OBJECTIVE：To investigate neurotoxic effects of chronic cobalt exposure on human cerebral organoids and to provide experimental evidence for assessing potential health risks of heavy metal cobalt. METHODS：Human iPSC-derived cerebral organoids at day 28 of differentiation were randomly divided into the control group， 5， 10， and 20 μmol/L CoCl₂ exposure groups， with continuous exposure for 28 days. Samples of human cerebral organoids were collected on day 56. Immunofluorescence staining was used to systematically characterize the differentiation status (SOX2/TBR2/CTIP2/TUJ1/NeuN/SYN1)，expression of hypoxia-inducible factor-1α，cellular hypoxia status (Hypoxyprobe)，proliferation and apoptosis levels (Ki-67/TUNEL)， and astrocyte damage (GFAP) of human cerebral organoids.RESULTS： Day56 organoids maintained high proliferative activity. Neural progenitor cells self-organized into ventricular zone-like structures， forming physiological lamellar architectures with intermediate progenitors and deep-layer cortical neurons. Chronic cobalt exposure significantly upregulated HIF-1α protein expression (P<0.01) and increased hypoxic cells versus controls. TUNEL-positive apoptotic cells showed dose-dependent elevation (P<0.01)，predominantly localized in intermediate progenitor/neuron interface regions. Bright-field monitoring revealed progressive disintegration of ventricular zone structures in medium/high-dose groups. GFAP fluorescence intensity was markedly attenuated in exposure groups， indicating astrocyte impairment. CONCLUSION： Chronic cobalt exposure stabilizes HIF-1α to induce pseudohypoxia， leading to three neurotoxic outcomes： increased neuronal apoptosis，ventricular zone collapse，and astrocyte damage.

OBJECTIVE： To investigate subacute effects of polystyrene microplastics (PS-MPs) on the structure and function of adipose tissue in mice. METHODS：Healthy 6-week-old SPF-grade C57BL/6 mice were randomly divided into a control group (normal saline)，an 80 nm PS-MPs group，and a 5 μm PS-MPs group，with 16 mice in each group，half male and half female. The PS-MPs group was orally exposed to 100 mg/kg of PS-MPs continuously for 7 days. Peripheral blood，inguinal fat，perigordal fat，and brown fat of the neck and shoulder were collected，and lipid levels and fat weight were measured. Adipose tissue structure was observed after HE staining，and expression levels of adipocytokines and genes related to lipid metabolism were measured. RESULTS：Compared with the control group，the 80 nm PS-MPs group showed an increase in the number of peripheral blood leukocytes， neutrophils， and lymphocytes in female mice (P <0.05 or P <0.01)，while only the number of leukocytes increased in male mice (P <0.05). Regarding blood lipids， the 80 nm PS-MPs group showed an increase in triglycerides and low-density lipoprotein (LDL) in female mice (both p < 0.05)，while only the triglyceride level increased in male mice (P <0.05). The 80 nm PS-MPs group showed a decrease in subcutaneous fat，an increase in visceral fat，and an increase in white adipocyte area in female mice (all P <0.05). Visceral fat increased by 76.0% in male mice (P <0.05). Serum leptin， adiponectin， and insulin levels increased in female mice (all P <0.05)， while only leptin increased in male mice (P <0.05). Correspondingly，expression of lipid synthesis genes in white fat of female mice was enhanced while expression of oxidative utilization and decomposition genes was inhibited，and the effect was stronger in the female and 80 nm PS-MPs groups. CONCLUSION：Subacute exposure to PS-MPs led to disordered lipid metabolism and white adipose tissue redistribution in mice. The underlying mechanisms involved promotion of lipid synthesis and inhibition of lipid breakdown and utilization， with effects demonstrating sex-specific and size-dependent characteristics. These findings provide evidence supporting the association between MPs exposure and metabolic disorders.

OBJECTIVE：This study was aimed to explore the genotoxicity of methylmalonic acid (MMA) based on in vitro and in vivo micronuclei assays， and potential factors influencing its genotoxicity. METHODS：For in vitro studies，human umbilical venous endothelial cells (HUVEC) were treated with 0， 0.1，0.5，1，5，and 10 mmol/L MMA at different times (7 d or 72 h)，and frequencies of micronuclei (MN)， nucleoplasmic bridge (NPB) and nuclear bud (NB) and genomic instability (GIN) were assessed using by the cytokinesis-blocked micronucleus assay (CBMN). In addition， the CBMN assay was employed to detect the impact of mitomycin C，homocysteine (Hcy) and folic acid on the genotoxicity of MMA in HUVEC cells. For in vivo studies，the genotoxicity of MMA was verified by the bone marrow micronucleus assay in CF-1 mice. RESULTS： Compared with control and groups of low-concentration MMA (0.1-5 mmol/L)，10 mmol/L MMA significantly increased rate of MN，NPB，and GIN in HUVEC (all P <0.01)，and the genotoxicity was derived from the intrinsic toxicity and acidic nature of MMA. When HUVEC were treated with 10 mmol/L MMA and 0.1 μg/mL mitomycin C together，rate of MN，NB and GIN were significantly elevated as compared to these of separately treated groups (P <0.05 and P <0.01). Furthermore，10 mmol/L MMA significantly reduced rate of MN and GIN induced by 100 μmol/L Hcy (P <0.05 and P <0.01). Compared with control，short-term (72 h) folic acid deficiency had no significant effect on genotoxicity of MMA， but supplementation of folic acid (45.4-90.7 μmol/L) significantly reduced rate of MN，NPB and GIN induced by 10 mmol/L MMA (P <0.05 and P <0.01). In CF-1 mice， high doses of MMA (200-400 mg/kg) exhibited significant acid-independent genotoxicity (MN rate) when compared with control (P <0.01). CONCLUSION：MMA showed intrinsic and acidmediated genotoxicity. Synergistic genotoxicity of MMA and mitomycin C was detected. Genotoxicity of MMA was mitigated by folic acid， and MMA ameliorated the genotoxicity of Hcy. This study provides new information for better understanding the genotoxicity of MMA and its intervention.

OBJECTIVE：To investigate the significance of systemic immunoinflammatory index (SII) in the clinical diagnosis and progression monitoring of patients with non-small cell lung cancer (NSCLC). METHODS： A total of 60 patients with NSCLC admitted to the Fourth Hospital of Hebei Medical University from December 2020 to February 2024 were selected as the NSCLC group，and the clinical data and hematological indexes of the patients at the time of initial diagnosis were collected. In addition， 20 patients with benign pulmonary nodules without malignant lesions and 30 healthy subjects without benign and malignant tumors were selected as the benign pulmonary nodules group and control group，respectively. Differences in indicators among the three groups were compared，and the expression levels of indicators in benign pulmonary nodules and different TNM stages were analyzed. ROC was used to evaluate the value of inflammatory indicators such as SII and carcinoembryonic antigen (CEA) in the differential diagnosis and prediction on progression of NSCLC. Their correlations with clinical pathological indicators of NSCLC patients. RESULTS：The levels of SII， ratio of neutrophil to lymphocyte (NLR)， ratio of platelet to lymphocyte(PLR)， CEA， neutrophil count (NE) and lymphocyte count (LY) in NSCLC group were significantly higher than those in control group (P <0.05)，and the median values of SII，NLR and NE were significantly higher than those in benign pulmonary nodule group. SII combined with CEA and SII， NLR， PLR， and CEA in combination had the highest clinical value for distinguishing NSCLC from benign disease group and had a higher predictive value for clinical progression of NSCLC than single index detection. The T stage，M stage，and TNM stage were significantly higher in the high SII group and high NLR group compared with the low-SII and low-NLR group (P <0.05)，respectively. Compared with the low PLR group， the T stage was significantly higher in the high PLR group， with a statistical difference (P <0.05). Compared with the low CEA group， the N stage， M stage， and TNM stage were significantly higher in high CEA group，with statistically significant differences (P <0.05). CONCLUSION：Our data shows that SII was related to clinically assisted diagnosis and progression monitoring of NSCLC. The combination of SII and other inflammatory indicators demonstrated higher efficacy in clinically assisted diagnosis and prediction of progression of NSCLC than CEA alone，with higher clinical application value.

OBJECTIVE：This study aimed to explore relationships between CDP-diacylglycerol synthase 1 (CDS1) and various cancers through bioinformatics analysis， and to further validate expression and prognostic value of CDS1 in breast cancer viain vitro experiments. METHODS：Using RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)，expression patterns and prognostic value of CDS1 in various cancer types were systematically analyzed. Relationships between CDS1 expression and immune subtypes were further investigated. Functional enrichment analysis of differentially expressed genes in breast cancer was performed，and a gene co-expression network was constructed. Immunohistochemistry (IHC) was used to detect differences in CDS1 protein expression levels between normal and cancerous tissues in breast cancer patients (BRCA). Lastly， a survival prediction nomogram model incorporating CDS1 expression was constructed and validated. RESULTS： Compared with adjacent non-tumorous tissues， CDS1 exhibited significantly higher expression in multiple cancer tissues (P <0.05). Importantly，breast cancer patients with high CDS1 expression demonstrated a significantly shorter recurrence-free survival (P <0.01). Furthermore， CDS1 expression differed significantly across breast cancer immune-histochemical subtypes (P <0.01). Functional enrichment analysis suggested that CDS1 was involved in the lipid metabolism regulatory pathway and the PI3K-Akt signaling pathway. Correlation analysis revealed significant associations between CDS1 expression and expression of PIK3CA (r=0.415， P <0.01) and ERBB2 (r=0.361， P <0.01). IHC results confirmed that CDS1 expression was significantly elevated in breast cancer tissues compared to adjacent tissues (P <0.01)， and correlated with shorter overall survival in patients with high expression (P <0.05). Additionally， HER-2 expression showed significant variations among breast cancer patients with different CDS1 expression levels (χ²= 6.176， p=0.013). The constructed nomogram exhibited good predictive performance for survival (concordance index=0.746， p=0.018). CONCLUSION： CDS1 was highly expressed in breast cancer and was significantly correlated with HER-2 expression， making it a valuable prognostic biomarker. Its potential role in lipid metabolism and the PI3K-Akt signaling pathway suggests that CDS1 contributed to breast cancer progression. The constructed nomogram model incorporating CDS1 expression provides an effective tool for survival prediction in breast cancer patients.

OBJECTIVE： To evaluate inhibitory effects of photodynamic therapy (PDT) on the cervical cancer cell lines，HeLa，with different Ki-67 expression levels. METHODS：HeLa cells with different Ki-67 expression levels were constructed by RNA interference technology： Blank control group， Negative control group (treated with negative control siRNA) and Ki-67 knockdown group (treated with Ki-67 siRNA). Western blot was used to detect Ki-67 protein expression to verify the knockdown effect. CCK8 assay and wound healing assay were used to assess cell proliferation rate and wound healing rate in each group. PDT treatment was performed on each group of cells (the cells in each group were incubated with 5-ALA photosensitizer at a concentration of 3 mmol/L for 6 hours under the conditions of laser wavelength 630 nm，energy 15 J/cm² ， and maximum output power 2 W). Morphological changes were observed post-PDT，and cell proliferation rate and wound healing rate were re-evaluated. RESULTS：Western blot analysis showed that the grayscale of the Ki-67 protein expression band in the Ki-67 knockdown group was weaker than that in the two control groups (P <0.05). CCK-8 assay results showed that the D(450) of the Ki-67 knockdown group was lower than that of the blank control group at each time point from day 1 to day 5 (P <0.05). The scratch test showed that the migration rate of the Ki-67 knockdown group was lower than that of the blank control group (P <0.05). After PDT treatment， the proliferation activity of the cells in the blank control group and the Ki-67 knockdown group was significantly decreased. On days 4 and 5，the proliferation inhibition rate of the cells in the Ki-67 knockdown group was higher than that in the blank control group (P <0.05). At 24 h after PDT treatment，the scratch test results showed that the migration rate of the cells in the blank control group and the Ki-67 knockdown group was decreased，and the decrease in the blank control group was more significant (P <0.05). After PDT treatment，morphological observations under a microscope showed that the cell morphology underwent changes similar to cell pyroptosis，including a decrease in cell volume，movement of the cell nucleus to the edge，and a large vesicle bulging out from the other side of the cell. CONCLUSION：PDT had an inhibitory effect on the proliferation and migration of cervical cancer HeLa cells，and its inhibitory effect on cells with high expression of Ki-67 was stronger. After PDT，cell morphology showed changes like those of pyroptosis.

OBJECTIVE：To investigate diagnostic and prognostic values of multi-biomarker detection in patients with early renal damage due to multiple myeloma (MM). METHODS：From November 2018 to May 2023，newly diagnosed MM patients admitted to the Department of Hematology of the Fourth hospital of Hebei Medical University were recruited as study subjects. According to the blood creatinine (SCr) detection level， the patients were divided into two MM groups with or without kidney injury，and the clinicopathological data， blood routine， coagulation function， biochemistry and other related laboratory detection indicators were collected. In addition， 30 healthy volunteers without benign or malignant tumors nor cardiovascular diseases were selected as the control group. The ROC curve was drawn to evaluate the predictive value of neutrophil-to-lymphocyte ratio (NLR)， monocyte-to-lymphocyte ratio (MLR)， systemic inflammation response index (SIRI) and fibrinogen-to-albumin ratio (FAR) in the occurrence of kidney injury in MM patients，and the correlation with tumor stage and tumor load of MM patients was analyzed. RESULTS： From our recruitment， 95 patients and 30 controls were selected. The levels of NLR， MLR， SIRI and FAR in MM patients with kidney injury were significantly higher than those in control group and MM patients without kidney injury group (P<0.05). ROC curves showed that NLR，MLR，SIRI and FAR had predictive value in MM patients with kidney injury (P<0.05). Combined detection using the four biomarkers showed higher diagnostic values for the MM patients with kidney injury. Logistic regression analysis showed that the level of NLR， MLR， SIRI and FAR were closely related to the occurrence of kidney injury in MM patients. High NLR was an independent risk factor for kidney injury in MM patients. Chi-square test results showed that MLR was closely correlated with ISS stage in MM patients (P<0.05). CONCLUSION：NLR，MLR，SIRI and FAR showed value in the diagnosis of kidney injury in MM patients. Combined diagnosis improved the diagnostic efficiency，and provided a basis for the application of inflammatory markers in the clinical diagnosis and treatment of MM patients with kidney injury.

OBJECTIVE：The aims of this paper were to analyze the incidence and mortality trends of colorectal cancer in China from 1990 to 2021，to explore the impact of age，period and cohort effects，to predict the future trend of colorectal cancer from 2022 to 2045， and to provide data support for control strategies and resource allocation. METHODS： Based on the Global Burden of Disease (GBD) database， Joinpoint regression analysis was used to evaluate the trend of changes in different time periods. The age-period-cohort model was used to analyze the age effect，period effect and cohort effect of the incidence and mortality of colorectal cancer in China from 1992 to 2021. Through Nordpred prediction model，combined with gender differences， the standardized morbidity and mortality of colorectal cancer in 2022—2045 were predicted. RESULTS：From 1990 to 2021，the standardized incidence of colorectal cancer in China continued to rise，with an average annual percentage change (APC) of 1.64% [95%CI (1.38%，1.89%)，P<0.01]. The increase was particularly significant in men. The standardized mortality rate showed an overall downward trend， with an APC of -0.41% [95%CI (-0.58%，-0.24%)，P<0.01]，but rebounded between 2014 and 2021. The incidence and mortality of colorectal cancer were affected by the complex interweaving of age， period and cohort effects. The age effect shows that the elderly group was a high-risk group. The period effect and cohort effect show that the risk of disease decreased year by year，while the risk of death increased. The gender difference was significant，and the morbidity and mortality of males were higher than those of females. The prediction results show that the standardized incidence of colorectal cancer in China will continue to rise in the future. CONCLUSION： From 1990 to 2021， the incidence of colorectal cancer in China showed a continuous increase，whereas the mortality rate declined overall but rebounded in recent years. Age，period， and cohort effects significantly contributed to the disease burden， with older adults and males as high-risk populations. Projections suggest that the incidence of colorectal cancer will continue to rise in the coming decades，indicating a persistent public health challenge. Strengthening early screening，timely diagnosis，and standardized treatment， along with optimizing resource allocation， particularly for male and elderly high-risk groups，will be essential to reduce the future burden of colorectal cancer.

OBJECTIVE： To investigate effects of whole blood inoculation and culture systems on formation of nucleoplasmic bridges (NPB) and on formation of radiation-induced NPB，for providing scientific basis for radiation biological dosimeters. METHODS：Human venous blood and fingertip blood were cultured as follows：400，300，200，100 and 50 μL of venous blood were inoculated into 1 or 2 mL medium，100 μL of fingertip blood were inoculated into 1 mL medium. These cultures were irradiated with 0 Gy (control group) and 2 Gy ⁶⁰Co γ radiation at a dose rate of 1.0 Gy/min. NPB specimens were prepared by cytokinesis-block method. The proportion of mononucleated，binucleated and multinucleated cells，as well as the NPB and micronucleus (MN) frequencies of each group were analyzed. RESULTS：In the 0 Gy group， 1 048~9 768 binucleated cells were analyzed in different blood inoculation groups. The NPB frequency did not change significantly with the whole blood inoculation (P>0.05). The MN frequency in the 50 μL group was higher than that in the other three groups (U=3.61，P<0.01). In the 2 Gy group，there was no cell available for analysis in the 50 μL group，and 1 569-4 400 binucleated cells were analyzed in other blood inoculation groups. The NPB frequency was 0.009-0.013 cells/cell，and the MN frequency was 0.317-0.337 cells/cell，and there was no significant difference with the whole blood inoculum (P > 0.05). The NPB and MN frequencies of the 2 Gy group were significantly higher than those of the 0 Gy group (U=4.24-34.48， P<0.05). Fingertip blood culture failed to observe cells for analysis. CONCLUSION： The minimum 50 μL and 100 μL peripheral blood culture combined with 1 mL culture medium can be used to study the background level of the nucleoplasmic bridge and the radiation-induced nucleoplasmic bridge level respectively. The feasibility of fingertip blood culture for nucleoplasmic bridge analysis still needs further study.

OBJECTIVE：To investigate mechanisms of RNA-binding motif protein X-linked(RBMX) on biological behavior of esophageal cancer cells in vitro. METHODS：Logarithmic Eca109 cells in culture were divided into control and experimental groups. Lipofectamine^TM 3000 was used to transfect small interfering RNA (siRNA) and overexpression vector of RBMX. The mRNA and protein expression levels of RBMX were detected by RT-qPCR and Western blot，respectively. CCK-8，Transwell and Western blot were used to detect changes of cell proliferation， migration and EMT marker protein expression after transfection. RESULTS： Following transfection with RBMX siRNA， the mRNA and protein expression levels of RBMX in Eca109 cells were markedly reduced compared to the control group (P<0.05). Conversely， transfection with the overexpression vector resulted in a significant increase in RBMX mRNA and protein expression levels (P<0.05). After 24 hours of siRNA transfection，proliferation and migration of Eca109 cells were significantly inhibited (P<0.05)， accompanied by an increase in E-cadherin protein expression and a decrease in N-cadherin and Vimentin protein expression (P<0.05). In contrast，48 hours post-transfection with the overexpression vector，proliferative and migratory capabilities of Eca109 cells were notably enhanced (P<0.05)，with decreased E-cadherin protein expression and increased N-cadherin and Vimentin protein expression (P<0.05). CONCLUSION： RBMX influenced the proliferation and migration of Eca109 cells in vitro，potentially contributing to esophageal cancer development through its impact on the epithelial-mesenchymal transition process.