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.

Objective To assess stromal fibrosis in epidermal growth factor receptor(EGFR)mutant lung adenocarcinoma and its association with resistance to targeted therapy and patient prognosis.Methods Medical records of 207 patients diagnosed with EGFR-mutant advanced lung adenocarcinoma who received treatment at a hospital between January 2021 and December 2022 were reviewed.A total of 86 patients were ultimately included based on their prognosis and survival duration.These patients were categorized into a resistance group(32 cases)and a non-resistance group(54 cases),depending on whether they developed resistance to targeted therapy within one year.Additionally,patients were classified into mild,moderate,and severe fibrosis groups according to the extent of fibrosis observed.Clinical and pathological characteristics,as well as fibrosis levels,were compared between the two groups.Factors influencing the development of resistance to targeted therapy in patients with EGFR-mutant lung adenocarcinoma were analyzed,and the survival outcomes of patients with varying degrees of fibrosis were evaluated during follow-up.Results In the resistance group,the prevalence of EGFR exon 20 insertion mutations,elevated CA125 levels,and the presence of moderate-to-severe fibrosis were significantly higher compared to the non-resistance group(P<0.05).Multivariate logistic regression analysis revealed that EGFR exon 20 inser-tion mutation(OR=3.691,95%CI:1.043～13.057),elevated CA125 levels(OR=4.104,95%CI:1.160～14.517),and moderate-to-severe fibrosis(OR=3.959,95%CI:1.410～11.115)were independent risk factors associated with resistance to targeted therapy among patients with EGFR-mutant lung adenocarcinoma(P<0.05).The Cox proportional hazards model demonstrated a C-index of 0.72(95%CI:0.65～0.79),with area under the curve(AUC)values for 1-year and 2-year survival predictions of 0.781 and 0.734,respectively.EGFR exon 20 insertion mutation(HR=3.691),moderate-to-severe fibrosis(HR=3.959),and elevated CA125 levels(HR=4.104)were identified as independent prognostic factors for overall survival in these patients following targeted therapy.The median progression-free survival(PFS)for patients with mild,moderate,and severe fibrosis was 10.5 months,7.2 months,and 3.9 months,respectively,while the median overall survival(OS)was 21.4 months,16.1 months,and 11.5 months,respectively.Statistically significant differences in both PFS and OS were observed across the three fibrosis severity groups.(P<0.05).Conclusion The extent of stromal fibrosis in EGFR-mutant lung adenocarcinoma influences resistance to targeted therapy,and the progression of fibrosis is correlated with an unfavorable prognosis.

Lung cancer is one of the malignant tumours with the highest morbidity and mortality rates worldwide today, posing a major threat to human health. Accurate diagnosis and standardised treatment play a crucial role in improving the survival rate of lung cancer patients. In recent years, the rapid rise of artificial intelligence (AI) has brought about significant changes in the medical field, providing a new diagnostic and treatment model for lung cancer, and making a series of breakthroughs in lung cancer diagnostic imaging, pathological diagnosis, surgical oncology, radiotherapy, and drug development and treatment. This article introduces the current status of AI application in the field of lung cancer diagnosis and treatment, and extensively discusses the current challenges and future prospects, hoping to provide references and suggestions for future clinical practice.

Lung cancer is one of the malignant tumours with the highest morbidity and mortality rates worldwide today, posing a major threat to human health. Accurate diagnosis and standardised treatment play a crucial role in improving the survival rate of lung cancer patients. In recent years, the rapid rise of artificial intelligence (AI) has brought about significant changes in the medical field, providing a new diagnostic and treatment model for lung cancer, and making a series of breakthroughs in lung cancer diagnostic imaging, pathological diagnosis, surgical oncology, radiotherapy, and drug development and treatment. This article introduces the current status of AI application in the field of lung cancer diagnosis and treatment, and extensively discusses the current challenges and future prospects, hoping to provide references and suggestions for future clinical practice.

Objective To assess stromal fibrosis in epidermal growth factor receptor(EGFR)mutant lung adenocarcinoma and its association with resistance to targeted therapy and patient prognosis.Methods Medical records of 207 patients diagnosed with EGFR-mutant advanced lung adenocarcinoma who received treatment at a hospital between January 2021 and December 2022 were reviewed.A total of 86 patients were ultimately included based on their prognosis and survival duration.These patients were categorized into a resistance group(32 cases)and a non-resistance group(54 cases),depending on whether they developed resistance to targeted therapy within one year.Additionally,patients were classified into mild,moderate,and severe fibrosis groups according to the extent of fibrosis observed.Clinical and pathological characteristics,as well as fibrosis levels,were compared between the two groups.Factors influencing the development of resistance to targeted therapy in patients with EGFR-mutant lung adenocarcinoma were analyzed,and the survival outcomes of patients with varying degrees of fibrosis were evaluated during follow-up.Results In the resistance group,the prevalence of EGFR exon 20 insertion mutations,elevated CA125 levels,and the presence of moderate-to-severe fibrosis were significantly higher compared to the non-resistance group(P<0.05).Multivariate logistic regression analysis revealed that EGFR exon 20 inser-tion mutation(OR=3.691,95%CI:1.043～13.057),elevated CA125 levels(OR=4.104,95%CI:1.160～14.517),and moderate-to-severe fibrosis(OR=3.959,95%CI:1.410～11.115)were independent risk factors associated with resistance to targeted therapy among patients with EGFR-mutant lung adenocarcinoma(P<0.05).The Cox proportional hazards model demonstrated a C-index of 0.72(95%CI:0.65～0.79),with area under the curve(AUC)values for 1-year and 2-year survival predictions of 0.781 and 0.734,respectively.EGFR exon 20 insertion mutation(HR=3.691),moderate-to-severe fibrosis(HR=3.959),and elevated CA125 levels(HR=4.104)were identified as independent prognostic factors for overall survival in these patients following targeted therapy.The median progression-free survival(PFS)for patients with mild,moderate,and severe fibrosis was 10.5 months,7.2 months,and 3.9 months,respectively,while the median overall survival(OS)was 21.4 months,16.1 months,and 11.5 months,respectively.Statistically significant differences in both PFS and OS were observed across the three fibrosis severity groups.(P<0.05).Conclusion The extent of stromal fibrosis in EGFR-mutant lung adenocarcinoma influences resistance to targeted therapy,and the progression of fibrosis is correlated with an unfavorable prognosis.

OBJECTIVE To observe the effect of early warning mechanisms based on nosocomial infection surveil-lance system on precise prevention and control of spread of multidrug-resistant organisms(MDROs)infections in intensive care unit of neurosurgery department.METHODS The dynamic monitoring was performed in the ICU of neurosurgery department of a three-A general hospital by using real-time surveillance system of nosocomial infec-tion from Jan.2023 to Dec.2023.The warning information was sent to the doctor' station immediately once the MDROs infections were detected,the detection of drug-resistant bacteria was carried out for the relevant personnel and their surroundings,and the precise prevention and control measures were implemented.The impact on the iso-lation rate of MDROs,isolation rate of MDROs from the relevant personnel and surroundings,incidence of noso-comial MDROs infections and incidence of surgical site infection was observed after the measures were taken.RESULTS The carrying rate of MDROs was decreased from 21.80％to 5.74％among the relevant personnel after the precise prevention and control measures were taken(P＜0.05),which was improved remarkably among the doctors(decreasing from 21.43％to 6.07％),nurses(decreasing from 23.68％to 3.98％),nursing workers(decreasing from 25.15％to 8.65％),and cleaning staff(decreasing from 25.49％to 5.05％)(P＜0.001).The isolation rate of MDROs was decreased from 20.77％to 7.12％among the surroundings(P＜0.05),which was decreased most remarkably among head cushions(decreasing from 32.28％to 12.13％),bed rails(decreasing from 16.70％to 3.27％),ventilator panels(decreasing from 23.00％to 6.95％)and bedside floors(decreasing from 31.99％to 9.96％)(P＜0.001).The incidence of nosocomial MDROs infections declined from 3.84％to 1.71％(P＜0.05),with incidence of incision infections decreasing from 4.00％to 1.45％(P＜0.05),the inci-dence of intracranial infections decreasing from 2.38％to 0.56％(P＜0.05).CONCLUSION The detection of drug-resistant bacteria is carried out immediately and precisely for the patients with MDROs infection,relevant personnel and their surroundings by using the real-time surveillance system of nosocomial infection,which achieve remarkable effect on prevention of transmission of MDROs and reduction of incidence of hospital-associated infec-tions and surgical site infections.

OBJECTIVE To observe the effect of early warning mechanisms based on nosocomial infection surveil-lance system on precise prevention and control of spread of multidrug-resistant organisms(MDROs)infections in intensive care unit of neurosurgery department.METHODS The dynamic monitoring was performed in the ICU of neurosurgery department of a three-A general hospital by using real-time surveillance system of nosocomial infec-tion from Jan.2023 to Dec.2023.The warning information was sent to the doctor' station immediately once the MDROs infections were detected,the detection of drug-resistant bacteria was carried out for the relevant personnel and their surroundings,and the precise prevention and control measures were implemented.The impact on the iso-lation rate of MDROs,isolation rate of MDROs from the relevant personnel and surroundings,incidence of noso-comial MDROs infections and incidence of surgical site infection was observed after the measures were taken.RESULTS The carrying rate of MDROs was decreased from 21.80％to 5.74％among the relevant personnel after the precise prevention and control measures were taken(P＜0.05),which was improved remarkably among the doctors(decreasing from 21.43％to 6.07％),nurses(decreasing from 23.68％to 3.98％),nursing workers(decreasing from 25.15％to 8.65％),and cleaning staff(decreasing from 25.49％to 5.05％)(P＜0.001).The isolation rate of MDROs was decreased from 20.77％to 7.12％among the surroundings(P＜0.05),which was decreased most remarkably among head cushions(decreasing from 32.28％to 12.13％),bed rails(decreasing from 16.70％to 3.27％),ventilator panels(decreasing from 23.00％to 6.95％)and bedside floors(decreasing from 31.99％to 9.96％)(P＜0.001).The incidence of nosocomial MDROs infections declined from 3.84％to 1.71％(P＜0.05),with incidence of incision infections decreasing from 4.00％to 1.45％(P＜0.05),the inci-dence of intracranial infections decreasing from 2.38％to 0.56％(P＜0.05).CONCLUSION The detection of drug-resistant bacteria is carried out immediately and precisely for the patients with MDROs infection,relevant personnel and their surroundings by using the real-time surveillance system of nosocomial infection,which achieve remarkable effect on prevention of transmission of MDROs and reduction of incidence of hospital-associated infec-tions and surgical site infections.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Objective:The characteristics of women with false elevated testosterone were analyze and the literature was reviewed to provide reference for clinical laboratory identification of false elevated testosterone.Methods:The characteristics of three patients with false elevated testosterone in Peking Union Medical College Hospital were analyzed retrospectively, and the results of different detection platforms and methods for the determination of testosterone levels were compared. International and domestic literatures related to false elevation of testosterone and detection methods of testosterone were searched for a comprehensive analysis from PUBMED and CNKI.Results:The levels of testosterone in 3 female patients were elevated by immunoassay and normal by mass spectrometry. They were excluded from the diagnosis of hyperandrogenemia. A total of 38 literatures related to testosterone detection were retrieved, of which 9 case reports of pseudohyperandrogenemia, among which 12 cases of pseudohyperandrogenemia were reported in 2 domestic literatures in 2021. All cases were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Previous studies have clearly indicated that the result of routine immunoassay in clinical laboratory for the determination of female testosterone have poor correlation with the results of LC-MS/MS, with varying degrees of deviation.Conclusions:Immunoassay tests for female testosterone is susceptible to interference and lead to elevated false results. It is suggested that clinical laboratories evaluate the detection methods used and establish a identification program, and confirm samples with suspected pseudoelevated testosterone elevation using other immune platforms or LC-MS/MS.