[Research progress on the association of occupational antimony exposure with lung cancer and its carcinogenic mechanism].

Previous epidemiological studies suggested that occupational antimony exposure was associated with an increased risk of lung cancer. The evidence is sufficient for carcinogenicity of trivalent antimony in experimental animals, and strong mechanistic evidence has been observed in human primary cells and experinental systems. Thus, trivalent antimony has been classified as possibly carcinogenic to humans (Group 2A) by International Agency for Research on Cancer (IARC) , and the United States National Toxicology Program (NTP) classified Sb(2)O(3) as a human carcinogen. Antimony and its compounds could induce chromosome breakage and/or DNA damage. Oxidative damage of DNA under oxidative stress and inhibition of DNA damage repair may be the main mechanism of antimony carcinogenesis. This review summarizes the epidemiological investigation of occupational antimony exposure and lung cancer, as well as the experimental research progression on the carcinogenic effects of antimony exposure, and discusses the limitations of previous studies and future research directions.

[Clinical analysis of 31 cases of fetal umbilical artery thrombosis].

Objective: To analyze the ultrasonic manifestations, clinical features, high risk factors and key points of pregnancy management in prenatal diagnosis of umbilical artery thrombosis (UAT). Methods: The data of 31 pregnant women of UAT diagnosed by prenatal ultrasonography and confirmed after birth from July 2017 to July 2022 at the Women's Hospital, Zhejiang University School of Medicine were retrospectively analyzed, including the maternal characteristics, pregnancy outcomes and fetal complications. In addition, the baseline data and pregnancy outcomes were compared in 21 patients who continued pregnancy after diagnosis of UAT. Of the 21 UAT cases that continued pregnancy, 10 cases were treated with low molecular weight heparin (LMWH; LMWH treatment group), while the other 11 patients had expectant treatment(expectant treatment group). Results: The age of the 31 pregnant women was (30.2±4.7) years, of which 5 cases (16%,5/31) were advanced age pregnant women. The gestational age at diagnosis was (32.9±4.0) weeks, and the gestational age at termination of pregnancy was (35.6±2.9) weeks. In 31 fetuses with UAT, 15 cases (48%) had fetal distress, 11 cases (35%) had fetal growth restriction, and 3 cases (10%) had intrauterine stillbirth. There were 28 cases of live births, including 26 cases by cesarean section and 2 cases by vaginal delivery. There were also 3 stillbirths, all delivered vaginally. Four neonates had mild asphyxia and two newborns had severe asphyxia. Among the 31 cases, 10 cases were terminated immediately after diagnosis, the gestational age at diagnosis was (35.9±2.9) weeks. Another 21 pregnancies continued, and their gestational age at diagnosis was (31.4±3.7) weeks. The median prolonged gestational age in LMWH treatment group was 7.9 weeks (4.6-9.4 weeks), and all were live births. The median prolonged gestational age in the expectant treatment group was 0.6 weeks (0.0-1.0 weeks), and 2 cases were stillbirths. There was a statistically significant difference in prolonged gestational age (P=0.002). Conclusions: Ultrasound is the preferred method for prenatal detection of UAT. Clinicians need to be vigilant for UAT when a newly identified single umbilical artery is detected by ultrasound in the second or third trimesters. The decision to continue or terminate the pregnancy depends on the gestational age and the condition of fetus. Attention should be paid to fetal movements as the pregnancy continues. The treatment of LMWH as soon as possible after diagnosis of UAT may improve the pregnancy outcome.

[Establishment of clinical features and prognostic scoring model in early-stage hepatitis B-related acute-on-chronic liver failure].

Objective: To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF). Methods: Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients. Results: Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs(P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion: HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

AK5, a novel prognosis marker, inhibits apoptosis and promotes autophagy as well as proliferation in human gastric cancer.

OBJECTIVE: To explore the relationship between AK5 and gastric cancer. MATERIALS AND METHODS: The in situ levels of AK5 in the GC tissues from 255 patients were detected by immunohistochemistry (IHC). The correlation between AK5 expression and the clinicopathological parameters was analyzed by Pearson correlation, and the prognostic factors were identified by Cox regression analysis. The transcriptome data of 14 human GC cell lines deposited in the CCLE database were analyzed, and two lines were selected for functional studies. AK5 was knocked down in the AZ521 and MKN74 cells using siRNA, and their proliferation and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay and Annexin-V staining, respectively. In addition, the apoptosis and autophagy of the markers were detected by Western blotting. RESULTS: Patients expressing high AK5 levels in the tumor tissues had significantly shorter survival compared to low-expressing group. In addition, AK5 expression was associated with T stage and N stage and was an independent prognostic factor. AK5 knockdown in the AZ521 and MKN74 cells significantly inhibited proliferation and autophagy, and increased apoptosis. CONCLUSIONS: AK5 is a potential prognostic marker and therapeutic target for GC.

Studies on expression of p14ARF and MDM2 in human thyroid neoplasms.

AIM: We sought to evaluate the expression and clinical significance of p14ARF and MDM2 proteins in thyroid neoplasm. METHODS: Immunohistochemical streptavidin-peroxidase (S-P) method was used to detect the expression of p14ARF and MDM2 proteins in 78 cases of papillary thyroid carcinoma (PTC), 34 cases of papillary thyroid microcarcinoma (PTMC) and 45 cases of thyroid adenoma. RESULTS: The expression of p14ARF and MDM2 protein differed significantly (P<0.01) among three group. The positivity rate of p14ARF protein in PTC was significantly lower than that in thyroid adenoma (P=0.002) and PTMC (P=0.008). While the positivity rate of MDM2 protein in PTC was significantly higher than that in thyroid adenoma (P=0.000) and PTMC (P=0.009). There was a significant correlation found between the expressions of p14ARF and MDM2 proteins in PTC (P=0.013) and PTMC (P=0.012). Also, a significant correlation was found between p14ARF protein expression and lymph node metastasis in PTC (P=0.011). CONCLUSION: It was concluded that p14ARF and MDM2 proteins might be involved in the induction and development of PTC and PTMC whereas p14ARF also had diagnostic value in determining the biological behavior of PTC.

Expression features of CXCR5 and its ligand, CXCL13 associated with poor prognosis of advanced colorectal cancer.

OBJECTIVE: CXCL13 plays a unique role in the trafficking and homing of B1 cells associated with its cognate receptor, CXCR5. The CXCR5-CXCL13 axis has been previously demonstrated to be a poor prognosis factor in malignancies. However, the clinical significance of the CXCR5-CXCL13 expression in colorectal cancer carcinoma (CRC) remains unclear. The aim of this study was to investigate the CXCR5-CXCL13 expression in CRC and determine its correlation with the progression and prognosis of the tumor. PATIENTS AND METHODS: A total of 144 paraffin-embedded specimens with advanced colon cancer were assessed for CXCR5 and CXCL13 by immunohistochemistry. Patients' long-term survival was also monitored. There were significant differences in lymph node metastasis (p = 0.0066), neural invasion (p = 0.0061) and neural invasion (p = 0.0001) between high and low expression of CXCR5. RESULTS: There were significant differences in distant metastasis (p = 0.0261), TNM stage (p = 0.0409), differentiation (p < 0.0001) and neural invasion of the CXCL13. Both CXCR5 and CXCL13 was associated with poor correlation with the overall survival (OS) and relapse-free survival (RFS). CONCLUSIONS: Our data suggest that the CXCR5 and CXCL13 may play a crucial role in the development, metastasis and relapse of advanced colon cancer. They can be used as prognostic markers of colon cancer in clinical practice.

Comparative evaluation of the in vitro micronucleus test and the comet assay for the detection of genotoxic effects of X-ray radiation.

The genotoxic effects of X-ray radiation on human lymphocytes were measured using the single cell gel electrophoresis (SCGE) assay (comet assay) and the cytokinesis-blocked micronucleus (CBMN) test; both were carried out in vitro on isolated human lymphocytes in order to compare the relationship and sensitivity of these two detecting methods. The radiation-doses were 0.00, 0.02, 0.05, 0.10, 0.25, 0.50, 1.00 and 2.00 Gy. In the comet assay, the average comet length (38.6+/-0.8 microm) of 0.05 Gy was significantly longer than that (29.4+/-1.1 microm) of 0 Gy (P<0.01), moreover, the average comet length increased with the dose of X-ray radiation. In the CBMN, both the average micronucleus rate (MN) and micronucleated cell rate (MNC) of 0.05 Gy were 11.5+/-4.5 per thousand, which showed no difference with that (7.5+/-0.5 per thousand) of 0 Gy (P>0.05). The lowest dose, which induced significant increase of average MN and MNC, was 0.25 Gy. The average MN and MNC rates increased with radiation-dose. The results showed that there was correlation between SCGE and CBMN, and the sensitivity of SCGE was significantly higher than that of CBMN.

Monitoring of human exposure to radiation with the binucleated lymphocyte micronucleus assay.

The micronuclei (MN) of peripheral blood lymphocytes from radiation-exposed people were monitored with the binucleated lymphocyte micronucleus assay (CBMN). MN rates in people with radiation-disease, radiation exposed and a control group were 12.57/1000, 4.20/1000 and 3.26/1000, respectively. The MN rate of patients with radiation-disease was significantly higher than those of other groups (P < 0.01). The difference between the radiation-exposed group and control group was not significant (P > 0.05). Meanwhile, chromosome aberrations (CA) of 3 groups were determined. The results were similar to those seen while the MN assay. CA rates were 2.06%, 0.93% and 0.69%, respectively. CA rate of the radiation-disease group was significantly higher than that of other groups (P < 0.05, P < 0.01). The difference between the radiation-exposed group and the control group was not significant (P > 0.05). The study indicates that the CBMN assay is a rapid, sensitive and accurate method which can be used to monitor a large population exposed to radiation.

Antitumor components from an actinomycete strain 6011W.

Three bioactive compounds that inhibited nucleoside transport were isolated from the cultured broth of Streptoverticillium sp. 6011W. The structures of those compounds were characterized as cinnamamide, N-(tetrahydro-2-oxo-3-thienyl)-acetamide and benzamide, respectively. They all inhibited radiolabeled thymidine transport into Ehrlich carcinoma cells, with IC50 values of 30.4, 97.2 and 85.4 microM, respectively. When administered i.p., cinnamamide not only inhibited the growth of transplanted tumors but also reduced the number of lung metastases in mice bearing Lewis lung carcinoma. The results suggest that nucleoside transport inhibition assay is a valuable model to search for antitumor agents of natural origin.

Detection of cytogenetic effects in peripheral lymphocytes of students exposed to formaldehyde with cytokinesis-blocked micronucleus assay.

Cytokinesis-blocked micronucleus assay was applied as a biological dosimeter to detect abnormalities in human peripheral lymphocytes of thirteen students exposed to formaldehyde (FA) during a 12-week (10 h per week) anatomy class. Breathing-zone air samples collected during dissection procedures showed a mean concentration of 2.37 ppm (3.17 mg/m3). Ten students from the same school but without FA exposure served as controls. Chromosome aberrations (CA) and sister chromatid exchanges (SCE) were detected in both groups. The micronuclei (MN) rate (6.38 +/- 2.50 /1000) and CA rate (5.92 +/- 2.40%) in the FA-exposed group showed a significant increase (P < 0.01) when compared with those of the controls (3.15 +/- 1.46 /1000 and 3.40 +/- 1.57% respectively). A correlation between MN and CA in individuals was observed. SCE in the exposed group were also increased (P < 0.05), but not so greatly as MN or CA. The results indicated that FA might damage the chromosomes of human lymphocytes.