Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

One patient with kidney stones was prescribed Paishi granules and diclofenac sodium sustained-release tablets for pain relief in the outpatient setting.That evening,the patient took 1 sachet of Paishi granules and 1 diclofenac sodium sustained-release tablet together.The patient subsequently developed a generalized rash with itching.Liver function indexes of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(T-BiL),direct bilirubin(D-BiL),and alkaline phosphatase(ALP)were all 2 to 6 times higher than the upper limit of normal.After symptomatico treatment,the patients systemic rash had subsided,and the liver function indicators have returned to normal.

Objectives:To analyze whether there is a causal relationship between plasma proteins and the risk of coronary atherosclerosis(CAS)based on a two-sample Mendelian randomization(MR)analysis and to identify potential therapeutic targets for CAS.Methods:Single nucleotide polymorphisms(SNP)associated with plasma proteins from the UK Biobank Pharmacoproteomics Program(UKB-PPP)database were used as instrumental variables and outcome data were obtained from genome-wide association study databases.The Wald ratio method and inverse variance weighted(IVW)method in two-sample MR were employed as the primary approaches to assess the causal relationship between plasma proteins and CAS.Colocalization analysis was conducted as a sensitivity analysis to ensure the robustness of the MR findings.Results:A total of 132 plasma proteins were found to have causal associations with an increased risk of CAS.Colocalization analysis revealed that 12 plasma proteins shared genetic variants with CAS.Among them,Proprotein convertase subtilise/kexin type 9(PCSK9)(OR=1.23,95%CI:1.15-1.32,P<0.01)and neurocan(NCAN)(OR=1.35,95%CI:1.21-1.52,P<0.01)exhibited posterior probability of hypothesis4(PPH4)values<0.80 in the colocalization analysis,indicating strong support for colocalization and suggesting their potential as primary plasma protein drug targets for CAS.Conclusions:PCSK9 is associated with an increased risk of CAS and is confirmed as a therapeutic target for CAS.NCAN emerges as another potential therapeutic target for CAS.

Objective To explore the value of 3D and 2D radiomics features models based on multiparameter MRI in predicting Ki-67 expression(with 14%and 20%as the critical values,respectively)in breast cancer.Methods The MRI images of 147 patients with pathologically confirmed Luminal breast cancer were analyzed retrospectively.The patients were randomly divided into training set and test set according to the ratio of 7︰3.The 3D and 2D radiomics features of intratumor and peritumor were extracted from diffusion weighted imaging(DWI),dynamic contrast enhancement(DCE)mask(S0)and DCE phase 3(S3)images.Then the models were constructed by multiple pipeline combinations of three feature normalization methods,two feature dimensionality reduction methods,four feature selection methods,and ten classifiers.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to evaluate the prediction performance of the models in order to select the best 3D and 2D single parame-ter(DWI,S0,S3)and multiparameter combination(S0+S3,S0+DWI,S3+DWI,S0+S3+DWI)models.Finally,the differ-ences between the models were compared by De Long test.Results With 14%as the critical value,the AUC of 3D and 2D models in the training set were 0.726-0.824 and 0.707-0.835,respectively,and those in the test set were 0.724-0.82 and 0.701-0.805.With 20%as the critical value,the AUC of 3D and 2D models in the training set were 0.743-0.868 and 0.793-0.881,respectively,and those in the test set were 0.738-0.853 and 0.743-0.814.There was no significant statistical difference between 3D and 2D models with the same parameter in the two critical values standards.Conclusion The multiparameter MRI-based radiomics models can bet-ter predict the expression of Ki-67 in breast cancer,and the models based on intratumor and peritumor 3D and 2D features have the same prediction efficiency.

Objective:To develop a deep learning-based segmentation model for anterior segment ultrasound biomicroscopy (UBM) images to automatically segment the anterior segment tissues of patients with primary angle-closure glaucoma (PACG).Methods:A single-center retrospective case series was conducted.A small-scale dataset comprised 468 UBM images of the anterior chamber angle closure from 156 patients with PACG who underwent the UBM examination at Tianjin Medical University Eye Hospital between July 12, 2022, and February 20, 2023.The UBM images were randomly split into a training dataset of 228 images and a testing dataset of 152 images using a random seed method in a ratio of 6∶4.The models were trained using the PSPNet model with MobileNet V2 and ResNet50 as backbones, the DeepLab v3+ model with MobileNet V2 and Xception as backbones, and the SegFormer model with MiT-B0 and MiT-B2 as backbones.The testing dataset was used for result prediction and to achieve segmentation of four regions: the cornea and sclera, iris, ciliary body, and anterior lens surface.To evaluate the performance of the models in segmenting the anterior segment structures, multiple metrics were assessed, including the mean intersection over union (mIoU), Dice coefficient, precision, recall, false negative rate, and specificity.A comparative analysis of the test results across the different models was subsequently performed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2023KY-05).Results:The two models with the best segmentation performance were PSPNet and DeepLab v3+ .The PSPNet model with ResNet50 as the backbone achieved the mIoU of 85.11%, Dice coefficient of 91.38%, precision of 91.83%, recall of 90.94%, false negative rate of 9.06%, and specificity of 98.89%.The DeepLab v3+ model with MobileNet V2 as the backbone achieved an mIoU of 85.84%, Dice coefficient of 92.01%, precision of 92.67%, recall of 91.36%, false negative rate of 8.64%, and specificity of 98.90%.Among the five key metrics, mIoU, Dice coefficient, recall, false negative rate, and specificity, DeepLab v3+ exhibited the best segmentation performance.In addition, the DeepLab v3+ model with Xception as the backbone had the highest precision among all models, reaching 92.77%.Conclusions:The deep learning-based DeepLab v3+ model achieves precise segmentation of anterior segment tissue structures in PACG anterior segment UBM image segmentation, providing auxiliary support for clinical diagnosis.

Objective:To develop a deep learning-based segmentation model for anterior segment ultrasound biomicroscopy (UBM) images to automatically segment the anterior segment tissues of patients with primary angle-closure glaucoma (PACG).Methods:A single-center retrospective case series was conducted.A small-scale dataset comprised 468 UBM images of the anterior chamber angle closure from 156 patients with PACG who underwent the UBM examination at Tianjin Medical University Eye Hospital between July 12, 2022, and February 20, 2023.The UBM images were randomly split into a training dataset of 228 images and a testing dataset of 152 images using a random seed method in a ratio of 6∶4.The models were trained using the PSPNet model with MobileNet V2 and ResNet50 as backbones, the DeepLab v3+ model with MobileNet V2 and Xception as backbones, and the SegFormer model with MiT-B0 and MiT-B2 as backbones.The testing dataset was used for result prediction and to achieve segmentation of four regions: the cornea and sclera, iris, ciliary body, and anterior lens surface.To evaluate the performance of the models in segmenting the anterior segment structures, multiple metrics were assessed, including the mean intersection over union (mIoU), Dice coefficient, precision, recall, false negative rate, and specificity.A comparative analysis of the test results across the different models was subsequently performed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2023KY-05).Results:The two models with the best segmentation performance were PSPNet and DeepLab v3+ .The PSPNet model with ResNet50 as the backbone achieved the mIoU of 85.11%, Dice coefficient of 91.38%, precision of 91.83%, recall of 90.94%, false negative rate of 9.06%, and specificity of 98.89%.The DeepLab v3+ model with MobileNet V2 as the backbone achieved an mIoU of 85.84%, Dice coefficient of 92.01%, precision of 92.67%, recall of 91.36%, false negative rate of 8.64%, and specificity of 98.90%.Among the five key metrics, mIoU, Dice coefficient, recall, false negative rate, and specificity, DeepLab v3+ exhibited the best segmentation performance.In addition, the DeepLab v3+ model with Xception as the backbone had the highest precision among all models, reaching 92.77%.Conclusions:The deep learning-based DeepLab v3+ model achieves precise segmentation of anterior segment tissue structures in PACG anterior segment UBM image segmentation, providing auxiliary support for clinical diagnosis.

Objectives:To analyze whether there is a causal relationship between plasma proteins and the risk of coronary atherosclerosis(CAS)based on a two-sample Mendelian randomization(MR)analysis and to identify potential therapeutic targets for CAS.Methods:Single nucleotide polymorphisms(SNP)associated with plasma proteins from the UK Biobank Pharmacoproteomics Program(UKB-PPP)database were used as instrumental variables and outcome data were obtained from genome-wide association study databases.The Wald ratio method and inverse variance weighted(IVW)method in two-sample MR were employed as the primary approaches to assess the causal relationship between plasma proteins and CAS.Colocalization analysis was conducted as a sensitivity analysis to ensure the robustness of the MR findings.Results:A total of 132 plasma proteins were found to have causal associations with an increased risk of CAS.Colocalization analysis revealed that 12 plasma proteins shared genetic variants with CAS.Among them,Proprotein convertase subtilise/kexin type 9(PCSK9)(OR=1.23,95%CI:1.15-1.32,P<0.01)and neurocan(NCAN)(OR=1.35,95%CI:1.21-1.52,P<0.01)exhibited posterior probability of hypothesis4(PPH4)values<0.80 in the colocalization analysis,indicating strong support for colocalization and suggesting their potential as primary plasma protein drug targets for CAS.Conclusions:PCSK9 is associated with an increased risk of CAS and is confirmed as a therapeutic target for CAS.NCAN emerges as another potential therapeutic target for CAS.

ObjectiveTo understand the infection characteristics of multidrug-resistant organisms (MDROs) in hospitalized patients in a tertiary sentinel hospital in Shanghai, so as to provide an evidence for the development of targeted prevention and control measures. MethodsData of MDROs strains and corresponding medical records of some hospitalized patients in a hospital in Shanghai from 2021 to 2023 were collected, together with an analysis of the basic information, clinical treatment, underlying diseases and sources of sample collection. ResultsA total of 134 strains of MDROs isolated from hospitalized patients in this hospital were collected from 2021 to 2023 , including 63 strains of methicillin-resistant Staphylococcus aureus (MRSA), 57 strains of carbapenem-resistant Acinetobacter baumannii (CRAB), and 14 strains of carbapenem-resistant Klebsiella pneumoniae (CRKP). Of the 134 strains, 30 strains were found in 2021, 47 strains in 2022 and 57 strains in 2023. The male-to-female ratio of patients was 2.05∶1, with the highest percentage (70.90%) in the age group of 60‒<90 years. The primary diagnosis was mainly respiratory disease, with lung and respiratory tract as the cheif infection sites. There was no statistically significant difference in the distribution of strains between different genders and infection sites (P>0.05). However, the differences in the distribution of strains between different ages and primary diagnosis were statistically significant (P<0.05). Patients who were admitted to the intensive care unit (ICU), had urinary tract intubation, were not artery or vein intubated, were not on a ventilator, were not using immunosuppresants or hormones, and were not applying radiotherapy or chemotherapy were in the majority. There was no statistically significant difference in the distribution of strains for whether received radiotherapy or chemotherapy or not (P>0.05), while the differences in the distribution of strains with ICU admission history, urinary tract intubation, artery or vein intubation, ventilator use, and immunosuppresants or hormones use or not were statistically significant (all P<0.05). The type of specimen was mainly sputum, the hospitalized ward was mainly comprehensive ICU, the sampling time was mainly in the first quarter throughout the year, the number of underlying diseases was mainly between 1 to 2 kinds, the application of antibiotics ≥4 kinds, and those who didn’t receive any surgery recently accounted for the most. There were statistically significant differences in the distribution of strains between different specimen types, wards occupied and history of ICU stay (P<0.05), but no statistically significant difference in the distribution of strains between different sampling times, number of underlying diseases and types of antibiotics applied (P>0.05). ConclusionThe situation of prevention and control on MDROs in this hospital is still serious. Focus should be placed on high-risk factors’ and infection monitoring and preventive measures should be strengthened to reduce the incidence rate of MDROs infection.

To analyze the current status and epidemiological trends of the disease burden of gastric cancer among adolescents and young adults in China, so as to provide a basis for formulating public health policies and reducing the disease burden.