correlated with mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) (r = -0.223, -0.242, -0.261, -0.292, all P values < 0.01). CONCLUSION: Combined chromium and iron exposure existed in the workplace. Adverse effect of Chromium on human erythrocyte may via folate and vitamin B12 metabolism, while iron may via copper metabolism.

CD74 and macrophage migration inhibitory factor as therapeutic targets in gastric cancer.

AIM: To investigate the relationship and molecular features of CD74/macrophage migration inhibitory factor (MIF)/Toll-like receptor 4 (TLR4) in gastric cancer. METHODS: CD74, MIF and TLR4 expression in the paraffin-embedded sections of gastric cancer from 120 patients were detected by immunohistochemical staining. Knock down of CD74 expression in gastric cancer cell line MKN-45 was performed by lentivirus transduction and detected by Western blotting. MKN-45 cell proliferation assay under the stimulants was measured by the cell counting kit 8 (CCK8) assay and MIF concentration in the culture medium was detected by enzyme-linked immunosorbent assay. Surface staining of CD74 in the MKN-45 cell line under the stimulation of lipopolysaccharide (LPS) was measured by flow cytometry. MIF, CD74 and TLR4 co-localization in the MKN-45 cell line was performed by the immunoprecipitation. RESULTS: CD74, MIF and TLR4 were found to be expressed in gastric cancer and increased significantly in the advanced stage, and were also associated with lymph node metastasis. Correlation analysis revealed that CD74 was positively correlated with MIF (r = 0.2367, P < 0.01) and both proteins were also associated with TLR4 (r = 0.4414, r = 0.5001, respectively, P < 0.01). LPS can significantly promote MKN-45 cell proliferation (3.027 ± 0.388 vs 4.201 ± 0.092, P < 0.05), induce MIF production (54.333 ± 2.906 pg/mL vs 29.667 ± 3.180 pg/mL, P < 0.01) and cell surface expression of CD74 (75.6% ± 4.046% vs 9.4% ± 0.964%, P < 0.01) at LPS concentration of 1 µg/mL compared to medium control. Knockdown of CD74 or using anti-CD74 and MIF antagonist ISO-1 significantly reduced LPS-induced MKN-45 cell proliferation (4.201 ± 0.092 vs 3.337 ± 0.087, 4.534 ± 0.222 vs 3.368 ± 0.290, 4.058 ± 0.292 vs 2.934 ± 0.197, respectively, P < 0.01). MIF, CD74 and TLR4 could co-localize in the MKN-45 cell line. CONCLUSION: Upregulation of MIF, CD74 and TLR4 are associated with increasing clinical stage and provide an opportunity as novel gastric cancer chemoprevention and/or treatment strategy.

Effects of chronic chromate exposure on human serum prostate specific antigen: a cross sectional study.

The detrimental effect of chronic chromium (Cr) exposure on the prostate has never been studied. Here, we report the prostate specific antigen (PSA) changes in occupational chromate exposed workers. In this study, eighty six male occupational chromate exposed workers and forty five age-matched controls were recruited. The concentration of Cr in urine (U-Cr), serum total PSA (tPSA), free PSA (fPSA), high sensitive C reactive protein (Hs-CRP) and peripheral white blood cells count (WBC) were measured. The results show that the U-Cr, serum tPSA, Hs-CRP and WBC were significantly higher in Cr exposed workers when compared to the controls. Contrastively, the serum fPSA level in Cr exposed workers was lower than controls. A significant positive correlation between U-Cr and serum tPSA was observed. Multiple linear regression analysis revealed that serum tPSA and fPSA level was statistically associated with the serum Hs-CRP and U-Cr concentration in Cr exposed workers. These observations suggested that chronic Cr exposure could produce potential prostate injury and the nonspecific inflammation at least might be one of the reasons to explain the elevated concentration of tPSA in chronic occupational chromate exposed workers.

Vitamin B12 and folate deficiency and elevated plasma total homocysteine in workers with chronic exposure to chromate.

OBJECTIVES: Chronic occupational exposure to chromium can result in a broad range of adverse effects including multiple organ damage, genotoxicity and carcinogenesis. However, the metabolic consequences of chromium exposure have not been fully investigated. This study was designed to examine vitamin B12, folate and homocysteine metabolic changes in workers chronically exposed to chromate. The potential association between metabolic alteration and renal impairment induced by chromate exposure was also assessed. METHODS: The level of chromium exposure was evaluated by measuring chromium concentrations in red blood cells (RBC-Cr) and urine (U-Cr). Renal impairment was assessed with serum cystatin C (Cys-C) and urinary ß2-microglobulin (ß2M). Serum vitamin B(12), folate and plasma total homocysteine (tHcy) were measured and correlations analysed. RESULTS: Significant increases in RBC-Cr, U-Cr, serum Cys-C, plasma tHcy and urinary ß2M concentrations were observed in workers chronically exposed to chromate compared to controls. In the exposed workers, serum vitamin B12 and folate levels were decreased and significantly inversely correlated with RBC-Cr concentrations, and increased plasma tHcy concentrations were mirrored by decreased serum vitamin B12 and folate levels. Elevated plasma tHcy concentrations were positively related to serum Cys-C concentrations. CONCLUSIONS: Hyperhomocysteinemia in chronically exposed workers was primarily induced by vitamin B12 and folate deficiency. This metabolic change might be associated with renal dysfunction in chromate processing workers after long term exposure.

Gastric cancer cells induce human CD4+Foxp3+ regulatory T cells through the production of TGF-ß1.

AIM: To elucidate the molecular and cellular features responsible for the increase of regulatory T cells (Tregs) in gastric cancer. METHODS: The frequencies of CD4(+)Foxp3(+) Tregs and the level of transforming growth factor-ß1 (TGF-ß1) were analyzed from 56 patients with gastric cancer by flow cytometry and enzyme-linked immunosorbent assay respectively. Foxp3 gene expression was analyzed by real-time polymerase chain reaction. The gastric cancer microenvironment was modeled by establishing the co-culture of gastric cancer cell line, MGC-803, with sorting CD4(+) T cells. The normal gastric mucosa cell line, GES-1, was used as the control. The production of TGF-ß1 was detected in supernatant of MGC and GES-1. The carboxyfluorescein diacetatesuccinimidyl ester (CFSE) dilution assay was performed to evaluate the proliferation characteristics of induced Tregs. Neutralizing anti-TGF-ß1 antibody was added to the co-culture system for neutralization experiments. RESULTS: The level of serum TGF-ß1 in gastric cancer patients (15.1 ± 5.5 ng/mL) was significantly higher than that of the gender- and age-matched healthy controls (10.3 ± 3.4 ng/mL) (P < 0.05). Furthermore, the higher TGF-ß1 level correlated with the increased population of CD4(+)Foxp3(+) Tregs in advanced gastric cancer (r = 0.576, P < 0.05). A significant higher frequency of CD4(+)Foxp3(+) Tregs was observed in PBMCs cultured with the supernatant of MGC than GES-1 (10.6% ± 0.6% vs 8.7% ± 0.7%, P < 0.05). Moreover, using the purified CD4(+)CD25(-) T cells, we confirmed that the increased Tregs were mainly induced from the conversation of CD4(+)CD25(-) naive T cells, and induced Tregs were functional and able to suppress the proliferation of effector T cells. Finally, we demonstrated that gastric cancer cells induced the increased CD4(+)Foxp3(+) Tregs via producing TGF-ß1. Gastric cancer cells upregulated the production of TGF-ß1 and blockade of TGF-ß1 partly abrogated Tregs phenotype. CONCLUSION: Gastric cancer cell can induce Tregs development via producing TGF-ß1, by which the existence of cross-talk between the tumor and immune cells might regulate anti-tumor immune responses.

[The effect of inhalable titanium dioxide on the oxidative stress among occupational population].

OBJECTIVE: To investigate the inhalable titanium dioxide exposure level and make an assessment of its oxidative effect on occupational exposed population. METHODS: A total of 7 workers occupationally exposing to inhalable titanium dioxide were recruited into the study. The basic information and occupational history were collected by interview, while their blood sample (10 ml for each subject) were collected before and after the investigation, respectively. Pre- and post-work shift urine samples (60 ml for each subject) were collected for 29 days consecutively. The daily personal titanium dioxide exposure level, temperature and relative humidity were detected too. Urinary 8-hydroxy-deoxyguanosine (8-OHdG) and serum high-sensitivity C-reactive protein (hs-CRP) were detected by ELISA and latex immunoturbidimetric assay, respectively. RESULTS: The mean concentration of air inhalable titanium dioxide was (1.194 ± 1.015) mg/m(3). Serum hs-CRP level before and after the investigation was (1.13 ± 1.08), (1.33 ± 1.01) mg/L, respectively. No statistical significance was observed between hs-CRP level before and after the investigation (t = -0.848, P = 0.425). Pre- and post-work shift urinary 8-OHdG was (3.51 ± 1.39), (3.65 ± 1.06) µmol/mol Cr, respectively. A positive correlation was found between the concentration of inhalable titanium dioxide and the changes of 8-OHdG level (r = 0.192, t = 2.09, P = 0.039). Linear mixed-effect models, adjusted by work shift, years of employment, age, body mass index, smoking status, temperature and relative humidity, showed no significant exposure-respond trend between the inhalable titanium dioxide concentration and 8-OHdG level (ß = 0.288, t = 1.940, P = 0.055). CONCLUSION: Our findings do not support the potential link between occupationally exposure to inhalable titanium dioxide and high induction of DNA oxidative stress.

[The effects of occupational soluble chromate exposure on immunological function of T-cell].

OBJECTIVE: To investigate the early changes of some immunological function of T-cell in chromate workers. METHODS: A total of 115 workers exposed to different levels of soluble chromate were enrolled in exposed group; while 90 non-exposure workers who lived far away from the chromate plant were enrolled as control. The air concentration of soluble chromate was determined by atomic absorption spectrometry. CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)/CD8(+) of T-cell were determined by flow cytometry analysis. RESULTS: The individual air chromate concentration in the exposed group was (27.51 +/- 33.25) microg/m(3), and the control group was (0.16 +/- 0.15) microg/m(3). The significant difference between the two groups was observed (z = 8.045, P < 0.01). The levels of the lymphocyte subsets (CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)/CD8(+)) in exposed group were (30.08 +/- 17.75)%, (1.04 +/- 1.73)%, (11.94 +/- 9.78)%, 0.10 +/- 0.14. While, those of control group were (63.00 +/- 13.57)%, (30.51 +/- 5.16)%, (14.82 +/- 4.59)%, 2.17 +/- 0.53, higher than that of the exposed group (z values were 4.484, 5.227, 1.976, -5.218, respectively, P < 0.05). CONCLUSION: On the basis of individual air monitoring, the cellular immune function affected by soluble chromate is mainly based on T lymphocyte inhibition. The indicators CD3(+)CD4(+) mentioned above may be considered as efficient biomarkers in further research.